Utilization of and Its Products*

ROBERT D. LANGDELL, M.D.

Professor of Pathology, School of Medicine, University of North Carolina, Chapel Hill

The development of a system of plastic bags for transfusion purposes for 21 days when stored connected by integral tubing for the collection, under standard conditions. The obvious advantage processing and storage of blood has made it pos­ of transfusing is that the sible for selective transfusion of appropriate blood circulating erythrocyte mass of the recipient can components. It is now possible to select the blood be increased without increasing the circulating component that will correct a patient's physiologic volume. This minimizes the possibility of deficiency. This has resulted in better patient care circulatory overload. It has been estimated that up and in better utilization of blood since a single to 80 percent of the transfusions should be in the unit of blood can be used to supply erythrocytes for form of packed red blood cells (2). an anemic patient, for a patient with Along with the plasma, most of the sodium thrombocytopenia and factor VIII concentrate for added in the solution is removed. This a patient with hemophilia. can be an important factor when transfusions are In order to utilize blood and its components necessary in patients requiring limited sodium in­ optimally, there must be a close working arrange­ take. In addition to the excessive amounts of elec­ ment between the personnel and the trolytes and , the plasma contains anti­ clinical staff. At the time when blood is obtained bodies. One of the dangers in the universal donor from a donor, a decision should be made con­ concept is that the plasma of group O individuals cerning how the blood will be used. Several of contains against group A and group B the components can be prepared only from fresh cells. These antibodies are removed along with blood. The equipment, supplies and personnel time the plasma. Although type specific compatible should be used to produce the maximum benefit erythrocytes are the treatment of choice, in an to the recipients of the blood. Although each unit emergency situation when such blood is not avail­ of blood could be separated into several useful com­ able, group O packed red blood cells are an ac­ ponents, it is a wasteful procedure if the com­ ceptable form of therapy. ponents are not used. Each institution must deter­ Factor VIII Concentrates. The treatment of mine its need for blood and blood components. hemophilia with plasma rather than Those responsible for the operation of the blood was an early form of component therapy. It was bank should not make unilateral decisions about found that plasma contains the material lacking in the preparation of blood components and the hemophilia and except for the occasional patient clinical staff should not make unilateral decisions with , whole blood is seldom needed for about the use of blood components. the treatment of hemophilia. Although the anti­ Packed Red Blood Cells. When blood is col­ hemophilic factor in plasma is relatively labile, it lected in the proper closed bag system, it is possible can be maintained in plasma stored below -18 °C. to remove much of the plasma after sedimentation Until relatively recently, plasma removed from or centrifugation without opening the container. whole blood within a few hours of collection and The resulting packed red blood cells remain viable then promptly frozen was the only available source of factor VIII for human use. Because of the rela­ ,:, Presented by Dr. Langdell at the 44th Annual Mc­ Guire Lecture Series, March 23, 1973, at the Medical Col­ tively small amount of antihemophilic activity in lege of Virginia, Richmond. plasma, large amounts of fluid had to be infused

