Circulation and Hemostatic Effectiveness of Platelets Stored at 4 C or 22 C : Studies in Aspirin-Treated Normal Volunteers C. R. VALERI From the Naval Blood Research Laboratory Chelsea, Massachuserrs
THE GOAL of platelet preservation is to provide circulating platelets that are hemostatically effective. Some believe that a parallel exists between platelet circulation and hemostatic effecti~eness.~.".~~ Others believe this relation is not absolute, since there are times when the viable platelets are incorporated into the cytoplasm of the endothelial cells lining the blood vessel^.^^.^^ The need to establish tests for measuring platelet function in vivo is critical. Harker and Slichter'O have reported a relationship between the number of platelets in the circulation and the bleeding time.I7 However, the platelet count and the bleeding time are not related in von Willebrand's disease, uremia, and idiopathic thrombocytopenic purpura. von Willebrand's disease and uremia are conditions in which there is functional impairment of the platelets with an adequate number of platelets. Dialysis of the uremic patient will restore platelet function, and the administration of a plasma component such as cryoprecipitate will restore platelet function in patients with von Willebrand's disease. The bleeding time in patients with idiopathic thrombocytopenic purpura (ITP) is not as prolonged as would be estimated from the platelet count, indicating that platelets in patients with ITP are he-
mostatically more effective than are normal platelets. Preservation procedures may activate the platelets, maintain normal platelet function, or produce a reversible platelet dysfunction. The donor platelets may not immediately reduce the bleeding time, but a reduction in bleeding time may occur after a period of circulation has restored platelet function. When a triple or quadruple plastic bag system is used for blood collection, the recovery in vivo of platelets isolated under sterile conditions and stored at 22 to 24 C (room temperature) for 24 hours is about 50 per cent; for platelets stored at 22 to 24 C for 48 hours it is about 40 per cent; and for platelets stored at 22 to 24 C for 72 hours it is about 30 per cent.'8~L9,20*21 The lifespan of platelets stored at 22 to 24 C for as long as 72 hours is normal, with linear lifespan of eight days and 5'Cr T-1/2 value of four days. Platelets that are irreversibly damaged during storage at 22 to 24 C for three days are removed during the first two-hour posttransfusion period. When platelet concentrates are stored at 4 C for 24 hours, recovery values in vivo are about 38 per cent, with reduced lifespan, 5LCrT-1/2 values of 1- 1/2 days, and exponential lifespan values of about three days. Investigators agree that storage at 4 C shortens the lifespan of platelets, whereas storage at 22 to 24 C does ~ot.3.4.19,20.21.26,27.30.31
This work was supported by the U.S. Navy. The opinions or assertions contained herein are those of the author, and are not to be construed as official or reflecting the views of the Navy Department or Naval Service at large.
Investigators disagree as to whether 4 C storage or 22 to 24 C storage will maintain platelet function better. In vitro measure-
20 Transfusion
Jan.-Fcb. 1976
Volume 16 Number I
Volume 16 Number I
PLATELET TRANSFUSIONS
ments of platelet function using platelet aggregation response to ADP, epinephrine, and collagen suggest that these functions are betBecker ter maintained at 4 C.5.7.13,14,15.L6.24.33 and Aster and their a s s ~ c i a t e s ~have .~+~ reported that, when stored at 4 C rather than 22 to 24 C for three days, platelets do a better job of reducing the bleeding time and increasing the platelet count in thrombocytopenic patients during the first fourhour posttransfusion period. Slichter and H a ~ k e r , on ~ ~the . ~ other ~ hand, report that platelets stored at 22 to 24 C for three days increased platelet counts and reduced bleeding time in thrombocytopenic patients better than did platelets stored at 4 C. Their data indicate that the function of these platelets is impaired during the first four-hour posttransfusion period in patients with aplastic anemia and thrombocytopenia. They report that although the number of platelets in the circulation during the first four hours after transfusion did not correlate with the bleeding time, it did 24 hours after transfusion. In our laboratory we have used a model to study the circulation and function of platelets in healthy volunteers treated with a ~ p i r i n . ' The ~ . ~ ~aspirin produces a thrombocytopathy manifested by an increase in bleeding time and an abnormal response of platelet aggregation in vitro to ADP, epinephrine, and collagen. The volunteers were given 650 mg of aspirin to provoke prolongation of bleeding time and to induce abnormal platelet aggregation patterns. These effects of the single dose of aspirin persist for at least 24 hours after aspirin ingestion. The platelets were administered so that the aspirin would be cleared from the blood and would not affect the transfused platelets. In some cases, the platelet concentrates were stored at 22 to 24 C for less than four hours (fresh platelet concentrates), in other cases they were stored at 22 to 24 C for 24 hours or 48 hours, and in others at 4 C for 24 hour^.^.^^
