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Chapter VI

Contents

CHAPTER VI

The Blood Program

Brigadier General Douglas B. Kendrick, Jr., USA

    How many thousands of lives were saved in World War II by the use of whole blood and plasma in the management of battle casualties will never be accurately known. The almost blind dependence originally placed on plasma proved erroneous, but this blood component never lost its value as a means of keeping casualties alive until they could be brought to Army medical installations in which whole blood was available. The use of whole blood was, however, the keystone of the arch of resuscitation, and resuscitation was, in turn, the keystone of all surgery.

    In World War I, men died without surgery because the means of resuscitation were not available. In World War II, men survived because they were operated on, but the fundamental reason for their survival was that they lived or, more correctly, were kept alive until they were fit to be operated on. They were kept alive by plasma until they could be given whole blood. They were resuscitated--which means, literally, brought back to life--by whole blood, which made operation possible. Very often they were kept alive during operation by the continued use of whole blood. Finally, many times, their recovery after operation was expedited by the use of whole blood, even if it was not again necessary to keep them alive.

    There is no exaggeration in any of these statements, sweeping though they may be. They are generalizations, it is true, but they present the correct picture of how surgery was made possible in World War II and how it saved the lives of thousands of soldiers who otherwise would have died.

    Since the importance of whole blood in resuscitation was realized almost from the beginning by all the personnel and agencies connected with the program, it is difficult to understand why its procurement, distribution, and employment got off to such a slow start in World War II. Any explanation must be a mixture of opinion and fact. It seems fair to say that the chief reason was that over enthusiasm for the potentialities of plasma as an almost complete blood substitute tended to minimize the consideration which might otherwise have been given to the developments of methods for making the use of whole blood practical.

    Before World War II began, as will be pointed out later ( p.141), there had been only one practical demonstration, by DeGowin and his associates1 at

1DeGowin, E. L., and Hardin, R. C.: A Plan for Collection, Transportation, and Administration of Whole Blood and of Plasma in Warfare. War Med. 1:326-341, May 1941.


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the State University of Iowa College of Medicine, Iowa City, of the possibility of storing whole blood for any extended periods of time and shipping it. over considerable distances. More important, as the discussion at the first, meeting of the Committee on Shock and Transfusions, Division of Medical Sciences, National Research Council,2 clearly shows, the feasibility of such a project had to be developed and accepted as a concept. This consideration was much more important than the existing lack of means to store blood and to transport it safely over long distances. It was even more important, for that matter, than the fact that an oversea air transportation system had not yet been developed when World War II began.

    Finally, those in charge of the blood program, while they clearly understood that large amounts of whole blood would be required in the management of battle casualties, did not begin to make their voices heard until 1943. It was not until the end of that year that strong, constructive, concrete recommendations began to be made, and it was not until the following year, 2 months after D-day in the European theater, that these recommendations were finally accepted and implemented in the Office of the Surgeon General.

    The whole program for the provision of blood and blood substitutes in World War II was a superb national effort. Both Federal and civilian agencies participated in it, but its lifeline was provided by the millions of volunteer donors who gave their blood to supply blood, plasma, and other blood substitutes for the Army, including the Army Air Forces, and the Navy. Over the period of the conflict, total bleedings of these volunteer donors numbered 13,326,242.3 This gigantic pool of what was truly a life giving fluid contributed immeasurably, intangibly as well as tangibly, to the successful outcome of the war. It was a visible manifestation of the loyalty to their country of the individual donors who gave their blood and who thus demonstrated their belief in the way of life, for which the United States of America stands.

BLOOD AND BLOOD SUBSTITUTES AT THE BEGINNING OF WORLD

WAR II

Historical Note

    The need for transfusions of whole blood in casualties with battle-incurred wounds had been recognized in World War I, and the effectiveness of this method of combating shock had been demonstrated by Robertson 4 and others, as early as 1916. Blood transfusion increased in popularity as the war progressed, but for practical reasons it was never used routinely, and it was attended with a number of disadvantages and risks.

2 Minutes, meeting of Committee on Shock and Transfusions, Division of Medical Sciences. National Research Council, 31 May 1940.
3
Robinson, G. Canby : American Red Cross Blood Donor Service During World War II: Its Organization and Operation. Washington: The American National Red Cross, 1 July 1946.
4
Robertson, L. Bruce The Transfusion of Whole Blood. A Suggestion for Its More Frequent Employment in War Surgery. Brit. M. J. 2:38-40. 8 July 1916.


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    The use of blood plasma as a substitute for whole blood was also proposed in World War I. In March 1918, Ward 5 pointed out that the administration of citrated plasma, which could be preserved easily and injected safely, would meet the need of casualties in shock from hemorrhage, who, in his opinion, required replacement, of depleted fluid more than replacement of host hemoglobin. He also noted that the risk of hemolysis of the donors corpuscles by the recipients plasma would thus be eliminated. Earlier that year, Rous and Wilson 6 had advanced the same theory and had reported the experimental use of plasma for resuscitation of animals after massive blood loss.

    Later in 1918, Mann 7 proposed that blood serum be used for the treatment of surgical shock, on the basis of the good results which he had obtained with it in experimental shock. He also suggested that homologous serum might be of value in circumstances in which serum could be stored and whole blood could not be obtained.

Interval Between the World Wars

    It required the experience of Wor1d War II to establish the efficacy of large volumes of blood, administered rapidly, in the resuscitation of exsanguinated casualties and their conversion to acceptable candidates for surgery. The interval between this experience and the tentative experience of World War I was characterized by a number of developments, which may be briefly summarized as follows:

1. Outstanding contributions to the literature of shock were made during this period by Cannon,8 Parsons and Phemister, 9 Moon,10 and Blalock,11 among others. As time passed, Cannon's original theory, that shock is produced by the absorption of toxic materials from the site of injury, was supplanted by the work of Parsons and Phemister, and later by the work of Blalock. These observers demonstrated that shock is the result of loss of fluid locally, at the site of injury, and that the local loss causes, in turn, a significant decrease in the circulating blood volume. By 1940, the concept had been generally accepted that the basis of shock is a decrease in the circulating blood volume, as just stated, or a discrepancy between the blood volume and the volume capacity of the vascular system, or a combination of these two alterations in the normal physiologic processes, with resulting tissue anoxia,

5 Ward, G. R.: Transfusion of Plasma. Correspondence. Brit. M. J. 1:301, 9 Mar. 1918.
6
Rous, P., and Wilson, G. W.: Fluid Substitutes for Transfusion After Hemorrhage. First Communication.. J.A.M.A. 70: 219-222. 26 Jan. 1918.
7
Mann, F.C.: Further Experimental Study of Surgical Shock. J.A.M.A. 71: 1184-1188, 12 Oct. 1918.
8
Cannon, Walter B.: Traumatic Shock. New York and London: D. Appleton and Company. 1923.
9 Parsons, B., and Phemister, D. B.: Hemorrhage and ''Shock'' in Traumatized Limbs. An Experimental Study. Surg., Gynec. & Obst. 51:196-207. August 1930.
10
Moon, Virgil H: Shock and Related Capillary Phenomena. New York: Oxford University Press, 1938.
11
Blalock, Alfred: Principles of Surgical Care: Shock and Other Problems. St. Louis: The C. V. Mosby Company, 1940.


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which, if not. reversed, leads to death. It is upon these concepts that the modern use of whole blood in the management of shock is based. Strumia and his associates,12 whose first work was done with intravenous serum in the treatment of severe infections, later substituted plasma for serum because of its greater simplicity of preparation and the greater yield from the same amount of whole blood. In 1935 Filatov and Kartasevskij 13 reported the use of intravenous plasma as a hemostatic agent, and in the same year Heinatz and Sokolow 14 used Plasma in the treatment of hemolytic shock. The following year, Elliott 15 suggested that untyped serum and plasma be used when transfusion was indicated in the management of surgical, traumatic, and obstetric shock. His reasoning was that the maintenance of osmotic pressure is a function of the plasma proteins and that the need for replacing lost blood volume is more important than the need for replacing red blood cells. During the next 2 or 3 years, a number of other observers also published reports on the use of plasma in the management of shock and described techniques for its preparation in the liquid, frozen, and dried states.

2. The considerable amount of work on the fractionation of plasma done by Cohn 16 and his associates led to the use of serum albumin for the treatment of shock.

BEGINNINGS OF THE BLOOD AND BLOOD SUBSTITUTES PROGRAM

    When it became increasingly evident, early in 1940, that the United States might eventually become involved in the hostilities in Europe and that the Medical Department of the Army might be called upon to care for mass casualties resulting from enemy action, the major problem which confronted the Department was the development of an improved method of treating traumatic shock.

    At this time (the spring of 1940), the situation with respect to the use of blood and blood substitutes in the management of shock may be summarized as follows:

    1. The use of type-specific whole blood had become a practical procedure in civilian hospitals, but it was still given in only small amounts and, as a rule, heroically; that is, transfusion was still being resorted to chiefly in critically, or at. least gravely, ill patients, whose status was truly desperate.

12 (1) Strumia, M. M., Wagner, J, A., and Monaghan, J. F.: The Intravenous use of Serum and Plasma, Fresh and Preserved. Ann, Surg. 111: 623-629, April 1940. (2) Strumia, M. M., and McGraw, J. J.: The Development of Plasma Preparations for Transfusions. Ann. Int. Med, 15 : 80-88, July 1941.
13
Filatov, A., and Kartasevskij, N. G. : Die Transfusion von menschlichem Blutplasma als blut-stillendes Mittel, Zentralbl. f. Chir. 62:441-445, 23 Feb. 1935.
14
Heinatz, S.W., and Sokolow, N.I.: Plasmatransfusion als Methode der Wahl in der Behandlung des hänolytischen Schocks, Zentralbl. f. Chir. 62:1753-1755, 27 July 1935.
15
Elliott, J.: A Preliminary Report of a New Method of Blood Transfusion. South. Med. & Surg. 98: 643-645, December, 1936.
16
Cohn, E. J.: Properties and Functions of the Plasma Proteins, With a Consideration of the Methods for Their Separation and Purification. Chem. Rev. 28: 395-417, April 1941.


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    The concept that blood should be used liberally to prevent the development of situations of desperation was still very far off. 
    2. Direct techniques of transfusion were still in frequent use, though a gradual shift to indirect techniques was occurring. The changeover, however, was slow for two reasons; namely, lack of satisfactory equipment and the reactions credited to the use of citrate as a preservative fluid.
    3. Reaction rates from blood transfusions were still sufficiently high to alarm even the most enthusiastic proponents of the liberal use of whole blood There was
almost complete ignorance concerning pyrogenic reactions, which were the most frequent variety and which occurred most insidiously.
    4. The use of blood plasma was still chiefly experimental.
    5. The use of blood serum (the liquid portion of the blood separated from the solid elements after clotting) was also almost entirely experimental, its administration at this time being advocated by only a. few pioneers.
    6. The use of serum albumin had not yet been developed.

