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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Jan 17;92(2):397–401. doi: 10.1073/pnas.92.2.397

Preservation of hemostatic and structural properties of rehydrated lyophilized platelets: potential for long-term storage of dried platelets for transfusion.

M S Read 1, R L Reddick 1, A P Bode 1, D A Bellinger 1, T C Nichols 1, K Taylor 1, S V Smith 1, D K McMahon 1, T R Griggs 1, K M Brinkhous 1
PMCID: PMC42747  PMID: 7831298

Abstract

Currently, therapeutic platelet concentrates can be stored for only 5 days. We have developed a procedure that permits long-term storage of fixed and lyophilized platelets that retain hemostatic properties after rehydration. These rehydrated lyophilized platelets (RL platelets) restore hemostasis in thrombocytopenic rats and become incorporated in the hemostatic plug of bleeding time wounds of normal dogs as well as von Willebrand disease dogs with partially replenished plasma von Willebrand factor. Ultrastructurally, these platelets are well preserved and are comparable to control normal washed platelets. Flow cytometry analysis shows that RL platelets react with antibodies to the major surface receptors, glycoprotein (GP)Ib and GPIIb/IIIa. These receptors are involved in platelet agglutination, aggregation, and adhesion. In vitro functional tests document the ability of RL platelets to adhere to denuded subendothelium and to spread on a foreign surface. Circulating RL platelets participated in carotid arterial thrombus formation induced in normal canine subjects. The participation of RL platelets in these vital hemostatic properties suggests that with further development they could become a stable platelet product for transfusion.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARNOLD P., DJERASSI I., FARBER S., FREEMAN G., KLEIN E., TOCH R. The preparation and clinical administration of lyophilized platelet material to children with acute leukemia and aplastic anemia. J Pediatr. 1956 Nov;49(5):517–522. doi: 10.1016/s0022-3476(56)80138-8. [DOI] [PubMed] [Google Scholar]
  2. Anderson N. A., Pamphilon D. H., Tandy N. J., Saunders J., Fraser I. D. Comparison of platelet-rich plasma collection using the Haemonetics PCS and Baxter Autopheresis C. Vox Sang. 1991;60(3):155–158. doi: 10.1111/j.1423-0410.1991.tb00892.x. [DOI] [PubMed] [Google Scholar]
  3. Bode A. P., Holme S., Heaton W. A., Swanson M. S. Extended storage of platelets in an artificial medium with the platelet activation inhibitors prostaglandin E1 and theophylline. Vox Sang. 1991;60(2):105–112. doi: 10.1111/j.1423-0410.1991.tb00882.x. [DOI] [PubMed] [Google Scholar]
  4. Bode A. P., Holme S., Heaton W. A., Swanson M. S. Sustained elevation of intracellular cyclic 3'-5' adenosine monophosphate is necessary for preservation of platelet integrity during long-term storage at 22 degrees C. Blood. 1994 Mar 1;83(5):1235–1243. [PubMed] [Google Scholar]
  5. Bode A. P., Knupp C. L., Miller D. T. Effect of platelet activation inhibitors on the loss of glycoprotein Ib during storage of platelet concentrates. J Lab Clin Med. 1990 Jun;115(6):669–679. [PubMed] [Google Scholar]
  6. Bode A. P., Norris H. T. The use of inhibitors of platelet activation or protease activity in platelet concentrates stored for transfusion. Blood Cells. 1992;18(3):361–382. [PubMed] [Google Scholar]
  7. Brinkhous K. M., Hedner U., Garris J. B., Diness V., Read M. S. Effect of recombinant factor VIIa on the hemostatic defect in dogs with hemophilia A, hemophilia B, and von Willebrand disease. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1382–1386. doi: 10.1073/pnas.86.4.1382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brinkhous K. M., Read M. S. Preservation of platelet receptors for platelet aggregating factor/von Willebrand factor by air drying, freezing, or lyophilization: new stable platelet preparations for von Willebrand factor assays. Thromb Res. 1978 Oct;13(4):591–597. doi: 10.1016/0049-3848(78)90148-2. [DOI] [PubMed] [Google Scholar]
  9. Buttrum S. M., Hatton R., Nash G. B. Selectin-mediated rolling of neutrophils on immobilized platelets. Blood. 1993 Aug 15;82(4):1165–1174. [PubMed] [Google Scholar]