21
O'Brien22 has reported that when fresh platelets from donors not treated with aspirin were used to correct an aspirintreated platelet response to ADP in vitro, only about 10 per cent of the total number of platelets were required. In our study of the correction of an aspirin-induced thrombocytopathy by the transfusion of fresh and liquid-preserved platelets, we designed to have about 15 per cent of the platelets in the circulation to be from donors not treated with a ~ p i r i n . ' . ~Data . ~ ~ obtained by Handin and Valerig showed that when fresh platelet concentrates stored at 22 to 24 C for less than four hours were used, it took four units to correct the defect immediately after transfusion. When platelet concentrates stored at 22 to 24 C for 24 hours were used, it took about eight units, and when platelet concentrates were stored a t 22 to 24 C for 48 hours it took about 12 units to correct the prolonged bleeding time and to correct the platelet aggregation response within two to 24 hours after the transfusion. Our data have also shown that one unit of a platelet concentrate stored a t 4 C for 24 hours will correct an aspirin-induced thrombocytopathy in healthy volunteers within 24 hours after transfusion, whereas one unit of fresh platelet concentrate or one unit of a platelet concentrate stored at 22 C to 24 C for 24 hours will Becker and his a ~ s o c i a t e shave ~ * ~ reported similar results. Apparently, platelets are activated in some way during storage at 4 C, whereas after storage at 22 to 24 C the platelets require in vivo circulation to restore their hemostatic effecti~eness.~ Because of the poor understanding of the aspirin defect, there is some opposition to treating healthy volunteers with aspirin in order to study the function of preserved platelets. Previous data had suggested that aspirinated platelets have an irreversible defect which can be corrected by nonaspirinated platelets.9.22-28~31-32 However, Slichter and Harker27have suggested that the aspirin
22
VALERI
defect can be corrected in vivo after four hours of circulation in patients with aplastic anemia. Obviously, data obtained from studies of platelet viability and function in normal volunteers treated with aspirin cannot be applied directly to patients with thrombocytopenia. However, these data support the recommendation that patients with dilutional thrombocytopenia secondary to massive blood transfusion or with thrombocytopenia secondary to platelet destruction during extracorporeal circulation should be treated with platelets that have been stored at 4 C, whereas prophylactic treatment of thrombocytopenia produced by impaired platelet production may be better treated with platelets that have been stored a t 22 C. References I. 2.
3.
4.
5.
6.
7.
8. 9.
Allen, J. E., and C. R. Valeri: Prostaglandins in hematology. Arch. Int. Med. 13336, 1974. Aster, R. H., and G. A. Becker: Platelet preservation. In: Progress in Transfusion and Transplantation, P. J. Schmidt, Ed. Washington, D.C. American Association of Blood Banks, 1972, p. 35. -, G. A. Becker, M. Hamid, and D. N. Calvert: Storage of platelet concentrates at 4 C; use of refrigerated platelet concentrates in the treatment of hemorrhage in thrombocytopenic patients. In: Platelets-Production, Function, Transfusion, and Storage, M. G. Baldini and S. Ebbe, Eds. New York, Grune & Stratton, 1974, p, 361. Baldini, M., N. Costea, and W. Dameshek: The viability of stored human platelets. Blood 16:1669, 1960. Becker, G. A,, M. Tuccelli, T. Kunicki, M. K. Chalos, and R. H. Aster: Studies of platelet concentrates stored at 22 C and 4 C. Transfusion 13:61, 1973. -, T. Kunicki, and R. H. Aster: Effect of prostaglandin E, on harvesting of platelets from refrigerated whole blood. AABB 26th Annual Meeting, Bal Harbour, Fla., 1973. Caen, J., C. Cousin, H. Vainer, and H. Michel: Enzymatic activities, ADP-induced aggregation and survival in vivo as criteria of platelet viability during storage. Transfusion 7:143, 1967. Cronkite, E. P.: Measurement of the effectiveness of platelet transfusions. Transfusion 6:18, 1966. Handin, R. I., and C. R. Valeri: Hemostatic effec-
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22. 23.
24.
25.
