CHAPTER XX
The Blood, Plasma, and Related Programs inthe Korean War
Part I. Administrative Background
GENERAL CONSIDERATIONS
When the Korean War broke out on 25 June 1950,1 less than10 years after the United States had entered World War II and less than5 years after that war had ended, the situation was improved over the situationin December 1941 in only one respect: No well-organized blood bank systemwas in operation, but a plan for the supply of whole blood and plasma didexist. The plan had not been implemented, however, because it had beenprepared only a short time before the outbreak of hostilities. It is extremelyunfortunate that planning had not begun earlier, for the need for wholeblood arises whenever combat commences; the Korean War proved again thatwhole blood cannot be provided promptly and efficiently unless supplies,equipment, trained personnel, and a detailed plan for its collection, processing,transportation, and distribution have already been set up.
When the Korean War broke out, the course of events in respect to theblood program was as follows:
1. Blood collecting teams were immediately utilized in Japan, to meetthe first need for blood in the field.
2. These supplies proved inadequate as action became more intense, andrequests for whole blood were sent to the Zone of Interior.
3. The American Red Cross was asked, as in World War II, to become thecollecting agency for blood for the oversea airlift. Fortunately, thisagency already had in operation a blood collecting program to supply bloodto civilian hospitals in the United States, and could build upon it.
4. Later, when the initial program proved inadequate, an Armed ForcesBlood Program and a National Blood Program were established and remainedin operation until the end of active fighting in Korea.
5. A plasma program was also developed which later had to be discontinuedbecause of the risk of serum hepatitis associated with plasma infusions(p. 776). The production of human serum albumin was substituted for theproduction of plasma and was supplemented by the production of plasma expanders(the so-called blood substitutes of World War II).
1 That date should be borne in mind. Unlessthe dates of the various activities to be described are borne in mind andare related to the dates of the Korean War (25 June 1950, when the invasionof South Korea occurred, and 27 July 1953, when the armistice was signed),it will not be realized that, in many instances, the actions were almosttoo late.
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In spite of the expedient nature of the blood program, casualties inKorea never lacked the blood they needed, but the comment is justifiedconcerning this war, as it was concerning World War II, that the efficientway to provide blood for combat casualties is not to wait for the needfor it to arise and then to provide it, at least initially, by a seriesof improvisations.
It is interesting, and somewhat depressing, to note in various reportsof conferences concerning the blood and blood-derivatives program in theKorean War how quickly the World War II experience seemed to have beenforgotten and how the tendency was again evident to concentrate on agentsother than whole blood in the management of combat and other casualties.At a meeting of the Subcommittee on Shock, Committee on Surgery, NRC (NationalResearch Council), on 14 November 1951 (1), Dr. Walter L. Bloomrather impatiently called the attention of the members to the fact thatthe entire philosophy of plasma expanders was questionable. Military andsurgical groups, he said, should define the limitations of these substitutes,and they should be considered as suitable for emergency use only. The firstneed of combat casualties was for whole blood.
THE INTERIM BETWEEN THE WARS
A knowledge of certain background facts is essential to the story ofthe blood, plasma, and plasma-expanders program in the Korean War, beginningwith one major difference between this program and the similar programin World War II: In the Korean War, the program covered civilian defenseas well as military needs. In World War II, the two responsibilities wereentirely separate. The development of the program that provided blood andplasma in the Korean War is best described chronologically.2
1945-46
In September 1945, with the end of hostilities in World War II, thewhole blood program was discontinued immediately, and the plasma programwas terminated as promptly as contracts could be ended. The research thathad been a part of both programs also came to an end except for the plasma-fractionationstudies, which were continued in Dr. Edwin J. Cohn's laboratory at Harvard.
During the interim between the wars, needs for whole blood in Army hospitalswere met within the hospitals. There were no plans, militarily or otherwise,to stockpile reserves of plasma for a national emergency. Indeed, had sucha disaster occurred, there would have been no program to put into effect.The whole blood program would have died between the wars except for thestimulus provided by the activities of the American Red Cross.
2 Unless otherwise indicated, the data in thissection of this chapter are derived from the excellent and well-documentedaccount of the blood, blood derivatives, and plasma-expanders program inthe first 2 years of the Korean War prepared by Col. Patrick H. Hoey, MC,USAF, Chairman of the blood and blood derivatives group (2), andthe convenient account of the historical development of the Office of AssistantSecretary of Defense (Health and Medical) prepared by Miss Elsie LaMantia(3).
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1947
Postwar activities in respect to blood began on 26 July 1947, with thepassage of the National Security Act (Public Law No. 253, 80th Congress),which established the Department of Defense (2). This act providedfor the establishment of NSRB (National Security Resources Board) to advisePresident Harry S. Truman on policies relating to industrial and civilianmobilization. It also provided for the policy just mentioned, the integrationof civilian and military health resources. Finally, it authorized stepsleading toward a more unified control of national medical services.
1948
On 1 January 1948, the then Secretary of Defense, Mr. James V. Forrestal,appointed a Committee on Medical and Hospital Services of the Armed Forces,to study all questions of common interest to the three medical services,with a view to obtaining maximum efficiency and economy in all their operations.Secretary Forrestal's committee consisted of Maj. Gen. Paul R. Hawley (Ret.),chairman (hence, the Hawley Committee); the Surgeons General of the Army,the Navy, and the Air Force; and Rear Adm. Joel T. Boone, MC, USN, whoserved as executive secretary.
In the meantime, the President had appointed a Commission on Reorganizationof the Executive Branch of Government under Ex-President Herbert Hoover(the Hoover Commission), which, by the middle of 1948, had two task forcesworking on the coordination of health and medical matters in the NationalMilitary Establishment:
1. The Task Force on National Security (the Eberstadt Committee).
2. The Task Force on Federal Medical Services (the Voorhees Committee).
The Hawley Committee had recommended that a civilian committee be established,to serve in a consultant and advisory capacity to the Secretary of Defenseon medical and health affairs, and both of these task forces made similarrecommendations.
On 9 November 1948, still another committee was appointed, the ArmedForces Medical Advisory Committee. Its chairman, Mr. Charles P. Cooper(hence, the Cooper Committee), also served as Deputy to the Secretary ofDefense in the fields of medicine and health. The committee consisted ofthe Surgeons General of the three services, General Hawley, and a numberof distinguished civilian physicians.
The recommendations of this committee immediately identified a structuralweakness in the Office of the Secretary of Defense: There was no agencyor personnel in it to implement committee recommendations after the Secretaryhad approved them. The Surgeons General, who were members of the committee,were in the untenable position of making recommendations to the Secretaryand then receiving these same recommendations from him for comment. Thisphase of the problem was solved by removing the Surgeons General from membershipon the Cooper Committee.
1949
In February 1949, the Joint Chiefs of Staff asked that the Cooper Committeeconsider the entire question of "unification or coordination"of the Armed Forces medical services, including the possible developmentof a single medical service. At the end of 2 months of intensive study,the committee recommended against a single Tri-Force medical service. Instead,it recommended that the recommendations of the Eberstadt, Voorhees, andHawley Committees should be implemented and that an organization be establishedin the Office of the Secretary of Defense, with authority to act on committeeand other recommendations.
In accordance with this recommendation, the Medical Service Divisionwas set up in the Office of the Secretary of Defense in May 1949, witha director who had authority to
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establish general policies for the medical services of all three ArmedForces. The Hawley Committee was then dissolved and its subcommittees weretransferred to the Medical Service Division. The Cooper Committee continuedto function.
On 29 September 1949, the Medical Service Division was renamed the Officeof Medical Services. Its current director, Dr. Richard L. Meiling, wasnamed Director of Medical Services and Assistant to the Secretary of Defensefor Medical Affairs. Dr. Meiling established a Medical Advisory Councilconsisting of the three Surgeons General, who met weekly in his office.After the Korean War broke out, the Surgeon General of the U.S. PublicHealth Service and the Medical Director of the Veterans' Administrationwere added to the membership of the Council.
1951
The Cooper Committee continued to function throughout 1950, as did theOffice of Medical Services. On 2 January 1951, the Cooper Committee andthe Office of Medical Services were replaced by an Armed Forces MedicalPolicy Council, whose director was named Assistant to the Secretary ofDefense for Health Affairs. The Council consisted of the three SurgeonsGeneral; a dental surgeon; and two other civilians, Dr. Isidor S. Ravdinand Dr. W. Randolph Lovelace III, both of whom had had wide medicomilitaryexperience. With the establishment of this council, there was now fullycarried out, for the first time, the intent of Congress as expressed inthe National Security Act of 1947 (p. 715). Also for tile first time:
1. There existed in the DOD (Department of Defense) an organizationwith authority to coordinate medical policy within the department as wellas between the department and other governmental agencies and civilianmedical and allied health organizations.
2. The three Surgeons General had authority to represent their respectivedepartments in the formulation of medical and health policies at the levelof the Department of Defense.
1953
There were no further changes of consequence in the medical structureof the Department of Defense until 1 April 1953, when DOD Directive 5136.4established the position of Assistant to the Secretary of Defense (Healthand Medical) in the Office of the Secretary of Defense. This was a considerableforward step. All medical and health policies, plans, standards, criteria,and other aspects of medical service could now be reviewed in the Officeof the Assistant to the Secretary of Defense (Health and Medical), whoalso maintained liaison, on both a national and an international basis,with all other governmental and civilian health and medical agencies andassociations. The advice of the Surgeons General was made available tothe Assistant to the Secretary of Defense as necessary.
On 30 June 1953, Congress approved Reorganization Plan No. 6 for theDepartment of Defense. This plan authorized, among nine Assistant Secretariesof Defense, an Assistant Secretary of Defense (Health and Medical); thus,in effect, regularizing and giving authority to the plan adopted in theOffice of the Secretary of Defense in April 1953. On 2 September 1953,the Secretary of Defense, by DOD Directive 5136.4, established a Healthand Medical Advisory Council composed of civilians.
Meantime, the NSRB chairman, former Secretary of the Air Force W. StuartSymington, had set up a Health Resources Office, which reported directlyto him and which was responsible for the development of plans and recommendationsrelative to mobilization and allocation of health resources and for themedical aspects of civilian defense. Dr. Howard A. Rusk was appointed chairmanof the special committee to advise Mr. Symington on broad policies relatingto health resources. When these last actions were taken, the armisticeof 27 July 1953 had already ended the fighting in the Korean War.
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Comment
The organizational steps just outlined were all extremely importantand are entirely relevant to the blood program in the Korean War. Theymeant that, for the first time, the Department of Defense would coordinateand integrate all phases of its health program, including the blood program,to with broad policies established at the presidential level. It also meantthat recommendations of task groups concerning coordination with otheragencies would no longer be conflicting, since both military and civiliannational health agencies would now act jointly, to meet the overall requirementsof national mobilization.
INITIAL STEPS IN THE NATIONAL BLOOD PROCUREMENTPROGRAM
One of the joint problems that came to the attention of the Directorof Medical Services, Office of the Secretary of Defense, in 1949, soonafter the establishment of his position, concerned military and civilianrequirements for whole blood and blood derivatives. An inventory of existingstocks of plasma and other derivatives, early in October of that year,indicated that they were very low (p. 772); that there was no coordinatedplan to expand them; and that, if an emergency should arise, there wereno facilities for their augmentation. Only four laboratories were producingplasma commercially. Their combined annual production was about 300,000units, and they had no incentive to expand it, for plasma was a nonprofititem.
This situation was viewed with the seriousness it deserved, and, on26 October 1949 the Director of Medical Services, acting for the Secretaryof Defense, appointed a task group to study the whole problem of providingblood, blood derivatives, and plasma substitutes (expanders) for the ArmedForces in peacetime and in war. The investigation was to cover such relatedmatters as supplies and equipment for transfusion; training of personnelin the technical aspects of procurement, control, storage, transportation,and use of blood and blood derivatives to meet expanded requirements ofan emergency program; and the development of a system of logistics capableof meeting requirements on a global scale (4).
The members of this Task Group included Capt. Hilton W. Rose, MC, USN;Capt. Lloyd R. Newhouser, MC, USN; Col. William S. Stone, MC, USA; andLt. Col. (later Col.) Alonzo A. Towner, Jr., MC, USAF. The comprehensivereport which they submitted to the Secretary of Defense on 15 March 1950(4) had been approved by the Military Medical Advisory Council (the predecessorof the Armed Forces Medical Policy Council) on 14 February 1950. On 5 May1950, the report was approved by the Secretary of Defense, in a memorandumaddressed to the three Service secretaries, and thus became official DODpolicy (5).
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As of this date, the retrenchment that had characterized all activitiesrelating to blood in the postwar period began to be reversed, but it wasalmost too late: It was less than 2 months later that the outbreak of hostilitiesin Korea required the immediate translation of still theoretical conceptsof a national emergency into a stern reality, though, fortunately, severaladditional weeks were to elapse before a request for whole blood carneto the Zone of Interior from the combat area.
REPORT OF TASK GROUP
The report by the Task Group to the Director of Medical Services on"A Suggested Program of Whole Blood and Blood Derivatives for theArmed Forces" in March 1950 analyzed the problem; summarized the commercialpotential for dried plasma; and outlined the requirements for stockpilingplasma and for the collection, distribution, and use of whole blood. Insubstance, the report was as follows:
The Problem
Whole human blood, required in modern therapy, cannot be stockpiledbecause it is extremely labile; it requires constant refrigeration andprecise technical control and handling; and, under present procedures,it cannot be stockpiled for more than 30 days.
The Armed Forces can operate blood banks to meet peacetime requirementsbut cannot supply wartime necessities. It is not desirable to use combattroops as donors. Neither in peacetime nor in war can the Armed Forcesprovide blood derivatives.
The reserves of blood derivatives left from World War II will largelybe outdated by the end of 1950, though some can be reprocessed, at abouta third of the cost of new products. The total amount that has been reprocessed,however, will provide only a third to a half of the required war reserve(set at a million units) for the Armed Forces. Reprocessing and handlingcan be carried out only by specially trained personnel, with considerabletechnical background.
The present civilian program for blood and blood derivatives is notadequately organized or planned to meet the requirements of the Armed Forces,the civil defense program, and other civilian needs in time of war.
The wartime needs can therefore be met only by a national program, whichmust be organized in peacetime.
The Present Situation
At this time (March 1950), the blood procurement situation in tile UnitedStates is as follows:
1. Twenty-one blood banks are in operation in Armed Forces installations.All have standardized equipment and supplies, are centrally controlled,and would be capable of
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operating under wartime conditions. Four of these banks are each collecting300 pints a month. The others are collecting from 50 to 250 pints each.
2. Some two or three thousand nonprofit blood banks are in operation,most of which belong to the American Association of Blood Banks.3About half of these banks actually draw and process blood. The remainder,whose chief function is to serve their own hospitals and adjacent ruralcommunities, act merely as storage and issue points for blood drawn elsewhere.When the operations of these banks are entirely intrastate, they are underno control and their equipment, supplies, and procedures are not standardized.If, however, these hospital banks would adopt NIH (National Institutesof Health) standards and could produce significant surpluses above theirown needs, they could contribute to the national blood program.
3. Four commercial blood banks are in operation in New York. Othersare in operation in Dallas, San Francisco, and Chicago, and there are afew smaller banks in other locations. They lack trained personnel and uniformstandards, and it is doubtful that they could expand significantly in timeof war.
4. Only three commercial biologic laboratories are now collecting bloodfor plasma: Cutter Laboratories, 100,000 pints per year; Hyland Laboratories,40,000 pints per year; and Sharp & Dohme, 150,000 pints per year. Allthese laboratories produced plasma during World War II, and Sharp &Dohme also produced plasma fractions, which only Cutter Laboratories isnow producing.
Equipment can be manufactured by a number of larger firms as well assome smaller firms, on reasonably short notice, with certain exceptions.There would be difficulty, for instance, supplying 15- to 20-gage needlesfor intravenous and donor sets if they should be required at once, thoughwithin 6 months, well over a million could easily be produced.
Recommendations
The Task Group, on the basis of the World War II experience factor, set the replacement requirements for each combat casualty who survived to be hospitalized at one 500-cc. unit of whole blood and the same amount of plasma or other blood-derivative. Only group 0 blood would be used, preserved in ACD (acid-citrate-dextrose) solution; typed for the Rh factor; and refrigerated at 4° to 10° C. from collection until administration.
The Task Group did not think that the Department of Defense of itselfcould procure such amounts of blood and blood derivatives and thereforerecommended immediate coordination with other interested governmental andnon-governmental agencies in the development of a program that would meetthe standards and fulfill the requirements of the Department of Defense,as well as civilian requirements, in peacetime and in wartime.
The Task Group also recommended that the Department of Defense assumeresponsibility for the direction and implementation of the whole bloodprogram and its coordination with other agencies, including the AmericanRed Cross; Armed Forces blood banks; commercial biologic agencies; andnonprofit and commercial blood banks. It was noted that, if these variousseparate groups were to serve as an integrated national blood group, theymust be tightly controlled because of the multiple risks attending theuse of blood, including its perishability; incompatibility; possible errorsin grouping, typing, and cross-
3 Although this is the figure used by the TaskGroup, it seems high unless every hospital laboratory storing a few pintsof blood is considered a blood bank.
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matching; contamination from unsound techniques; unsatisfactory conditionsof storage; and possible transmission of such diseases as malaria, syphilis,and hepatitis.
Finally, the Task Group recommended that the Director of Medical Servicesshould be responsible for, and direct, the continued study and implementationof the Department of Defense blood program and till coordination of tileactivities of tile department with those of other agencies.
In addition to these basic recommendations, the Task Group made tilefollowing specific recommendations:
1. That transfusion supplies, equipment and procedures as standardizedfor the Armed Forces be standardized by all participating agencies, withthe Director of Medical Services, DOD, taking the necessary steps to accomplishthis objective.
2. That biologic standards for blood and blood derivatives be uniformthroughout the country, with necessary legislation to assure the adoptionof the desired criteria.
3. That all military combat plans include logistic requirements forblood.
4. That all blood donations be voluntary.
5. That a war reserve be established for plasma, plasma substitutes(expanders), and transfusion supplies and equipment, with economical maintenanceof estimated requirements, and that a system be devised for replacing deterioratedsupplies, so as to maintain a satisfactory and economical reserve.
6. That research on blood preservation and on improvement of transfusionequipment be emphasized by the Department of Defense. It was suggestedthat the sum of $100,000 be allocated annually for the next 2 or 3 yearsto provide for additional research in these fields.
It was essential, the report of the Task Group concluded, that the agencyfor civilian and military whole blood requirements that was developed inpeacetime should be of such a character that it could be expanded in timeof war to meet logistic requirements and organization, training, and operatingprocedures. Such an agency should have ramifications down to the communitylevel, so that, in an emergency, all potential sources of blood could betapped. Also, the personnel of such an agency should be so organized andtrained that, in time of war, its existing operational activities wouldsimply have to be expanded.
Continuing misconception of requirements for whole blood.- Anotherdepressing phase of the development of the blood program after World WarII was the position taken by the Director of Military Supply and the ActingChief, Requirements Coordination, Munitions Board, in April 1950, in connectionwith the recommendations of the Task Force (6).
Both granted the necessity for a national blood program, the importanceof its prompt development, and the wisdom of correlating military and civilianrequirements, policies, standards, and procedures. These officers, however,could not agree with the recommendation that the Director of Medical Services,Department of Defense, be responsible for, and direct continued study andimplementation of, the DOD blood program and its coordination with otheragencies. Nor could they agree that the director should take steps to accomplishstandardization of related military and civilian supplies, equipment, andprocedures, for the following reasons:
1. Blood and blood derivatives are considered a supply commodity ormunition.
2. The Munitions Board is legally responsible for developing coordinatedpolicies relating to military supplies.
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3. The blood program is no different from other programs and must behandled in the same manner as other programs.
It would be hard to imagine a more total misconception of the requirementsand implications of a whole blood program. The position of these officers,obviously taken in complete ignorance of how whole blood must be procured,handled, and administered, represented everything the Subcommittee on BloodSubstitutes, NRC, the Blood Transfusion Branch, Office of The Surgeon Generaland other agencies and personnel had fought against during World War II.Had these ideas been permitted to prevail, the entire whole blood programfor Korea would have foundered and many lives would probably have beenlost from the use of incorrectly handled blood. The controversy had nochance to develop, however, for the Secretary of Defense, in August 1950,gave the operational responsibility of the blood program to the Directorate,Armed Services Medical Procurement Agency, and directed the Director ofMedical Services, DOD, to prescribe the policies and standards for theimplementation of the program (7).