Program at the Army Medical School

    The first steps in the solution of the problem were taken by Col. (later Brig. Gen.) Charles C. Hillman, MC, Chief, Professional Service. Division, Office of the Surgeon General. Colonel Hillman's first action was to request Col. (later Brig. Gen.) George R. Callender, MC, Commandant., Army Medical School, to organize. a blood research branch in the Department of Surgical Physiology at the school.

    This department had been set up in 1936 by Capt. (later Col.) Sam F. Seeley, MC, but, in 1938, when Captain Seeley had been transferred elsewhere, it had ceased to function, after 2 years of very active operation. Capt.. (later Col.) Douglas B. Kendrick, MC. (fig. 23) was selected to head the reactivated department because of his earlier training.17 The original personnel consisted of himself and an enlisted man who served as his technical assistant.

Program of the National Research Council

At the time that Colonel Hillman requested Colonel Callender to set up a blood research program at the Army Medical School, he also, acting for The

17 During a civilian surgical residency at Grady Hospital in Atlanta, under Dr. Daniel C. Elkin. Captain Kendrick had had a considerable experience in the large amount of traumatic surgery handled at that institution, with its attendant problems, including shock. He had also served under Dr. Fred Rudder, who was greatly interested in the use of whole blood in shock and who had devised an ingenious apparatus for direct transfusion.
    After his service at Grady Hospital, Captain Kendrick entered the Army Medical Corps and, because of his previous experience, was sent for a year to the Institute of Experimental Medicine at the Mayo Clinic, Rochester, Minn., where he worked on shock, replacement fluids, gas gangrene, and special uses of the sulfonamides. He also did work in anesthesia under Dr. John S. Lundy. The plan had been that on Captain Kendrick's return to the Army Medical School he should continue Captain Seeley's work. Funds for research, however, proved so inadequate that this plan could not be carried out and he was therefore assigned to the orthopedic service, Walter Reed General Hospital, and was on this service when, at Colonel Hillman's request. the Department of Surgical Physiology at the Army Medical School was reactivated, with research in blood and blood substitutes as its chief objective - J. B.C., Jr.


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FIGURE 23. - Col. Douglas B. Kendrick, MC, Chief, Division of Surgical Physiology, Army Medical School, Walter Reed General Hospital.

Surgeon General, requested the Division of Medical Sciences, National Research Council, to assemble a civilian committee which could act informally, in an advisory capacity, to the Surgeons General of the Army and the Navy. The Committee on Shock and Transfusions, which was appointed in response to this request, held its first meeting on 31 May 1940. 18 Dr. Walter B. Cannon, Professor of Physiology, Harvard Medical School, Boston, Mass., served as chairman of the meeting, and the Subcommittee on Blood Substitutes was appointed with Dr. Cyrus C. Sturgis, Professor of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich., as chairman. In April 1941, Dr. Sturgis was succeeded by Dr. Robert. F. Loeb, Professor of Medicine at the same school.19

    Other members of the Subcommittee were Dr. Elmer L. DeGowin, who served as secretary, Dr. Cornelius P. Rhoads, Dr. O. H. Robertson, Dr. John Scudder, Dr. Max M. Strumia, and Dr. Owen H. Wangensteen. The initial meeting, held on 19 April 1941, was also attended by Dr. Lewis H.. Weed,

18 See footnote 2, p. 122.
19
Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, National Research Council, 19 Apr. 1941.


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Chairman, Executive Committee, Division. of Medical Sciences, National Research Council; Dr. Milton V. Veldee, Chief, Biologics Control Laboratory, National Institute of Health; Lt. Comdr. Lloyd R. Newhouser, MC, USN; and Captain Kendrick. All the members of the Subcommittee had done outstanding work in the field of blood and blood substitutes.

Program in the Office of the Surgeon General

    Until 1942, the primary responsibility for the program on blood and blood substitutes rested with the Blood Research Division, Army Medical School. In that year, the responsibility for the program in the Office of the Surgeon General was assigned to the Surgical Consultants Division. At the same time, Lt. Col. B. Noland Carter, MC, assistant chief of the division, was made responsible for all matters concerning fluid replacement in shocked patients. On 24 November 1943, the Transfusion Branch was created in the Surgical Consultants Division with Colonel Carter as chief and Maj. (later Lt.. Col.) Frederic N. Schwartz, MAC, as operations officer.20 The Transfusion Branch was eventually given the entire responsibility for the blood procurement program up to the point at which the blood was placed on aircraft for oversea shipment.

    For a. 3-month period in 1943, Col. Charles F. Shook, MC, had served as special representative to The Surgeon General on blood and plasma transfusions. When the Transfusion Branch. was created, Colonel Kendrick assumed these duties. In November 1944, when Colonel Kendrick was transferred to the Pacific, he was succeeded by Maj. John J. McGraw, Jr., MC. The duties of the special representative to The Surgeon General on blood and plasma transfusions were to formulate policy, to estimate blood requirements, and to evaluate the efficiency and suitability of apparatus, equipment, and technical procedures. Major Schwartz handled administration, supply, and personnel. Recommendations were channeled through Colonel Carter.

    In all his connection with the blood program, Colonel Kendrick served as chief of the blood research program at the Army Medical School. When he was assigned to the Office of the Surgeon General in 1943, as special representative on blood and plasma transfusions, it seemed more advisable for him to continue to operate under the table of allowances at the Army Medical School, in order to provide free access to the research facilities still needed in the program. During the entire war, there was always the closest possible cooperation between the school and the Office of the Surgeon General. Both General Callender at the school and General Hillman in the Office of the Surgeon General gave unlimited support in all Colonel Kendrick's activities, and all matters dealing with blood, shock, or resuscitation were automatically referred to Colonel Kendrick.

20Annual Report, Surgery Division, Surgeon Generals Office, Fiscal Year 1944.


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Cooperation With the Navy Program

    In April 1940, shortly after Captain Kendrick had been assigned to the Division of Surgical Physiology at the Army Medical School, Lt. Comdr. Lloyd R. Newhouser, MC, USN, was assigned to the National Naval Medical Center, Bethesda, Md., with duties very similar to Captain Kendrick's. The two officers encountered each other in the course of their work, and, since they were trying to accomplish the same results, it seemed only sensible to pool their efforts, which they did until late 1944, when both were transferred to oversea duty. The collaboration, while entirely unofficial, was approved and encouraged by the superior officers in both services and proved extremely fruitful.

    Commander Newhouser and Colonel Kendrick kept themselves closely informed of each other's plans and progress. As a result, many items were standardized by both the Army and the Navy and most orders were placed with a consideration of joint needs. The intimate liaison between the Army and the Navy was an important factor in the maintenance of a smoothly running program for the procurement of plasma, albumin, and, later, whole blood. It was out of this informal arrangement that formal plans were eventually consummated for the Navy to assume the responsibility of flying blood to the Pacific.

IMMEDIATE PROBLEMS IN 1940

    Among the major problems to be solved when the blood and blood substitutes program was set up at the Army Medical School in the spring of 1940 were the following:

    1. How could blood for transfusion be provided in sufficient quantities for the large numbers of casualties to be expected in modern warfare ?
    2. How could blood be safely stored?
    3. How could the current high incidence of transfusion reactions be reduced?
    4. What type of equipment could be developed to provide sterile, pyrogen-free, easily dispensable transfusion fluids?
    5. What types of blood substitutes could be provided? How could they he stored safely? How could they be used in the field?
    6. How could the medical profession, which was still, for the most part, highly skeptical of these various points, be convinced of the safety and desirability of employing whole blood and blood substitutes in the management of trauma?

    The first step in the solution of these problems was to collect as much information as possible on the following points:

    1. The clinical use of whole blood.
    2. The availability of blood plasma and its clinical use.


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    3. The processing of fluids for intravenous use.
    4. The development, manufacture, and testing of equipment for the administration of fluids intravenously.

    The literature was surveyed and analyzed, and a. large collection of reprints was built up. At this time, the literature on shock was voluminous, but the literature on plasma and other blood substitutes was rather scanty, and contributions on liquid plasma were just beginning to appear.

    Information on these subjects was also collected, by personal visits, from the following sources:

    Dr. (later Capt., MC) John Elliott, pathologist at the Cabarrus Hospital, Salisbury, N.C., who had developed a method of processing sterile, pyrogen-free plasma in liquid form. When Dr. Elliott later entered the U.S. Army, he was assigned to the Army Medical School, where he instructed personnel in the processing of the liquid plasma used in Zone of Interior hospitals. He also contributed to the development of the vacuum bottle manufactured by the Baxter Company and used, with certain modifications, for both plasma and whole blood during the war.

    Dr. Max M. Strumia, pathologist at the Bryn Mawr Hospital, whose work on dried plasma has already been mentioned.

    Dr. John Reichel, of the Reichel Laboratories, Kimberton, Pa., who had worked with Dr. Strumia on the development of equipment for drying plasma.

    Dr. Stuart Mudd, Professor of Bacteriology, School of Medicine, University of Pennsylvania, Philadelphia, Pa., and Dr. Earl W. Flosdorf, an experienced refrigeration engineer who had worked with Doctor Mudd as his research assistant on the preparation of serum and on freezing and drying plasma.

    Information was also secured from Sharp &. Dohme, a firm which had long been interested in the preparation of antisera and other immunizing agents. Thus company had done considerable work with typhoid and other vaccines, and, with the help of Dr. John Reichel, had pioneered in the development of vacuum-drying equipment.

    Many of the manufacturers of intravenous solutions and blood transfusion apparatus both at this time and later worked in chose cooperation with the Blood Research Division, Army Medical School, in the development of a closed system for the collection of blood to insure sterile, pyrogen-free storage. When the blood program was more fully developed, all the laboratories of the commercial pharmaceutical houses also worked in close cooperation with each other, exchanging information and reporting problems and their solutions. Sharp & Dohme, which held many patents on various drying processes, offered the use of these patents without charge to the other laboratories working on plasma. for use in the Armed Forces during the war emergency.


130

PLASMA PROGRAM

Dried Plasma

    Development of the plasma program began with the distribution, for testing purposes, of dried plasma prepared in Dr. Strumia's laboratory at the Bryn Mawr Hospital to the Army and Navy Medical Schools and to members of the Subcommittee on Blood Substitutes, National Research Council. Blood for this program was collected by the Southwestern Pennsylvania Chapter, American Red Cross (p.135). The dried plasma proved both safe and effective, and on 19 April 1941 the Subcommittee recommended that either frozen or dried plasma be employed as a blood substitute in the treatment of shock.