  10. Cahill M. R., Macey M. G., Newland A. C. Fixation with formaldehyde induces expression of activation dependent platelet membrane glycoproteins, P selectin (CD62) and GP53 (CD63). Br J Haematol. 1993 Jul;84(3):527–529. doi: 10.1111/j.1365-2141.1993.tb03112.x. [DOI] [PubMed] [Google Scholar]
  11. Dardik R., Ruggeri Z. M., Savion N., Gitel S., Martinowitz U., Chu V., Varon D. Platelet aggregation on extracellular matrix: effect of a recombinant GPIb-binding fragment of von Willebrand factor. Thromb Haemost. 1993 Sep 1;70(3):522–526. [PubMed] [Google Scholar]
  12. Dascombe W. H., Hong C., Garrett K. O., White J. G., Lyle V. A., Miller J. L., Johnson P. C. Artificial microvascular graft thrombosis: the consequences of platelet membrane glycoprotein Ib inhibition and thrombin inhibition. Blood. 1993 Jul 1;82(1):126–134. [PubMed] [Google Scholar]
  13. Duguid J. K., Carr R., Jenkins J. A., Hutton J. L., Lucas G. F., Davies J. M. Clinical evaluation of the effects of storage time and irradiation on transfused platelets. Vox Sang. 1991;60(3):151–154. doi: 10.1111/j.1423-0410.1991.tb00891.x. [DOI] [PubMed] [Google Scholar]
  14. Eaton L. A., Jr, Read M. S., Brinkhous K. M. Glycoprotein Ib bioassays. Activity levels in Bernard-Soulier syndrome and in stored blood bank platelets. Arch Pathol Lab Med. 1991 May;115(5):488–493. [PubMed] [Google Scholar]
  15. FLIEDNER T. M., SORENSEN D. K., BOND V. P., CRONKITE E. P., JACKSON D. P., ADAMIK E. Comparative effectiveness of fresh and lyophilized platelets in controlling irradiation hemorrhage in the rat. Proc Soc Exp Biol Med. 1958 Dec;99(3):731–733. doi: 10.3181/00379727-99-24481. [DOI] [PubMed] [Google Scholar]
  16. Farrell D. H., Thiagarajan P., Chung D. W., Davie E. W. Role of fibrinogen alpha and gamma chain sites in platelet aggregation. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10729–10732. doi: 10.1073/pnas.89.22.10729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fijnheer R., Veldman H. A., van den Eertwegh A. J., Gouwerok C. W., Homburg C. H., Boomgaard M. N., de Korte D., Roos D. In vitro evaluation of buffy-coat-derived platelet concentrates stored in a synthetic medium. Vox Sang. 1991;60(1):16–22. doi: 10.1111/j.1423-0410.1991.tb00865.x. [DOI] [PubMed] [Google Scholar]
  18. Fox J. E., Phillips D. R. Polymerization and organization of actin filaments within platelets. Semin Hematol. 1983 Oct;20(4):243–260. [PubMed] [Google Scholar]
  19. George J. N. Changes in platelet membrane glycoproteins during blood bank storage. Blood Cells. 1992;18(3):501–515. [PubMed] [Google Scholar]
  20. Ginsberg M. H., Xiaoping D., O'Toole T. E., Loftus J. C., Plow E. F. Platelet integrins. Thromb Haemost. 1993 Jul 1;70(1):87–93. [PubMed] [Google Scholar]
  21. Goodrich R. P., Sowemimo-Coker S. O., Zerez C. R., Tanaka K. R. Preservation of metabolic activity in lyophilized human erythrocytes. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):967–971. doi: 10.1073/pnas.89.3.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Griggs T. R., Potter J. S., McClanahan S. B., Webster W. P., Brinkhous K. M. Macromolecular factor VIII complex: functional and structural heterogeneity observed in von Willebrand swine with transfusion. Proc Natl Acad Sci U S A. 1977 Feb;74(2):759–763. doi: 10.1073/pnas.74.2.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hamaguchi M., Bunce L. A., Sporn L. A., Francis C. W. Spreading of platelets on fibrin is mediated by the amino terminus of the beta chain including peptide beta 15-42. Blood. 1993 May 1;81(9):2348–2356. [PubMed] [Google Scholar]
  24. JACKSON D. P., SORENSEN D. K., CRONKITE E. P., BOND V. P., FLIEDNER T. M. Effectiveness of transfusions of fresh and lyophilized platelets in controlling bleeding due to thrombocytopenia. J Clin Invest. 1959 Oct;38:1689–1697. doi: 10.1172/JCI103947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. LANGDELL R. D., WAGNER R. H., BRINKHOUS K. M. Effect of antihemophilic factor on one-stage clotting tests; a presumptive test for hemophilia and a simple one-stage antihemophilic factor assy procedure. J Lab Clin Med. 1953 Apr;41(4):637–647. [PubMed] [Google Scholar]
  26. Lüscher E. F., Weber S. The formation of the haemostatic plug--a special case of platelet aggregation. An experiment and a survey of the literature. Thromb Haemost. 1993 Aug 2;70(2):234–237. [PubMed] [Google Scholar]
  27. Mann K. G., Nesheim M. E., Church W. R., Haley P., Krishnaswamy S. Surface-dependent reactions of the vitamin K-dependent enzyme complexes. Blood. 1990 Jul 1;76(1):1–16. [PubMed] [Google Scholar]