IMPLEMENTATION OF TASK GROUP PROPOSALS
In May 1950, Dr. Meiling assumed the chairmanship of a Blood and BloodDerivatives Committee in the Department of Defense, which had the functionof determining the need of the Armed Services for plasma and whole blood.He at once appointed an ad hoc committee on blood and blood derivativesto serve in an advisory capacity to him.
At its meeting on 28 July 1950- a month after the outbreak of the KoreanWar- the Military Medical Advisory Group, in a full discussion of the Bloodand Blood Derivatives Program, decided that the American Red Cross shouldbe the coordinating blood procurement agency for the Department of Defenseand that the Armed Services Medical Procurement Agency should be assignedoperational responsibility for the program in the Department of Defense.
A week later, when the Secretary of Defense formally assigned operationaland technical responsibility for the program to the Directorate of theArmed Services Medical Procurement Agency, the directorate at once requestedthe chief of this agency to establish a blood and blood derivatives divisionwithin the agency. At the same time, the directorate requested that thedirector of Medical Services, Office of the Secretary of Defense, grantmembership in the Task Group studying the Whole Blood and Blood DerivativesProgram to the chief of the Procurement Agency and the chief of its Bloodand Blood Derivatives Division.
All of these requests were granted. Col. Douglas B. Kendrick, MC, whohad been in charge of the Army blood program in World War II from its inceptionuntil November 1944, was named chairman of the Blood and Blood DerivativesGroup, which position he held for the next 2 years. On 1 May 1952, he wassucceeded by Col. Patrick H. Hoey, MC, USAF, who held this position
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CHART 11.-Structural organizationof blood and blood derivatives program, 1949
until the end of the war. Lt. Col. Arthur J. Carbonnell, MC, was theArmy member of the group from 15 February 1951 to 18 February 1952.
On 12 September 1950, the Armed Services Blood and Blood DerivativesDivision (which became the Armed Services Blood and Blood Derivatives Groupa few days later) was officially established. It consisted of a professionalstaff and of administrative, field, laboratory, and liaison branches. Itsmission was as follows:
1. To provide whole blood for FECOM (Far East Command).
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CHART 12.-Structural organizationof blood and blood derivatives program, 1950
2. To provide whole blood for the production of dried plasma for theDOD War Reserve stockpile.
3. To reprocess outdated stocks of plasma produced in World War II.
4. To investigate developments in the field of plasma-expanders.
The actual division of responsibility for the blood and plasma programwas that the Committee on Blood and Blood Derivatives recommended policyand the Blood and Blood Derivatives Group had the operational responsibilityfor its implementation.
The structural evolution of the blood and blood derivatives programin the Department of Defense between 1949 and 1953 is shown in charts 11,12, and 13.
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CHART 13.-Structural organizationof blood and blood derivatives program, 1952
NATIONAL RESEARCH COUNCIL
Organization and Functions
The Subcommittee on Blood Substitutes, Committee on Shock, Divisionof Medical Sciences, NRC, had done such important work on the collectionand distribution of whole blood and its derivatives, and had supervisedso much valuable research, in World War II, that it was reactivated in1948 as the Committee on Blood and Blood Derivatives. The work of the subcommitteehad lapsed at the end of World War II, but in the interim before its reconstitution,the American Red Cross, which was entrusted with returning surplus
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blood derivatives to the people of the United States who had contributedthem, used many of the same physicians who had served on the subcommitteeon its own Committee on Blood and Blood Derivatives, thus maintaining theircontacts with the blood program. The reason for the reactivation of theWorld War II subcommittee was the realization that a national emergencywould demand huge amounts of blood and blood derivatives for civilian aswell as military uses, and the subcommittee was promptly enlarged becauseof the complexity of the problems to be solved.
As soon as it was activated, the Committee on Blood and Blood Derivativeswent actively to work. At its first meetings, the stage of existing knowledgein the special fields of blood and blood derivatives was assessed. Ad hocresponsibilities were delegated to particular members, who were directedto investigate equipment, preservatives, and sterilization of blood andblood derivatives. Contracts for research in the field of blood and bloodderivatives were reviewed for the National Military Establishment and theVeterans' Administration.
At the meeting of the Committee on Blood and Blood Derivatives on 3December 1949, much of the agenda concerned general principles and policies(8). Dr. Charles A. Janeway, chairman of the committee, pointedout that the blood program was an integral part of national defense andthat the counterpart of this committee during World War II had sat as anadvisory group to all agencies and organizations concerned in any way withblood. Its successor committee would perform the same functions.
Dr. Meiling, Director of Medical Services, Office of the Secretary ofDefense, explained the functions of his office. Dr. Cohn spoke of the importanceof the cooperation of all agencies concerned in the blood program. DuringWorld War II, he noted, no decision regarding blood products was ever madewithout the approval of the Laboratory of Biologics Control, National Institutesof Health. Many of these matters were within the province of the Food andDrug Administration. The World War II subcommittee had been careful neverto recommend any action or procedure on the basis of research alone; thepracticability of all recommendations was tested by pilot operations. Itwas possible that blood might be collected by some agency other than theRed Cross, which was now operating with no obligations to turn over anymaterial to the Armed Forces in an emergency. The important considerationwas that there must be a single blood program, cooperative and not competitive.In conclusion, said Dr. Cohn, "Failure to act until an emergency entailsaccepting the responsibility for being unprepared."
By this time (December 1949), a great many problems had already beenreferred to the Committee on Blood and Blood Derivatives, NRC, and manymore were to be referred to it before and during the Korean War. The recommendationsmade concerning them are discussed under appropriate headings. The contributionof the committee was incalculable. There were, however, many perfectionistson it, and, at intervals, the more practical-minded members felt constrainedto remind them of current needs. If, for
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instance, excessive and unnecessary standards of accuracy were required,the volume of production would be impractically small. The point at issuewas the quick determination of what agents were safe to put into people'sveins from the standpoint of immediate or delayed antigenicity and toxicity.
At the December 1949 meeting, an ad hoc committee was appointed to considerall phases of the blood program, talk with civilian defense planning groupsand other agencies, and then make recommendations to the Committee. Themembership of this committee included Dr. Janeway, Dr. Cohn, Dr. Ravdin,Dr. Carl V. Moore, and Dr. Charles A. Doan.
At this same meeting, a number of changes were recommended in the 13May 1943 agreement with the American Red Cross, both to bring the textinto agreement with the current organizational situation and to indicatethat collections of blood were for civilian needs as well as for needsof the Armed Forces. It was also recommended that a committee be formedto serve in an advisory capacity to the American Red Cross, Departmentof Defense, National Institutes of Health, Veterans' Administration, AtomicEnergy Commission, and whatever agency would be responsible for civiliandefense.
Some of the problems referred to the Committee on Blood and Blood Substitutes,NRC, might be mentioned here, to indicate their range and importance:
1. Could not a preservative solution be devised in whichblood for transfusion and blood intended for plasma could both be collected?
2. What measures should be adopted to safeguard plasma tobe stockpiled while it was being processed?
3. How could transmission of virus infections from plasmainfusions be prevented?
4. Could the dating period of blood be extended?
5. How could the incidence of clots in collected blood bereduced?
6. Would siliconing the inside of collecting bottles improvethe product?
7. What was the present estimate of the value of gelatin?Oxypolygelatin? Dextran? Periston? Inquiries concerning these and otherplasma-expanders were to come up repeatedly.
THE AMERICAN RED CROSS PARTICIPATION
The Committee on Blood and Blood Derivatives, DOD, recommended to theSecretary of Defense on 2 October 1948 and 10 January, and 13 February1949 that the American Red Cross be officially designated as the agencyto collect blood for the National Military Establishment. The Subcommitteeon Burns, Committee on Surgery, NRC, also recommended, in November 1949,that some large-scale machinery for the collection of blood be set up.
On 20 July 1950, the Secretary of Defense, then Mr. Louis Johnson, recommendedto the Chairman of the American Red Cross, then Gen. George C. Marshall,that the relation which had existed during World War II between that organizationand the War and Navy Departments be reestablished between it and the Departmentof Defense to meet the needs of the Armed Forces for blood and blood derivatives(9). On 22 July, General Marshall replied that the Red Cross wouldat once increase its blood collections and that Adm.
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Ross T McIntire, MC, USN (Ret.), who was assigned to the Red Cross NationalBlood Program, would be assigned to work with Dr. Meiling on the necessaryplans (10).
On 30 August 1950, Mr. Symington, as Chairman, NSRB, formally requested,through General Marshall, that the American Red Cross accept the responsibilityfor coordinating a nationwide civil defense blood program for recruitmentof donors and for the collection, storage, processing, and preparationfor shipment of blood and blood derivatives collected under the program(11). On 7 September 1950, General Marshall replied that the RedCross would accept the specified responsibilities, on the assumption thatlocal civil defense units would coordinate their planning with the nationalprogram (12).
The Boston Agreement.- Meantime, on 11 and 12 July 1950, the Committeeon Blood and Blood Derivatives, American Red Cross, and the Red Cross MedicalAdvisory Committee on the National Blood Program met in Boston with representativesof the American Medical Association, the American Association of BloodBanks, and the American Hospital Association, to determine their relationswith each other. The so-called Boston Agreement provided that these fouragencies would cooperate with each other in peacetime and with the NationalSecurity Resources Board in time of war (13). In peacetime, therewould be a free exchange of blood on a unit-for-unit basis, as would bestserve community needs. As a matter of principle, surplus blood would begiven to the Red Cross or other designated agencies for conversion intoblood derivatives. In time of war, procurement agencies would be set upin communities not already served by Red Cross regional blood centers.
It was recognized at this conference that standardization of equipmentfor the blood program was desirable in peacetime and imperative in a nationalemergency. It was also recommended that all blood banks cooperating inthe joint program should meet the minimum standards of the National Institutesof Health.
Part II. The Whole Blood Program
Section I. Blood Procurement in Japan
INITIATION OF PROGRAM
The blood program for the Korean War began in Japan. Here, in the interimbetween the wars, a few Army hospitals, all of which were authorized toprovide definitive surgical care, collected blood from donor lists in accordancewith Army Regulations No. 40-1715. These hospitals, located mainly in theTokyo and Osaka areas, operated small banks, sufficient for their own needs.
Within 10 days after the outbreak of the Korean War (then consideredonly a police action), it became apparent that the Armed Forces in combatwould
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require blood in large amounts, and plans were at once made for a centrallycontrolled blood procurement program in Japan (2, 14). Three initialsteps were taken:
1. A special blood bank unit was formed from personnelof the 406th Medical General Laboratory to operate a blood bank there.As the bank was first set up, it consisted of a collecting and processingcenter in Tokyo, a transportation and courier center (later called theBlood Bank Storage Depot and Shipping Section) in Tokyo, and an advanceblood bank depot at the 118th Station Hospital in Fukuoka.
2. 8090th Blood Bank Laboratory Detachment was organizedas a temporary duty unit in August 1950 and was assigned to the 406th MedicalGeneral Laboratory. The detachment consisted of two mobile bleeding unitsand a laboratory unit. It functioned until 5 November 1951, when it wasreplaced by the 48th Blood Bank Laboratory Detachment.
3. Blood bank sections were activated in Korea, as organicparts of medical supply depots.
The necessary organizational steps were taken quickly, donors were recruited(fig. 167), and the first shipment of blood from Japan (69 bottles) wassent to the 8054th Evacuation Hospital in Pusan, Korea, on the night of7 July 1950.
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SUBSEQUENT DEVELOPMENTS
For the first 5 weeks, the blood bank operated on an emergency basis,as troop strength built up rapidly and field medical installations weresent to Korea to care for casualties. It then became evident that the combatin which the U.S. troops were engaged would be considerably more than alocal engagement, rapidly terminated, and that blood bank operations mustbe put on a firmer basis.
The first step was to determine a working ratio between anticipatedcasualties and future needs for whole blood. By the use of figures suppliedby the Assistant Chief of Staff, G-1 (personnel), which were availabledaily and were regarded as accurate, a ratio was developed of 0.82 pintof blood to each casualty wounded in action and surviving to be hospitalized.
At this time, the donor panels in the Tokyo-Yokohama areas could supply,at the most, 100 pints of blood per day. Official approval had not yetbeen obtained for the use of Japanese donors, and, until the end of 1950,blood was secured only from noncombatant Army, Navy, and Air Force personnel;Allied Forces personnel; civilian employees of the U.S. Armed Forces; foreignnationals other than Japanese; and adult dependents of these groups.
When the needs of anticipated casualties were surveyed realistically,it was at once clear that available local donors could not possibly meettheir requirements, and a request for blood was made on 15 August 1950to the Zone of Interior (15) and promptly acceded to (p. 713). Itwas hoped, however, that local sources could continue to meet emergencyneeds and could also supply group-specific and Rh-specific bloods, which,as in World War II, would not be sent from the Zone of Interior.
After 6 months of combat, and after blood from the Zone of Interiorhad been reaching Korea for over 4 months, it was found that the ratioof blood to casualties had undergone a change. The factor then used, 3.32pints of blood for each combat casualty who was hospitalized, was basedon an experience factor for logistic blood requirements that included notonly the blood actually used but the blood wasted in storage and distribution,a wastage that was then considered unavoidable in such a perishable productas blood in such combat circumstances as Korea.
The first bloods collected in Japan were transported from the bank atthe 406th Medical General Laboratory to the advance depot at the 118thStation Hospital in Fukuoka in railway baggage cars, three of which hadbeen equipped with reach-in reefers (refrigerators) for this purpose. Later,air transport was used almost exclusively (p. 752).
JAPANESE DONORS
Techniques of collection of blood in Japan generally followed thoseemployed in Red Cross bleeding centers in World War II until donationsfrom Japanese began to be accepted, at the end of 1950. Then, certain changesin
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procedure were necessary. For one thing, language difficulties madeit necessary to employ a small Japanese staff, as well as to use nursesand volunteers supplied by the Japanese Red Cross (fig. 168). For another,Japanese medical authorities were at first reluctant to depart from theirstandard practice of limiting donations to 200 cc. Some concessions, naturally,had to be made to the small size of the Japanese, who could not routinelygive 500 cc. of blood as did U.S. donors, and tables of maximum collectionsfor bleeding them and others of similar stature were therefore worked out(table 34). When these standards were adhered to, there was never any evidenceof immediate or delayed harmful effects from the donations.
TABLE 34. - Authorized collection of blood,from Japanese nationals and other donors of small stature
[Per pound of body weight]
| Body weight | Authorized collection | Blood and anticoagulant | |||
| Male | Female | Male | Female | Male | Female |
| Pounds | Pounds | cc. | cc. | cc. | cc. |
| 100 | 105 | 250 | 230 | 370 | 350 |
| 105 | 110 | 260 | 240 | 380 | 360 |
| 110 | 115 | 275 | 250 | 395 | 370 |
| 115 | 120 | 290 | 260 | 410 | 380 |
| 120 | 125 | 300 | 275 | 420 | 395 |
| 125 | 130 | 310 | 285 | 430 | 405 |
| 130 | 135 | 325 | 295 | 445 | 415 |
| 135 | 140 | 330 | 310 | 450 | 430 |
| Over | 145 | Maximum | 320 | Maximum | 440 |
| --- | 150 | --- | 330 | --- | 450 |
| --- | Over | --- | Maximum | --- | Maximum |
PUBLICITY
Publicity for the blood program in, Japan was provided by the U.S. andthe Japanese Red Cross, the Armed Forces radio station in Tokyo, the Pacificedition of the Stars and Stripes, and similar sources. Documentary filmsshowing blood bank operations were made by the Army Signal Corps and byJapanese photographers for use locally as well as in the United States.Posters, pictures, and stories were provided for both local and statesiderelease by General Headquarters and Joint Logistical Command Public InformationOffices.
On one occasion, a spectacular air rendezvous was made with the U.S.S.Boxer, then in Korean waters; her crew donated 2,407 pints of blood in4 days. On another occasion, Gen. Douglas MacArthur publicly received atoken
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shipment of blood from the German employees of a commercial airline.On 4 July 1951, the medical section of the Joint Logistical Command, ata carnival at Meiji Park, staged a complete demonstration of blood bankoperations; the processing of the blood was carried out in full view ofthe spectators. The Gallon Club, instituted in August 1951, had almost150 members within a few weeks.
STATISTICAL DATA
During fiscal year 1951, a total of 43,479 donors were interviewed atthe blood bank in Japan and more than 39,000 pints of blood were collectedfrom them through the efforts of the central bank and its mobile teams.The chief reason for refusing donors was a history of disease, includingmalaria and infectious hepatitis, and of hypertension. Only 175 positiveserologies were encountered, 0.4 percent.
The low incidence of Rh-negative blood (table 35), a Japanese racialcharacteristic, limited to a considerable degree any extensive use of Japanesedonors if Rh-compatible blood was to be given to a recipient populationcomposed chiefly of Americans and Europeans. In the first 2,784 Japanese
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bloods collected, there were only 19 Rh-negative bloods, 0.68 percent.The distribution according to type in 39,100 units of Japanese blood collectedin 1951 is shown in table 35. Statistics for 1952 and 1953 were of thesame order.
In 1951, almost 25 percent of the blood received in Japan by the bloodbank was procured in that country (table 36). Something over a third ofthis amount was collected in Tokyo. The remainder was collected by mobileteams at various stations in the vicinity, including 6,456 pints from theU.S. Naval Hospital in Yokosuka and 3,308 pints from the U.S. Army Hospitalin Yokohama.
TABLE 35. - Type distribution of bloodcollected in Japan, 1951
Blood type |
| Blood type |
Number | Percent | |
Type O: | ||
| Rh positive, high titer | 10,378 | 56.2 |
| Rh positive, low titer | 5,142 | 29.7 |
| Rh negative, high titer | 1,848 | 10.0 |
| Rh negative, low titer | 1,070 | 5.9 |
| 18,438 | 47.1 |
Type A: | ||
| Rh positive | 12,309 | 84.5 |
| Rh negative | 2,251 | 15.5 |
| 14,560 | 37.2 |
Type B: | ||
| Rh positive | 3,722 | 85.9 |
| Rh negative | 608 | 14.1 |
| 4,330 | 11.0 |
Type AB: | ||
| Rh positive | 1,511 | 85.2 |
| Rh negative | 261 | 14.8 |
| 1,772 | 4.7 |
All types: | ||
| Rh positive | 33,062 | 84.5 |
| Rh negative | 6,038 | 15.5 |
| 39,100 | --- |
TABLE 36. - Receipts of blood, TokyoBlood Depot, 1951-52
Month |
| 1952 | ||||
| Received from Zone of Interior | Total | Collected in Japan | Received from Zone of Interior | Total | |
| Number | Number | Number | Number | Number | |
January | 2,614 | 7,060 | 9,674 | 3,274 | 9,648 | 12,922 |
February | 4,233 | 9,264 | 13,497 | 3,509 | 8,328 | 11,837 |
March | 2,319 | 9,224 | 11,543 | 2,218 | 8,472 | 10,690 |
April | 2,952 | 13,466 | 16,418 | 2,163 | 8,640 | 10,803 |
May | 3,287 | 15,032 | 18,319 | 2,177 | 8,976 | 11,153 |
June | 3,053 | 10,528 | 13,581 | 2,725 | 7,920 | 10,645 |
July | 2,454 | 10,392 | 12,846 | 1,986 | 7,368 | 9,354 |
August | 1,926 | 9,048 | 10,974 | 2,356 | 7,415 | 9,771 |
September | 2,722 | 11,496 | 14,218 | 2,555 | 7,558 | 10,113 |
October | 5,769 | 14,424 | 20,193 | 5,882 | 9,360 | 15,242 |
November | 3,871 | 10,632 | 14,503 | 2,337 | 8,112 | 10,449 |
December | 3,572 | 8,639 | 12,210 | 3,321 | 8,760 | 12,081 |
| 38,772 | 129,205 | 167,977 | 34,503 | 100,557 | 135,060 |
Section II. The Development of the Whole BloodProgram in the Zone of Interior
THE FIRST YEAR
Collections of blood by the American Red Cross for the Department ofDefense began in August 1950. By the middle of 1951, those responsiblefor the blood and plasma program in the Department of Defense were increasinglyconcerned because procurement was lagging far behind requirements and commitments(2). Whole blood requirements for the Armed Forces were being met, butreserves of plasma were in alarmingly short supply because of lack of bloodto process.