    This recommendation was accepted by the Armed Forces for the following reasons:

    1. Supplying whole blood to the Armed Forces in the quantities likely to be needed, together with the safe storage and transportation of the blood, presented logistic problems of enormous proportions which could not be solved in the light of either the knowledge possessed or the facilities available in 1940-41. Preservative solutions which would permit long storage periods were just being developed. Investigations on thoroughly dependable, avid grouping sera were in their early stages. The development of adequate equipment for the collection, storage, and dispensing of whole blood was in its infancy. Refrigeration equipment for use in the field under varying conditions of heat, cold, and humidity had not yet been manufactured. Finally, an airlift capable of delivering blood to the far reaches of the battlefield was still almost 3 years away.
    2. Plasma is a homologous protein fluid with the osmotic equivalent of blood. Separated from its cellular components, it can be frozen and dried to less than 1-percent moisture content. In this state, it can be packaged under vacuum and preserved for years, without refrigeration and without being affected by extremes of heat and cold.
    3. Plasma can be administered without typing or cross-matching.
    4. The of plasma is attended with a very low incidence of reactions. When it first began to be distributed commercially, each package contained a questionnaire to be filled out and returned to the Army Medical School after the plasma had been administered. The reports on 9,161 plasma transfusions given in oversea hospitals showed only 249 pyrogenic reactions (2.7 percent) and only 106 allergic reactions (1.2 percent). These rates corresponded with those reported from hospitals in the Zone of Interior. All the reported reactions were mild.
    5. The equipment necessary for the reconstitution and intravenous administration of dried plasma could be incorporated in a small kit, which could be made
available under almost all conditions of war.


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    6. The yield of plasma was greater - from 15 to 20 cc. more per pint of blood - than the yield of serum.
    7. Most important of all, in the light of the immediate needs, plasma. could be easily and safely produced commercially in large quantities.

    These inherent organic characteristics of plasma, particularly the ease with which it could be manufactured, stored, and transported, obviously made it a practical and desirable agent. The reasons for its selection in 1941, while not fully explaining the failure to supply whole blood to field units at this time, did take cognizance of obstacles which went far toward discouraging even the most ardent advocates of whole blood as a feasible replacement fluid in Zone of Interior hospitals. These reasons were considerably more valid in the recommendation of plasma as a feasible and practical agent for blood replacement in oversea hospitals.

    Packaging. - As soon as the decision was made to employ dried plasma as a blood substitute, it became necessary to standardize a method of packaging it. The Blood Research Division of the Army Medical School cooperated with the Subcommittee on Blood Substitutes, National Research Council, and with the National Institute of Health to devise a standard package, which could be used by both the Army and the Navy.

    The package which was eventually developed (fig. 24) contained a waterproof fiberboard box a rubber-stoppered bottle of dried plasma, evacuated to 28 inches of vacuum, with the sterile, pyrogen-free equipment to administer it, contained in a sealed tin can evacuated to 26 inches of vacuum and a rubber- stopped bottle of distilled water, with the equipment necessary to combine it with the plasma, contained in a tin can.

    After some changes in the initial specifications, this package, which was first produced by commercial laboratories in 1941, was used with satisfaction throughout the war.

    The first packages which were put up contained 250 cc.. of dried plasma, together with the appropriate amount of diluent fluid. Late in 1943, the amount of plasma in each package was increased to 500 cc. The change was made for the following reasons : (1) The realization, gained with increasing experience, that the average wounded man required at least. 500 cc. of plasma for resuscitation and (2) the increasing necessity for conserving scarce materials, such as rubber tubing and needles, and for utilizing scarce shipping space to the fullest extent.

    The new program created one major problem. For physical reasons, since the speed of drying was partly a function of the surface area of plasma exposed and the thickness of the plasma shell, it was found difficult to dry 500 cc. of plasma in a bottle not much larger than the bottle designed to contain half that amount. Within a short time, however, this problem was solved in commercial production, as it had been solved in the laboratory.

    By the time the change in packaging was made, medical officers had fully realized the need for larger quantities of plasma and were delighted to have


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FIGURE 24. - Preparation for plasma transfusion. A. Army-Navy plasma package (250 cc.). B. Contents of package (dried plasma and sterile diluent). C. Reconstitution of plasma. D. Reconstituted plasma ready for injection.

them provided so conveniently. The larger package saved 50 percent of the rubber tubes, needles, and other material necessary when the plasma was put up in smaller amounts, and the savings were tremendous because such enormous quantities of plasma had to be provided. Thousands of feet of rubber tubing were conserved, for instance; this was a significant saving, since rubber was then in very short supply. The larger package also provided, in about a third more of the space previously used, twice the amount of plasma previously provided; this was an important consideration in view of the shortages in shipping space.


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    Production. - In all, 10,299,470 pints of the 13,326,242 pints of blood collected by the American Red Cross in its blood procurement program were processed into dried plasma.21 More than 3,000,000 packages were put up containing 250 cc. of dried plasma and more than 3,000,000 packages containing 500 cc.

    Homologous serum jaundice. - In the light of the postwar incidence of homologous serum jaundice attributable to plasma transfusions, it is important to emphasize certain facts about the wartime use of plasma. Although plasma was used in enormous quantities for battle casualties, it was not until late in 1945 that pooled plasma was indicted as the vehicle for the causative agent of this disease. Numerous cases of jaundice had occurred previously in military personnel after plasma transfusions, but the causative connection between the jaundice and the transfusion was not immediately realized. In retrospect, what happened is clear. A single transfusion of blood is likely to cause jaundice in only a small percentage of the recipients. When, however, blood is pooled, as it is when plasma is processed, the chances of contracting jaundice are correspondingly increased. Furthermore, whereas only 8 pints of blood were pooled in the preparation of the liquid plasma used in Zone of Interior hospitals, amounts as large as 50 pints were pooled in the early stages of the dried plasma program for overseas, and later, in 1944-45, even larger amounts were frequently pooled. The relation of these various facts to the development of jaundice is now perfectly evident, but the causal sequence was not appreciated until the war had ended.

Liquid Plasma

    One of the first projects of the Blood Research Division at the Army Medical School With an investigation of the possibility of supplying liquid plasma to hospitals in the Zone of Interior. Experience in a number of civilian hospitals had indicated that the plan could be operated successfully, through, because of the high rate of contamination, the collection and processing of plasma in this form in the United States for the British had not proved practical. The explanation was the unsatisfactory equipment used. The Blood-for-Britain experience demonstrated that a completely closed, sterile system was necessary for the collection and processing of plasma, and, unfortunate though it was, it undoubtedly saved the Army program from mistakes which otherwise certainly would have been made.

    The first liquid plasma for Army use was prepared in December 1940 in the small blood-donor center set up at the Army Medical School. An average of 6 donors a day were secured by phoning persons whose names were provided, in groups of 10, by the American Red Cross. The calls were made at night, and the donors were asked to report the following day.

21 See footnote 3, p.122.


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    On 1 June 1941, a bleeding center was opened in Washington, D.C., as an Army-Navy project. The American Red Cross procured the donors and operated the center with technical help furnished by the Army Medical School and the Navy. The blood secured was divided between the Army and the Navy, and the Army share was processed into liquid plasma at the Army Medical School. In January 1942, regular shipments of liquid plasma to a number of Zone of Interior hospitals were begun.

    The experimental program proved so successful from the outset that plans were made to supply all Zone of Interior hospitals with liquid plasma. Several medical officers and a number of enlisted technicians were attached to the Division of Surgical Physiology, Army Medical School, for training, and were then sent out to establish five other centers in various parts of the country. These centers supplied the requirements of the hospitals in adjacent service commands. In 1943, four of the six centers were converted to bleeding centers for dried plasma and albumin, leaving the other two centers (in Washington, D.C., and Denver, Cob.) to collect blood and process it into liquid plasma for all Zone of Interior hospitals.

    There were no confirmed reports of the distribution of contaminated plasma to any hospital, and the incidence of transfusion reactions was small.

    Of the 310,135 blood donations delivered from bleeding centers to military medical hospitals, 295,200 were converted to liquid plasma for utilization in the military services in the Zone of Interior. The remainder were used for whole blood transfusions at hospitals near the centers and for dried plasma prepared at the Army Medical School for use by Army Air Force units in the Zone of Interior.

Participating Agents in the Plasma Program

    Commercial laboratories. - The processing of whole blood into dried plasma for the Armed Forces was a function of the large biologic and pharmaceutical laboratories. The first contract, for 15,000 packages, was made with Sharp & Dohme, because of the previous experience of this firm in allied fields. The first plasma was processed commercially in February 1941, and, before the declaration of war on 8 December 1941, three other laboratories had received contracts. Eventually, nine laboratories were processing plasma for the Armed Forces, as follows:

    Sharp & Dohme, beginning 4 February 1941.
    Eli Lilly & Co., beginning 1 October 1941.
    Lederle Laboratories (Division of American Cyanamid Co.), beginning 14 October 1941.
    Reichel Laboratory (later, Reichel Division of Wyeth, Inc.), beginning 18 November 1941.
    Ben Venue Laboratories, beginning 10 January 1942.


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    Cutter Laboratories, beginning 12 January 1942.
    Hyland Laboratories, beginning 13 May 1942.
    Parke, Davis & Co., beginning 29 June 1942.

    National Institute of Health. - The National Institute of Health exercised no control over the preparation of blood substitutes until Cohn's 22 fractionation of plasma proteins and the preparation of dried plasma. Up to that time, no question of interstate commerce was involved. With these accomplishments, however, the products became biologics, over whose manufacture, storage, and utilization this agency had to exercise control. To produce and sell biologics, including serum, albumin, and dried plasma, a license from the National Institute of Health was required.

    Close liaison was maintained by the Army and Navy throughout the war with Dr. Milton V. Veldee, Chief, Biologics Control Laboratory, National Institute of Health. Minimum specifications were prepared for the processing and packaging of plasma and the products of plasma fractionation. All modifications in both apparatus and techniques for the dried plasma program were made only after consultation with, and approval by, Dr. Veldee, Commander Newhouser, and Colonel Kendrick. Representatives of the National Institute of Health frequently visited the commercial laboratories, aiding them in the setting up of routine techniques for the preparation of dried plasma and assisting them in the solution of special problems.

    American Red Cross. - When the decision was made to use commercially dried plasma as a blood substitute in the war emergency, the American Red Cross was selected as the collecting agency. Several of this agency's chapters had had some previous experience in the procurement of blood donors in cooperation with several civilian hospitals. Further experience had been gained in the Blood-for-Britain Program conducted in New York City from August 1940 to January 1941.

    The first phase of the national program to secure blood for dried plasma was inaugurated by the Southeastern Pennsylvania Chapter in Philadelphia, in September 1940. This chapter, as has been mentioned, procured the donors for the study of the preparation and use of dried plasma then being conducted by Dr. Strumia, under the auspices of the Subcommittee on Blood Substitutes, Division of Medical Sciences, National Research Council.

    The formal request that the American Red Cross undertake the responsibility of collecting blood for the dried plasma program was made on 8 January 1941 by the Surgeons General of the Army and the Navy, after extended discussions. The program was formally inaugurated on 4 February 1941, in New York City, and was continued until 15 September 1945. In all, 35 chapters participated.

    The initial phases of the program were directed and supervised by Dr. William DeKleine, Medical Director, American Red Cross. In July 1941, Dr.

22 See footnote 16, p 124.


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G. Canby Robinson was appointed National Director for the American Red Cross Blood Donor Service, and Dr. (later Major, MC) Earl S. Taylor was appointed technical director. Major Taylor had worked in the blood bank at Presbyterian Hospital, New York, N.Y., and therefore came to these duties with a wide experience in the blood bank field.