  28. Melaragno A. J., Carciero R., Feingold H., Talarico L., Weintraub L., Valeri C. R. Cryopreservation of human platelets using 6% dimethyl sulfoxide and storage at -80 degrees C. Effects of 2 years of frozen storage at -80 degrees C and transportation in dry ice. Vox Sang. 1985;49(4):245–258. doi: 10.1111/j.1423-0410.1985.tb01119.x. [DOI] [PubMed] [Google Scholar]
  29. Molino M., Di Lallo M., Martelli N., de Gaetano G., Cerletti C. Effects of leukocyte-derived cathepsin G on platelet membrane glycoprotein Ib-IX and IIb-IIIa complexes: a comparison with thrombin. Blood. 1993 Oct 15;82(8):2442–2451. [PubMed] [Google Scholar]
  30. Murphy S., Kagen L., Holme S., Gottlieb B., Heaton W., Grode G., Davisson W., Buchholz D. Platelet storage in synthetic media lacking glucose and bicarbonate. Transfusion. 1991 Jan;31(1):16–20. doi: 10.1046/j.1537-2995.1991.31191096178.x. [DOI] [PubMed] [Google Scholar]
  31. Murphy S., Rebulla P., Bertolini F., Holme S., Moroff G., Snyder E., Stromberg R. In vitro assessment of the quality of stored platelet concentrates. The BEST (Biomedical Excellence for Safer Transfusion) Task Force of the International Society of Blood Transfusion. Transfus Med Rev. 1994 Jan;8(1):29–36. doi: 10.1016/s0887-7963(94)70095-x. [DOI] [PubMed] [Google Scholar]
  32. Nichols T. C., Bellinger D. A., Johnson T. A., Lamb M. A., Griggs T. R. von Willebrand's disease prevents occlusive thrombosis in stenosed and injured porcine coronary arteries. Circ Res. 1986 Jul;59(1):15–26. doi: 10.1161/01.res.59.1.15. [DOI] [PubMed] [Google Scholar]
  33. Nichols T. C., Bellinger D. A., Reddick R. L., Smith S. V., Koch G. G., Davis K., Sigman J., Brinkhous K. M., Griggs T. R., Read M. S. The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A. Blood. 1993 May 15;81(10):2644–2651. [PubMed] [Google Scholar]
  34. Plow E. F., D'Souza S. E., Ginsberg M. H. Ligand binding to GPIIb-IIIa: a status report. Semin Thromb Hemost. 1992;18(3):324–332. doi: 10.1055/s-2007-1002571. [DOI] [PubMed] [Google Scholar]
  35. Read M. S., Potter J. Y., Brinkhous K. M. Venom coagglutinin for detection of von Willebrand factor activity in animal plasmas. J Lab Clin Med. 1983 Jan;101(1):74–82. [PubMed] [Google Scholar]
  36. Read M. S., Smith S. V., Lamb M. A., Brinkhous K. M. Role of botrocetin in platelet agglutination: formation of an activated complex of botrocetin and von Willebrand factor. Blood. 1989 Aug 15;74(3):1031–1035. [PubMed] [Google Scholar]
  37. Reddick R. L., Griggs T. R., Lamb M. A., Brinkhous K. M. Platelet adhesion to damaged coronary arteries: Comparison in normal and von Willebrand disease swine. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5076–5079. doi: 10.1073/pnas.79.16.5076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rock G., White J., Labow R. Storage of platelets in balanced salt solutions: a simple platelet storage medium. Transfusion. 1991 Jan;31(1):21–25. doi: 10.1046/j.1537-2995.1991.31191096179.x. [DOI] [PubMed] [Google Scholar]
  39. Saelman E. U., Nieuwenhuis H. K., Hese K. M., de Groot P. G., Heijnen H. F., Sage E. H., Williams S., McKeown L., Gralnick H. R., Sixma J. J. Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin). Blood. 1994 Mar 1;83(5):1244–1250. [PubMed] [Google Scholar]
  40. Sanders W. E., Read M. S., Reddick R. L., Garris J. B., Brinkhous K. M. Thrombotic thrombocytopenia with von Willebrand factor deficiency induced by botrocetin. An animal model. Lab Invest. 1988 Oct;59(4):443–452. [PubMed] [Google Scholar]
  41. Savage B., Ruggeri Z. M. Selective recognition of adhesive sites in surface-bound fibrinogen by glycoprotein IIb-IIIa on nonactivated platelets. J Biol Chem. 1991 Jun 15;266(17):11227–11233. [PubMed] [Google Scholar]
  42. Shattil S. J. Regulation of platelet anchorage and signaling by integrin alpha IIb beta 3. Thromb Haemost. 1993 Jul 1;70(1):224–228. [PubMed] [Google Scholar]
  43. Smyth S. S., Joneckis C. C., Parise L. V. Regulation of vascular integrins. Blood. 1993 Jun 1;81(11):2827–2843. [PubMed] [Google Scholar]
  44. White J. G., Escolar G. Induction of receptor clustering, patching, and capping on surface-activated platelets. Lab Invest. 1990 Sep;63(3):332–340. [PubMed] [Google Scholar]

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