On 20 July 1951, the chairman of the Armed Forces Medical Policy Council,Dr. Lovelace, projecting present trends into the future, reported to theSecretary of Defense that the blood procurement program of the Departmentwas in serious need of revision. On the basis of a report made to the PolicyCouncil on 16 July 1951 by an ad hoc committee,4 Dr. Lovelacerecommended that the program be referred to the newly established HealthResources Advisory Committee of the Office of Defense Mobilization forinformation and assistance. He also recommended that the American Red CrossBlood Donor
4 This committee consisted of Colonel Kendrick,Chairman; Captain Newhouser, Department of Defense; Maj. Gen. David N.W. Grant, USAF (Ret.), and Mr. Richard Swigart, American Red Cross; andDr. F. Douglas Lawrason NRC.
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Program be stimulated with the assistance and cooperation of the Departmentof Defense, as follows:
1. There should be a continuously active advertising campaignfor donors.
2. Additional collection centers should be established.
3. Blood procurement should be stimulated on the local levelin every possible way, especially when blood banks were located in heavilypopulated areas and within reasonable shipping distance of existing plasmaplants.
4. The Red Cross should be requested to establish prioritiesfor blood for the Department of Defense.
In addition to these steps, which should be taken jointly with the AmericanRed Cross, Dr. Lovelace recommended that the Department of Defense:
1. Should establish a military blood collection programto reach military personnel and civilian employees on military bases.
2. Should institute a policy of purchasing plasma from civiliancommercial laboratories which met NIH specifications.
THE ARMED FORCES BLOOD DONOR PROGRAM
On 2 August 1951, in a DOD directive, the Acting Secretary of Defense,Mr. Robert D. Lovett, announced the establishment of an Armed Forces BloodDonor Program, "to provide a continuous and vigorous campaign, inconjunction with the Red Cross, to persuade the civilian and military populationto contribute whole blood to the Armed Forces" (16). The programwould be launched on 10 September 1951.
The Director of Information, Office of the Secretary of Defense, wouldbe responsible for directing publicity and information concerning the program.Policy guidance would be provided by the Armed Forces Medical Policy Council,Office of the Secretary of Defense. All programs would be coordinated throughthe Armed Services Medical Procurement Agency.5
The success of the military program was immediate (figs. 169-172). Withina few months there were more donors than facilities to handle them. Theattitude of the Air Force was typical of all the Services. On 6 September1951, the Air Adjutant General directed that "every level of commandof the Air Force give its whole-hearted cooperation to insure the successof the program." Effective on 10 September, the date of initiationof the program, or as soon thereafter as possible, Air Force collectioncenters would be established at Lowry Air Force Base, Denver, Colo., LacklandAir Force Base, San Antonio, Tex., and Sheppard Air Force Base, WichitaFalls, Tex. Tentative sites were also selected for other collection centers,to be activated as necessary later.
5 The National Advertising Council worked closelywith the Director of Information, DOD, and deserves much of the creditfor the outstanding success of the program.
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FIGURE 169.-Official poster of ArmedForces Blood Donor Program instituted September 1951.
THE NATIONAL BLOOD PROGRAM
One of the major problems of blood procurement was the necessity ofproviding blood for civil defense as well as for combat needs. It was studiedby Dr. Rusk, Chairman, Health Resources Advisory Committee, and his staff;on their recommendation, on 10 December 1951, President Truman issued anExecutive order to the effect that the Director of the Office of DefenseMobilization would provide, within his office, "a mechanism for theauthoritative coordination of an integrated and effective program to meetthe nation's requirements for blood, blood derivatives and related substances"(17). In this order, it was pointed out that a subcommittee on bloodhad been appointed within the Health Resources Advisory Committee, to develop"a single National Blood Program encompassing all phases of the problem."It was the President's desire that the activities of all departments andagencies in the field be coordinated "through this mechanism."
736
737
On 18 February 1952, the Subcommittee on Blood (the Cummings Committee)submitted a statement of basic principles upon which the reorganized programshould be based. The substance of this report, which was immediately transmittedto the Secretary of Defense, Mr. Lovett, was as follows (18):
1. The program created to meet the blood needs of the nation in thetime of national emergency and to be known as the National Blood Programwould represent a coordination of the blood programs already in existence.
2. No agency would duplicate the efforts of another agency unless the taskcould not otherwise be performed adequately. Before such a duplicationoccurred, there must be agreement for it among the agencies involved andthe Office of Defense Mobilization.
3. The recruitment program for volunteer donors would emphasize the NationalBlood Program as a whole and not any specific part thereof.
4. The Department of Defense and the Federal Civil Defense Administrationwould be authorized to establish and maintain separate plasma reserves.
5. The Red Cross would continue to be the blood collecting agency for theNational Defense Program except for the facilities (then 34) of the Departmentof Defense in Armed Forces installations located in areas not covered bythe collecting facilities of the National Red Cross. These collecting facilitiesnow included 44 regional programs covering 1,540 local chapters and cooperatingblood banks.
738
6. Priorities for allocation of blood would be as follows:
a. The Armed Services, for whole blood transfusions.
b. Civilian needs for whole blood and blood derivatives.
c. Allocation of the remaining blood collected for the production of plasmaand blood derivatives to meet immediate needs and establish national reserves.
7. In the event of enemy action, the total reserves of plasma, bloodderivatives, and plasma expanders would be allocated as necessary by Executiveorder.
8. The Red Cross would continue to operate, for military use only, 15 centersserving 258 local chapters and would participate in a cooperative programwith 35 civilian blood banks which would coordinate supply.
9. Research on blood and related problems would be coordinated througha committee set up by the National Research Council and composed of expertsin the field, including liaison representatives from the Department ofDefense. Funds would be provided for the research projects by the participatingagencies.
10. There would also be a continuing effort to train personnel in the laboratoryand clinical phases of blood supply and to foster and provide for research,so that, in the event of another emergency, any blood bank system setupwould be operated by well-trained medical officers thoroughly versed inall phases of military blood banking and logistics.
These recommendations were put into effect and the national blood programwas successfully operated according to them for the remaining years ofthe war.
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Section III. The Oversea Airlift to Korea
GENERAL CONSIDERATIONS6
The Korean War began on 25 June 1950, and active fighting ended on 27July 1953, with the signing of an armistice. The formal Zone of Interiorblood supply program for Korea began on 15 August 1950, with a radio requestfrom the Far East Command for shipments of blood from the Zone of Interiorto augment the quantities collected and distributed by the 406th MedicalGeneral Laboratory in Tokyo (15). The first blood shipped in responseto this message, which had been requested for 30 August, left the temporarylaboratory at the U.S. Naval Hospital in Oakland, Calif., for Japan on26 August 1950. On 8 February 1954, a dispatch from the Far East Commandrecommended that the service be terminated, and the last blood was flownto Japan on 13 February 1954 from the Armed Services Whole Blood ProcessingLaboratory, Travis Air Force Base, Calif. Between the dates of the firstand last shipments, this laboratory had received and handled 397,711 pintsof whole blood, of which 340,427 pints had been shipped to Japan for transshipmentto Korea for distribution to the various medical units of the United Nationsthere. The Travis laboratory was placed on a standby basis on 13 February1954 and was deactivated a month later. This program was the largest operationof its kind in the history of military medicine in the United States.
The important steps in the development of the administrative backgroundof the airlift of blood in the Korean War have been described in detailelsewhere (p. 713). Many of the most important actions, it will be remembered,were taken after fighting had commenced.
PROCESSING LABORATORY, TRAVIS AIR FORCE BASE
Establishment
In order that the military might have a central processing facilityin which to receive blood collected by the American Red Cross, performnecessary laboratory tests on it, package it, and ship it to Japan fortransshipment to Korea, a processing laboratory was established at TravisAir Force Base (then Fairfield-Suisun Air Force Base), Calif., where aMilitary Air Transport Service group of the Pacific Division was located.The building selected had to be renovated and converted for this purpose,and until it was ready, on 25 September 1950, a temporary laboratory wasset up and operated in the U.S. Naval Hospital at Oakland, Calif., about50 miles away.
6 Unless otherwise specified, the materialconcerning the airlift is derived from the history of the Armed ServicesWhole Blood Processing Laboratory, Travis Air Force Base, Calif., 25 August1950-15 March 1954 (19).
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During the war, a number of attempts were made to establish a bloodprocessing laboratory on the east coast, but no definitive action was evertaken, though supplies and personnel were earmarked for an emergency standbyfacility at the U.S. Naval Hospital, Chelsea, Mass. This facility was notcalled upon, but it was expected that, if it had been, it could have begunto ship blood to Japan within 24 hours after activation.
Functions
The Armed Services Whole Blood Processing Laboratory at Travis Air ForceBase performed the following functions:
1. It received whole blood from the American Red Cross, performed appropriatelaboratory tests on it, and shipped it to the Far East Command for usein Korea.
2. It maintained a record of all bloods received in the laboratory andtheir disposition.
3. It coordinated whole blood requirements with the Armed Services Bloodand Blood Derivatives Group and the appropriate representatives of theAmerican Red Cross.
4. It maintained a close working arrangement with the medical supply sectionof the Travis Air Force Base in requisitioning and drawing of suppliesrequired in the day-to-day operations of the laboratory.
5. It maintained liaison with other military organizations and civilianagencies as necessary for efficient accomplishment of its mission.
6. It prepared and submitted to the chairman of the Armed Services Bloodand Blood Derivatives Group routine reports and such special reports aswere requested.
Facilities and Equipment
Structures of the permanent laboratory included a building of 3,400sq. ft. and two warehouses, respectively 2,786 and 800 square feet. Allbuildings, office equipment and supplies, housekeeping items, heat, electricity,gas, communication services, and motor vehicle transportation were furnishedto the laboratory and maintained by the Travis Air Force Base. Billetingand messing facilities for laboratory personnel were also furnished byTravis Air Force Base. A Navy panel truck, on loan from Oakland Naval Hospital,was assigned to the laboratory for general use.
The building at Travis Air Force Base that was converted into a laboratorywas an old hospital messhall. The conversion required the installationof lighting fixtures, water-distilling apparatus, refrigerators, sinks,laboratory counters and workbenches, and natural gas fixtures. The precoolingroom and warehouses were not completed until about 8 months after the laboratorywas occupied. When the converted building was taken over, however, on 25September 1950, everything else was in such good order that a shipmentof blood could be sent to Japan the same day.
Initial medical supplies and equipment were procured directly from theOakland Naval Medical Supply Depot. Later, by agreement among the threeServices, the requirements and stock control section of the Supply
741
Division, Office of The Surgeon General, U.S. Army, was given the responsibilityof furnishing medical supplies and equipment to the laboratory. All requisitionswent through the Travis Air Force Base medical supply section to the AlamedaArmy Medical Supply Depot.
The operational cost of this laboratory was estimated at over $1 milliona year. It cost approximately $17.83 to procure and process a pint of bloodand transport it from the United States to the Far East Command in Japan,this sum including $6.56 paid to the Red Cross for processing services,$9.40 for laboratory expenses, and $1.87 for transportation costs.
Personnel
Four Navy blood bank technicians arrived from the east coast at thelaboratory on 23 August 1950. Office, laboratory, and cold storage spaceswere made available to them at once, and supplies and equipment were procuredfrom the hospital and from the U.S. Naval Medical Supply Depot in Oakland.As a result, 48 hours after these technicians had arrived, the first wholeblood shipment (1,488 pints) was received, processed, and delivered tothe Military Air Transport Service at Travis Air Force Base for transshipmentto Japan.
Requests for additional laboratory personnel were at first handled veryslowly, and, by the middle of September 1950, the staff working in theOakland laboratory included, in addition to the four original technicians,only one Navy Medical Service Corps officer and three laboratory technicians.Laboratory technicians were borrowed from Oakland and Mare Island NavalHospitals and from Letterman General Hospital, San Francisco, Calif. Clericaland some general duty helpers were borrowed from Travis Air Force Baseand the Oakland Naval Hospital. Additional duty corpsmen and convalescentpatients aided on a day-to-day basis. All of these men were returned totheir duty stations when additional permanent personnel began to arriveabout the middle of October. In spite of its personnel difficulties, thelaboratory handled over 7,000 pints of whole blood during the weeks ofits operation at the U.S. Naval Hospital in Oakland.
In the approximately 42 months of its operation, an average of 35 personswere regularly attached to the laboratory, including an average of 11 fromthe Army, 10 from the Navy, and 14 from the Air Force (fig. 173).
Training.-A quick, efficient blood bank technique can be acquiredonly by experience, and most of the personnel assigned to the Travis laboratorywere inexperienced. All therefore worked long hours while they were receivingindividual instruction. A formal training program was set up a few monthsafter the laboratory was activated, and 59 persons completed the courseof instruction, including 14 Air Force Medical Service Corps officers,34 Army enlisted men, and 11 Air Force enlisted men.
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Work Schedules
Because of its short life, 21 days at best, expeditious as well as experthandling of blood is necessary, and the work schedule at the Travis laboratorywas geared to that consideration. Blood from the collection centers wasshipped by air, rail, or motor transport, as most convenient. Centers nearthe laboratory delivered their blood by motor transport. Blood from distantcollection centers arrived by air. The shipments were offloaded at airportsin San Francisco or Oakland, where they were picked up by the Railway ExpressAgency and transshipped by train to Fairfield-Suisun, about 7 miles fromTravis. Here, they were offloaded and trucked to the laboratory by theagency. Blood from centers nearer the laboratory was sent by train anddelivered to the laboratory by the Railway Express Agency. Because theagency worked on a 5-day workweek schedule, arrangements were made withthe motor pool at Travis Air Force Base to meet trains on Saturdays, Sundays,and holidays, pick up the blood and deliver it to the laboratory.
The Red Cross blood donor centers also worked on a 5-day week, usuallyMonday through Friday. Few collections were made on Saturdays, Sundays,and holidays.
Each Friday, and oftener if requirements changed, the officer in chargeof the laboratory at Travis Air Force Base notified the central officeof the Red Cross of the quotas of blood desired for the following week.The Red Cross, in turn, designated the donor centers which would collect,process, and ship these quotas. A number of attempts were made, all unsuccessful,to have the weekly quotas collected in equal amounts on each of the 5 daysweekly that the centers operated. Few bloods were received from Mondaythrough Wednesday, often not the equivalent of the amounts shipped to Japan.Most bloods were processed from Thursday through Sunday. By Sunday night,the refrigerators were filled, and there was sufficient blood on hand forthe Monday-through-Wednesday shipments.
Although bloods arrived in the laboratory at all hours of the day andnight, most of them arrived twice daily, at 1000 and 1800 hours. On Sundaysand holidays, the bulk of the blood usually arrived at 1800 hours.
Because of these various circumstances, the Travis laboratory had tooperate 7 days a week, day and night. After additional personnel arrivedat the laboratory in October 1950, separate day- and night-working sectionswere established to receive, process, and ship blood. The two sections,each composed of equal numbers of clerical, laboratory, and general dutypersonnel, alternated day- and night-working hours at weekly intervals.A third section, composed of administrative and supply personnel, carriedon the administrative and supply duties of the laboratory. This sectionworked a regular day shift, but its personnel were subject to night callas necessary.
LABORATORY ROUTINE
Collection and Initial Processing
Only proved group-O blood, of low titer and Rh-verified, was sent toKorea. As in World War II, about 45 percent of random donors proved tobe group O, and about a quarter of this group had agglutinin titers above1:64.
The technique of collection was essentially that employed in World WarII (p. 145). Donors were screened to make sure that they were group O.Whole blood intended for oversea use was collected in ACD solution (bloodintended for plasma was collected in sodium citrate solution). The bloodwas collected in 500-cc. amounts in sterile, pyrogen-free bottles; samplesfor serologic testing and crossmatching were collected into pilot tubes.The collection bottles were not entered again until the recipient setswere attached just before the transfusions were to be given. With thisprecaution, there was no possibility of contamination and there is no recordthat any occurred.
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After the blood had been collected, two technicians performed two separatetests for specificity. With this doublecheck, the percentage of error didnot exceed 0.5 percent, and there was not a single report of incompatibilityduring the course of the war. This was a remarkable record, for the bloodthat arrived at the processing center at Travis Air Force Base came fromdonor centers all over the United States.
Serologic tests were also performed, even though by this time therewas valid evidence that syphilis could not be transmitted by blood thathad been stored longer than 3 days (p. 143).7
Later Processing
After the collected blood had been chilled to 39.2º to 42.8ºF. (4º to 6° C.), it was shipped by truck, rail, or air to theprocessing center in insulated Church shipping cases, refrigerated withwet ice (p. 204). Blood usually arrived within 48 hours after it had beencollected. At the base, it was taken to the receiving, storage, and shippingsection; logged in; placed in a walk-in refrigerator maintained in thetemperature range just mentioned; and there unpacked, inventoried, andstored. Two such refrigerators were available, each capable of holding2,500 pints of blood. The empty insulated blood shipping container wasreaddressed to the blood donor center whence it had come, and was returnedto the center by Railway Express.
The pilot tube containing 6-8 cc. of whole blood was detached from thebottle and taken to the laboratory section, where the sample was regrouped,retyped, and retitered (fig. 174). The repetition of these tests servedtwo purposes: (1) It eliminated units of blood that were not group 0. (2)It served, to a degree, as a crossmatch; it was not always possible formedical units in Korea to type and crossmatch their patients before transfusingthem.
Each year the Travis laboratory used approximately 9,600 cc. of anti-Aand anti-B, and 5,800 cc. of anti-Rh, blood typing sera. During the lastmonth the laboratory operated, the sera were used in dried form. The liquidform, which had been used up to this time, was thought more satisfactory,for several reasons: It contained fewer artifacts. It saved time becauseit did not have to be reconstituted. It was packaged in smaller units,and less warehouse space was required to maintain an adequate supply. Onthe other hand, the dried form cost a little less and had a longer usefullife, 60 months, against 12 months for the liquid form. There was no significantdifference in the number of bloods that could be tested with given amountsof each form.
After testing, a label was securely glued to each bottle, containingthe unit blood number, blood group, Rh-factor, point of origin, and originalblood donor center number. Although the expiration date did not ordinarilyexceed
7 At the meeting of the Committee on Bloodand Blood Derivatives on 23 September 1953 (after the armistice bad beensigned), it was proposed by Dr. William G. Workman that serologically positivebloods be used for the preparation of dried plasma, and that bloods intendedfor these purposes should not be tested serologically (20). These proposalswere concurred in by Dr. Thomas B. Turner, Dean, Johns Hopkins UniversitySchool of Public Health, and were recommended for action by the committee.
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21 days, an expiration date of 22 days from the date of collection wasplaced on each bottle because this blood would be shipped across the internationaldate line for use in a later time zone. If the serum agglutinin titer ofa unit exceeded 1:256, the label read, High Titer Group "O"Blood-For Group "O" Recipient Only. If the titer was lessthan 1:256, the label simply read Low Titer.
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Shipment
During the Korean War, the processing laboratory at Travis Air ForceBase maintained in store two or three times the estimated daily requirementof blood, so that emergency requests could be met without delay. When sucha request was received, the blood was given a No. 1 priority and sent toJapan immediately on a cargo or passenger plane.
If circumstances permitted, the blood was held in the refrigerator for8 to 12 hours, so that it could be examined grossly for hemolysis, clots,or excessive fat content. Frequently, however, because of the heavy demands,bloods were processed and shipped out on the same day that they were received.They were packed for shipment in the walk-in refrigerators.
Except in emergencies as just noted, all whole blood shipped from theUnited States to the Far East Command was transported in aircraft of theMilitary Air Transport Service (figs. 175 and 176). It was flown from TravisAir Force Base to Haneda Air Force Base near Tokyo, with stops at Honoluluand Wake Island (map 7). It was reiced at these stops if necessary. Assoon as the blood arrived in Japan (fig. 177), it was removed from theplane, trucked to the blood storage section of the 406th Medical GeneralLaboratory, and stored there until it was shipped to Tokyo and thence toKorea (fig. 178). All blood moved in Korea was transported by plane orhelicopter (fig. 179).
747
STATISTICAL DATA
The largest number of bloods received, tested, and labeled in the Travislaboratory in a single day was 1,881 pints. The overall daily average was319 pints, based on a 7-day week for the almost 42 months during whichthe laboratory operated.
The largest number of bloods handled in a single day by the receivingand shipping section was 2,500 pints, this number including both unitsreceived and units shipped. The largest shipment placed in a single planefor shipment to Japan was 1,488 pints. The average daily shipment was 273pints.