    The processing of donors and the collection of blood under the rigid technical controls imposed by the National Institute of Health was an operation of real magnitude. The Red Cross accepted the responsibility of establishing donor centers, recruiting donors, providing administrative personnel, and also providing part of the professional personnel. Because of the immensity of time undertaking, however, and the military need for physicians, it eventually became unnecessary for the Red Cross to ask help from the Army and the Navy for the operation of their 35 blood centers and their associated mobile units. At one period of the program, the services of 127 physicians were necessary.

    The 60 medical officers supplied by the Army were assigned to the Army Medical Purchasing Office and were placed under the operational control of the Office of the Surgeon General. They were directly supervised by Major Taylor; for practical reasons, after he had been commissioned in the Medical Corps, he retained his position in the Red Cross, so that medical officers working in the blood collection centers would be under the supervision of a medical officer. Essential as was the work of these centers, it was neither an interesting nor a desirable assignment. Attempts were made to rotate the officers assigned to the centers, but they were not particularly successful, and many of the officers remained in an assignment for 2 or more years.

    During 1940 and 1941, before the entry of the United States into the war, the response of the public to appeals for donations of blood was not encouraging. After the attack on Pearl Harbor, on 7 December 1941, the number of donors increased sharply, and it became necessary to schedule appointments and control the donations with due regard for the facilities available for drying plasma; these facilities were developed as rapidly as the necessary equipment could be provided for them.

    As the war progressed and the numbers of casualties increased, calls for blood donors increased correspondingly. In 1944, more than 5,000,000 pints of blood were collected, and donations averaged 100,000 pints per week. After blood began to be flown to the Pacific areas, in November 1944 (p. 158), appeals for donors were regulated according to the needs reported by the officer on Guam who was in charge of the program.

    National Research Council. - On 7 January 1941, at the same time that Maj. Gen. James C. Magee, The Surgeon General of the Army, requested the American Red Cross to initiate a blood donor program for supplying plasma for the Armed Forces, he addressed a letter to Dr. Lewis H. Weed, Chairman, Executive Committee, Division of Medical Sciences, National Research Council, in which he requested that the Division of Medical Sciences undertake general supervision of the professional services involved in this project. Dr. Weed


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replied on 9 January 1941 that the Division of Medical Sciences would gladly undertake the responsibility and would do everything possible to make the cooperation effective. The Division's personnel rendered invaluable services throughout the period of the emergency.

SERUM PROGRAM

    In the early days of the Army blood program, there was considerable discussion concerning the possible advantages of human serum over plasma. Serum has a number of advantages, the chief advantage being that it does not contain fibrinogen, which is easily precipitated from liquid plasma. On the other hand, plasma, from the technical standpoint, is somewhat easier to prepare, and the yield from a given portion of blood is somewhat larger than the yield of serum. Reports that human serum had given adverse reactions in some instances, particularly when it was very fresh, were not confirmed in a series of 24 cases in which it was tested clinically. The number of cases was too small to warrant conclusions, but the satisfactory results cast considerable doubt on the risk of reactions after its use.

    As a matter of fact, the advantages of plasma and serum were admittedly about equal, but the National Research Council chose to recommend the use of plasma for the Armed Forces, and the Army and the Navy chose to accept the recommendation for the practical reasons already listed (p. 130), chiefly the greater yield of plasma per pint of blood and the fact that it could be produced safely and readily, in the large quantities necessary, by commercial houses. In addition, the widest previous experience had been with plasma, and the urgency of the situation did not permit delay for further testing before the initiation of mass production.

    The results achieved by the use of plasma fully justified its selection, though the Canadian Army, in which serum was used, had equally good results with that blood substitute.

HUMAN SERUM ALBUMIN PROGRAM

    Early discussions of the Committee on Shock and Transfusions, Division of Medical Sciences, National Research Council, had dealt with the possible use of both bovine and human albumin in shock. It had been hoped that bovine albumin, which could be procured in almost unlimited quantities from abattoirs all over the country, might prove an effective blood substitute. The first studies were encouraging, but later investigations showed that this substance was not entirely safe for intravenous use, and its employment did not progress beyond the experimental stage.

    For a number of years before the war, Dr. Edwin J. Cohn, Professor of Physical Chemistry at Harvard University, and his associates had been working on methods for the fractionation of plasma proteins. Early in 1941,


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both Cohn23  and Janeway24  suggested the possibility of using human serum albumin in the treatment of shock and hypoproteinemia. After adequate testing, this substance, in contrast to the bovine product, was found to be a safe and effective blood substitute. On 5 January 1942, the Conference on Albumin of the National Research Council recommended to the Surgeons General of the Army and the Navy that it be adopted for clinical use and that the Red Cross be requested to add to its program the procurement of donors for the processing of blood into albumin. 25

    The first successful use of human albumin was reported by Major Kendrick.26 The patient, who had multiple compound fractures, was in serious shock, with a blood pressure of 76/30, when he was admitted to Walter Reed General Hospital in May 1941. The response to therapy was prompt, and within a few hours reduction of all his fractures was possible. In all, albumin was used with excellent results in 87 cases at this hospital. Other tests were carried out at Peter Bent Brigham Hospital, Boston, Mass.; the University of Minnesota Hospital, Minneapolis, Minn.; the Presbyterian Hospital, New York City, N.Y.; and the U.S. Naval Medical Center, Bethesda, Md.

    Albumin was dispensed in 25-percent solution in 100 cc. of distilled water. At first, the intrinsic sodium chloride content was allowed to remain in situ. Later, albumin was dispensed salt-free. It was packaged in a glass vial, with a rubber stopper at each end to facilitate its administration (fig. 25).

    The small size of the package in which albumin was dispensed led to its selection by the Navy as the preferred blood substitute because of space limitations on destroyers and other small craft. Albumin was also utilized, for the same reason, by the Marines in their island operations in the Pacific. The Army continued to use the standard Army-Navy package of plasma both because of the good results obtained with plasma and because of one of the disadvantages of albumin, the necessity of administering isotonic fluids with it to dehydrated casualties.

    The high concentration of albumin in the standard package made its physiologic effect dependent upon the rapidity with which it mobilized interstitial fluid. In a well-hydrated patient, this was not problem; the circulating blood volume was promptly increased, and the intravascular discrepancy characteristic of shock was promptly overcome. in the dehydrated casualty, the problem was different, and, since the majority of wounded soldiers, under the rigorous conditions of combat, were dehydrated, the administration of isotonic fluids along with the albumin was necessary in most cases, even though it was not always practical.

23 See footnote 16, p. 124.
24
Janeway, C. A.: War Medicine, with Special Emphasis on the Use of Blood Substitutes. New England J. Med. 225: 371-381, 4 Sept. 1941.
25
Minutes, meeting of Conference on Albumin, Division of Medical Sciences, National Research Council, 5 Jan. 1942.
26
Mudd, Stuart, and Thalhimer, William: Blood Substitutes and Blood Transfusion. Springfield: Charles C. Thomas, 1942, p. 200.


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FIGURE 25. - Serum albumin transfusion. A. Standard Army-Navy serum albumin package (3 units). B. Contents of package ( 3 cans of albumin with dispensing equipment for each). C. Double-ended glass vial containing 1 unit of albumin: dispensing set. D. Recipient set connected and ready for use. E. Demonstration of the administration of serum albumin.


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    Another disadvantage of albumin was that its yield per pint of blood was less than the yield of plasma; 3.2 to 4.0 pints of blood were required for each 100 cc. of albumin, against only 2.4 pints of blood for a 500-cc. unit of plasma.

    Albumin, nonetheless, had a number of advantages, as follows:

    1. It was stable in solution for protracted periods and over a wide temperature range.
    2. It was therefore suitable for use in almost any part of the world in which the Armed Forces might be called upon to operate.
    3. It was ready for immediate use, without reconstitution.
    4. It occupied little more than a tenth of the space occupied by the standard Army-Navy package of plasma.
    5. Later, albumin was proved to be nonicterogenic. It remains stable after heating to 60C. (140F.) for 10 hours.

WHOLE BLOOD PROGRAM

Initial Obstacles

    As has already been pointed out, the use of plasma as a replacement fluid in shocked casualties was never regarded by knowledgeable authorities as anything more than a compromise which was required by the exigencies of the first months of the emergency. At the first meeting of the Committee on Shock and Transfusions, National Research Council, in May 1940, the question of the possibility or likelihood of improving present methods of preservation of whole blood was raised, as well as the possibility of increasing the safe period. Dr. Plass stated that he had already used blood more than 30 days old without any serious reactions, and that he believed that it would be possible, by varying the preservative fluid, to extend the safe period even longer.27

    In the beginning, however, not a great many observers believed that the extensive use of whole blood would be feasible in forward hospitals in wartime. Very few members of the medical profession, whether military or civilian, foresaw that a situation would arise in which the quantities of whole blood required for the adequate treatment of battle casualties in theaters of operations would necessitate the shipment of blood from the Zone of Interior. Such a contingency seemed particularly unlikely after large amounts of plasma began to be shipped to oversea forces. Experienced physicians, both civilian and military, thought that the brevity of its useful life would make it impractical to ship blood over long distances. Finally, as has already been mentioned, dependable air transport service, a sine qua non of a blood program for oversea troops, was not available in 1940, when the emergency began to develop.

27 See footnote 2. p.122.


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    An additional reason for skepticism about the practicality of a whole blood program was the lack at this time of a satisfactory preservative solution which would permit the storage of blood for more than a few days. Many believed, in fact, that it would never be practical to store blood in any solution for much longer periods.

    Not all authorities accepted this reasoning. Even before the outbreak of the war in 1939, as already mentioned, DeGowin and his associates had transported blood, chilled and kept cold by wet ice, in a solution of their own devising. It had been moved great distances both by land and by air, then returned to the laboratory, checked, and finally used for clinical transfusions without complications.

    Although shipment of blood overseas was not seriously considered when the emergency first became evident, investigations were nonetheless continued to develop dependable typing sent, preservative solutions, blood-collecting equipment, and refrigerated shipping containers. The result was that when logistic support for an oversea blood program, in the form of a dependable airlift, did become available, the procurement, safe storage, and safe transportation of blood were no longer impractical.

Early Experience in North Africa

    The British, with the outbreak of war in 1939, immediately organized a blood transfusion service, under the full-time direction of Brigadier Lionel E. H. Whitby, RAMC. Experiences in the North African fighting demonstrated the necessity for large quantities of whole blood in the management of wounded casualties, and a blood transfusion unit was promptly organized to supply the British Eighth Army. Several thousand pints of blood were provided to forward hospitals from this unit in Cairo, and when the Eighth Army moved into Italy, its hospitals continued to receive blood from North Africa until the transfusion unit moved to Bari, Italy.