298 MCV QUARTERLY 9(4): 298-300, 1973 LANGDELL: UTILIZATION OF BLOOD 299 to significantly increase the circulating level in the as rich plasma. It is usually necessary, patient. In addition, the infused activity was re­ however, to give the platelets recovered from six tained in the circulation for only a short period units of blood to achieve the desired effects and it of time (4). Thus, therapy was restricted to the is normally not desirable to give this amount of amount of fluid that could be infused without caus­ fluid. The usual practice is to concentrate the ing overload. platelets by centrifugation and remove all but ap­ In 1965, Pool and her associates (5) reported proximately 30 ml of plasma. Following centrifuga­ that when frozen plasma was thawed slowly, a tion, it may be difficult to resuspend the platelets. poorly soluble, gelatinous precipitate was formed. Gentle agitation after storage for about one hour This material, called , was found to has been found to result in a satisfactory product. contain a considerable amount of the antihemo­ It is generally recommended that platelets be in­ philic activity of plasma. Thus, it became possible fused through a filter to remove any large to concentrate and collect factor VIII of plasma aggregates. in a closed bag system. The resulting material con­ . One of the limitations of ob­ tains, on the average, about half of the antihemo­ taining blood is that approximately six-to-eight philic activity of the original plasma and in a weeks are required for the regeneration of eryth­ relatively small volume. rocytes. For this reason, the interval between in­ Although the treated plasma can be returned dividual donations of blood should be at least eight to the cellular component and used as whole blood, weeks. The regeneration of the fluid volume and most have found it better to utilize the plasma for plasma is more rapid. With a series of other purposes. The residual plasma can be used bags connected by integral tubing, it is possible to for all conditions where plasma is indicated other withdraw blood from a donor, separate the eryth­ than for the treatment of hemophilia. rocytes from the platelet rich plasma and return Platelet Concentrates. Fresh whole blood con­ the erythrocytes to the donor. This process, called tains viable platelets which will function when plasmapheresis, can be repeated at frequent intervals transfused. When platelets are needed to control without danger to the donor. bleeding in a patient with thrombocytopenia, how­ This technique has several advantages when ever, a large amount of blood must be infused to the needs for platelets and plasma are great. A increase the platelet level in the circulation. Platelets relatively small number of donors can supply con­ can be separated from whole blood and transfused siderable amounts of platelets and plasma. There in a relatively small volume. is increasing evidence that when platelets are given Platelets have a specific gravity of 1.040 while over a prolonged period, antibodies to platelets the specific gravity of erythrocytes is about 1.095 develop in the multitransfused patient. These anti­ (3). Since platelets are lighter than erythrocytes, bodies appear to be directed against the histo­ the red blood cells can be sedimented by low speed compatibility of the HL-A system. Those centrifugation while the platelets remain suspended institutions which use platelet transfusions on a in plasma. In this way platelets can be separated long-term basis have found that best platelet sur­ from whole blood in a closed bag system. Platelets, vival occurs when there is an HL-A compatibility however, have a very short shelf life and to be between donor and recipient. It is generally felt effective must be infused promptly after collection. that if a series of platelet transfusions are required, Although platelets lose viability rapidly, approxi­ it is best to obtain platelets by plasmapheresis from mately half of the recovered platelets are still effec­ a few histocompatible donors rather than utilizing tive after 72 hours of storage. Most workers, though, platelets from a number of random blood donors feel that platelets should be used within the first (7). 48 hours after collection. Although there is some Frozen Red Blood Cells. With currently avail­ evidence that room temperature storage has some able techniques, erythrocytes retain sufficient via­ advantages, it is felt that best results are obtained bility for transfusion purposes for only 21 days. when platelets are stored at 4 °C. Additional studies For this reason blood supplies must be continuous of storage are necessary to determine optimal and the blood bank must be able to predict its conditions ( 1). needs so that sufficient blood will be available and Platelets can be given along with the plasma yet there will not be wastage due to excessive 300 LANGDELL: UTILIZATION OF BLOOD amounts of erythrocytes lost by out-date. An ob­ are techniques by which most of the leukocytes can vious solution would be to develop a method of be separated from erythrocytes but these techniques preservation of blood for longer periods. are tedious and time consuming. In order to remove A number of chemical additives have been the leukocytes and their antigens it is necessary used in an attempt to prolong the viability of that fresh blood be used. In those institutions that erythrocytes. The most promising has been adenine have a frozen blood program, it has been found (6). With the addition of adenine at the time of that this preparation is an excellent source of collection, there is evidence that erythrocytes re­ leukocyte-poor erythrocytes. main viable up to 40 days under the usual storage Summary. At the present time there are a conditions. At the present time, however, there is number of blood components that are more suitable not sufficient evidence to be certain of the safety for transfusion purposes than is whole blood. In of this material for human use. order to make maximum use of blood, it is neces­ Other workers have demonstrated that eryth­ sary that there be close cooperation between the rocytes suspended in cryoprotective solutions retain blood bank personnel and those responsible for viability almost indefinitely when stored at low patient care. temperatures. Before the erythrocytes can be in­ fused, the cryoprotective materials must be removed. The supplies and equipment necessary for prepara­ REFERENCES tion, storage and washing make this technique rather expensive. Although the techniques are practical, 1. ASTER, R. H . AND BECKER, G. A. Platelet preservation. the cost for a unit of such blood is almost pro­ In: Transfusion and Transplantation, ed. P . S. Schmidt, Am. Assoc. of Blood Banks, 1972, p. 35. hibitive for routine use. If methods can be de­ veloped to decrease the cost, there are many ad­ 2. GREENWALT, T. J. AND PERRY, s. Preservation and utili­ vantages to such a technique. zation of the components of human blood. In: Hema­ Leukocyte-Poor Blood. There are many known tology, Vol. VI, eds. E. B. Brown and C. V. Moore antigens associated with erythrocytes, but most of (Grune & Stratton, New York, 1969), p. 148. these are only occasionally of clinical significance. 3. HUESTIS, D. w., BOVE, J. R. AND BUSCH, S. Practical For practical purposes, it is only necessary to . (Little Brown & Co. Boston, 1969), routinely test for ABO and Rh antigens. In a p. 300. similar way there are a number of antigens as­ sociated with leukocytes, but these are usually of 4. LANGDELL, R. D., WAGNER, R. H. AND Bil.INKHOUS, K. M. little clinical significance. In multitransfused pa­ Antihemophilic factor (AHF) levels following transfu­ tients, however, the leukocytes may cause reactions. sion of blood, plasma and plasma fractions. Proc. Soc. To prevent these reactions it may be necessary to Expt. Biol. Med. 88:212, 1955. give leukocyte-poor blood. Recently it has been 5. PooL, J. G . AND SHANNON, A. E. Production of high­ recognized that leukocyte antigens may have an potency concentrates of antihemophilic in a adverse effect on organ transplantation. It has been closed-bag system. N . Engl. ! . Med. 273 : 1443, 1965. suggested that patients with chronic renal disease who may be candidates for renal transplantation 6. SIMON, E. R., CHAPMAN, R. G. AND FINCH, C. A. Adenine should be given only leukocyte-poor blood. in red cell preservation. /. Clin. Invest. 41 :351, 1962. The specific gravity of is 1.087- 1.092 and the specific gravity of lymphocytes is 7. YANKEE , R. A., GRUMET, F . C. AND ROGENTINE, G. N . The selection of compatible platelet donors for refractory 1.070 ( 3). Thus differential centrifugation to prepare patients by lymphocyte HL-A typing. N. Engl. !. Med. leukocyte-poor erythrocytes is rather difficult. There 281 : 1208, 1969.