The total weight of the blood and recipient sets shipped to Japan was1,782,434 pounds (891 tons) and the total space required for the shipments,426,379 cubic feet.
Of the 397,711 pints of whole blood received in the processing laboratory,340,427 (about 85 percent), were shipped to the Far East Command for usein Korea. The remaining 15 percent included surplus bloods and bloods whichfor other reasons (hemolysis, clots, breakage, excessive fat content, volumeless than 500 cc.) could not be used for transfusions. Most of it (56,809pints) was sent to the Cutter Laboratories, Berkeley, Calif., for plasmafractionation, but 347 pints were used in local military hospitals. Breakageinvolved only 128 bottles; 94 were received broken, and 34 were brokenduring processing.
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Only 144 of the bloods received in the laboratory were not group O;116 were group A, 24 group B, and 4 group AB. These units had been eithermistyped or mislabeled at the original blood donor centers, and the errorswere caught when they were retyped in the laboratory. The remarkably lowpercentage of misgrouped blood indicates the skill and care of the technicianswho did the initial grouping and labeling. Theirs was a most responsibletask, for, as already mentioned, most group-O blood used in Korea, as inWorld War II, was not crossmatched before it was used.
About 10 percent of all the blood received had an agglutinin titer of1:256 or higher. During the first 18 months the laboratory operated, lessthan 9 percent of the bloods received were Rh-negative. During the last2 years, because of repeated requests for such bloods, the proportion roseto 12 percent. Rh-negative blood was not sent to Korea but was used inthe fixed installations in Japan, since it was in them that Rh-negativecasualties might receive repeated transfusions 10 to 14 days after theyhad received Rh-positive blood in forward hospitals.
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Losses.- As has just been indicated, most of the blood rejectedfor oversea shipment for various reasons was made into albumin and immuneserum globulin, so that the overall loss was very slight.
Losses remained at about the same level during most of the war. Theheaviest losses occurred in the winter of 1950-51, when, because of inadequateprocessing facilities in the East, bloods intended for plasma, which hadto be shipped to a laboratory on the west coast, froze en route. Otherwise,losses remained at about the same level during most of the war. In March1952, losses amounted to 4.4 percent (2 percent hemolysis, 2 percent shortamounts, 0.004 percent lipemia, and 0.4 percent other causes).
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Section IV. The Whole Blood Oversea Experience
ESTIMATE OF NEEDS
Experience in the European theater in World War II showed that an armyin action, meeting stiff resistance would require about 500 pints of blooda day, the requirement varying with the type of fighting (p. 557). As wouldbe expected, it was found that the faster an army moved, as in a breakthrough,the less blood would be required. During conventional fighting, in orderto keep units supplied with their daily requirements, theater inventoriesof blood had to be maintained at two to three times normal daily requirements.
These rules of thumb proved quite acceptable for conventional militaryrequirements in Korea (table 37). Estimates for total blood needs werepredicated on estimated casualty rates. Requirements usually worked outat 1½ to 2 pints for each hospitalized casualty.
Since delivery of blood from the Zone of Interior could not immediatelyreflect increased demands from Korea, the policy was to maintain a ratherconstant demand upon Zone of Interior sources and adjust collections ofblood as necessary in Japan.
DISTRIBUTION
At the beginning of the oversea blood program, all blood received inJapan from the Zone of Interior was sent to Korea, while blood collectedat the 406th Medical General Laboratory blood bank was used only at fixedhospitals in Japan. Within a short time this policy was changed and allblood was handled at the bank on an integrated basis.
When requisitions from Korea were received, the blood was flown to adistribution point in Korea (chart 14), where a distribution team receivedit from the courier who had accompanied it. Early in the war, when thefighting was highly fluid, two blood depots were maintained, both in thesouthern part of the peninsula. Later, as the front stabilized, severalsubdepots were established farther north. By the end of 1951, three depotswere in close support of the front, and two supplied rear areas. Helicoptersproved the most efficient way of distributing blood to forward units (fig.179) as they could evacuate casualties on the return trip.
During 1952, reserve blood depots were maintained in Korea at Pusanand Seoul, and three advanced depots were maintained in Eighth U.S. Armyareas. In addition, many hospitals stored reserves of blood to meet possibleemergencies.
In Korea, although whole blood was considered a special item, it washandled in medical supply channels. The Supply Service deserves great creditfor its cooperation and competence, but personnel intimately connectedwith the blood program could not accept this concept of handling wholeblood. The operation of a blood bank system, including distribution,
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TABLE 37. - Ratio of blood issued to woundedin action, 1951-52
Month | 1951 |
| |||||||||
WIA1 | Blood sent to Korea2 | Ratio WIA/ |
| Blood sent to Eighth U.S. Army | Ratio WIA/blood | ||||||
| U.N. forces | ROK forces | Total | U.S. forces | U.S.-U.N. forces | Total3 forces | |||||
January | 2,789 | 4,989 | 1.79 | 727 | 88 | 1,208 | 2,023 | 7,432 | 10.22 | 9.12 | 3.67 |
February | 4,731 | 9,178 | 1.94 | 550 | 99 | 570 | 1,219 | 7,008 | 12.74 | 10.80 | 5.75 |
March | 4,834 | 9,629 | 1.99 | 477 | 117 | 367 | 961 | 7,440 | 15.60 | 12.53 | 7.74 |
April | 4,853 | 12,108 | 2.49 | 726 | 107 | 742 | 1,575 | 7,200 | 9.92 | 8.64 | 4.57 |
May | 4,507 | 13,366 | 2.97 | 882 | 170 | 795 | 1,847 | 7,056 | 8.00 | 6.71 | 3.82 |
June | 3,436 | 10,366 | 3.02 | 1,869 | 212 | 1,948 | 4,029 | 7,448 | 3.98 | 3.58 | 1.85 |
July | 1,628 | 9,624 | 5.91 | 1,594 | 251 | 1,694 | 3,539 | 6,321 | 3.97 | 3.43 | 1.79 |
August | 1,707 | 8,112 | 4.75 | 1,594 | 241 | 1,043 | 2,878 | 6,209 | 3.90 | 3.38 | 2.16 |
September | 6,539 | 9,864 | 1.51 | 1,874 | 256 | 2,563 | 4,693 | 6,801 | 3.63 | 3.19 | 1.45 |
October | 9,968 | 14,056 | 1.41 | 3,767 | 303 | 9,583 | 13,643 | 9,571 | 2.55 | 2.36 | 0.70 |
November | 2,647 | 12,482 | 4.72 | 1,262 | 383 | 4,079 | 5,724 | 6,720 | 5.32 | 4.09 | 1.17 |
December | 1,147 | 10,036 | 8.75 | 607 | 114 | 1,511 | 2,232 | 7,497 | 12.35 | 10.40 | 3.36 |
|
|
|
|
|
|
|
|
|
|
|
|
1U.S. and U.N. forces, without ROK forces.
2In 500-cc. units.
3U.S., U.N., ROK forces.
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CHART 14.-Organization for distributionof whole blood for Korea
these personnel argued, is not a supply problem but a professional logisticproject requiring the highest degree of coordination on the part of skilledprofessional personnel. In their opinion, later concurred in by the investigatingofficer who made a special survey of the blood program in Korea (p. 755),there should be in every theater a transfusion officer with the responsibilityof supplying blood to the armies. By supply standards, the multiple supplypoints just listed were entirely reasonable. By standards of trained transfusionofficers, this policy was inefficient and wasteful because it permittedblood to age in storage.
Aging
It was almost impossible to collect precise data concerning the ageof blood received and used in Eighth U.S. Army installations in Korea afterit had left the base depot. In 1951, it was estimated that when blood reachedthe Haneda Air Force Base in Japan from the Zone of Interior, it was 6days old, which meant that it had an average usable remaining life of 15days
(table 38). When the blood was received in Korea, the average remaininglife was 9.4 usable days. Fragmentary reports from forward hospitals indicatedthat when it was used, it was from 9 to 20 days old.
TABLE 38. - Remaining usable days of bloodreceived from Zone of Interior and shipped to Korea, 1951
Month |
| Average number usable days | Shipments to Korea | Average number usable days |
January | 7,064 | 9.5 | 4,989 | 7.1 |
February | 9,264 | 13.6 | 9,178 | 12.4 |
March | 9,224 | 13.9 | 9,629 | 10.2 |
April | 13,466 | --- | 12,108 | 10.0 |
May | 15,032 | 12.3 | 13,366 | 10.3 |
June | 10,528 | 13.5 | 10,368 | 9.3 |
July | 10,392 | 13.5 | 9,624 | 7.1 |
August | 10,974 | 12.0 | 8,112 | 8.2 |
September | 11,496 | 13.5 | 9,960 | 9.5 |
October | 14,424 | 12.6 | 14,046 | 9.2 |
November | 10,632 | 13.8 | 11,676 | 9.9 |
December | 8,639 | 10.1 | 9,138 | 9.3 |
Medical officers and trained blood bank workers realize the importanceof issuing blood that is as fresh as possible, knowing that the older theblood, the faster will red cells break down after transfusion, the lesseffective is the transfusion, and the more blood must eventually be used.Since supply personnel did not realize this, their policy in Korea in respectto blood was, as with other supplies, to issue the oldest blood first,to get rid of it.
A number of studies by the fragility test were made daily for 10 dayson blood that was 8 to 10 days outdated, in the hope that some safe extensionof the expiration date could be determined. Although cell fragility wasnot notably increased over the testing period, no evidence was adducedto encourage the idea that overage blood should be used deliberately.
SURVEY OF WHOLE BLOOD EXPERIENCE, FAR EAST COMMAND
On 11 March 1953, Lt. Col. Arthur Steer, MC, submitted a report to theChief Surgeon, U.S. Army Forces, Far East, on a 14-day survey made in October1952 and dealing with the use and supply of whole blood in this command(21). During October, both U.S. and ROK (Republic of Korea) troops sustainedhigher casualties than at any other time in 1952. The survey was confinedto the Eighth U.S. Army area.
Use factor.-Colonel Steer noted that the data he had collectedwere somewhat difficult to interpret because no policy had been establishedfor the
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issuance of blood to ROK units. ROK units were not supposed to be evacuatedthrough Eighth U.S. Army installations, but a significant, though unknown,number, particularly in troops attached to U.S. units, had thus been evacuatedand so had been transfused by U.S. Army standards.
During the period of the survey, approximately 20 percent of all U.S.and U.N. (United Nations) casualties, other than ROK wounded, were transfused,at an average rate of 4.4 bottles per casualty or 0.9 bottles per U.S.wounded who reached a medical treatment facility. On the basis of U.S.casualties only, 5.54 bottles were issued per each soldier wounded in action.If all casualties, including ROK casualties, are considered, 1.95 bottleswere issued per each soldier wounded in action. The true issue factor thuslay somewhere between 1.95 and 5.54 bottles per U.S. and other U.N. casualtiesexcept ROK casualties.
Reserves.-All medical installations and depots surveyed werefound to maintain reserves of blood which provided, in toto, an averagestock on hand of 7.87 times the average daily amount used and 3.1 timesthe maximum ever used on any single day. In a sense, this blood was notwasted because aging blood was sent to ROK installations, which were givenit at an average age of 16.1 days. The figures, however, "illustratethe compounding effect of reserve levels resulting from the maintenanceof multiple depots." Furthermore, the existence of these multipledepots and the maintenance of reserve stocks inevitably resulted in theaging of blood on the shelves. This policy also made the control of reservelevels, as well as flexibility in the use of reserves, extremely difficult.When activity was increased in one portion of the line, for instance, increasedneeds should have been met by transferring blood to it from a hospitalor depot supporting an inactive portion of the front. Instead, they weremet by requisitioning more blood from rear areas, where it was suppliedwithout question because there was no single medical officer in chargeof the blood supply and with authority to question the requisitions.
Reactions.-During the survey period, there were only 19 reactions(2.5 percent) in the 757 identified patients who received blood. Most ofthe reactions were mild and of the urticarial type. One hospital, whichgave transfusions to 57 patients, reported 11 of the 19 reactions.
Recommendations
Colonel Steer's most important recommendation was that a continuingstudy be made of the use of whole blood and blood substitutes in Korea,with particular reference to the establishment of a separate medical unit,commanded by a medical officer, whose sole responsibility would be theprocurement, storage, and distribution of blood and blood substitutes.For two reasons, such a study should be made by a team sent from the Zoneof Interior to the Far East Command by the Department of the Army: (1)Numerically, there were no personnel in the theater who could be detachedfor the purpose and (2) more important, there were no experienced bloodbank operators in the
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command. Colonel Steer also considered it important that the group whichmade the study should have had no previous experience with the controlof blood in supply channels and thus would be entirely free from bias.
Another recommendation in Colonel Steer's March 1953 report was thatgeneral hospitals outside the Tokyo-Yokohama area in Japan establish smallblood banks, subject to frequent supervisory inspections. In the eventof emergency, these banks would be provided with blood from the Tokyo bank.
In a later communication to Colonel Kendrick on 15 December 1953, ColonelSteer again emphasized the need for a medical officer in a theater of combat,under the theater surgeon, able to travel in all zones, and to be totallyresponsible for this blood program (22). This would involve the settingup of minimum standards for local blood collection practices and for shippingand storage procedures, control of the flow and distribution of blood,establishment of minimum bank levels, advice to the surgeon on policiesand publicity concerning blood, and constant inspection of all agenciesinvolved in the handling or using of blood. When this recommendation wasmade, the armistice had been signed, and, within another 2 months, theoversea airlift would be discontinued.
STATISTICAL DATA
The distribution of blood by the Tokyo Blood Depot to hospitals in Japanand in Korea for 1951-52 is contained in table 39.
TABLE 39. - Distribution of blood by TokyoBlood Depot, 1951-52
Month |
| Distribution, 1952- | |||||
| To depots in Korea | Total | To hospitals in Japan | To Communications Zone, Korea | To Eighth U.S. Army, Korea | Total | |
January | 2,295 | 4,989 | 7,284 | 2,026 | 3,504 | 7,432 | 12,962 |
February | 2,546 | 9,178 | 11,724 | 1,776 | 2,221 | 7,008 | 11,005 |
March | 2,588 | 9,629 | 12,217 | 1,380 | 3,010 | 7,440 | 11,830 |
April | 2,132 | 12,108 | 14,240 | 1,611 | 2,319 | 7,200 | 11,130 |
May | 2,540 | 13,366 | 15,906 | 1,029 | 3,424 | 7,056 | 11,509 |
June | 2,466 | 10,368 | 12,834 | 1,473 | 2,292 | 7,448 | 11,213 |
July | 2,037 | 9,624 | 11,661 | 1,420 | 1,615 | 6,321 | 9,356 |
August | 1,664 | 8,112 | 9,776 | 1,478 | 1,312 | 6,209 | 8,999 |
September | 2,574 | 9,864 | 12,438 | 1,591 | 1,392 | 6,801 | 9,784 |
October | 6,150 | 14,056 | 20,206 | 2,484 | 2,568 | 9,571 | 14,623 |
November | 2,517 | 12,482 | 14,999 | 1,951 | 2,724 | 6,720 | 11,395 |
December | 2,299 | 10,036 | 12,335 | 1,488 | 2,712 | 7,497 | 11,697 |
| 31,808 | 123,812 | 155,620 | 19,707 | 29,093 | 86,703 | 135,503 |
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Section V. Equipment and Refrigeration forAirlift
PLASTIC CONTAINERS
Development of Criteria
Plastic equipment came under discussion at the Symposium on Blood Preservationheld under the auspices of the Committee on Blood and Blood Derivatives,NRC, on 2 December 1949 (28). Dr. Carl W. Walter, who had been workingon its development for some time for the American Red Cross, laid downthe criteria for it as follows:
1. Simple, one-piece equipment that would permit hermetic sealing duringprocessing, storage, and transportation of the blood and that could beemployed with a bacteriological safe technique.
2. A slow rate of collection, causing minimal physiologic disturbance tothe donor.
3. The elimination of air vents, both during collection (by venous pressureand gravity) and during administration.
4. Transparency.
5. Nonwettability.
6. Compressibility, to permit positive pressure infusion.
7. Stability to sterilizing temperatures (121' C. for 30 minutes).
8. Low vapor transmission.
9. Good tissue tolerance.
It was additionally specified, in view of the logistic difficultieswhich the use of blood presents in times of war and disaster, that plasticequipment recommended must be lightweight, nonbreakable, collapsible, andsized to accommodate the volume of liquid it was intended to contain. Also,it must be inexpensive enough to warrant discarding after a single usingbut, at the same time, it must be so designed that, in emergencies, itcould be cleaned and reused without risk of pyrogenic reactions.
First Model
Dr. Walter's studies had been carried out with equipment fabricatedfrom elastic thermoplastic vinylite resin that incorporated an ion-exchangecolumn (p. 770) of sulfonated polystyrene copolymer. It was sealed by dielectricallyinduced heat and was sufficiently elastic to yield a hermetic seal if asingle throw knot in it were stretched tightly and then released. It wastough and flexible and provoked minimal tissue reaction. The tubing forboth donor and recipient sets was extruded with a lumen 3 min. in diameterand a wall 0.5 mm. thick.
The bag was available in any desired capacity and could be so compartmentalizedthat a single donation of blood could be subdivided into multiple isolatedamounts, each with its own delivery tube for use in multiple small transfusions.
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The bag, together with tile filled exchange column, fitted with a needleand cannula, was sterilized at 250° F. (121° C.) for 30 minutes.Compressed air was then admitted to the sterilizing chamber to maintaina pressure of 1.4 kg. per square centimeter until the bag had cooled to194° F. (90° C.). The assembly was ready for use as soon as thepressure had vented.
The cost of the equipment described by Dr. Walter was then $1.48 perunit, but, when the bags were in mass production, it was expected thatthe unit cost would be reduced to 45 to 50 cents.
Operation.-Blood was collected in this apparatus essentiallyas in regular collecting bottles. After the bag had been filled by gravity,the tourniquet was released and a spring clip was placed across the tubedistal to the exchange column. Samples for testing were collected in pilottubes before the needle was removed from the vein. The tube was sealedor knotted close to the bag, and the bag of blood, after being hermeticallysealed, was refrigerated.
The transfusion could be given by suspending the bag from a gravitypole by the grommet provided, or the blood could be squeezed into the recipient'svein by placing the bag under his shoulder or buttock. If rapid transfusionwas desired, the intra-arterial technique was used, or the operator couldstand on the bag.
Comment.-The bag described by Dr. Walter had obvious advantages.Although it took slightly longer to collect the blood than when collectingbottles were used, the quality and yield of blood collected was equal,if not superior, to the quality and yield of blood collected in bottles.Moreover, blood collected in plastic bags practically never had to be discardedbecause of hemolysis. The bags did not require refrigeration before theblood was collected. A plastic bag containing 500 cc. of blood occupiedin the refrigerator only half the space of a bottle holding the same amount.Finally, the insulated containers developed toward the end of the war forthe transportation of blood held 48 bags instead of 24 bottles.
Testing and Adoption
By March 1950, the Walter apparatus was in commercial production, bythe Fenwal Co., and comparable equipment had been developed by the AbbottLaboratories.
When the ad hoc committee on plastic bag collecting equipment reportedon 8 October 1951, plastic equipment had received sufficiently extensivetesting in various military and civilian hospitals to establish its desirabilityand efficiency (24). Further testing was planned for civilian hospitalsand Red Cross blood donor centers, and field trials were planned for theArmy under what was termed extreme conditions. Figures 180 and 181 illustratethe final type of plastic equipment developed in the Korean War and demonstrateits use. These bags were never formally used in the blood program in Koreabecause of objections raised to them by
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the American Red Cross. They came into general use in military hospitals,though only after some indoctrination. Medical officers at first did notlike the plastic equipment, particularly the resin column, and there wassome resistance to the use of the bags, even when the blood was collectedin ACD solution. At Walter Reed General Hospital, Washington, D.C., wherea large-scale test was conducted, it was found worthwhile to have an experiencednurse indoctrinate all personnel in their use.
REFRIGERATED SHIPPING CONTAINERS
Up to the spring of 1951, blood was shipped from the Whole Blood ProcessingLaboratory at Travis Air Force Base in the Navy (fig. 139, p. 611) andthe Army (fig. 182, p. 762) insulated containers developed for use in WorldWar II. The Army boxes did not hold up too well (fig. 183), and when thesupply was exhausted, other models were tested (19).
Bailey container.-The first shipping container procured fromthe Bailey Co. was designed on the principle of the Army box. It had anoutside measurement of 8 cu. ft., held 24 pints of blood, and weighed 115pounds when fully packed and iced.