    Reports of the British experience in North Africa were made available to the Office of the Surgeon General, U.S. Army, through Col. Frank S. Gillespie, RAMC, British medical liaison officer, who was stationed at the Medical Field Service School, Carlisle Barracks, Pa., during the early months of the war. Colonel Gillespie made every effort, as the British experience progressed, to keep The Surgeon General informed of changing concepts in the care of battle casualties. Colonel Kendrick, The Surgeon General's special representative for blood and transfusion, was exceptionally fortunate in having his complete cooperation and support at a time when medical intelligence was relatively limited.

    The whole British experience in North Africa proved that plasma was not enough, although extremely valuable, in the provision of temporary circulatory support for patients who had suffered multiple extensive wounds, accompanied by massive hemorrhage, from mortars, high explosives, and land-


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mines. Whole blood, which had the oxygen-carrying property lacking in plasma, was essential for the support of casualties during the period of anesthesia and initial wound surgery.

    Because he had been kept so well informed on these matters by Colonel Gillespie, Colonel Kendrick had had extended discussions on the subject of whole blood versus plasma with personnel of the Surgical Consultants Division, Office of the Surgeon General. He considered it essential that Col. Edward D. Churchill, MC, who was ordered to North Africa in January 1943 to serve as consultant in surgery, North African Theater of Operations, U.S. Army, should have the same information before the landings which were to take place in Italy later in 1943. The opportunity to inform him arose during his predeparture briefing in the Office of the Surgeon General, while he was reviewing the filmstrips which had been prepared by Colonel Kendrick on first aid in the field and on resuscitation, including the use of whole blood as well as plasma. Colonel Churchill was also informed that one of the main functions of the Department of Surgical Physiology, Army Medical School, was to investigate and evaluate equipment by which blood could be collected and shipped long distances with expedition and safety. It was suggested to him that, upon his arrival in North Africa, he undertake a study of the whole problem, with the twofold objective of determining (1) whether, with plasma readily available, blood was really needed and (2) if blood was needed, how it could best be provided.

    Almost as soon as Colonel Churchill arrived in North Africa and reviewed the situation, he concluded that there was no doubt of the need for large quantities of blood in combat areas to treat casualties with severe wounds. During the next several months, he wrote of this need to The Surgeon General; Brig. Gen. Fred W. Rankin, MC, Chief Consultant in Surgery, Surgical Consultants Division; Colonel Carter; and Maj. (later Lt. Col.) Michael E. DeBakey, MC, Chief, General Surgery Branch, Surgical Consultants Division.

    Establishment of transfusion unit. - Shortly after U.S. forces landed in Italy, in September 1943, Col. (later Maj. Gen.) Joseph I. Martin, MC, Surgeon, Fifth U.S. Army, urged the theater Surgeon, then Brig. Gen. Frederick A. Blessé, MC, to form a transfusion unit to support Fifth U.S. Army field and evacuation hospitals. In December 1943, Colonel Churchill delegated Maj. (later Lt. Col.) Eugene R. Sullivan, MC, to survey blood transfusion needs and facilities in the Army area.

    Meanwhile, General Martin requested British assistance for the landings planned for January 1944 in the Anzio-Nettuno area by British and United States components of the Fifth U.S. Army. In response to this request, the British supplied a blood transfusion unit, which was located with the field and evacuation hospitals near Anzio. Blood was received by this unit from the British blood transfusion unit at Foggia; a large part of the supply was collected from U.S. Army Air Forces personnel in the Foggia area, but the work of collecting and processing was done by British personnel, with British


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equipment. U.S. hospitals in time Anzio-Nettuno area received approximately 4,000 pints of blood from this source.

    In January 1944, the blood situation was reviewed in all its aspects by General Martin; Col. Richard T. Arnest, MC, Surgeon, Peninsular Base Section; Col. Virgil H. Cornell, MC, Commanding Officer, 15th Medical General Laboratory; and Major Sullivan, representing General Blessé. The need for whole blood was evident, and, as a result of the meeting, plans were made for the establishment of a blood transfusion unit to be located at the 15th Medical General Laboratory, near Naples, Italy.28 The first blood was collected by this unit on 23 February 1944, and between that date and 9 May 1944 approximately 4,000 pints were collected, most of which was sent to the Anzio beachhead. Even before operation of the unit had begun, it was obvious that the original estimates for collection of an average of 100 pints of blood daily for the use of field and evacuation hospitals were unrealistically low, and the plan was modified to provide, for the collection of 200 pints daily.

Development of Equipment and Containers

    From the time of the reactivation of the Division of Surgical Physiology, Army Medical School, in 1940, the personnel of the Division had been keenly aware of the following facts:

    1. Wounded men who had lost large quantities of blood in combat were poor surgical risks, even though they had received plasma in large quantities.
    2. They must receive whole blood in large quantities before they could become safe risks for anesthesia and surgery.
    3. A whole blood program would become practical only when an acceptable type of transfusion equipment and satisfactory containers for transportation had been developed.

    Long before the reports of the British and U.S. experience in the North African Theater of Operations had begun to be received in the Office of the Surgeon General, the Division of Surgical Physiology, Army Medical School, had been investigating the development, for use in the field, of efficient transfusion equipment which would meet the following requirements:

    1. Whole blood could be collected and stored safely only if donors were bled by the utilization of a closed sterile system.
    2. The blood must be collected in a preservative solution in which it could be stored safely for 2 or 3 weeks.
    3. The chief cause of transfusion reactions is the presence of pyrogens in the recipient sets, usually as the result of improper cleaning. Therefore, the only practical solution of the problem of administering blood in the field would be the employment of an expendable transfusion set, to be used once and then discarded. Under field conditions, the difficulties of cleaning and

28 Organizational History, 1944, 6703d Blood Transfusion Unit (Overhead).


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preparing collecting and recipient sets would make the use of standard equipment both impractical and unsafe.

    The equipment eventually developed at the Army Medical School for the storage of whole blood consisted of a 1-liter vacuum bottle for the preservative solution (Alsever's solution) and an expendable recipient set consisting of Monel-metal filters, rubber tubing, and an intravenous needle. Each package also contained typing serum.

    All equipment was packaged under sterile conditions and hermetically sealed in an easily opened aluminum cartridge. The cartridges were packed six to a box for export.

Development of Refrigeration

    The program for providing whole blood for oversea use could not become a reality until, in addition to the development of equipment for collecting and administering the blood, means of refrigeration had been developed for its storage and for its preservation during transportation. Work was begun as early as 1942 on a light-weight transportable aluminum refrigerator. The model which was eventually developed held 50 bottles of blood and could be operated either from the usual power outlets or from the 24-volt battery ordinarily used in transport planes.

    When the need for whole blood in ETOUSA (European Theater of Operations, U.S. Army) became urgent in August 1944, no refrigerated container for the transportation of whole blood had yet been developed, though other organizations had been working with the Division of Surgical Physiology, Army Medical School, on a fiberboard container for this purpose. Even had this container been ready for use when the emergency arose, it is doubtful that it would have been used; the urgent need at that time was for transporting as much blood as possible and utilizing all shipping space in planes for this objective. Refrigeration was then a secondary consideration.

    The first blood which was sent to Europe, in August 1944, was therefore shipped without refrigeration. By November 1944, when the shipment of blood to the Pacific was begun, the Navy had developed an excellent refrigerated shipping case. It was a double-walled cardboard box, insulated with 2 inches of cotton waste and with an inner and outer lining of aluminum foil. It held 16 bottles (of 600 cc. content) in a wire rack, in the center of which was a large tin can which held 19 pounds of wet ice. By this device, which was used in all shipments to the Pacific, blood could be kept at a constant temperature for about 24 hours.

    Work on the Army refrigerated container was completed shortly after the Navy container became available, but it was not put into use by the Army until April 1945. In the meantime, other expedients were employed, as necessary, in transporting blood to Europe.


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Development of Preservative Solutions

    Another essential requirement for the shipping of whole blood overseas was the development of a satisfactory preservative solution. Early in 1943, the Army Medical School began comparative studies of various solutions and soon arrived at the conclusion that Alsever's solution was superior to the other solutions then available. This solution, which contains 2.05 gm. of dextrose, 0.42 gm. of sodium chloride, and 0.8 gm. of sodium citrate per 100 cc. solution, was one great disadvantage, that it must be used in 500-cc. amounts for each 500 cc. of blood. This was a serious consideration, particularly in wounds of the head and chest, in which overloading the circulation with excessive fluids could be dangerous.

    Otherwise, Alsever's solution had a number of advantages, which were evident in the more than 2,000 transfusions in which it was employed at Walter Reed General Hospital. Criteria of evaluation were (1) the amount of supernatant hemolysis and (2) evidences of clinical improvement after transfusion. Blood collected in this solution had been shipped, unrefrigerated, from Washington, D.C., to the west coast and back and also to Prestwick, Scotland, and back and had been suitable for use at the end of the journeys. It withstood the shaking, as well as the changes of temperature, incident to transportation and storage over long periods of time under adverse conditions. Blood collected in this solution also appeared to store well from 21 to 30 days at 4 C. (approximately 40 F.). It could also be exposed to average room temperature (20 C., 68 F.) for a period of hours without undergoing changes which would make it no longer safe or useful in the treatment of hemorrhagic shock. Finally, Alsever's solution was more easily administered through standard Army filters than was blood preserved in other solutions, which tended to clog these filters, particularly after the blood had been stored for more than 7 days. The explanation probably was the greater dilution of the blood in Alsever's solution; the dilution minimized the precipitation of fibrinogen which occurs when blood is stored in a cold environment. This factor was of special importance in forward hospitals, in which ease of administration was essential.

    On 24 September 1943, at the request of the Army and the Navy, the Subcommittee on Blood Substitutes had recommended the use of Alsever's solution for the preservation of blood to be stored more than 5 days.29 This solution was therefore employed in August 1944, when it became necessary to fly blood to Europe, because it was the only solution immediately available which had been tested in large numbers of cases and which had been approved by the Subcommittee on Blood Substitutes.

    Progress had been made, however, in the development of other suitable preservative solutions, and the Loutit-Mollison, A.C.D. (acid-citrate-dextrose)

29 Minutes, meeting of the Subcommittee on Blood Substitutes, Division of Medical Sciences National Research Council, 24 Sept. 1943.


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solution seemed particularly promising. On 30 August 1944, the Subcommittee on Blood Substitutes recommended that Alsever's solution be replaced by the Loutit-Mollison solution. 30 This solution, 25 cc. of which is used for each 100 cc. of blood, consists of 1.33 percent trisodium citrate, 0.47 percent citric acid, and 3 percent dextrose; the pH is in the neighborhood of 5.0.

    The recommendation of the Subcommittee was not immediately accepted by the Army, on the ground that the A.C.D. solution had not yet been tested in a sufficient number of cases. Moreover, some concern was felt over the increased precipitation of fibrinogen which occurred when it was used and which tended to plug the filters in the recipient sets. Additional studies, however, indicated that this solution preserves red blood cells somewhat better than Alsever's solution, and, in addition, the Navy, which had used it in all the blood flown to the Pacific, had an unbroken record of success with it. These facts, combined with the undeniable advantage of its smaller bulk, were responsible for the Army's changeover to this solution on 1 April 1945.