Transfusion Jan.-Fcb. 1976
tiveness of platelets stored at 22 C. N. Engl. J. Med.285538, 1971. Harker, L. A., and S. J. Slichter: The bleeding time as a screening test for evaluation of platelet function. N. Engl. J. Med. 287:155, 1972. Jackson, D. P., D. K. Sorenson, E. P. Cronkite, V. P. Bond, and T. M. Fliedner: Effectiveness of transfusions of fresh and lyophilized platelets in controlling bleeding due to thrombocytopenia. J. Clin. Invest. 38:1689, 1959. Johnson, S. A,, D. L. VanHorn, H. J. Pederson, and J. Marr: The function of platelets: a review. Transfusion 6:3, 1966. Kattlove, H. E., and B. Alexander: The effect of cold on platelets. I. Cold induced platelet aggregation. Blood 38:39, 197 1. -, B. Alexander, and F. White: The effect of cold on platelets. 11. Platelet function after short-term storage at cold temperature. Blood 40:688, 1972. -: The effect of cold on platelets. 111. Adenine nucleotide metabolism after brief storage at cold temperature. Blood 42557, 1973. -: Platelet preservation-what temperature? A rationale for strategy. Transfusion 14:328, 1974. Mielke, C. H., Jr., M. M. Kaneshiro, 1. A. Maher, J. M. Weiner, and S . 1. Rapoport: The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 34:204, 1969. Murphy, S., and F. H. Gardner: Platelet preservation-effect of storage temperature on maintenance of platelet viability-deleterious effect of refrigerated storage. N. Engl. J. Med. 280:1094, 1969. -, S. N. Sayer, and F. H. Gardner: Storage of platelet concentrates at 22 C Blood 35549, 1970. -, and F. H. Gardner: Platelet storage at 22 C, metabolic, morphologic, and functional studies. J. Clin. Invest. 50:370, 1971. -: The storage of platelets for transfusion at 22 C. In: Platelets-Production, Function, Transfusion, and Storage, M. G. Baldini and S. Ebbe, Eds. New York, Grune & Stratton, 1974, p. 371. OBrien, J. R.: Effects of salicylates on human platelets. Lancet 1:779, 1968. Quick, A.: Salicylates and bleeding time: the aspirin tolerance test. Am. J. Med. Sci. 252:265, 1966. Shively, J. A., C. L. Gott, and D. S. deJongh: The effect of storage on adhesion and aggregation of platelets. Vox Sang. 18:204, 1970. Shulman, N. R.: Immunological considerations attending platelet transfusion. Transfusion 6:39, 1966.
Volume 16 Number I
PLATELET TRANSFUSIONS
26. Slichter, S. J., and L. A. Harker: Variables affecting the viability and function of stored platelets. AABB 26th Annual Meeting, Bal Harbour, Fla., 1973. 27. ~, and L. A. Harker: Preparation and storage of platelet concentrates. Seminar on Current Technical Topics-AABB, 1974, p. 87. 28. Stuart, M. J., S. Murphy, F. A. Oski, A. E. Evans, M. H. Donaldson, and F. H. Gardner: Platelet function in recipients of platelets from donors ingesting aspirin. N. Engl. J. Med. 287:1105, 1972. 29. Valeri, C. R., C. G. Zaroulis, J. C . Rogers, R. I. Handin, and L. D. Marchionni: Prostaglandins in the preparation of blood components. Science 175539, 1972. 30. -, H. Feingold, L. D. Marchionni, and J. C. Rogers: Hemostatic effectiveness of preserved human platelets. In: Erythrocytes, Thrombocytes, and Leukocytes: Recent Advances in
31.
32.
33.
34.
23
Membrane and Metabolic Research, E. Gerlach, K. Moser, E. Deutsch, and W. Wilmanns, Eds. Stuttgart, Georg Thieme Publishers, 1973, p. 312. -: Hemostatic effectiveness of liquid and previously frozen human platelets. N. Engl. J. Med. 290:353, 1974. Weiss, H. J., L. M. Aledort, and S. Kochwa: The effect of salicylates on the hemostatic properties of platelets in man. J. Clin. Invest. 47:2169, 1968. White, J. G.: Physicochemical dissection of platelet structural physiology. In: PlateletsProduction, Function, Transfusion, and Storage, M. G. Baldini and S. Ebbe, Eds. New York, Grune & Stratton, 1974, p. 235. Wojcik, J. D., D. L. VanHorn, A. J. Webber, and S. A. Johnson: Mechanism whereby platelets support the endothelium. Transfusion 9:324, 1969.