The outer shell of the Bailey box was made of fiberboard or V-board,which was supposed to be water-resistant. The insulating mechanism moisture-vaporbarrier, lid, and ice cans were similar to those used in the Army container.
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Sufficient space was allotted for recipient sets, but, in the firstmodel, the wire racks were so close together that the larger type of bloodbottle did not fit between the separators.
When the box was closed, it was secured by wingnuts on each side, andhandles of sashcord were attached on the same sides. This arrangement madeit impossible for personnel to lift the container by the cord handles withoutscraping their hands on the nuts. As long as the first Bailey containerwas used, shipping and receiving personnel at the Travis laboratory couldbe identified by their bruised hands.
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In spite of its defects, this container maintained the proper temperaturefor blood during its transportation to Japan, and about 2,000 were used.In the meantime, a new model was devised, with a number of improvements,including the attachment of the cord handles and the nuts on differentsides. This model, 1,200 of which were delivered, had, like the first model,an outside measurement of 8 cu. ft., held 24 pints of blood, and, whenpacked, weighed 132 pounds.
The wire racks were so designed that the larger bottles could easilybe inserted. This container was, like the first Bailey model, too bulkyfor one man to handle, and, like the first, it did not withstand adverseweather conditions.
Hollinger container.-Containers made by the Hollinger Corp. wereput into use in October 1951, after the supply of Bailey containers wasexhausted. This container (fig. 184) was built like a trunk. Its outsidemeasurement was 6.4 cu. ft. and it weighed 115 pounds when fully packed.The exterior shell was of plywood covered with laminated fiber to makeit waterproof. Insulation was provided by 2-inch slabs of Styrofoam, whichwere snugly fitted and attached to the inside of the plywood shell by cement.Each of the two wire racks held twelve 500-cc. bottles of blood, and thetin container in the center held about 20 pounds of wet ice. Between theinsulation and the wire racks was a moisture-vapor barrier of corrugatedpaper.
The insulated lid of the Hollinger container was attached by hinges,and the box could be closed and latched like a trunk or footlocker. A stripof rubber around the rim of the box increased its insulating properties.Metal handles
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attached to the sides facilitated handling. Although it could not behandled by one man, this box was easier to move than the containers previouslyused.
The original Hollinger model was very sturdy, withstood rough handlingand bad weather conditions, and maintained the correct temperature en route.Approximately 600 were employed, and each made an average of 10 to 12 roundtrips from the Travis laboratory to Japan.
While the original Hollinger container was still in use, another containerwas obtained from this manufacturer. It was also a trunk type, but larger(8.1 cu. ft.), heavier (133 pounds), and better insulated than the firstmodel. The insulating layer, which consisted of 3 inches of Styrofoam insteadof the 2 inches used in the smaller container, was supplemented by an aluminummoisture-vapor barrier instead of the corrugated paper barrier used inthe original model. The strip of rubber around the rim of the box was wider.
The improvement in insulation, which amounted to less than 0.5°F. over 36 to 40 hours, was not considered enough to compensate for theincreased size And weight of this second model. Nonetheless, about 900were used, each making an average of four round trips from the Travis laboratoryto Japan.
Evaluation
Of all the insulated shipping containers used at the Travis processinglaboratory, the Navy plywood container and the 6.4-cu. ft. Hollinger trunk-typecontainer were considered the most practical, though the Navy container
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could be used for only two or three round trips against the 12 or moretrips the Hollinger container could make.
Fiberboard or V-board containers did not prove practical for field use.They did not lend themselves to long-distance shipping, rough handling,and adverse weather conditions, and they were good for only a single trip.They made difficulties in FECOM, and personnel were understandably reluctantto ship blood to forward areas in them because they sometimes fell apart.The
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blood distribution center of the 406th Medical General Laboratory inTokyo had the Navy plywood container (16-pint capacity) duplicated; mostof the whole blood shipped from Japan to Korea during the last 2 yearsof the war went in these boxes.
In all, about 15,000 containers were shipped from Travis Air Force Baseto Japan during the course of the war. Of the reusable Hollinger trunktype, 1,500 were the only ones used between October 1951 and February 1954.Though some of them made as many as 12 round trips, they were still ingood condition when the program was terminated.
One disadvantage of the Hollinger containers was that they had no spacefor recipient sets. During the time they were in use, therefore, the setshad to be packed in separate crates, which were shipped with the containers.In all, over 350,000 recipient sets were shipped to the Far East.
The price of insulated shipping containers ranged from $25-$30 for theNavy plywood type to $40-$50 for the Hollinger container.
Shortly after the war in Korea ended, another refrigerated container,which is still in use (1962), was developed at Fort Totten. This box (fig.185) has
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FIGURE 186.-Refrigerator units forstorage of blood at medical depot, Chunchon, Korea, December 1951.
space for 24 bottles of blood, weighs only 20 pounds loaded, and costsonly $4.80. The ice is in the plastic bag in the cover, and the arrangementprovides better insulation: In the refrigerated container originally developedat Fort Totten, as the ice in the center melted, the tops of the bottlesof blood were left unrefrigerated.
REFRIGERATION FACILITIES IN THE FAR EAST
Refrigeration facilities in Japan and Korea (figs. 186, 187, and 188)were generally satisfactory.
Section VI. Techniques of Preservation
PRESERVATIVE SOLUTIONS
Whole blood.-The first blood sent to the Far East from the Zone of Interiorduring the Korean War was collected in the ACD formula used during WorldWar II, 25 cc. of which was used for each 100 cc. of blood (p. 227). Atthe 23 September 1950 meeting of the Committee on Blood and Blood Derivatives(25), on the advice of Dr. William G. Workman, Chief, Laboratory.of Biologics Control, National Institutes of Health, the amount of solutionused was left unchanged but the formula was altered to 2.45 gm. of dextrose;137 gm. of U.S.P. sodium citrate, and 5 gm. of U.S.P. citric acid per 100cc.
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of solution. The recommended change was accepted because it was expectedthat temperature controls would be less precise during the airlift of theblood than during its storage.
Plasma.-Blood intended for plasma was usually collected in a4-percent trisodium citrate solution during the Korean War. When it wascollected in ACD solution, the plasma was difficult to dry, and the qualityof the product varied from lot to lot.
The question of using a single solution for the collection of blood,no matter for what purpose it was intended, came up a number of times inthe Committee on Blood and Blood Derivatives. On 26 August 1952, the BloodGroup, Department of Defense, in cooperation with the National ResearchCouncil, American Red Cross, and National Institutes of Health, agreedto enter upon a formal investigation of the use of ACD solution in theprepara-
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tion of plasma. By the plan adopted, 240 units of blood collected inthe NIH ACD formula would be shipped to each of two processing laboratories,and samples of the dried plasma produced would be sent to NIH for routinetesting. The National Research Council would conduct the clinical investigations.
The investigation, which was not finished during the war, gave onlyinconclusive results.
RED BLOOD CELL PRESERVATION
It was the consensus of the Committee on Blood and Blood Derivativesthat the crux of the problem of blood preservation was the vitality ofred blood cells. On 2 December 1949, Dr. Colin, reporting to the Committeefor the Formed Elements Group, stated that all the evidence indicated thatintact erythrocytes were necessary if blood was to fulfill its respiratoryfunction (23). He thought it possible that optimum preservationmight be achieved only after separation of the red blood cells from alldestructive enzymes for which each element served as a substrate.
As time passed, the Committee on Blood and Blood Derivatives, NRC, becamemore and more convinced that no very great advances could be expected inred blood cell preservation until more basic knowledge concerning thesecells was available. The committee (now known as the Committee on Bloodand Related Problems) therefore sponsored two symposia on the subject.The first, a Conference on the Differential Agglutination of Erythrocytes,was held on 17 September 1952 (26), and the second, a Symposiumon the Structure and Cellular Dynamics of the Red Blood Cell, was heldon 11-12 June 1953 (27).
In spite of all the work done on red blood cell preservation beforeand during the Korean War, the statement made at the 4 March 1953 meetingof the Committee on Blood and Related Problems (28) remained trueuntil the end of the war, that the last great advance in blood preservationwas the addition of glucose to the preserving medium. (p. 217). This additionmarked the first time that the energy of red blood cells had been takeninto consideration in attempts to preserve them. On the other hand, whilethe addition of glucose was an improvement, it did not prevent cellularenergy from deteriorating during storage.
Space does not permit the account of several related conferences heldduring the Korean War under the auspices of various committees and subcommitteesof the Division of Medical Sciences, National Research Council. They included,among others, several conferences on blood coagulation and a conferenceon fibrinolysis.
EXCHANGE RESINS
At the Symposium on Blood Preservation held on 2 December 1949 (23),Dr. John G. Gibson II, Harvard University Medical School, and Dr. Edward
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S. Buckley, Jr., Peter Bent Brigham Hospital, reported their work onexchange resins in the preservation of blood as follows:
Reduction of the calcium content of the blood below the critical levelwill prevent blood clotting by preventing the formation of thrombin byprothrombin, a reaction for which calcium is apparently essential. Whencitrate is added to blood, a soluble calcium-citrate complex results whichdoes not dissociate sufficiently to provide enough calcium for the reactionjust described to occur. presumably, other divalent ions are also "complexed"by the citrate ion. The same principle is involved in the use of an ion-exchangeresin except that the calcium-resin complex is insoluble, as are also theother ion complexes formed. The degree of reduction in effective concentrationmay therefore be quantitated.
Collecting blood directly into a flask containing the resin did notprove feasible. Best results were obtained when the blood was allowed toflow through a column of resin into the collecting vessel.
Blood collected by this technique did not clot. It showed no significantchanges in pH, freezing point, or sodium concentration. The calcium concentrationwas reduced to less than 1 percent and the potassium to about 1 milliequivalentper liter. Zinc was not removed from either cellular or plasma components.Two in vivo canine experiments showed a post-transfusion red blood cellsurvival of approximately 90 percent.
At the conclusion of this report, Dr. Colin commented that the mostremarkable recent advance in the preservation of blood was the introductionof an ion-exchange resin, which apparently removed not only the calciuminvolved in coagulation of the blood but also some of the metals utilizedin enzyme activity. The collection of blood over an exchange resin intoa vessel without a wetting surface, which did not contain an anticoagulant,would, however, make necessary the determination of a new baseline regardingthe optimal environment for its formed elements. Except for a few small-scaleexperiments, blood had never been studied in the absence of citrate concentrations,which were usually quite high.
Among other reports at this same symposium was one by Dr. Charles P.Emerson, Jr., Boston University School of Medicine, which showed that theimmediate decalcification of fresh blood by passing it through a resincolumn had no immediate discernible effect on the osmotic fragility ofred blood cells. When, however, the blood thus collected was stored, therewas, as in blood stored in ACD solution, a progressive increase in theirfragility. Moreover, the magnitude of the changes observed was considerablygreater, particularly after the 10th day, than in ACD solution. Resin-collectedblood stored less than 10 days without removal of plasma but with the additionof a saline-dextrose diluent seemed comparable in stability to ACD-collectedblood stored without modification for a similar length of time. Resin-collectedblood stored without further modification was essentially nonviable whentransfused on the 20th day; 80 percent was eliminated from the recipient'scirculating
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blood within 10 minutes and the remainder within 48 hours. The periodof survival was essentially the same whether the pH was 7.2 or 6.8.
It was considered possibly significant that poor survival of storedcitrate-free, calcium-free blood was invariably associated with the findingof a dextrose concentration below 100 mg. percent.
At a meeting of the Panel on Preservation of Whole Blood and Red Cellson 28 March 1951 (29), it was agreed that none of the studies carriedout with ion-exchange resins or anything, else had produced sufficienteffects on red blood cell survival to warrant changes in the preservativesolution in use. It was urged that testing techniques used in the variouslaboratories be standardized, to facilitate comparison of results and thusaid in the evaluation of the solutions used. Particular emphasis was placedupon the temperature of collection and storage of the blood and upon therapidity of cooling.
FREEZING
The preservation of whole blood at subzero temperatures, although ithad been discussed before the Korean War, was not seriously consideredduring it.
At the 2 December 1949 Symposium on Blood Preservation (23),Dr. Max M. Strumia reported on the extensive experiments he had conductedwith this technique. From them, he concluded that optimal preservationof whole blood for up to 2 months could be accomplished if it were storedat 26.6° F. (-3° C.). The temperature range, however, was relativelynarrow. With a variation of more than 1.5° C., even though the physicalstatus of the blood remained unchanged (that is, whether it were liquidor solid), the status of the red blood cells showed considerable deterioration.In all of his experiments, therefore, Dr. Strumia used the temperatureof -3° C. as optimal and kept variations within plus or minus 0.2°C. If preliminary shrinkage of the red blood cells, which he consideredessential, was carried out by the correct technique before the blood wasfrozen, the period of preservation was materially lengthened. Cells thusshrunken returned to normal size when they were immersed in plasma butnot when they were immersed in physiologic salt or other isotonic solutions.When the cells were used for transfusion, they resumed their normal shapeand size within an hour of the transfusion.
The concentration of glucose in the preserving fluid when the cellswere frozen at -3° C. was found to be critical. If the level was below40 mg. percent, preservation was bad. If it was greater, it was fair. Ifthe level was below 20 mg. percent, preservation was "terrible."
At this same meeting, Dr. Walter stated that he had been able to reproduceDr. Strumia's work; that his laboratory had repeated the work on vitrificationdone 10 years earlier, with the same results; namely, that approximately50 percent of morphologically intact erythrocytes were present after thawing.He thought that the problem was one of thawing and that it might be a blindalley.
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Part III. The Plasma Program
PLASMA SUPPLIES BETWEEN THE WARS
The details of the disposition of surplus plasma at the end of WorldWar II are related elsewhere (p. 310). In substance, all the surplus, exclusiveof certain amounts retained for Army use, was transferred to the AmericanRed Cross, for use by the public which had provided it originally. Thestocks transferred amounted to 960,183 250-cc. packages and 1,386,726 500-cc.packages. When the Korean War broke out, a large part of this plasma hadbeen utilized by hospitals, clinics, private physicians, and research workers.What was left had become outdated and required reprocessing, which hadbeen accomplished in only a small number of units.
At the end of World War II, the production facilities for plasma, whichhad been established by the Federal Government through the Defense Plants'Corp., were dismantled. Equipment was declared surplus. A small portionwas purchased by individual laboratories, and the remainder was disposedof by public sale.
STOCKPILES AND FUTURE REQUIREMENTS
Current Stockpiles
Army and Navy inventories as of September and November, 1949, respectively,were as follows:
1. No blood was on band except for day-by-day requirements.
2. The Army had on hand 16,695 250-cc. packages of plasma and 92,865 500-cc.packages.
3. The Navy had on hand 722,171 500-cc. packages of plasma.
4. The Army had on hand 17,869 standard packages, and 2,679 salt-poor packages,of albumin.
5. The Navy had on hand 242,194 standard packages, and 5,967 salt-poorpackages, of albumin.
An Army contract with Cutter Laboratories to reprocess 40,000 packagesof outdated dried plasma had gone unexpectedly well. The percentage ofloss, which was only 0.3 percent, was chiefly caused by subjecting thematerial to intense heat and by failure of proteins to go into solutionwhen the plasma was reconstituted. The cost of reprocessing was about athird of the cost of processing fresh plasma obtained from voluntary donors.The National Institutes of Health was willing to approve reprocessed plasmafor 5 years. The manufacturers thought a longer dating period was justified.
Stocks of plasma, albumin and gamma globulin on hand were consideredtemporarily adequate for peacetime requirements. Most of the plasma, however,would become outdated during 1950, and none of it had been irradiated
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against the hepatitis virus (p. 778). Also, some plasma would not besatisfactory for reprocessing because of its fat content and because oforiginal inadequate drying. A considerable amount of albumin and otherfractions could probably be recovered from the plasma unsuitable for reprocessing,but the remaining stocks might not meet even peacetime needs, and replacementsmust be procured from agencies participating in the national blood program.
Although there was no substitute for whole blood, as the Task Groupemphasized, it could not be stockpiled, and blood derivatives and plasma-expandersmust be stockpiled for emergencies. Research must be pressed for betteragents for replacement therapy than were presently available.
Wartime Estimates
The March 1950 report of the Task Group (4) estimated that inthe event of war, requirements for the Zone of Interior from M-day to M+12(months) would be 290,000 units of blood and 510,000 500-cc. units of plasma.Oversea estimates were based on two units of blood and two units of plasmafor each thousand troops exposed to combat, with 10 percent added for lossesdue to breakage and outdating. Allowances were also made for shipping lossesin the first month, and for the needs of U.S. civilian casualties in thecombat zone.
The Task Group estimated that for wartime, at least 120,000 units ofblood would be required for shipment overseas during the first year ofcombat, with increasing amounts thereafter. Transportation of blood inwartime would require the highest priority. The capabilities of varioustypes of aircraft for this purpose were estimated.
The Task Group also recommended: 1. That at least a million 500-cc.packages of plasma should be stockpiled by 1 June 1951, with additionalincrements procured in yearly installments over the next 4 years. Provisionshould also be made for rotation of stock by withdrawals to meet currentmilitary and civilian needs. 2. That equipment should be stockpiled forthe collection and administration of blood and should be replaced by rotation.It was thought that there should be no difficulty in meeting this requirementif manufacturers were provided with the proper priorities.
PROCUREMENT OF PLASMA
Initial Planning
Since at this time there was neither a civilian nor a military bloodprogram in existence of sufficient scope to meet the needs of nationaldefense, the Task Group recommended that, as a first step in procurementof the desired amount of plasma, existing stores of plasma and blood derivativesbe reprocessed as they became outdated while additional plasma was beingprocured to bring the war reserve for the Armed Forces up to the desiredlevel. Along with the re-
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sponsibility of whole blood procurement for Korea, the American RedCross accepted the responsibility of coordinating the collection of bloodfor plasma.
In August 1950, after it complete survey of commercial laboratoriesby the Industrial Mobilization Board, DOD, it tentative production schedulewas established to meet the target of a million units of plasma by June1951, a target that had become both more urgent and more difficult becauseof the outbreak of the war in Korea on 25 June 1950.
Government-owned plasma-processing facilities were set up at once at,Sharp & Dohme, the Upjohn Co., and Eli Lilly and Co. Litter contractswere made with Hyland Laboratories; Courtland Laboratories; Cutter Laboratories;Armour Laboratories; and E. R. Squibb and Sons. These firms, which werevariously located on the west and east coasts and in the midportion ofthe country, were selected on the principle of locating commercial processinglaboratories as near to donor collecting centers as possible, since plasmaand red cells must be separated from each other within 24 to 30 hours afterthe blood is collected.
In October 1950, before planning had proceeded very far, it became necessaryto replace the stockpiling program because of unexpectedly heavy demandsfor blood from the Far East Command, as well as because of processing delays.The original goal of a million units by June 1951 was halved, but eventhis objective could not be met, and, by the end of the fiscal year, only87,279 units of plasma had been delivered. At this time, seven of the eightplants listed were in operation. Their joint monthly capacity was 58,600units, and their final capacity as of April 1952 was set at 148,000 unitsper month.
Procurement Difficulties
For the first 6 months of the new plasma operation, the largest availabledrying capacity was in the three laboratories on the west coast. By February1951, the east coast laboratories had a capacity of 10,000 packages permonth, but it, was not until August 1951 that the laboratories in the middleof the country had completed the installation of their drying equipment.On the east coast, the opening of bleeding centers had been set far aheadof scheduled production, while on the west coast, the reverse was true.As a result, blood had to be shipped to the west coast production laboratoriesfrom the east coast bleeding centers. Shipping of blood in ACD solutionlong distances by air was not desirable technically or economically whenthe blood was to be used for plasma, and some of it froze during the bitterwinter weather, but this plan had to be employed as a matter of expediency.
In January 1951, representatives of the Department of Defense and theAmerican Red Cross were assigned to the processing laboratories to ironout difficulties as they arose and to take corrective action at once. Productionat one laboratory, for instance, was held up until administrative and personnelproblems were corrected by the appointment of a new laboratory director.
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Another laboratory was inoperative for 2 weeks because of trouble withits shell-freezing technique.