Development of Blood-Grouping Sera

    Studies were also made on blood-grouping sera in the Division of Surgical Physiology, Army Medical School, in collaboration with the Division of Chemistry. Eventually, a highly satisfactory, extremely avid serum was developed, each lot of which, when it was manufactured commercially, was tested at the Army Medical School before it was used.

    An effective technique was also devised at the Army Medical School for the rapid identification of group O donors.31 This was an urgent and important consideration, since only group O blood was sent overseas.

Training of Personnel

    Even though blood was not shipped overseas until the summer of 1944, all personnel attending courses given by the staff of the Blood Research Division, Army Medical School, had, since 1943, been trained in the collection of blood, the preparation of equipment, and the typing and cross-matching of blood.

    Related programs at the Army Medical School, such as the programs for liquid plasma and dried plasma, afforded some training for a small number of medical officers and enlisted technicians, who were capable of operating blood donor centers. Similar training was given to the officers assigned to the Red Cross blood donor centers. This training included the theory and practice of blood grouping, details of transfusion therapy, and similar matters. All courses conducted at the school for medical officers also included 10 hours' instruction on shock and fluid-replacement therapy.

30 Report, Third Conference on Blood Storage, Division of Medical Sciences, National Research Council, acting for the Committee on Medical Research, Office of Scientific Research and Development, 30 Aug. 1944.
31
Kendrick, D. B., Jr., Elliott, J., Reichel, J., Jr., and Vaubel, E. K.: Supply of Preserved Blood to European Theater of Operations. A Preliminary Report. Bull. U.S. Army M. Dept. 84: 66-73, January 1945.


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    All through 1943 and 1944, the Committee on Shock and transfusions and the Subcommittee on Blood Substitutes, National Research Council, emphasized the need of placing trained personnel in charge of the blood program in all phases and at all stages. After the Mediterranean and European theaters had formed their own blood transfusion units, the Transfusion Branch, Surgical Consultants Division, Office of the Surgeon General, and the Division of Surgical Physiology, Army Medical School, collaborated in drawing up tables of organization and equipment for blood transfusion teams. These tables were submitted for approval to Headquarters, Army Service Forces, late in 1944 and were approved early in 1945.32

EVOLUTION OF THE OVERSEA BLOOD PROGRAM

Blood Banks in Oversea Theaters

    The completion of the various projects just outlined made it practical in the fall of 1943 to draw up a plan for the establishment of blood banks and the development of transfusion services in oversea theaters. There were now available, as the result of the joint activities of the Division of Surgical Physiology, Army Medical School, and the Subcommittee on Blood Substitutes, National Research Council, the following items: (1) An expendable transfusion set, (2) a satisfactory preservative solution, (3) a refrigerator for the storage of blood for as long as 21 days, and (4) satisfactory grouping sera. The safety and efficiency of all of these items had been thoroughly tested, which made it feasible to propose that this equipment be sent to oversea theaters and that the theaters be authorized to train their own personnel in the collection and distribution of blood to all forward and fixed hospitals. The proposed system, on the most exacting analysis, seemed almost foolproof. In particular, it disposed of the chief cause of anxiety in transfusion, the reuse of equipment, a practice which inevitably increases the incidence of pyrogenic reactions under circumstances of warfare.

    On 5 October 1943, Colonel Kendrick addressed a memorandum to Colonel Carter on the subject of transfusions in theaters of operations. The plan proposed in this memorandum, which provided for the use of whole blood in general, evacuation, and field hospitals in theaters of operations, was based on the fundamental concept that the handling and use of whole blood and other replacement fluids is a specialized branch of medicine and that to collect blood, to group it correctly, and to transport and preserve it safely requires the services of specially trained personnel. These functions cannot be delegated to untrained personnel because any slip, however trivial, in the collection, processing, and use of whole blood may result in severe and even fatal reactions, in addition to unnecessary and sometimes excessive losses of a scarce and valuable substance.

32 War Department Table of Organization and Equipment No. 8-500, 18 Jan. 1945.


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    A memorandum for The Surgeon General, incorporating the essentials of this plan, was prepared the following month by General Rankin 33 and was hand carried to The Surgeon General by Colonel Carter and Colonel Kendrick.

    The plan was rejected on the following grounds:

    1. Plasma was regarded as adequate for the resuscitation of wounded men.
    2. It was considered impractical, from a logistic standpoint, to make locally collected blood available farther forward than general hospitals in the communications zone.
    3. Shipping space was too scarce to warrant using it to send disposable transfusion equipment overseas.

    In the light of these facts, it was The Surgeon General's decision that the provision and rise of blood in oversea theaters should be limited to the instructions set forth in Circular Letter No. 108. 34 This letter outlined the techniques to be followed in the transfusion of fresh whole blood in general hospitals in oversea theaters within 4 hours after it had been collected. It also provided for the transfusion of stored blood, to be collected by a closed system and to be used within 7 hours after its collection.

    The plan which had been proposed to The Surgeon General and had been rejected was presented to the Subcommittee on Blood Substitutes by Colonel Kendrick at the meeting on 17 November 1943. 35 After the matter had been thoroughly discussed from the standpoint of its practical implications, the following motion was moved and passed:

    RESOLVED: That the Subcommittee on Blood Substitutes recommend through channels that the Surgeon General of the Army give consideration to the transportation of whole blood by airplane to certain theaters of operations.36

    Although a satisfactory airlift was available when this plan was presented to The Surgeon General, the proposal was rejected, principally, again, on the grounds that (1) plasma was adequate for resuscitation of battle casualties and (2) flying blood overseas was not practical.

    Although personnel in charge of the blood program were not in agreement with The Surgeon General's decision, they had no choice but to accept it. The basic reason for The Surgeon General's refusal to consider the proposed program was undoubtedly that he shared the still rather general opinion

33 Memorandum, Brig. Gen. F. W. Rankin for The Surgeon General, 6 Nov. 1943, subject: Transfusion of whole Blood in the Theaters of Operations.
34
Circular Letter No. 108, Office of the Surgeon General, U.S. Army, 27 May 1943, subject: Transfusion of Whole Blood in the Theaters of Operations.
35
At the meeting of the Subcommittee on Blood Substitutes on 24 September 1943, everyone who had been present at the meeting of the Committee on Shock and Transfusion held on 3 November 1941 agreed that it had been the consensus of the group that the Armed Forces should use whole blood in the treatment of shock whenever possible. The discussion had been omitted, unfortunately, from the minutes of the meeting, and it was suggested that the minutes be corrected to conform with the facts.
36
Minutes, meeting of the Subcommittee on Blood Substitutes, Division of Medical Sciences, National Research Council, acting for the Committee on Medical Research, Office of Scientific Research and Development, 17 Nov. 1943.


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that plasma was a satisfactory agent of resuscitation and that the use of whole blood in large amounts in battle casualties was not necessary. Undoubtedly also, he had been directed by higher authority to limit the amount of medical supplies shipped overseas. It therefore seems reasonable to assume that, since he shared the general belief that plasma was adequate for resuscitation, he did not consider that supplying transfusion equipment in order to liberalize the use of whole blood was sufficiently important either to substitute the equipment for other supplies and thus keep within the allowable tonnage, or to point out to the Commanding General, Army Service Forces, under whom his office operated, the urgency of making an exception in order to supply whole blood for wounded men.

Provision of Blood From Zone of Interior for European Theater

    Early in 1943, Brig. Gen. (later Maj. Gen.) Paul R. Hawley, MC, Chief Surgeon, ETOUSA, had directed that provision be made for supplying whole blood to combat casualties. Plans for obtaining the blood and flying it from the United Kingdom Base after D-day had been completed by 31 May 1944. 37 The operation was conducted with great efficiency by Maj. (later Lt. Col.) Robert C. Hardin, MC, Senior Consultant in Shock and Transfusion, amid Lt. Col. (later Col.) James B. Mason, MC, Chief, Operations Division, Office of the Chief Surgeon, ETOUSA.38

    As early as April 1944, those responsible for the provision of blood for the European theater had given urgent thought to the acquisition of type O whole blood from the Zone of Interior. Even before D-day, it had become evident that a sufficient supply of blood for the estimated combat casualties could not otherwise be provided, and urgent requests had been made for blood to be sent from the Zone of Interior to the European theater. After D-day, these requests increased in urgency as it became more and more evident that using troops in the United Kingdom Base as donors was completely impractical to supply the amount of blood needed for the adequate treatment of thousands of casualties with multiple wounds.

    Blood from the United Kingdom Base was in reasonably adequate supply from D-day until just before the operations in the Saint-Lô area which culminated in the breakthrough on 18-19 July 1944. Then it became a critical item of supply. It actually had to be rationed and allotted to the areas in which the greatest number of casualties were anticipated. The daily demand for blood had risen steadily and by the first of August was between 1,000 and 1,500 pints.

    On 3 August 1944, a radio request was received by The Surgeon General from General Hawley asking for one thousand 500-cc, units of whole blood per day for the European theater. On 13 August 1944, with General Hawley's

37 Mason, J. B.: Planning for the ETO Blood Bank. Mil. Surgeon 102: 460-468, June 1948.
38
Mason, J. B.: The Role of the ADSEC in the Supply of Whole Blood to the Twelfth Army Group. Mil. Surgeon 103: 9-14, July 1948.


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approval, Col. (later Brig. Gen.) Elliott C. Cutler, MC, Chief Consultant in Surgery, Office of the Chief Surgeon, ETOUSA, flew to the United States, accompanied by Major Hardin, to request The Surgeon General to supply generous quantities of whole blood to the troops in Europe by an airlift from the Zone of Interior. In their presentation, these officers made it perfectly clear that, unless blood could be made available in quantities far beyond the amounts which could possibly be provided overseas, wounded men with multiple wounds would receive less than optimum treatment and some of them would certainly die.

    The plan for an airlift of blood to Europe which had originally been proposed in November 1943 and which had not then been found acceptable was modified in certain details, to meet the exigencies of the present situation, and was again presented to The Surgeon General. It was approved at once.

    Colonel Cutler and Major Hardin made their request for an airlift of blood to Europe on 17 August 1944. Four days later, on 21 August, the first shipment was flown from the Zone of Interior to Prestwick, Scotland. It was transshipped to Salisbury, England, the base of the ETOUSA Blood Bank, and thence was flown to France. On 28 August, Colonel Kendrick left the Zone of Interior with a large shipment of blood. His request for orders for over-sea travel had been justified by the reasoning that it was simply not possible to put a system, however good it might be, on paper and expect it to work of itself. When blood was the substance to be transported, it was considered essential to follow it up, to see that it was properly handled at every point along the way, and also to see that it was properly used.