THE GOAL of platelet preservation is to provide circulating platelets that are hemostatically effective. Some believe that a parallel exists between platelet circulation and hemostatic effecti~eness.~.".~~ Others believe this relation is not absolute, since there are times when the viable platelets are incorporated into the cytoplasm of the endothelial cells lining the blood vessel^.^^.^^ The need to establish tests for measuring platelet function in vivo is critical. Harker and Slichter'O have reported a relationship between the number of platelets in the circulation and the bleeding time.I7 However, the platelet count and the bleeding time are not related in von Willebrand's disease, uremia, and idiopathic thrombocytopenic purpura. von Willebrand's disease and uremia are conditions in which there is functional impairment of the platelets with an adequate number of platelets. Dialysis of the uremic patient will restore platelet function, and the administration of a plasma component such as cryoprecipitate will restore platelet function in patients with von Willebrand's disease. The bleeding time in patients with idiopathic thrombocytopenic purpura (ITP) is not as prolonged as would be estimated from the platelet count, indicating that platelets in patients with ITP are he-
mostatically more effective than are normal platelets. Preservation procedures may activate the platelets, maintain normal platelet function, or produce a reversible platelet dysfunction. The donor platelets may not immediately reduce the bleeding time, but a reduction in bleeding time may occur after a period of circulation has restored platelet function. When a triple or quadruple plastic bag system is used for blood collection, the recovery in vivo of platelets isolated under sterile conditions and stored at 22 to 24 C (room temperature) for 24 hours is about 50 per cent; for platelets stored at 22 to 24 C for 48 hours it is about 40 per cent; and for platelets stored at 22 to 24 C for 72 hours it is about 30 per cent.'8~L9,20*21 The lifespan of platelets stored at 22 to 24 C for as long as 72 hours is normal, with linear lifespan of eight days and 5'Cr T-1/2 value of four days. Platelets that are irreversibly damaged during storage at 22 to 24 C for three days are removed during the first two-hour posttransfusion period. When platelet concentrates are stored at 4 C for 24 hours, recovery values in vivo are about 38 per cent, with reduced lifespan, 5LCrT-1/2 values of 1- 1/2 days, and exponential lifespan values of about three days. Investigators agree that storage at 4 C shortens the lifespan of platelets, whereas storage at 22 to 24 C does ~ot.3.4.19,20.21.26,27.30.31
This work was supported by the U.S. Navy. The opinions or assertions contained herein are those of the author, and are not to be construed as official or reflecting the views of the Navy Department or Naval Service at large.
Investigators disagree as to whether 4 C storage or 22 to 24 C storage will maintain platelet function better. In vitro measure-
20 Transfusion
Jan.-Fcb. 1976
Volume 16 Number I
Volume 16 Number I
PLATELET TRANSFUSIONS
ments of platelet function using platelet aggregation response to ADP, epinephrine, and collagen suggest that these functions are betBecker ter maintained at 4 C.5.7.13,14,15.L6.24.33 and Aster and their a s s ~ c i a t e s ~have .~+~ reported that, when stored at 4 C rather than 22 to 24 C for three days, platelets do a better job of reducing the bleeding time and increasing the platelet count in thrombocytopenic patients during the first fourhour posttransfusion period. Slichter and H a ~ k e r , on ~ ~the . ~ other ~ hand, report that platelets stored at 22 to 24 C for three days increased platelet counts and reduced bleeding time in thrombocytopenic patients better than did platelets stored at 4 C. Their data indicate that the function of these platelets is impaired during the first four-hour posttransfusion period in patients with aplastic anemia and thrombocytopenia. They report that although the number of platelets in the circulation during the first four hours after transfusion did not correlate with the bleeding time, it did 24 hours after transfusion. In our laboratory we have used a model to study the circulation and function of platelets in healthy volunteers treated with a ~ p i r i n . ' The ~ . ~ ~aspirin produces a thrombocytopathy manifested by an increase in bleeding time and an abnormal response of platelet aggregation in vitro to ADP, epinephrine, and collagen. The volunteers were given 650 mg of aspirin to provoke prolongation of bleeding time and to induce abnormal platelet aggregation patterns. These effects of the single dose of aspirin persist for at least 24 hours after aspirin ingestion. The platelets were administered so that the aspirin would be cleared from the blood and would not affect the transfused platelets. In some cases, the platelet concentrates were stored at 22 to 24 C for less than four hours (fresh platelet concentrates), in other cases they were stored at 22 to 24 C for 24 hours or 48 hours, and in others at 4 C for 24 hour^.^.^^