Early in January 1952, the Department of Defense learned that the Bureauof the Budget had allocated the funds for its 1953 plasma reserve to FederalCivil Defense, for inclusion in its estimates for stockpiling (2).The situation was considered at a meeting on 18 January 1952, in the Officeof the Directorate, Armed Services Medical Procurement Agency, which wasattended by both military and civilian personnel. It was agreed that theBlood Donor Program must continue to operate at its present level (300,000bleedings per month) and that plasma processing facilities be used withoutinterruption. Two general plans were considered:
1. That a single stockpile of plasma be set up for national defense,with both the Armed Services and Federal Civil Defense drawing from it.
2. That Federal Civil Defense take over all control of the Blood DonorProgram when existing contracts held by the Armed Services ran out.
Neither of these plans was desirable, but the second was consideredthe more undesirable of the two: It would require revision of the Currentprogram; initiation of new contracts with the American Red Cross and theplasma processing laboratories; hiring of additional personnel; and trainingthem in procurement, testing, inspection, and other procedures. It wouldalso require deemphasizing the program for blood for Korea, which had beengenerally successful, and stressing the requirements for stockpiling fornational defense, with little assurance that the new program would be completelysuccessful or have the same general appeal.
While these plans were being debated, a new factor entered the picture,which could not be ignored by the Department of Defense. This was the "alarming"percentage of hepatitis in persons who had received plasma infusions, especiallywhen the plasma had been prepared from large pools (p. 674). The reprocessingof World War II stocks of plasma had run into this problem, and the Departmentof Defense wanted no reserves of that kind.
At meetings of the Armed Forces Medical Policy Council on 17 March and28 April 1952 (2), it was agreed that, after some satisfactory methodof sterilization against the virus of hepatitis had been found, the plasmaprogram would be divided into two phases. In the first, priority wouldbe given to military and pipeline requirements for plasma. In the second,stockpile reserves would be accumulated. The Department of Defense wishedto continue its priority until such time as the first increment of itsreserves had been built up with plasma free from infection, after whichstocks would be divided equally between civilian and military agencies.At a joint meeting on 16 May 1952 of the Armed Forces Medical Policy Counciland the (Cummings) Subcommittee on Blood, Health Resources Advisory Board,the subcommittee agreed to accept the dual stockpile plan but not the proposalthat the Department of Defense build up an increment of infection-freeplasma before Federal Civil Defense secured any plasma at all. The Departmentof Defense, on the
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other hand, was entirely unwilling to use currently available plasma,from which a comparatively large proportion of recipients might be expectedto develop infectious hepatitis. The Armed Forces could not tolerate longperiods of incapacity among its personnel, their corresponding delay inreturn to duty, and a reduction in the effective military strength of thecountry. All of these losses could be better tolerated by civilian personnelthan by combat troops.
When the disagreement continued, with the Secretary of Defense supportingthe position of his Policy Council, it was agreed, on 2 June 1952, thatthe decision would have to be made by the President. The allocation ofplasma reserves was still undecided by the end of the year, but had becomelargely academic, since no satisfactory method of sterilization of plasmahad been devised. A lack of funds also made it impossible to meet the desiredgoals.
By the end of fiscal year 1952, the Federal Civil Defense Administrationhad contracted for 750,000 units of plasma, none of which had been delivered.In addition, it had not received any of the 300,000 units of dextran andthe 1.2 million units of polyvinylpyrrolidone that had also been ordered.
SERUM HEPATITIS
The potential problem of serum hepatitis, as mentioned elsewhere (p.776), began to be appreciated only shortly before World War II ended. Withthe end of the war, the massive use of plasma ceased, and, in the absenceof a central reporting agency, such cases of serum hepatitis as occurredafter plasma infusion did not have the impact which they would have hadin time of war and which they were to have when the outbreak of the warin Korea required a resumption of en masse plasma infusions.
Shortly before World War II ended, Dr. John W. Oliphant and his associatesat the National Institute of Health (30, 31) began their work onthe ultraviolet sterilization of plasma as part of its processing (fig.189). The first results were most encouraging, a particularly desirablefeature of the method being that the plasma proteins were apparently unaffectedby the amount of ultraviolet energy used. Unfortunately, the belief thatthe problem had been solved was to prove fallacious.
There was scarcely a meeting of the Committee on Blood and Blood Derivatives(the reconstituted Subcommittee on Blood Substitutes), NRC, at which serumhepatitis and attempts at sterilization of infected plasma did not comeup for discussion. Space does not permit an extended account of these matters,and the reader is referred to an excellent summary by Dr. Roderick Murray,Laboratory of Biologics Control, National Institutes of Health, who tookover the work on Dr. Oliphant's death. The report which contains a comprehensivelist of references, was presented at a Conference on Derivatives of PlasmaFractionation, on 28 October 1953 (32).
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Special Studies
The experience of the Armed Forces in Korea showed that, while 0.5 percentof recipients of whole blood developed hepatitis, 12 percent or more developedit after infusions of pooled plasma. In 1951, it was therefore decidedto use human volunteers for testing the infectivity of plasma and plasmaderivatives and evaluating the efficacy of various methods proposed forits sterilization (table 40).
TABLE 40. - Results of inoculationof volunteers with serum from six suspected donors
Volunteers inoculated | Interval since incriminated donation | Hepatitis cases- | Incubation period for- | |||
With jaundice | Without jaundice | Total | Volunteers1 | Original recipient | ||
| Days | Number | Number | Number | Days | Days |
10 | 203 | 0 | 0 | 0 | --- | 65 |
10 | 385 | 4 | 22 | 6 | (18), 30, 45, 46, (46), 56 | 48 |
5 | --- | 0 | 1 | 1 | (43) | --- |
10 | 356 | 1 | 20 | 1 | 48 | 40 |
10 | 149 | 1 | 20 | 1 | 84 | 70 |
10 | 135 | 4 | 0 | 4 | 35, 50, 56, 72 | --- |
5 | --- | 5 | --- | 5 | 43, 49, 56, 57, 63 | 44 |
10 | 43 | 2 | 31 | 3 | (50), 57, 67 | 32 |
1Incubation periods in parentheses refer to casesof hepatitis without jaundice.
2One additional subject presented equivocal or abnormal testssuggestive of hepatitis without jaundice.
3Three additional subjects presented equivocal or abnormal testssuggestive of hepatitis without jaundice.
By the time these studies were undertaken, numerous disquieting reportshad been received indicating that hepatitis was occurring after the useof irradiated plasma, which presumably had been rendered safe. One suchreport (33) showed an incidence of 11.9 percent in patients whohad been followed for at least 6 months and most of whom had received morethan one unit of plasma.
Sterilization Techniques
Ultraviolet irradiation.-Irradiation of plasma with ultraviolet lightwas usually carried out by exposing a thin film of plasma to radiationfrom a high intensity source (32). Various types of equipment wereused. In some, the plasma was passed through a narrow-bore, usually flat,quartz tube resembling a hollow ribbon. In others, the film was formedon the inside wall of a hollow cylinder or cone which rotated at high speedand in the cavity of which the ultraviolet lamps were located. In someof these lamps, quartz envelopes transmitted most of the ultraviolet light.In others, Vycor envelopes transmitted radiation only in the 2735 A. bandor higher. Apparatus of the latter type was most widely used in the plasma-processinglaboratories because of
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its ability to handle relatively large amounts of plasma, by the formationof films on the inner surfaces of cylinders or cones.
The NH studies on the effect of ultraviolet light on plasma were carriedout with three different machines of the type just described (table 41).An attempt was made to simulate actual processing conditions. Special attentionwas paid to the measurement of the ultraviolet output of the lamp used,to continuous monitoring of each irradiation run, and to accurate measurementof the rate of flow of plasma through the apparatus. Each run was alsochecked by the Aerobacter aerogenes test.
The results of this study eliminated the hope originally raised thatfailure of sterilization might be due to some defect in the apparatus orto inadequate exposure to ultraviolet irradiation. As this experience (table41) showed, the margin of safety between the sterilizing dose and the doseproducing unacceptable denaturation of plasma was not sufficiently greatto justify placing much reliance on this technique. Moreover, considerablechanges in plasma proteins were apparent after sterilizing dosages thatmight actually produce inadequate exposure.
TABLE 41. - Results of ultravioletirradiation of infected pooled plasma
Apparatus and conditions of irradiation | Volunteers | Volume of dose | Hepatitis cases- | Additional subjects with suggestive laboratory findings | ||
With jaundice | Without jaundice | Total | ||||
Number | ml. | Number | Number | Number | Number | |
Dill apparatus: | ||||||
| 515 ml./min. | 10 | 1.0 | 3 | 1 | 4 | 0 |
| 249 ml./min. | 10 | 2.0 | 2 | 1 | 3 | 1 |
| 73 ml./min. | 10 | 4.0 | 6 | 3 | 9 | 0 |
| Control | 10 | 1.0 | 4 | 2 | 6 | 1 |
Habel-Sockrider apparatus: | ||||||
| 1 passage | 10 | 1.0 | 4 | 1 | 5 | 1 |
| 5 passages | 10 | 2.0 | 0 | 0 | 0 | 0 |
| 10 passages | 10 | 4.0 | 0 | 0 | 0 | 0 |
| Control | 10 | 1.0 | 6 | 0 | 6 | 1 |
Oppenheimer-Levinson apparatus: | ||||||
| 10" bowl, standard lamp | 8 | 1.0 | 3 | 1 | 4 | 0 |
| 15" bowl, high-powered lamp | 8 | 1.0 | 2 | 1 | 3 | 0 |
| Control | 5 | 1.0 | 2 | 0 | 2 | 0 |
Controlled heating.-Samples of infected pooled plasma were subjectedto controlled heating by complete immersion in constantly agitated waterat 59.2° and 60.4° C. for 2 hours and 4 hours, respectively. Twobottles were tested for each time period, and a fifth bottle was kept atroom temperature during the heating process. All bottles were then immediatelyshell frozen
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by means of Dry Ice and alcohol and stored at -20° C. until theywere administered to volunteers. Some of the Dry Ice in which the materialwas transported to the using hospitals was still present when the flaskswere opened for the inoculations.
Two groups of 10 volunteers each, who had been carefully screened byliver function tests, were inoculated with the heated material, and 5 otherswere inoculated with the control plasma. Cases of hepatitis developed ineach group (table 42).
Storage at room temperature.- Room storage temperature, which had beendeveloped by Dr. J. Garrott Allen and his associates at the Universityof Chicago with extremely promising results (32, 34), was evaluatedin three groups of volunteers. There were three instances of hepatitisin a group of five subjects inoculated with plasma stored at an almostconstant temperature of 70° F. for 3 months against only one instancein 20 subjects inoculated with plasma stored at a similar temperature butfor 6 months. The single case of hepatitis in these patients occurred atthe end of 196 days, the longest incubation period on record, and was mild.
TABLE 42. - Results of heating infectedpooled plasma at 60° C.
Duration of heating | Volunteers | Hepatitis cases- | Incubation period | ||
| Without jaundice | Total | |||
Hours | Number |
| Number | Number | Days |
2 | 10 | 3 | 11 | 4 | 70, 170, 126, 147 |
4 | 10 | 3 | 22 | 5 | 284, 87, 88, 291, 97 |
Not heated | 5 | 1 | 1 | 2 | 77, 177 |
1Clinical signs and symptoms, no jaundice.
2Only abnormal laboratory findings.
Dr. Allen presented his own figures on plasma stored in the liquid stagefor 6 months before use: There was no instance of hepatitis in 1,546 plasmatransfusions, with a careful 6-month followup, while over the same periodthere were 49 cases of hepatitis, 0.4 percent, in 37,026 whole blood transfusions.
At this same meeting, it was reported that beta-propiolactone had failedin experiments involving the administration of transfusion sized (600 cc.)doses of known infected plasma treated with 3,000 mg. per liter of thisagent. Cathode-ray irradiation had proved lethal for the laboratory virusof hepatitis, but it had been given a relatively low priority in experimentson human volunteers because the outlook with beta-propiolactone had thenbeen considered more promising.
Termination of the Plasma Program
There would be little point to citing other clinical and experimentalstudies with treated plasma. A great many of them were extremely hopeful
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up to a point. In September 1950, a distinguished clinician was so impressedwith the results apparently being obtained from ultraviolet irradiationthat he declared that "the key to the control of homologous serumjaundice is now at hand." The blunt fact is that hepatitis continuedto follow the use of plasma, no matter how it was treated. Complete sterilizationwas never achieved. All methods failed in the end.
The crux of the matter was that the Armed Forces needed some agent touse for resuscitation until the casualty could reach an installation wherewhole blood was available. They therefore had no choice but to take thecalculated risk of using plasma, even though it might cause hepatitis.The risk was considerable. Late in 1951, the incidence of hepatitis afterplasma transfusion reached 21 percent, in sharp contrast to the reportedWorld War II incidence of 7.5 percent. Part of the explanation was thatmuch of the plasma used in Korea in the first months of the war had notbeen treated at all. Moreover, different diagnostic criteria were usedin the two wars. In World War II, the diagnosis was chiefly clinical. Inthe Korean War, any elevation of the serum bilirubin was considered anindication of hepatitis.
In January 1952, the National Institutes of Health agreed that poolsof plasma should be reduced from the approximately 400 bloods then beingused to not more than 50. The change could not be made immediately becausethe smaller pools required changes in equipment and techniques.
Hepatitis continued to occur, and at the 8 October 1952 meeting of theSubcommittee on Sterilization of Blood and Plasma, Committee on Blood andRelated Problems, it was recommended that, because of the risk of hepatitis,plasma should be used only in emergencies and when no plasma-expander wasavailable (85). Otherwise, serum albumin, which had proved to be extremelyeffective, or dextran, which had been tested extensively, should be used.The reduced yield from blood, as compared with the plasma yield (p. 342),would be compensated for by the other desirable byproducts secured by fractionationof plasma, and it was recommended that, as far as was practical, the presentplasma program be converted to large-scale production of human serum albumin.Meantime, the search for techniques of sterilizing plasma should be continued.It was brought out, however, that when such a method was found, the sterilizedplasma would be a new item, and an extensive program of testing and clinicalevaluation would be required before it could be recommended and standardized.Some doubt was expressed that the blood procurement program could be sufficientlyincreased to provide the extra blood needed for the production of serumalbumin.
At the 4 February 1953 meeting of the Subcommittee on Sterilizationof Blood and Plasma, the third death from hepatitis in a volunteer wasreported, and the testing program was suspended by action of the ArmedForces Epidemiological Board (36).8 It was recommendedat this meeting that
8 In his report at the Conference on Derivativesof Plasma Fractionation on 28 October 1953 (32), Dr. Murray gratefullyacknowledged the service of the volunteers in these studies, who were securedthrough the cooperation of the Bureau of Prisons, U.S. Department of Justice,and the staffs of the U.S. Penitentiaries at Lewisburg, Pa., and McNeilIsland, Wash., and the Federal Correctional Institution, Ashland, Ky.
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packages of plasma prepared for clinical use carry a conspicuous warningto physicians that, serum hepatitis could be transmitted by plasma, inspite of ultraviolet irradiation, and also advising careful selection ofblood donors.
On 20 August 1953, Circular No. 73, Department of the Army, directedthat, because of the risk of serum hepatitis, the higher cost, and theneed to use it for the production of specific globulins, plasma would notbe used "to support blood volume" unless dextran was not available(37).
Part IV. The Plasma Fractionation Program
SERUM ALBUMIN
When the Korean War broke out, the same reasoning that made the Armychoose plasma in preference to serum albumin as their agent of resuscitationin World War II led them to choose it again; that is, it took 4.2 bleedingsto provide 25 gm. of serum albumin, against only 1.2 bleedings to provide250 cc. of plasma. Also, it was usually necessary to supply water whenserum albumin was used, whereas the distilled water used in the reconstitutionof plasma was provided with it. Finally, the finished price of a unit ofalbumin was about $20, against about $4 for a unit of plasma.
When the military reverses suffered by the U.S. Army in Korea in thewinter of 1951 increased the need for replacement substances, 50,000 unitsof outdated serum albumin were obtained from the Navy and transferred tothe San Francisco medical depot for shipment to FECOM. Technically outdatedserum albumin proved perfectly satisfactory. One of its advantages wasthat the small size of the units made it possible for corpsmen to loadtheir pockets with it. Also, serum albumin did not freeze in the bitterwinter weather encountered, as reconstituted plasma did.
When the incidence of serum hepatitis made it necessary to discontinuethe use of plasma in Korea, serum albumin was the logical substitute. Extensivetests had shown that, when it was heated for 10 hours at 60° C., itcarried no risk of hepatitis (28, 38). Also, it could be made fromcontaminated plasma, which meant that a large quantity could be obtainedfrom the plasma on hand and no longer considered fit for use because ofthe risk of transmission of hepatitis; it was, of course, essential touse a therapeutic replacement agent that did not cause a second pathologiccondition.
Serum albumin was readily administered in forward areas.
GLOBIN
At the meeting of the Subcommittee on Shock, Committee on Surgery, NRC,on 11 December 1950, it was brought out that, though globin is of greatnutritive value as a protein, it was lost in 18 percent of the total proteinof the blood then being discarded in the form of red blood cells (39).It was
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also brought out that problems connected with its clinical use, chieflyhematuria and renal complications, had not yet been overcome.
At the 5 April 1951 meeting of the Committee on Blood and Blood Derivatives(40), it was reported that a modified form of globin, prepared bySharp & Dohme, from discarded red blood cells, had been used by some12 investigators to date as (1) a protein supplement and (2) as a plasma-expander.In about a hundred trials, there had been 10 to 15 percent of rather seriousreactions, but the processing procedure had recently been altered, andthere had been no reactions in the last 60 clinical trials.
Globin was used in 8-percent solution, in doses of about 16 gm. daily,for patients with hypoproteinemia, caused by cirrhosis, nephrosis, andother conditions in which there was a negative nitrogen balance. It hadbeen tested on only four patients in shock, and no evidence existed thatit possessed sufficient osmotic activity to become a satisfactory plasma-expander.The trials had not been entirely adequate because many investigators hadfailed to analyze the globin per se in the bloodstream.
GAMMA GLOBULIN
A Conference on the Uses of Gamma Globulin was held oil 5 August 1952,under the chairmanship of Dr. Milton C. Winternitz (41). Earlierin the war, there had been numerous meetings concerning this product atthe Office of Defense Mobilization, to discuss the amount available andthe anticipated needs if testing should indicate that it was effectivein preventing paralytic poliomyelitis. If it was proved effective, thenationwide demand for it expected during the summer of 1953 would havea tremendous impact on the blood program, affecting every phase of it fromthe donation to the final product.
An ad hoc committee which had been convened by the Committee on Bloodand Related Problems to assess the situation agreed in principle with proposalsdeveloped by the U.S. Public Health Service. It was recommended that theNational Research Council investigate current stockpiles of gamma globulinand present production capacities; consider production for the Armed Forcesand the civilian population and the equitable distribution of gamma globulinbetween them; assess the need for, and means of, increasing production;solicit the cooperation of both public and private groups working on thisproblem; conduct, or arrange for epidemiologic studies bearing on allocation;adopt such measures of allocation as might be necessary and set up prioritiesif it was thought that gamma globulin would be in short supply. It wasalso recommended that the U.S. Public Health Service and the American MedicalAssociation arrange for publicity on the production and use of gamma globulin.
Up to this time (August 1942), three field studies had been conducted,in Provo, Utah; Houston, Tex.; and Sioux City, Iowa. It was thought thata fourth might be necessary. Followup studies were still incomplete, andboth the potency and the dosage of gamma globulin remained to be established.
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Whether the ad hoc committee assumed that gamma globulin would be onlypartially successful, or successful in only some cases, it had to postulatesome measure of success to make plans for the future. It was most importantto be ready to expand production capacity to the limit as soon as possibleafter all field tests were completed, by 15 October 1952.
In a second report of the ad hoc committee on the uses of gamma globulinon 30 September 1952 (42), it was noted that the first knowledgethe National Research Council had of the possible magnitude of the problemwas at a meeting held in June 1952, with the Subcommittee on Blood of thePresident's Health Resources Advisory Committee. The Subcommittee on Bloodfully recognized its responsibility because of the possible effect a demonstrationof the preventive effect of gamma globulin in poliomyelitis might haveon the future of blood collections in the National Blood Program (p. 735)and on the allocation of blood and its derivatives between civilian andmilitary claimants. The present supply of gamma globulin was inadequate.The Office of Defense Mobilization had turned to the National ResearchCouncil for help, and the council had noted that its role was to advise,not to implement advice. The Office of Defense Mobilization was investigatingthe legal implications connected with the situation. The provision of gammaglobulin for military dependents was, of course, an Armed Forces responsibility.