Critique of Results

    From 6 June to 20 August 1944, all the blood used in all ETOUSA hospitals on the Continent was collected in England and flown across the Channel (fig. 26). Of the 385,231 pints of whole blood handled by the ETOUSA Blood Bank between 22 May 1944 and 24 May 1945, 197,712 pints (51.3 percent) were flown from the United States.40

    The ability to provide blood in such quantities so promptly when the need in the European theater became imperative was the end result of the previous activities of many persons and organizations, as follows:

    1. By this time (August 1944), the American Red Cross had 35 bleeding centers in operation throughout the country. The Red Cross program was well controlled by the appropriate committees of the National Research Coun-

39 Memorandum, Brig. Gen. F. W. Rankin for The Surgeon General, 3 Aug. 1944, subject: Provisions for Supplying Whole Blood to ETO From U.S.A.
40
See footnote 38, p. 149.


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cil, and cooperation between the Council and Army and Navy personnel working on the blood program was invariably excellent.

    2. All the equipment needed was ready, and ready in sufficient quantities. The Army and Navy personnel working on the blood program had for many years worked closely with the manufacturers of transfusion equipment, and, when the urgency of the situation was made known to these firms, they provided promptly all the help and cooperation required.
    3. A satisfactory preservative was available (p. 145). Alsever's solution had the disadvantage of bulk, and it is regrettable that the Loutit-Mollison (A.C.D.) solution, which had the advantage of less bulk and which was found later to be just as efficient, was not sanctioned earlier by the Subcommittee on Blood Substitutes, Division of Medical Sciences, National Research Council, and was not accepted earlier by the Army when it was later recommended by the Subcommittee. Alsever's solution, however, filled the initial needs of the situation admirably.
    4. Although a satisfactory refrigerated shipping case was not available when blood was first flown overseas to Europe, Alsever's solution permitted a 15-day storage period, and there was no spoilage because of this lack. The shipment of 500 bottles which Colonel Kendrick took over on his flight was checked at intervals, and the temperature in the pasteboard containers did not vary more than 6 F. (3.3 C.) in the approximately 12 hours which it took to cross the ocean from New York to Prestwick, Scotland. The aircraft flew at an altitude of from 8,000 to 10,000 feet, and it was cool all the way. Fortunately, fall was near when the demand for blood became urgent, and, before the need ceased, in May 1945, a refrigerated case was in use and the change had been made from Alsever's to the Loutit-Mollison solution.
    5. Although the training of personnel in the Zone of Interior had never been formalized, informal training had been provided, as far as this was possible, by those in charge of the blood program. It had always been recognized that blood would eventually be flown overseas and that it must be handled all along the way by specially trained personnel and not in routine medical supply channels.

    In addition to the personnel trained for direction of the centers in which blood was collected for liquid plasma (p. 134), the officers in the courses at the Army Medical School since 1943 had been instructed in resuscitation in all of its aspects and had also been taught to realize the importance of special handling of blood even though they did not, themselves, know the precise details. Trained personnel were already available in the European theater, and in the Mediterranean theater, although the latter theater never received blood from the Zone of Interior.

    6. Finally, an efficient airlift was available. From the geographic standpoint, the Red Cross bleeding center in New York was most suitable for the


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FIGURE 26. (See opposite page for legends.)


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FIGURE 26. - Processing of blood in European theater before airlift from Zone of Interior was instituted. A. Donor being bled by a collecting team. B. Addition of glucose as preservative to blood. C. Loading refrigerated truck with bottles of blood for shipment.

collection of blood for the European theater, since New York was the port of embarkation for this theater. All of the blood collected here, however, could not be sent overseas, because part of it had to be designated for an adjacent plasma processing center. The first shipments of blood sent to Europe were collected in New York, but, by the time the oversea program was fully operative and from 1,000 to 1,500 pints per day were being delivered to the European theater, blood designated for the theater was being collected from areas as far away as Washington, D.C., and Syracuse, N.Y. (fig. 27).

    With very occasional exceptions, whether the blood was flown from the United States or was procured locally, only type O blood was used for transfusion in all theaters of operations. In the Mediterranean theater, high-titer O blood was reserved for type O recipients, and only low-titer blood (not exceeding 1:64) was used universally.

    Blood was not routinely supplied to either collecting or clearing stations, on the logical ground that surgery was not permitted in them and that blood was most useful in installations in which surgery was performed. Blood was


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FIGURE 27. - Blood, donated in Brooklyn 10 days previously, being stored in the 48th Field Hospital, ETO.

used in surprisingly large quantities in both field and evacuation hospitals. A patient who had sustained multiple injuries associated with massive hemorrhage frequently had a hematocrit of 25 or 30, and frequently required 4 to 6 pints of blood before it was restored to a level at which initial wound surgery was practical.

    Furthermore, the fact that a low hematocrit had been raised to approximately normal by the transfusion of blood in a field or evacuation hospital, immediately after trauma, by no means indicated that the hematocrit would be maintained at this level. Wounded men with multiple wounds, even if they had withstood surgery in a field hospital after the transfusion of 6 or 8 pints of blood before or during operation, or both, often had to receive additional quantities before definitive surgery in a general hospital overseas. The liberal use of blood was often necessary in Zone of Interior hospitals also.

    Although general hospitals in oversea theaters could have operated their individual blood banks if they had had the necessary equipment, it does not follow that this would have been a desirable practice. One of the advantages of a special transfusion service is that control of the blood is never decentralized. The responsibility for maintenance of sterility and the provision of properly grouped blood is inherent in the laboratories on the special transfusion service. These precautions are as necessary in general hospitals as in field and evacuation hospitals.


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OVERSEA TRANSFUSION SERVICES

The European Theater of Operations

    After he had arrived in the European theater late in August 1944, Colonel Kendrick spent the next 2 months in England and on the Continent including Italy.41

    Information on developments in the use of whole blood had been sent to the Office of the Chief Surgeon, ETOUSA, by means of copies of the monthly Essential Technical Medical Data reports from other theaters and through other sources. In addition, Colonel Sullivan and Major McGraw, from the Mediterranean theater, had visited the European theater before D-day and had reported on the operation of the blood bank in the Mediterranean theater, which had been an active theater of operations for 21/9 years before D-day in Europe.

    It is important to realize that the military situation in the two theaters was entirely different and that the medical situation differed accordingly. In the Mediterranean theater, a single army was operating on a single land mass, within a relatively limited area. Although serious transportation problems existed in the Mediterranean theater, blood did not have to be flown across water. Blood was necessarily flown from England to the Continent, which meant that, in bad weather, no blood could be transported to the European theater. This was an extremely serious matter in the European theater, for the always limited supply of blood did not permit storage in any significant amounts.

    There were also other differences. In Italy, medical control could be uniform; there was one army and one army surgeon. In the European theater, several armies were operating, and each army surgeon, like each army commander, had his own concepts of how to care for patients. The use of blood was only one of many therapeutic methods in which medical personnel, inexperienced in the treatment of combat casualties, required careful indoctrination and instruction. The First and Third U.S. Armies had been in combat only a relatively short time when blood began to be supplied to them in liberal quantities. The Third U.S. Army, in fact, had been operational for less than 3 weeks. In either Army, there had been no chance to set up research teams and little time for operating surgeons to grasp the urgent need for the use of whole blood in liberal amounts.

    The transfusion service in operation when Colonel Kendrick arrived in the European theater showed how excellent such a service could be, even without support from the Zone of Interior, when it was under the control of a competent medical officer who used all the resources available to

41 Report, Lt. Col. Douglas B. Kendrick, Professional Service Division, Office of the Chief Surgeon, to Chief Surgeon, ETOUSA, 26 Sept. 1944, subject: Report of Trip to First and Third Army Medical Installations.


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FIGURE 28. - Administration of blood in a forward area in France.

him (fig. 28). The lesson that had to be taught in the European theater was not the value of whole blood for severely wounded men but the desirability of using it in liberal quantities and the availability of the supply. Colonel Kendrick's task in this theater was to convince operating surgeons who had been used to a mere trickle of blood, which had to be reserved for the casualties whose condition was poorest, that they could now be assured of all the blood they needed and that they could use it prophylactically as well as for casualties whose condition was dire. He had some difficulty in persuading these surgeons that all they needed to secure blood in any desired quantity was to ask for it in that quantity.

    One of the interesting developments in the European theater, as in the Mediterranean theater, was time increasing use of blood as experience increased. Eventually, in both theaters, the ratio of units of blood to wounded was close to 1:1.

The Mediterranean Theater of Operations

    In the Mediterranean theater, where the Fifth U.S. Army had been in combat for almost 2 years, the need for whole blood in the treatment of severely wounded battle casualties had been promptly recognized (p. 142). After repeated requests from the theater, transfusion equipment and refrigerating apparatus had finally been shipped from the Zone of Interior, and a transfusion service had been established early in 1944.


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    A highly efficient blood bank had been developed.42  Blood was obtained from volunteer donors who, it was certain, would not go into combat within a specified period of time. By the expedient of paying each donor $10 per pint, all the blood needed could be secured. A C-47 plane, which had been made available to the l5th Medical General Laboratory, flew the blood to designated centers, whence it was delivered to forward areas by truck and ambulance. Delivery was often an achievement of considerable magnitude, in view of the frequently unfavorable flying weather and the bad roads constantly crowded with military transport. The blood, however, always got through.

    This theater, in 1943, had set up a board for the study of the physiologic effects of wounds,43 and the interest of the board members and others in the whole question of shock and resuscitation, including posttransfusion anuria, had created a great interest in replacement fluids in all field and evacuation hospitals and had served as a real stimulus to the effective use of whole blood.

    In the Mediterranean theater, therefore, Colonel Kendrick's function was chiefly to listen and learn. He frequently regretted that circumstances had not permitted him to visit this theater before he visited the European theater. He brought back many valuable ideas to the Zone of Interior not only about the use of whole blood but also about the cardinal principles of resuscitation, including such details as the maintenance of an adequate airway and aspiration of pneumothoraxes to restore normal respiratory physiology and improve respiratory exchange by injections of procaine hydrochloride to control pain in patients with fractured ribs.

PROVISION OF BLOOD FROM ZONE OF INTERIOR TO PACIFIC AREAS

    Because of the close liaison maintained between Commander Newhouser of the U.S. Navy and Colonel Kendrick, it was logical that when the former was sent to the Far East in June 1944 to survey the situation in respect to the distribution and correct use of albumin, Colonel Kendrick should have been given orders to accompany him, to study the distribution and use of plasma, as well as time provisions for whole blood.

The Situation in June 1944

    Supplies of plasma in the Pacific had been adequate for a long time. Albumin, which was just beginning to arrive in June 1944, was never widely used in Army medical installations.

    In SWTA (Southwest Pacific area), blood had been provided up to this time from three sources as follows:

    1. It was collected locally in each installation, as the need for it arose.

42 See footnote 28, p. 141.
43
Medical Department, United States Army. Surgery in World War II. The Physiologic Effects of Wounds. Washington: U.S. Government Printing Office, 1952.


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    2. In January 1944, at the request of the Chief Surgeon, SWPA, it was supplied by the Australian Blood Distribution Chapter at Port Moresby, New Guinea.
    3. Later, it was supplied to some Army organizations at Hollandia, New Guinea, by a Navy blood bank operated on an LST (landing ship, tank).