21
O'Brien22 has reported that when fresh platelets from donors not treated with aspirin were used to correct an aspirintreated platelet response to ADP in vitro, only about 10 per cent of the total number of platelets were required. In our study of the correction of an aspirin-induced thrombocytopathy by the transfusion of fresh and liquid-preserved platelets, we designed to have about 15 per cent of the platelets in the circulation to be from donors not treated with a ~ p i r i n . ' . ~Data . ~ ~ obtained by Handin and Valerig showed that when fresh platelet concentrates stored at 22 to 24 C for less than four hours were used, it took four units to correct the defect immediately after transfusion. When platelet concentrates stored at 22 to 24 C for 24 hours were used, it took about eight units, and when platelet concentrates were stored a t 22 to 24 C for 48 hours it took about 12 units to correct the prolonged bleeding time and to correct the platelet aggregation response within two to 24 hours after the transfusion. Our data have also shown that one unit of a platelet concentrate stored a t 4 C for 24 hours will correct an aspirin-induced thrombocytopathy in healthy volunteers within 24 hours after transfusion, whereas one unit of fresh platelet concentrate or one unit of a platelet concentrate stored at 22 C to 24 C for 24 hours will Becker and his a ~ s o c i a t e shave ~ * ~ reported similar results. Apparently, platelets are activated in some way during storage at 4 C, whereas after storage at 22 to 24 C the platelets require in vivo circulation to restore their hemostatic effecti~eness.~ Because of the poor understanding of the aspirin defect, there is some opposition to treating healthy volunteers with aspirin in order to study the function of preserved platelets. Previous data had suggested that aspirinated platelets have an irreversible defect which can be corrected by nonaspirinated platelets.9.22-28~31-32 However, Slichter and Harker27have suggested that the aspirin
22
VALERI
defect can be corrected in vivo after four hours of circulation in patients with aplastic anemia. Obviously, data obtained from studies of platelet viability and function in normal volunteers treated with aspirin cannot be applied directly to patients with thrombocytopenia. However, these data support the recommendation that patients with dilutional thrombocytopenia secondary to massive blood transfusion or with thrombocytopenia secondary to platelet destruction during extracorporeal circulation should be treated with platelets that have been stored at 4 C, whereas prophylactic treatment of thrombocytopenia produced by impaired platelet production may be better treated with platelets that have been stored a t 22 C. References I. 2.
3.
4.
5.
6.
7.
8. 9.
Allen, J. E., and C. R. Valeri: Prostaglandins in hematology. Arch. Int. Med. 13336, 1974. Aster, R. H., and G. A. Becker: Platelet preservation. In: Progress in Transfusion and Transplantation, P. J. Schmidt, Ed. Washington, D.C. American Association of Blood Banks, 1972, p. 35. -, G. A. Becker, M. Hamid, and D. N. Calvert: Storage of platelet concentrates at 4 C; use of refrigerated platelet concentrates in the treatment of hemorrhage in thrombocytopenic patients. In: Platelets-Production, Function, Transfusion, and Storage, M. G. Baldini and S. Ebbe, Eds. New York, Grune & Stratton, 1974, p, 361. Baldini, M., N. Costea, and W. Dameshek: The viability of stored human platelets. Blood 16:1669, 1960. Becker, G. A,, M. Tuccelli, T. Kunicki, M. K. Chalos, and R. H. Aster: Studies of platelet concentrates stored at 22 C and 4 C. Transfusion 13:61, 1973. -, T. Kunicki, and R. H. Aster: Effect of prostaglandin E, on harvesting of platelets from refrigerated whole blood. AABB 26th Annual Meeting, Bal Harbour, Fla., 1973. Caen, J., C. Cousin, H. Vainer, and H. Michel: Enzymatic activities, ADP-induced aggregation and survival in vivo as criteria of platelet viability during storage. Transfusion 7:143, 1967. Cronkite, E. P.: Measurement of the effectiveness of platelet transfusions. Transfusion 6:18, 1966. Handin, R. I., and C. R. Valeri: Hemostatic effec-
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22. 23.
24.
25.