At this time (September 1952), the American Red Cross which had receivedthe bulk of the surplus gamma globulin at the end of World War II, wasdistributing between 700,000 and 800,000 2-cc. doses per year for theprophylaxisof poliomyelitis and was recovering 200,000. It was then producing 70 percentof the current output and commercial firms, 30 percent. The Red Cross wasalso distributing gamma globulin for the prophylaxis of measles and ofinfectious hepatitis. The Army was holding 12,000 10-cc. units and had1,013,450 gm. in the dried state. The Federal Civil Defense Administrationhad no reserves at all. On an assumed loss of 5 percent of current bloodcollections of 3,360,000 pints per year, 191,680 gm. of gamma globulincould be recovered.
The problem was discussed at several other meetings in 1952 and 1953(43, 44), including a conference on Epidemiology of Poliomyelitis(45). The end of active combat in June 1953 eliminated the needfor further action on the part of the National Research Council and theArmed Forces.
When final action was taken by the Office of Defense Mobilizationin June 1953 to terminate dried plasma contracts, in accordance with NRCrecommendations, because of the proved danger of serum hepatitis (32),it was agreed by the Department of Defense and the Federal Civil DefenseAdministration that the program for the current fiscal year should includeonly fractionation of plasma, with the production of serum albumin andgamma ( globulin. All gamma globulin produced would be made available tothe American Red Cross and the National Foundation for Infantile Paralysisat the cost of processing.
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RED BLOOD CELLS
During the Korean War, as in World War II (p. 313), packed red bloodcells were used extensively in the treatment of chronic and secondary anemiasand in the preparation of anemic patients for surgery. One of the chiefadvantages of this technique was that large quantities could be injectedwithin short periods without risk of overloading the circulation. No invitro tests were developed during the Korean War to determine the viabilityof these cells, and no gross or microscopic characteristics proved usefulfor this purpose. The only valid criterion of their viability continuedto be a study of their survival in normal human subjects, a test that wasboth difficult and cumbersome. Without a simple method for continuous qualitycontrol, rigid standards of collecting, processing, and storage were essentialprecautions.
CADAVERIC BLOOD
At the fourth meeting of the Committee on Blood and Related Problemson 10 December 1952 (46), an inquiry was received from the ArmyResearch and Development Board concerning the possibility of using cadavericblood. The American Red Cross had also received numerous letters on thesame subject.
In response to these inquiries, Dr. Strumia reported work he had donein this field in 1937-38. He considered only 12 of the 125 cadavers hehad examined usable. He obtained much less blood than he expected, an averageof 1,500 cc. per body. It was difficult to secure a free flow of blood,even shortly after death; the best flow was from patients who had diedof coronary occlusion. He found it impossible to secure a satisfactoryflow from the femoral vein, as the Russians had reported, and had to enterthe right auricle with a ½-inch trocar. In vitro tests were normalin all respects, but the incidence of contamination was very high unlessthe blood was drawn within 6 hours of death.
Dr. Strumia had not used cadaveric blood clinically, and it was theconsensus of the committee that there would be strong esthetic objectionsto it by both physicians and patients in the United States. It was alsopointed out that there was no need for the use of this method for the ArmedForces at this time since the country was still far from exhausting itsdonor supply.
Part V. The Plasma-Expanders Program
BIBLIOGRAPHY
It is not the function of this history to go beyond the important historicalfacts in the study of plasma expanders (the so-called blood substitutesof World War II). Attention should be called, however, to the excellentbibliog-
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raphy on plasma expanders (except those derived from human blood) preparedin the reference division of the Army Medical Library (now the, NationalLibrary of Medicine) in December 1951 (47). This is a most usefullist. The references under each major item are grouped according to subheadings;the number of references in each article is stated; and the substance ofthe article is summarized in one or more succinct sentences.
The need for such a reference list was pointed out in the preface: Thetreatment of shock was then (1951) the most pressing single medicomilitaryemergency. It was urgent both militarily arid in the event of a thermonuclearwar in which civilians would be involved. Since the prolonged storage ofwhole blood is not feasible, realism required that two facts be faced,(1) that it would be completely impractical to secure blood from donorsin the event of a thermonuclear attack, and (2) that potential donors mightwell themselves be victims of the attack and therefore candidates for blood.The solution of the military and civilian problem was the development ofplasma, volume expanders and their stockpiling. This collective bibliographywas a useful first step in such a task.
GELATIN AND OXYPOLYGELATIN
The extensive studies made on gelatin during World War II under theauspices of the National Research Council (p. 373) were resumed early inthe Korean War. Then, as in World War II, the major objection to gelatinfrom the military standpoint was that it gelled at about room temperature.It therefore could not be used in the field, and even in hospitals, itsuse furnished some problems, which would be intensified if bombing or someother catastrophe interrupted electricity and heat.
Some observers believed, in view of the nature of the emergency, thatgelatin manufacturers should be encouraged to begin production at once,even if the material might not be precisely what was wanted (39).The proposal that 30 gm. of urea be added to each 500 cc. of gelatin tokeep it liquid was considered ingenious, but unsafe unless there couldfirst be assurance that the recipient's urea clearance was normal (48).Such a specification was clearly impractical. Moreover, renal functionwas often sharply reduced in combat casualties, and if they were givengelatin infusions in the amount of 1,000 to 1,500 cc. in the course ofa few hours, they would also receive 60-90 gm. of urea, which was obviouslyundesirable.
At the 14 October 1950 meeting of the Committee on Shock (49),Dr. Ravdin reported on an oxypolygelatin of superior quality which hadbeen prepared in his laboratory. It did not gel at ordinary temperatures,but it gave rise to toxic reactions closely resembling certain reactionsto oxalic acid, and he was not prepared to recommend it at this time. Ayear later, it was still impossible to obtain production of oxypolygelatinsof uniform quality. Moreover, the amounts and rates of excretion variedfrom laboratory to laboratory, one probable reason being the variety ofanalytic methods in use.
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In February 1953, the outlook was even more discouraging (50).Oxvpolygelatin had proved to be antigenic. Its retention in the bloodstreamin normotensive patients as well as in bled patients was poorer than thatof dextrall or Periston (polyvinylpyrrolidone). If its melting point werelowered by further degradation, its molecular weight would also be so loweredthat it would not remain in the circulation long enough to have any effectat all. Moreover, the high initial elevation of the plasma volume achievedby gelatin preparations, followed by the rapid loss of the osmoticallyactive material, might, throw a patient in shock into it very dangerousstate. In fact, if hemorrhage were also present, he would be in real jeopardyunless he were given blood or a more effective plasma-expander than gelatin.
It had been brought out, at one of the earlier meetings of the Committeeon Blood and Related Problems (49), that gelatin, like other bloodsubstitutes proposed up to that time, lacked the capacity, essential inthe management of shock, to transport oxygen. It was also brought out atthis meeting that the Armed Forces must not assume that funds were unlimitedfor studies in all areas. On the contrary, the field must be narrowed toagents of reasonable cost, suitable for stockpiling, whose production couldbe expedited. In view of these criteria, it seemed to many members of thecommittee that further investigation of gelatin was not warranted.
In March 1953, it was reported to the Subcommittee on Shock that fluidgelatin had been sent to Korea for a field trial, and it was believed thatreports on it would be favorable, since it had been shown to restore bloodvolume for brief periods (51). On the other hand, the committeenoted that, if not more than 35 percent of the blood volume had been lostand if hemorrhage did not continue, the normal homeostatic mechanisms ofthe body would tend to maintain the restoration, in which gelatin wouldplay no part.
It was decided at this meeting that the investigation of gelatin andoxypolygelatin should be discontinued until a product could be suppliedthat could be characterized physicochemically; with evidence of reproducibilityand stability; and of higher molecular size, so that it would not be excretedat an excessive rate, as were the products then in use. Data on toleranceand toxicity in animals were also desired.
No further reports on gelatin and gelatin products were made to NRCcommittees during the Korean War.
POLYVINYLPYRROLIDONE (PERISTON, PVP)
Historical Note
Knowledge of polyvinylpyrrolidone, the plasma-expander more commonlyknown as Periston or PVP, reached the United States during 1943. The Subcommitteeon Blood Substitutes conducted a brief investigation on it (p. 380), butit was not used in the U.S. Army during World War II.
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This agent was developed in Germany in 1940, when the need was recognizedfor a colloidal solution for the emergency treatment of shock (52).It was selected from some 30 compounds studied at I. G. Farben Laboratories.When the choice fell upon polyvinyl esters, polyvinyl alcohol polymerswere first tested but were discarded when it was found that bone-marrowdepression occurred after their repeated injection. When polyvinylpyrrolidonewas synthesized from acetylene and ammonia, the polymers formed had molecularweights as high as 150,000 to 200,000.
According to the Germans, whose investigative methods were not consideredentirely satisfactory, about 20 percent of Periston was excreted in theurine in the first 3 days. The remaining 80 percent was thought to be phagocytosedafter 24 hours, stored in the reticuloendothelial system, and then probablyslowly excreted, perhaps in the bile. Qualitative tests indicated that some Periston remained in the tissues for several weeks after injection.
Development in the United States
Periston was first considered in the Subcommittee on Shock on 14 October1950 (49). Although it had been widely used in Germany during WorldWar II and about half a million cases had since been followed up, not muchwas known about its use in recent years. Apparently, it caused no lastingdamage to the tissues, but no definitive data were available on its coursein the body and on the amount that could be tolerated without depositionin the tissues. Some members of the committee considered it worthless.Others took the position that if it had any deleterious effects, they wouldhave been evident, even in the absence of expert observation, because ofthe large number of cases in which it had been used.
At the 11 December 1950 meeting of the Subcommittee on Shock (39),it was learned that the Schenley Corp. could then import 5,000 to 10,000bottles of Periston per month from Germany and by July 1951 expected toimport an intermediate form that could be processed further in the UnitedStates. Other manufacturers were also able to produce Periston.
The Subcommittee on Shock met with the manufacturers and potential manufacturersof Periston on 4 January 1951 (53). A research project had beenapproved in principle, but, up to this time, no funds had been assignedfor it (54). Some companies were making Periston that very closelyresembled the German product, but they stated that their progress wouldbe faster if the Army would reach a decision concerning its use. The Foodand Drug Administration was prepared to clear Periston as soon as the NationalResearch Council furnished precise data about it and recommended it. Thepoint was again made that the hundreds of thousands of cases in which ithad been used in Germany, plus a favorable report made on it by Dr. J.A. Walker, University of Pennsylvania, furnished sufficient basis for recommendingit without much further investigation. The Department of Defense, of course,was not in-
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terested in putting money into material coming from a source in whichresupply was not certain.
At a meeting of the Subcommittee on Shock on 26 September 1951(55), another study that had been made in Germany was reported.It had showed no deleterious effects, but it was not adequate by UnitedStates standards: Pathologic practices were different. Records were notprecisely kept. Sections were not studied carefully, and were not preserved.
Late in 1952, the Subcommittee on Shock recommended that Peristonproduced according to certain specifications should be stockpiled by theFederal Civil Defense Administration but should be used only in emergencies(56). Other recommendations were withheld until the long-term followupstudies then in progress had been completed and a more closely fractionedproduct of suitable molecular weight had become available and been tested.The effectiveness of Periston had been clearly established, but it wasstored in the body for undesirably long periods. Followup studies on Germanchildren showed no effect on hepatic and renal function, and post mortemstudies made up to 14 months after its injection revealed no abnormalities,but the sense of the committee was that the burden of proof still restedon those who claimed that Periston was perfectly safe.
At the February 1953 meeting of the Panel on Plasma Volume Expanders(50), data were reported on 48 German children which brought thetotal studied to 68. All had been treated with Periston between 1944 and1948, and none of them showed any abnormalities.
Special Studies
At the meeting just mentioned, Dr. Robert M. Zollinger reporteda number of special studies on Periston made in his clinic. All tests werewithin normal range except that bone abnormalities were observed in 2 (of18) examinations made on 14 patients. He and his associates were unwillingat this time to attribute these abnormalities to Periston.
Radioactive studies showed that from 95 to 100 percent of injectedPeriston was excreted via the urine within 72 hours; 40 percent was excretedwithin 20 minutes. Within 6 hours, virtually all circulating PVP had disappearedfrom the plasma. Excretion was thus too rapid for Periston to be of value,and it was recommended that general approval of it should be withheld,though again it was given limited approval for stockpiling for use in emergenciesif serum albumin and dextran were not available.
On 3 March 1953, a panel discussion at a meeting of the Subcommitteeon Shock brought out the following points (51):
1. Material found in many tissues, after study by various stains, wasconsidered to be Periston or a reaction induced by it.
2. Similar deposits were present in Kupffer and liver cells 14 months afterinjection.
3. The bone marrow changes just referred to were again present.
4. Abnormal mitoses were observed in embryonic cells grown in tissue culturesin media containing PVP.
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5. The anatomic and functional changes noted were mild, but it was thoughtthat their investigation must be pursued over longer periods of time. Itwas therefore not possible to approve Periston for any but limited stockpiling.It could not be approved for general use.
At a meeting of the Committee on Blood and Related Problems, also inMarch 1953 (28), radioautographs were reported on patients whohad been given K-30 Periston for 1 or 2 weeks before death. After a year'sexposure, the tissues showed no concentration greater than twice what wouldbe expected from uniform distribution in any tissues; the accuracy of thistechnique did not go beyond this level. Other studies showed that the goalsof complete elimination of PNT from the body and adequate plasma volumeexpansion by its use were not mutually compatible.
At the meeting of the Subcommittee on Shock on 20 May 1953 (57),it was reported that large amounts of Periston had been stockpiled by theGovernment, but further studies were still considered necessary beforeit could be recommended for any but emergency use. The Korean War endedbefore further action was taken on it.
DEXTRAN
Dextran came to the attention of the Subcommittee on Blood Substitutes,NRC, shortly before World War II ended (p. 381), but no action was takenon it at that time. Some experimental work was done on it in Army hospitallaboratories after the war, but it had not been used clinically in theUnited States when a request for information about it was received fromthe Food and Drug Administration at the meeting of the Committee on Bloodand Blood Derivatives on 3 December 1949 (8), in connection withan application for its import from a Swedish company (Pharmacia).
Composition and Properties
Dextran was developed in Sweden during the early part of World War IIand refined to the point at which it found wide clinical acceptance inScandinavian countries (58). It was made up of a variety of polysaccharidesof varying molecular sizes (59). Its production was quite simple.The only materials needed were sucrose and an organic solvent. Fermentationrequired only a day, and fractionation was not complicated. The chief bottleneckin production was the elimination of pyrogens and testing for sterility.
Smaller molecules of dextran were rapidly lost from the bloodstream,a matter of importance in military medicine, in which a considerable timemight elapse between infusions. About half of each dose was accounted forby excretion through the kidneys or the intestinal tract. The fate of theremainder was unknown when the Committee on Blood and Blood Derivativesbegan to investigate dextran, but it was thought that the larger moleculeswere probably
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deposited in the reticuloendothelial system and that they might benephrotoxic or hepatotoxic.
The committee, remembering that periods of 5 to 15 years had elapsedbefore it was found that gum acacia could lead to amylold degeneration,understandably took the position that great, caution should be exercisedin recommending dextran: macromolecular substances of this type were knownto cause rapid sedimentation of red blood cells as well as a tendency tosludging. It was necessary to consider whether dextran might give riseto breakdown products of hemoglobin, which might be nephrotoxic or hepatotoxic.Finally, it was necessary to investigate the maximum safe dosage and overwhat period this dosage could safely be administered.
Because of the commercial situation in Sweden, it was difficult to obtainpertinent chemical data on dextran (49), and the British, who werealso manufacturing it, did not have the desired information. The only dataon molecular size were based on viscosity measurement. Moreover, the clinicalstudies conducted in Europe had not been carried out with the precisionused in such studies in the United States.
Another reason for caution on the part of the Committee was pointedout by Col. (later Brig. Gen.) John R. Wood, MC, at the October 1950 meetingof the Subcommittee on Shock (49): The implications of the decisionto use dextran for combat and other casualties would, he pointed out, befar reaching. The adoption of any new technique would commit thousandsof medical officers to it, and the recommendation of the Committee wouldprobably be followed also by the civil defense organizations.
Experimental and Clinical Studies
Up to September 1950, the British experience with dextran covered 10,000540-ml. bottles (25). No untoward effects had been observed, butthe rate of excretion via the kidneys had varied widely, from 10 to 50percent. At the end of 9 months, no dextran had been found in the bodiesof rabbits except for slight traces in the lymph nodes and bone marrow.There was no histologic evidence of tissue damage. It was believed thatthe chief production problem was ridding the dextran of the small molecule,to reduce the rate of excretion.
Up to December 1950, the Swedish experience with dextran had covered200,000 cases (39). In the 10 years of its use, there had been nopost mortem evidence of tissue damage, and reactions were fewer than withthe use of either blood or plasma. A compilation of articles from the literatureby Pharmacia showed an impressive use of dextran by reliable investigatorsin Denmark, Finland, and Holland as well as in Sweden.
Between 24 and 69 percent of Swedish-produced dextran was excreted within24 hours. Its molecular weight ranged from 120,000 to 200,000, against80,000 to 100,000 for the British product. Swedish dextran was now fairlyuniform.
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Clinical testing, in the United States during 1950 produced the followingdata:
1. Dextran expands plasma volume in the normovolemic individual, andreturn to the normal level takes a surprisingly long time.
2. In shocked patients, many factors operate to expedite the return ofcirculatory dynamics to normal. Once normal balance is restored, the bodyhelps to maintain it.
3. A fairly sharp discrimination is exercised by the kidneys, based onmolecular size, but the exact size at which excretion occurs varies fromperson to person. In clinical use, there is no diuresis (as there is experimentallywhen the smaller molecules are removed), and the excretion of dextran iscomparable to the amount of the injection.
At a meeting of the Subcommittee on Shock on 30 January 1951 (52),it was reported that another review of the literature had shown no clinicallyundesirable renal, hepatic, hematologic, or circulatory changes after theuse of dextran. Hemodilution was maintained for at least 6 hours afterinjection. Between 30 and 50 percent of the injected material was excretedin the urine, but the fate of the remainder was still unknown.
At this meeting a number of clinical reports were made, all to the effectthat dextran was of great temporary value. Dr. John S. Lundy, who had hadsome anaphylactoid reactions with dextran when the material was importedfrom Sweden and bottled in the United States, had had no difficulty withthe total Swedish product.
The single adverse report at this meeting, and at several subsequentmeetings, came from Lt. Col. Edwin J. Pulaski, MC, and his group at BrookeGeneral Hospital, San Antonio, Tex., who reported 26 reactions in 105 patients(48, 52, 60), all after the use of Swedish and British dextran.Some of the reactions had been quite severe. A breakdown of the cases showedthat four reactions had occurred in 45 anesthetized patients. Seven differentlots of Swedish dextran had been used. There were no reactions in patientstreated with U.S.-produced dextran, which was now available.
Thirteen ambulatory patients, chiefly Korean veterans, hospitalizedat the Forest Glen Section of Walter Reed General Hospital, were given500-cc. injections of Swedish dextran (Macrodex). All but three had reactions,three of which were moderately severe. The experiment was not consideredconclusive. There were no controls, and the patients, who were an in thesame ward, were watched over by too many observers amid too much commotion.
Later in the year, 10 volunteers at Brooke General Hospital were studiedwith fractionated material from a lot of Swedish dextran (55). Theobservations suggested that the reactions which occurred must be explainedby factors other than high molecular weights or aggregates of molecules.
At a Conference on Radioactive Dextran held on 29 August 1951 (61),under the chairmanship of Dr. Ravdin, it was reported that the most precisechemical analyses of excreted dextran had accounted for only 50 percentof the amount injected; all excretion was via the urine. Dextran taggedwith
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radioactive carbon, prepared by Commercial Solvents Corp., in cooperationwith the Argonne National Laboratory, had been distributed to it numberof investigators, whose results suggested that 95 percent of the injectedmaterial would be either excreted or metabolized. Although the combinedstudies were limited both in number (three dogs, six rats, four mice) andtime (10 days), it was decided to test radioactive dextran clinically withoutfurther delay.
At the 13 February 1952 meeting of the Subcommittee on Shock (62),an ad hoc committee, appointed in December 1951, reported that there wasno doubt that dextran was antigenic in man and could produce precipitinsand skin sensitivity, with the degree of sensitivity apparently unrelatedto the occurrence of systemic reactions. All the reactions had occurredin first injections; none had been observed in a limited number of secondinjections. Immunization apparently played a negative role. Preparationsof higher molecular weight seemed to cause more systemic reactions thanthose of lower weight and also precipitated more antibodies in sensitivesubjects (63).