    All of these sources, although adequately supervised, were obviously improvisations, and none of them was capable of meeting total theater requirements.

    On this trip, Commander Newhouser and Colonel Kendrick visited Nouméa, New Caledonia; Brisbane and Sydney, Australia; New Guinea, where they spent a month; and various other points in the South Pacific and Southwest Pacific areas. The information collected on this trip proved invaluable later, in the planning of the blood supply for island operations and for the invasion of Japan.

Establishment of Airlift of Blood

    In November 1944, when Colonel Kendrick was in Italy and was preparing to go into the Seventh U.S. Army area in southern France, he was recalled by Colonel Carter to the Zone of Interior because the program for flying whole blood to the Pacific was soon to be inaugurated and Brig. Gen. John M. Willis, MC, Surgeon, POA. (Pacific Ocean Areas), had requested him as consultant in blood and shock in his headquarters.

    By this time, formal arrangements had been made for the Navy to be responsible for flying blood to the Pacific areas. Guam had been designated as a receiving, storage, and distribution center, and Lt. Herbert Brown, MC, USN, had been designated transfusion officer.

    The plan was that requests for blood from various areas in the Pacific should be transmitted to Guam by Navy channels and that Lieutenant Brown should, in turn, notify the Navy Blood Donor Service of the exact amounts of blood which would be needed over given periods of time. The requirements, of course, varied according to combat activity. In November 1944, all operations were of the island-hopping type, and little blood was needed during the periods of preparation for them. Once the campaigns began, however, a great deal of blood was needed over short periods of time.

    The system set up was operated with great efficiency by the U.S. Navy. Wastage was reduced to a minimum because, by virtue of excellent communications, needs could be cabled promptly to the Zone of Interior, and blood to meet the requirements could be flown over in the requested quantities. The blood was flown from San Francisco to Hawaii, where it was re-iced at the airfield on the naval base; the delay here was never more than 3 or 4 hours. Then the blood was flown to Guam, where it was received at the naval air base, checked to be sure that it was suitable for use, and placed under mechanical refrigeration until it was shipped to the points at which it was to be used.


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    At no stage along the way was the blood ever touched by any but trained, specialized personnel, whose assignments were permanent. In the Pacific, in fact, blood was consistently handled by what amounted to a special delivery service, which is the only safe and proper way to handle it. It is important to emphasize, however, that the highly efficient blood service in the Pacific had its roots in the experience gained in the Zone of Interior, the Mediterranean theater, and the European theater after 4 years of warfare.

    The first blood for the Pacific areas left the Zone of Interior on 25 November 1944 and was sent to Leyte via Guam. Colonel Kendrick reached Hawaii on 25 November and went to Leyte, also via Guam, to discuss the whole problem of the use and supply of blood with Lieutenant Brown and with medical officers in the office of Maj. Gen. Guy B. Denit, MC, Chief Surgeon, USASOS (U.S. Army Services of Supply), SWPA.

The Leyte and Luzon Operations

    The first blood shipped from Guam to Leyte provided a perfect illustration of what can happen to this precious commodity when once it leaves the care of personnel specially trained to handle it. When this blood, which had been so carefully protected all the way from the Zone of Interior, reached Leyte, it left the hands of trained personnel. It was at once taken out of the refrigerated containers in which it had been received, thrown into trucks, and transported, over a 4- or 5-hour period, to the medical installations which had requested it. At this season, Leyte was a place in which it was possible to have mud on the shoes and dust in the eyes at the same time. The temperature was 100 F. in the shade, and the humidity was extreme. The casual treatment of the blood under these circumstances rendered it entirely unusable, and the carefully worked out program was in a fair way to being wrecked.

    In November 1944, there were no personnel in the Pacific theaters with the responsibility of receiving and supervising the handling and distribution of blood, or with the authority to undertake these tasks. More important, there was no general recognition of the importance of the liberal use of blood in battle casualties. Colonel Kendrick's task of indoctrination was not particularly easy. He had to convince the medical officers of an army which had been fighting effectively for several years that the blood program had a great deal to offer them. He also had to convince the medical officers of an army which had never had enough of anything that they could have all the blood they needed and wanted merely by asking for it. It was fortunate that he had visited the Mediterranean and European theaters before he went to the Pacific, for he was able to bear eyewitness testimony to the feasibility and usefulness of the plan he was advocating.

    Through the wholehearted and efficient cooperation of Maj. (later Lt. Col.) Frank Glenn, MC, Consultant in Surgery, Office of the Surgeon, Sixth U.S. Army, a meeting was arranged with the senior medical officer of the Navy in the area; representatives of the Surgeon, Sixth U.S. Army; representatives


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of the Chief Surgeon, USASOS, SWPA; and a number of others who had a special interest in the use of whole blood. By a presentation of all the details of the program, Colonel Kendrick was able to show these officers that they could have all the blood they needed, sterile, safely refrigerated, and delivered according to their requests, if they merely made the requests.

    In the month Colonel Kendrick spent with the Sixth U.S. Army, which was staging for the Luzon operation, he worked out a whole-blood program for this invasion and arranged for the delivery of blood from Guam according to estimated needs from D-day onward. From the standpoint of the use of whole blood, the Leyte operation could have been more efficiently handled. The operation on Luzon was well handled from this standpoint, one of the chief reasons being that Colonel Kendrick had been able to locate, on Leyte, a trained pathologist and fine medical officer, Capt. Henning H. Thorpe, MC, who, with totally inadequate sources, had done his best to supply the Sixth U.S. Army needs for whole blood. When Captain Thorpe came into the program, most of the operational difficulties had been cleared away.

    The Luzon campaign was the first in the Pacific in which whole blood was given to nearly all casualties with moderate and severe wounds, regardless of whether or not they were in shock when they were received in field and evacuation hospitals. After this operation, it took little effort to convince Sixth U.S. Army medical officers, both at headquarters and in the field, of the value of the blood program.

The Okinawa Operation

    When Colonel Kendrick returned to Hawaii after his tour in the Southwest Pacific, which had included several days of conferences with Lieutenant Brown on Guam, he was relieved of his responsibilities for the blood program in the Pacific and was never replaced. He was assigned to command a Tenth U.S. Army field hospital, which was designated to land on Okinawa on D+60. Before Colonel Kendrick could report to this hospital, Col. Frederic B. Westervelt, MC, Surgeon, Tenth U.S. Army, assigned him to his headquarters as consultant on blood and shock for the Okinawa operation, for which this army was then staging. In this capacity, Colonel Kendrick was able to see that the ships which went to Okinawa from Saipan were loaded with all the blood likely to be needed for the first days of the operation.

    On the first days after time landings, Colonel Kendrick, accompanied by Col. George G. Finney, MC, Consultant in Surgery, Office of the Surgeon, Tenth U.S. Army, Lt. Col. (later Col.) Harold A. Sofield, MC, and Col. Walter B. Martin, MC, made daily trips ashore for indoctrination purposes. During this period, and for the first few days after the Tenth U.S. Army went ashore, the circumstances were peculiarly propitious for this purpose. The Japanese had retreated south as the landings had been made, and it was a week before real resistance was encountered. During this interval, it was


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therefore possible for these officers to visit every field and evacuation hospital ashore, whether Army or Navy, and to pass on to the hospital staffs all the information in their possession, including the information Colonel Kendrick had secured in the Mediterranean and European theaters, about the correct use of whole blood for battle casualties. When the hard fighting started, the medical officers responsible for the care of battle casualties were well trained, and the ratio of blood units used to casualties was 1:1 (40,000 casualties, 40,000 pints of blood used). At this time, in Europe, time ratio was 0.9:1.

    After the development of the blood program and indoctrination in resuscitation on Okinawa, Colonel Kendrick assumed command of the 31st Field Hospital, where observation of the approximately 10,000 casualties who passed through it gave him an excellent opportunity to study in detail the use of blood at this level.

Critique of Results

    The experience, in the Pacific demonstrated the following facts:

    1. It is perfectly practical to collect blood in the Zone of Interior and deliver it to a theater far removed from the mainland. It was not unusual for blood to be collected in the United States, sometimes in cities as far inland as Chicago, and to be used in places as remote from the point of collection as Okinawa within 6 days after it had been collected.
    2. A theater transfusion officer with his staff, attached to the office of the theater surgeon and given the proper authority and resources, can keep a combat force adequately supplied with blood.
    3. The resources made available to this officer must, however, include all the staff, personnel, and equipment necessary to collect, process, and deliver whole blood to any medical installation in the theater.
    4. In dealing with a commodity such as blood, which has only a brief life and which is easily contaminated and rendered not only useless but harmful, handling and distribution must be the responsibility of medical officers and other personnel trained in this particular specialty. Blood cannot be handled either efficiently or safely through conventional supply channels.

PLANNING FOR THE INVASION OF JAPAN

    Just before the end of the campaign on Okinawa, at the suggestion of Col. I. Ridgeway Trimble, MC, Consultant in Surgery, Office of the Chief Surgeon, SWPA, General Denit invited Colonel Kendrick to Manila to develop the planning for the blood program for the invasion of Japan (Operation OLYMPIC). There was sufficient time to send the plans to the Office of the Surgeon General, so that Major McGraw, then serving as representative on blood and transfusion, could comment on them in the light of his experiences in the Mediterranean theater. It was interesting that


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even at this late date, while Sixth U.S. Army medical personnel attached to the Chief Surgeon's office fully recognized the urgent need for whole blood, they were still doubtful that all that was regarded as necessary for the invasion of Japan could be supplied.

    After the program to supply blood from the mainland had once been instituted, there was never a shortage of blood in the Pacific Ocean areas. At times, when the weather was bad and supplies for only 24 hours were on hand, some concern was felt, but, as in the European theater, the blood never failed to arrive when and where it was needed. Had Operation OLYMPIC come to pass and had the estimated five or six hundred thousand casualties occurred, there seems little doubt that sufficient supplies of blood could again have been provided for all their needs.

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McGraw, J. J., Jr., Vaubel, E. K., Reichel, J., Jr., and Elliott, J.: Complications of Blood Transfusion. S. Clin. North America 25: 1042-1056, October 1945.
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Moloney, W. C.: The Rh Factor and Blood Transfusion; Observations on a Group of Rh-Negative Individuals Transfused With Rh-Positive Blood. Brit. M.J. 2: 916-918, 29 Dec. 1945.
    -.Lonnergan, L. R., and McClintock, J. K.: Syncope in Blood Donors. New England J. Med. 234: 114-118, 24 Jan. 1946.


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Newhouser, L. R., and Kendrick, D. B.: Human Plasma and Serum: Development and Clinical Indications. U.S. Nav. M. Bull. 39: 506-514, October 1941.
    -, and -: Blood Substitutes, Their Development and Use in the Armed Services. U.S. Nav. M. Bull. 40: 1-13, January 1942.
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Strumia, M., Newhouser, L. R., Kendrick, D. B., and McGraw, J. J.: Development of Equipment for Administration of Dried Plasma in the Armed Forces. War Med. 2: 102-113, January 1942.