Transfusion Jan.-Fcb. 1976
tiveness of platelets stored at 22 C. N. Engl. J. Med.285538, 1971. Harker, L. A., and S. J. Slichter: The bleeding time as a screening test for evaluation of platelet function. N. Engl. J. Med. 287:155, 1972. Jackson, D. P., D. K. Sorenson, E. P. Cronkite, V. P. Bond, and T. M. Fliedner: Effectiveness of transfusions of fresh and lyophilized platelets in controlling bleeding due to thrombocytopenia. J. Clin. Invest. 38:1689, 1959. Johnson, S. A,, D. L. VanHorn, H. J. Pederson, and J. Marr: The function of platelets: a review. Transfusion 6:3, 1966. Kattlove, H. E., and B. Alexander: The effect of cold on platelets. I. Cold induced platelet aggregation. Blood 38:39, 197 1. -, B. Alexander, and F. White: The effect of cold on platelets. 11. Platelet function after short-term storage at cold temperature. Blood 40:688, 1972. -: The effect of cold on platelets. 111. Adenine nucleotide metabolism after brief storage at cold temperature. Blood 42557, 1973. -: Platelet preservation-what temperature? A rationale for strategy. Transfusion 14:328, 1974. Mielke, C. H., Jr., M. M. Kaneshiro, 1. A. Maher, J. M. Weiner, and S . 1. Rapoport: The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 34:204, 1969. Murphy, S., and F. H. Gardner: Platelet preservation-effect of storage temperature on maintenance of platelet viability-deleterious effect of refrigerated storage. N. Engl. J. Med. 280:1094, 1969. -, S. N. Sayer, and F. H. Gardner: Storage of platelet concentrates at 22 C Blood 35549, 1970. -, and F. H. Gardner: Platelet storage at 22 C, metabolic, morphologic, and functional studies. J. Clin. Invest. 50:370, 1971. -: The storage of platelets for transfusion at 22 C. In: Platelets-Production, Function, Transfusion, and Storage, M. G. Baldini and S. Ebbe, Eds. New York, Grune & Stratton, 1974, p. 371. OBrien, J. R.: Effects of salicylates on human platelets. Lancet 1:779, 1968. Quick, A.: Salicylates and bleeding time: the aspirin tolerance test. Am. J. Med. Sci. 252:265, 1966. Shively, J. A., C. L. Gott, and D. S. deJongh: The effect of storage on adhesion and aggregation of platelets. Vox Sang. 18:204, 1970. Shulman, N. R.: Immunological considerations attending platelet transfusion. Transfusion 6:39, 1966.
Volume 16 Number I
PLATELET TRANSFUSIONS
26. Slichter, S. J., and L. A. Harker: Variables affecting the viability and function of stored platelets. AABB 26th Annual Meeting, Bal Harbour, Fla., 1973. 27. ~, and L. A. Harker: Preparation and storage of platelet concentrates. Seminar on Current Technical Topics-AABB, 1974, p. 87. 28. Stuart, M. J., S. Murphy, F. A. Oski, A. E. Evans, M. H. Donaldson, and F. H. Gardner: Platelet function in recipients of platelets from donors ingesting aspirin. N. Engl. J. Med. 287:1105, 1972. 29. Valeri, C. R., C. G. Zaroulis, J. C . Rogers, R. I. Handin, and L. D. Marchionni: Prostaglandins in the preparation of blood components. Science 175539, 1972. 30. -, H. Feingold, L. D. Marchionni, and J. C. Rogers: Hemostatic effectiveness of preserved human platelets. In: Erythrocytes, Thrombocytes, and Leukocytes: Recent Advances in
31.
32.
33.
34.
23
Membrane and Metabolic Research, E. Gerlach, K. Moser, E. Deutsch, and W. Wilmanns, Eds. Stuttgart, Georg Thieme Publishers, 1973, p. 312. -: Hemostatic effectiveness of liquid and previously frozen human platelets. N. Engl. J. Med. 290:353, 1974. Weiss, H. J., L. M. Aledort, and S. Kochwa: The effect of salicylates on the hemostatic properties of platelets in man. J. Clin. Invest. 47:2169, 1968. White, J. G.: Physicochemical dissection of platelet structural physiology. In: PlateletsProduction, Function, Transfusion, and Storage, M. G. Baldini and S. Ebbe, Eds. New York, Grune & Stratton, 1974, p. 235. Wojcik, J. D., D. L. VanHorn, A. J. Webber, and S. A. Johnson: Mechanism whereby platelets support the endothelium. Transfusion 9:324, 1969.