While the studies reported were still incomplete, it seemed to the confereesto be desirable, to minimize reactions, to avoid highly branched dextransand preparations of high molecular weight. No doubt was felt that reactionsto dextran could be extremely dangerous if they occurred in battalion aidstations, where medical supervision might be inadequate. Later, it wasrecommended that a warning be placed on bottles of dextran that if an anaphylactoidreaction developed, the infusion must be stopped at once and active treatmentinstituted (64).
At the 1 October 1952 meeting of the Subcommittee on Shock, it was reportedthat 125 units of dextran had been used in Korea, with good clinical resultsand no significant reactions (56). A 6-month study had been startedin Air Force installations in the United States.
At an ad hoc meeting on dextran fractions on 8 December 1952 (68),it was reported that a fairly large proportion of normal, healthy adultshad experienced allergic-type reactions after the use of both British andSwedish dextrans but that the rate with the United States products wasvery low. It was now possible to define the best possible dextran for massproduction. Determination of molecular weight was now quite accurate, andrefined analytic methods made it possible to detect even small quantitiesof dextran in plasma or urine.
Studies on dextran were conducted in Korea in July and August 1952,by members of the surgical research team, on the ground that it was notpossible to duplicate total combat situations in the wards and operatingrooms of civilian hospitals, or even military hospitals, in the Zone ofInterior (65).
During this investigation, 200 500-cc. units of 6 percent dextran wereused on 60 patients, 3 suffering from burns and the others from traumaof varying degrees. The total clinical response was excellent. The bloodpressure response was most satisfactory. The hematocrit showed a decrease,which was maintained. There were no allergic reactions. One patient received2,500 cc. of dextran solution in a single day with no ill effects. No
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abnormalities were observed at autopsy in the three patients who died.The best tribute to dextran was that the medical officers who used it wereuniformly eager for more.
Dextran was used in increasing amounts until the end of' the KoreanWar. To complete the record, one postwar matter should be mentioned: InSeptember 1953, a hitherto undescribed consequence of dextran injectionswas reported, a prolongation of the bleeding time, (66, 67). Ithad occurred in 2 normal subjects at Walter Reed General Hospital, andin 11 other normal subjects observed elsewhere; the product of four manufacturerswas involved. These observations were confirmed by a study of 121 normalsubjects at Bolling Air Force Base.
The change in the bleeding time occurred within 3 to 9 hours after thedextran had been given. There was usually a return to normal level within9-4 hours. The amount of dextran that had produced the alteration rangedfrom 500 cc. in a single dose to 6,500 cc. over a 5-day period. There wasno correlation between the maximum prolongation of bleeding time and themaximum expansion of plasma volume.
Recommendation and Production
At one of the first meetings after the outbreak of the Korean War atwhich dextran was discussed (25), Dr. Ravdin emphasized that inthe emergency that existed, this product must be investigated promptlyas well as thoroughly. He also stated that the Armed Forces must not relyon commercial firms to provide specifications and standardization.
The first contract for the production of dextran was set up with theCommercial Solvents Corp. (54). In December 1950, this firm reportedthat it was negotiating with Pharmacia to manufacture dextran under itspatents (39). The Schenley Corp., which was also producing dextran,had a similar agreement with a British company. Meantime, Pharmacia hadalready licensed Refined Syrups and Sugars Corp., whose product would probablybe bottled by the Abbott and Cutter Laboratories. The American Sugar RefiningCo. was working on a new fractionation method which did not require alcoholand which might prove of great value if alcohol should become in shortsupply. At the meeting at which these details were reported (Subcommitteeon Shock, 11 December 1950), it was recommended that the Department ofDefense begin to procure dextran that would meet British and Swedish specifications(39).
Encouraging reports on present and anticipated production were madeat a conference on 19 December 1950, under the auspices of the Subcommitteeon Shock, which was attended by manufacturers of dextran, including a representativeof Pharmacia, drug firms, and other interested parties (68). Atthis meeting the subcommittee recommended that all dextran produced belabeled For Stocking for Emergency Use.
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During the following month, arrangements were made to purchase 50,000units of Swedish dextran for the Armed Forces, to bridge the gap whileU.S. manufacturers were getting into mass production (69).
By the end of 1951, the National Research Council approved the stockpilingof U.S.-produced dextran and the Department of Defense entered into a contractfor its production with Commercial Solvents Corp., Terre Haute, Ind. (2).Delivery was delayed because of the necessity of developing large-scaleproduction facilities.
In April 1952, the Medical Policy Council directed that commitmentsfor the procurement of Periston be canceled and the funds allocated toit be diverted to the procurement of additional quantities of dextran (2).By this time, the risk of hepatitis in the use of plasma was fully appreciated.
By the end of September 1952, Commercial Solvents Corp. had delivered28,588 of the 810,000 units of dextran contracted for. The other threecompanies with which contracts had been made later had not yet producedanything, but their facilities were about completed and their potentialwas 3,060,000 units.
Early in 1953, dextran was approved by the Food and Drug Administration,and a larger proportion of the stockpile was set up with it, though theproportion between synthetic and natural plasma-expanders was deliberatelykept in balance. Later in the year, the manufacturers made it clear thatthey were losing interest in the production of dextran, in the absenceof definite commitments for its use by military and civilian agencies (67).The concern of the Subcommittee on Shock at this development was duly transmittedto the Office of Defense Mobilization and the Assistant Secretary of Defensefor Medical Affairs.
Plastic equipment.-The first attempt to put dextran up in plasticbags was a failure (51). Vapor transfer through the plastic wasso great that the dextran crystallized out in the recipient tube. A laterattempt was successful (57). The bags, which were tested in Koreaand in certain U.S. hospitals, could withstand sterilization temperatures,and long-term storage was apparently possible; they were tested at 60°C., considered equivalent to 2½ years' storage at room temperature.The vapor transfer problem was settled by the use of an aluminum foil barrier.
FAT EMULSIONS
Two ad hoc Conferences on Fat Emulsions for Intravenous Administrationwere held during the Korean War, on 24 May 1951 (70) and 19 March1953 (71). By the time the war broke out, these emulsions had beenused extensively enough to establish their clinical value, and it was believedthat there was a real need for them to maintain caloric intake in seriouslyill and wounded patients. It was true that less than 5 percent of thesepatients would need
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parenteral fat. On the other hand, their needs might be urgent. In Korea,the most imperative nutritional problems were encountered in seriouslywounded patients with renal dysfunction and oliguria, in whom it was necessaryto limit fluids to 500 cc. per day for about 10 days. During this period,these casualties often lost as much as 45 gm. of nitrogen per day, whichwas the equivalent of a total 25-pound loss of muscle weight. Wound healingwas slow, edema was frequent, and the incidence of wound dehiscence wasabnormally high. The desideratum, not yet achieved, was for the developmentof a pyrogen-free emulsion which would provide from 2,000 to 4,000 caloriesper day by parenteral administration, in as small a fluid volume as possible.
At the second of these ad hoc conferences, as at the first, there weretwo chief problems (1) the pyrogenicity of the preparations then available,and (2) their instability. Commercial preparation of consistently safeand satisfactory emulsions could not be expected until a solution was foundfor these problems. Some of the participants in the discussion thoughtthat if only a fraction of the funds expended in the development of plasmaextenders were allotted to this project, results would be prompt and beneficial,but no such allocation was made during the war.
Part VI. Clinical Considerations
THERAPEUTIC PRINCIPLES AND PRACTICES
General Considerations
The principles and practices governing the use of plasma (fig. 190)and albumin (fig. 191) were essentially the same in the Korean War as inWorld War II. The administration of whole blood also followed the samepattern (figs. 192, 193, 194, and 195) except that intra-arterial transfusionwas given a trial.
Intra-Arterial Transfusion
Historical note.-According to Lewisohn (72), the firstrecommendation for intra-arterial transfusion, by Huerter in 1871, containedthe report of eight cases in which defibrinated blood was injected by thisroute.. Not much more work was done on the subject until 1937, when Davis(73) showed, in a study of experimental shock, that the intra-arterialinjection of sodium chloride solution elevated the blood pressure but thata similar solution, given intravenously, lowered it. Kendrick and Wakim(74) confirmed these observations in dogs in 1939. They also demonstratedthat the intra-arterial administration of physiologic salt solution isnot a desirable emergency treatment for secondary shock. In spite of theimmediate vasopressor response and the maintenance of the elevated bloodpressure for a certain period of time, the end result was always severeinjury to the recipient.
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Field studies.-During the Korean War, Maj. Curtis P. Artz, MC,Capt. Yoshio Sako, MC, and Capt. Alvin W. Bronwell, MC, treated eight casualtiesby the intra-arterial route, the largest amount given being 4,500 cc. ofblood (75). The surgeon held the needle in the artery during thetransfusion, which was discontinued as soon as the systolic pressure reached100 mm. Hg.
One of the eight casualties died on the operating table, and three othersdied within 3½ hours of operation. Although the other four recovered,it was the impression of these observers that casualties given blood bythis route showed no appreciably improved response as compared with patientswho received blood at a comparable rate under pressure or in multiple veins(fig. 195). One of their patients, for instance, who was almost moribund,recovered after being given 5,500 cc. of blood into two veins through 15-gageneedles in 30 minutes; 3,500 cc. of blood was pumped into one vein in 21minutes.
Experimental studies by Major Artz and his group also failed to indicateany superiority of the intra-arterial over the intravenous route. Sincethe experimental data coincided with clinical impressions derived fromthe small groups of cases just described, this method of administrationwas discontinued in favor of rapid intravenous injection of blood throughmultiple large-gage needles or intravenous cannulas.
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Conclusions.-Intra-arterial transfusion was discussed in detailat a conference at Walter Reed Army Medical Center on 11 June 1953 (76).It was found, in extensive experimental studies, that there was no significantdifference in survival rates in experimental and control series, and nosignificant difference in the effectiveness of intra-arterial and intravenousadministration of blood. All studies pointed to the conclusion that itwas the rate of transfusion, not the route, that was the important factor.
In the general discussion that followed this presentation, Brig. Gen.Sam F. Seeley, then Chief of Surgery, Walter Reed General Hospital, statedthat, provided that an adequate amount of blood was given rapidly, thetechnique of transfusion probably made little difference as long as cardiacaction was still present. In deep shock, it was often mechanically difficultto introduce blood
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into a vein, but always quite easy to make a femoral arterial puncture.He also pointed out that a certain number of casualties could be expectedto die from the severity of their injuries, even if they received preferentialintra-arterial transfusion.
Other participants in the discussion took the position that intra-arterialtransfusion is an extremely dangerous technique; cases were cited in whichcomplete gangrene of the hand, requiring amputation, had followed its use(72). Others, however, in spite of the risk of ischemia, believedthat in strictly qualified circumstances intra-arterial transfusion mightbe justified.
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INVESTIGATIONS
Surgical Research Team
The request of the World War II Subcommittee on Blood Substitutes, Divisionof Medical Sciences, NRC, to send a team of observers to oversea theaterswas never granted (p. 79). The question of sending such a team to Koreawas brought up at the second meeting of the Subcommittee on Shock, Committeeon Surgery, on 2 November 1950 (54), and several times thereafteruntil such a team was sent to the Far East in December 1951 (65).The
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9 December 1952 meeting of the subcommittee was devoted chiefly to progressreports from the team (64).
The Surgical Research Team was organized by the Army Medical ServiceGraduate School and the Army Medical Research and Development Board, whichappointed personnel, set policies, established techniques, provided consultants,and furnished nonstandard supplies.
In Japan, the team was attached to the Far East Research Unit (406thMedical General Laboratory) in Tokyo for administrative purposes. Here,additional personnel, including consultants, were provided, and suppliesavailable on the Japanese market were obtained. In Korea, the team wasattached to the 11th Evacuation Hospital and the 8209th MASH (Mobile ArmySurgical Hospital) for standard supplies, day-by-day assistance, and theprovision of clinical opportunities.
The principal problems related to blood which were encountered by theteam were as follows:
1. During resuscitation, problems associated with the blood bank, theutilization of plasma, and the resulting high rate of homologous serumjaundice.
2. During operation, abdominal hemorrhage and vascular injuries.
3. Sequelae of trauma, including secondary hypotension, posttraumatic anuria,and infections.
The special studies on blood were made by Lt. Col. William H. Crosby,MC; Capt. John M. Howard, MC; and Lt. Col. Joseph H. Akeroyd, MSC (77-79).
Essential Data
General considerations.-When the Surgical Research Team reached theFar East in December 1951, it found blood plentiful in U.S. Army hospitals,as it had been all during the past year. The only blood available in ROKArmy hospitals was the amounts occasionally provided by U.S. units (p.803). The O blood used was now available between 12 and 14 days after collection,instead of 21 to 28 days as originally. Massive and repeated transfusionswere given with few reactions, and there were no records of deaths attributableto the use of blood.
A special investigation showed that transportation of blood over thethousands of miles between the United States and Korea had only minor effectson it. Generally, it arrived at forward hospitals in an excellent stateof preservation. In 300 pints examined at random, it was found that lessthan a quarter of 1 percent of the red blood cells had been lost, and,when the blood was transfused, few red cells were found nonviable. Theplasma hemoglobin rose from about 50 mg. percent on the 10th day aftercollection to 100 mg. percent on the 28th day. Harmful amounts of hemoglobinwere not released into the recipient's plasma from the transfused blood.Abnormally high plasma potassium was not encountered during or after massivetransfusions unless renal failure was also present. The plasma potassiumlevel of bottled blood was apparently a straight line function of time,the concentration increasing at the
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rate of approximately 1 milliequivalent per day. The osmotic fragilityof the red cells showed few changes during the first 2 weeks after collection.Then it rose sharply, suggesting the desirability, whenever practical,of using blood within the first 14 days after it had been drawn. All theevidence indicated that the use of properly stored blood had only beneficialeffects; few if any deleterious effects were observed even when as muchas 20 to 30 pints were given in less than 6 hours.
Continuous refrigeration, at temperatures of 0° to 10° C., wasabsolutely essential to the safe preservation of blood. If refrigerationwere omitted, even for brief periods, irreversible changes occurred inthe red cells. They might not hemolyze spontaneously in the bottle, butthey did not survive after transfusion.
Reactions and sequelae.-Reactions were remarkably infrequent.In 1,620 transfusions observed at the 46th Army Surgical Hospital (8209thMASH), there were only four urticarial reactions and no reactions due toincompatibility. Several hemoclastic reactions were considered as causedby gross contamination of the bloodstream from the sites of wounds or fromthe peritoneal cavity.
The practice of using O blood for massive transfusions of non-O recipientsdid not seem harmful provided that so-called dangerous universal donorswere avoided. These donors, who are extremely uncommon, have plasma thatcontains a high titer of anti-A antibodies, which can produce an unmistakablehemolytic transfusion reaction, with all the signs associated with majorincompatibility. Some of the recipient's own red blood cells might be eliminatedby antibodies in plasma from these donors, though there is no clinicalevidence of this phenomenon.
Casualties who received multiple transfusions over long periods of timetended to develop greater sensitivity to pyrogens. This observation, firstrecorded in 1951 (79), was never explained.9
These same casualties were also prone to develop hemosiderosis becauseof the excess iron deposited after increased erythrocytic destruction.It was suggested, with the fear of hemochromatosis in mind, that if thesepatients developed resistant chronic anemias, whole blood and red bloodcells should be used as sparingly as the circumstances justified.
Patients who received more than 15 pints of blood often showed a tendencyto ooze from cut surfaces. The condition regressed quickly, without treatment.
A patient in shock, who had been given a transfusion in excess of thenormal capacity of his circulatory system, sometimes developed polycythemia.In such cases, the excess blood was apparently carried in the dilated vesselsof the skeletal muscles, liver, and lungs. So-called overtransfusion, whichwas sometimes employed in severe shock, was surprisingly well tolerated.
9 In the light of present (1962) knowledge,this statement about sensitivity to Pyrogens may be erroneous. The patientsunder discussion become sensitized to known or unknown blood factors, andthe sensitization tends to cause reactions characterized by chills andfever during or after subsequent transfusions.
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Hematologic response.-A battery of hematologic studies was carriedout on 37 of the casualties received at the 46th Army Surgical Hospital,located several miles behind the infantry division that it supported, betweenOctober 1952 and January 1953. Between 2 and 42 transfusions were usedin each case. The plasma hemoglobin was determined in 300 of the unitsused. Particular attention was paid to the results of storage of blood(high plasma hemoglobin and potassium, low labile factor activity, nonviableplatelets and leukocytes). As already mentioned, changes in stored bloodwere slight and innocuous.
The important observations made in this study were as follows:
1. At the time of resuscitation and shortly thereafter, there was aremark able loss of circulating red blood cell mass in casualties withwounds associated with considerable tissue destruction. The loss was thoughtto be caused by hemolysis, though the exact mechanism was not determined.The loss of red cells was sometimes so rapid that a casualty withbilateral traumatic amputation of both legs, even if hemostasis was adequate,might become severely anemic if there was any hesitation in using massive,rapid transfusions. Shock associated with wounds which involved less tissuedestruction, such as lacerations of the colon, did not destroy red cellsin this fashion. After moderate transfusions, these patients often becamepolycythemic, and transfusions had to be carried out "rather gingerly,"because of the tendency for signs of congestion to appear.
2. During the early period of recuperation from severe wounds, casualtiestended to become anemic, apparently as the result of hemolytic processesplus a relative inhibition of red cell formation.
3. A particularly striking observation was that in patients not in groupO, massive transfusions of O blood resulted in the virtual replacementof the recipient's cells by cells of the O group. His plasma sometimescontained antibodies against red cells of his own hereditary blood group.Gradual hemolysis of native red cells by transfused antibodies was observed,but the hemolytic process was not evident clinically and did not appearto harm the patient. The presence of foreign antibodies, however, sometimesmade it impossible to crossmatch the patient with blood of his hereditarygroup, and it was believed that transfusions with the hereditary type ofblood might be dangerous. Severe reactions, in fact, sometimes occurredwhen type-specific blood was given after large transfusions of O blood.In the light of this new observation, it was recommended that, after transfusionsof universal donor blood had been given, no change should be made to bloodof another group until at least 2 weeks had elapsed.
Immunohematologic response.-Another special study by Colonel Crosbyand his associates was an investigation of 25 casualties from the standpointof the immunohematologic results of large transfusions of group O bloodin recipients of other blood groups. These patients were all received byambulance or helicopter between 1 and 3 hours after wounding. Transfusions
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of plasma or whole blood had often been begun at battalion aid stationsand they were continued during evacuation, and, as needed, through resuscitationand operation. Some patients received as much as 37 pints of blood within12 hours. One or two received 20 pints within an hour. Most of the bloodtransfused was used before the 15th day, and none was used after the 21stday, of shelf life. All the blood was group O, all was Rh-positive, andall was used without crossmatching. It was tested for the high titer isoagglutininsactive against group A and group B red blood cells.
The important observations made in this study were as follows:
1. After large transfusions of low titer group O blood into patientsof groups A, B, and AB, it was not possible to demonstrate foreign isohemolysinsor incomplete antibodies in the recipient serum. Cold isoagglutinins werefrequently evident immediately after the transfusion, but they usuallydisappeared rapidly. In several patients, the titer of foreign anti-A isoagglutininswas quite high, and the antibody persisted in the circulation for severaldays. A possible explanation was the relatively small amount of A substancein the recipient's blood; when the transfused isoagglutinins were foundpersistent, the patients usually proved to be weak secretors of A substancein the saliva, or complete nonsecretors.
2. In most of these patients there was evidence of selective destructionof recipient red blood cells after the transfusion of O blood, probablyas the result of activity of transfused isoantibodies in the plasma ofthe transfused blood. The hemolytic activity was observed in cases in whichit was not possible to demonstrate the presence of foreign isoantibodies.It was postulated that forms of antibodies might exist that could not bedemonstrated by available methods and that manifested themselves only bycausing destruction of red blood cells.
3. Clinically, as already mentioned, the hemolytic, process originatingfrom such transfused isoantibodies, while it caused destruction of nativered cells, did not threaten the lives or impede the recovery of these patients.No reactions, in fact, were encountered or heard of in Korea that mighthave been ascribed to so-called dangerous universal donors. In practice,the division of group O blood into high and low titer, on the basis ofdilution of 1:200 to 1:256, proved perfectly safe.
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