The Role of Membrane Glycoproteins in Platelet Formation, Circulation, and Senescence

Review and Hypotheses
  • James N. George

Abstract

Circulating blood platelets are required to form an immediate hemostatic plug at the site of a vascular endothelial gap. The properties of the platelet membrane glycoproteins related to the specific functions of adhesion and aggregation during this hemostatic reaction have been the focus of the preceding chapters of this book. This chapter will review current knowledge and hypotheses on the broader and less defined phenomena of platelet production from megakaryocytes and their appearance in the circulation, their lifespan and senescence, and finally their ultimate removal from the circulation. Each of these events seems to involve membrane contact phenomena that are unique to the platelet: (1) within the bone marrow the megakaryocyte occupies a special position adjacent to the sinusoidal wall; (2) platelets are released from fragmenting megakaryocyte cytoplasm either within the marrow sinuses or later within the pulmonary capillaries; (3) circulating platelets undergo reversible adhesion encounters during their lifespan, losing fragments of their surface membrane in the process; and (4) finally an unknown senescent change on the surface membrane signals the ultimate sequestration of the platelet. This entire process may be viewed as a sequence of reversible contact interactions among platelets as well as between platelets and the vessel wall resulting in surface glycoprotein changes and membrane fragmentation.

Keywords

Vortex Anemia Epinephrine Thrombocytopenia Thrombin 

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References

  1. Alderman, E. M., Fudenberg, H. H., and Lovins, R. E., 1981, Isolation and characterization of an agerelated antigen present on senescent human red blood cells. Blood 58:341–349.PubMedGoogle Scholar
  2. Ash, R. C., Detrick, R. A., and Zanjani, E. D., 1981a, Studies of human pluripotential hematopoietic stem cells (CFU-GEMM) in vitro. Blood 58:309–316.PubMedGoogle Scholar
  3. Ash, R. C., McEver, R. P., McGinnis, M., Lindquist, D., and Zanjani, E. D., 1981b, Growth of pure and mixed human megakaryocytic colonies identified by immunofluorescent labeling with monoclonal antibody, Tab, Blood 58:117a.Google Scholar
  4. Aster, R. H., 1966, Pooling of platelets in the spleen: Role in the pathogenesis of “hypersplenic” thrombo­cytopenia, J. Clin. Invest. 45:645–657.PubMedCrossRefGoogle Scholar
  5. Aster, R. H., and Jandl, J. H., 1964, Platelet sequestration in man. I. Methods, J. Clin. Invest. 43:843–855.PubMedCrossRefGoogle Scholar
  6. Baumgartner, H. R., and Muggli, R., 1976, Adhesion and aggregation: Morphological demonstration and quantitation in vivo and in vitro, in: Platelets in Biology and Pathology, Volume 1 (J. L. Gordon, ed.), Elsevier/North-Holland, Amsterdam, pp. 23–60.Google Scholar
  7. Behnke, O., 1968, An electron microscope study of the megakaryocyte of the rat bone marrow. I. The development of the demarcation membrane system and the platelet surface coat, J. Ultrastruct. Res. 24:412–433.PubMedCrossRefGoogle Scholar
  8. Bemdt, M. C., Gregory, C., Chong, B. H., Zola, H., and Castaldi, P. A., 1983, Additional glycoprotein defects in Bemard-Soulier syndrome: Confirmation of genetic basis by parental analysis. Blood 62:800–807.Google Scholar
  9. Bessis, M., 1973, Living Blood Cells and Their Ultrastructure, Springer-Verlag, New York.Google Scholar
  10. Blajchman, M. A., Senyi, A. F., Hirsh, J., Genton, E., and George, J. N., 1981, Hemostatic function, survival, and membrane glycoprotein changes in young versus old rabbit platelets, J. Clin. Invest. 68:1289–1294.PubMedCrossRefGoogle Scholar
  11. Buchanan, M. R., Carter, C. J., and Hirsh, J., 1979, Decreased platelet thrombogenicity in association with increased platelet turnover and vascular damage. Blood 54:1369–1375.PubMedGoogle Scholar
  12. Cartron, J.-P., Andreu, G., Cartron, J., Bird, G. W. G., Salmon, C., and Gerbal, A., 1978, Demonstration of T-transferase deficiency in Tn-polyagglutinable blood samples, Eur. J. Biochem. 92:111–119.PubMedCrossRefGoogle Scholar
  13. Charo, I. F., Feinman, R. D., and Detwiler, T. C., 1977, Interrelations of platelet aggregation and secretion, J. Clin. Invest. 60:866–873.PubMedCrossRefGoogle Scholar
  14. Cole, G. J., and Glaser, L., 1984, Inhibition of embryonic neural retinal cell-substratum adhesion with a monoclonal antibody, J. Biol. Chem. 259:4031–4034.PubMedGoogle Scholar
  15. Coller, B. S., and Zarrabi, M. H., 1981, Platelet membrane studies in the May-Hegglin anomaly. Blood 58:279–284.PubMedGoogle Scholar
  16. Coller, B. S., Kalomiris, E., Steinberg, M., and Scudder, L. E., 1984, Evidence that glycocaiicin circulates in normal plasma, J. Clin. Invest. 73:794–799.PubMedCrossRefGoogle Scholar
  17. Crosby, W. H., 1963, Hyposplenism: an inquiry into normal functions of the spleen, Anna. Rev. Med. 14:349–370.CrossRefGoogle Scholar
  18. Danielli, J. F., 1940, Capillary permeability and oedema in the perfused frog, J. Physiol. 98:109–129.PubMedGoogle Scholar
  19. Dodds, W. J., Raymond, S. L., and Pert, J. H., 1973, Isolated kidney perfusion: A model for testing platelet function, Proc. Soc. Exp. Biol. Med. 144:189–194.PubMedGoogle Scholar
  20. Evensen, S. A., Solum, N. O., Grottum, K. A., and Hovig, T., 1974, Familial bleeding disorder with a moderate thrombocytopenia and giant blood platelets, Scand. J. Haematol. 13:203–214.PubMedCrossRefGoogle Scholar
  21. Fedorko, M. E., and Lichtman, M. A., 1982, Megakaryocyte structure, maturation, and ecology, in: Hemostasis and Thrombosis (R. W. Colman, J. Hirsh, V. J. Marder, and E. W. Salzman, eds.), J. B. Lippincott, Philadelphia, pp. 210–224.Google Scholar
  22. Frojmovic, M. M., and Milton, J. G., 1982, Human platelet size, shape, and related functions in health and disease, Physiol. Rev. 62:185–261.PubMedGoogle Scholar
  23. George, J. N., 1978, Platelet behavior and aging in the circulation, in: The Blood Platelet in Transfusion Therapy (T. J. Greenwalt and G. A. Jamieson, eds.), Alan R. Liss, New York, pp. 39–64.Google Scholar
  24. George, J. N., and Lewis, P. C., 1978, Studies on platelet plasma membranes. III. Membrane glycoprotein loss from circulating platelets in rabbits: Inhibition by aspirin-dipyridamore and acceleration by thrombin, J. Lab. Clin. Med. 92:301–306.Google Scholar
  25. George, J. N., Lewis, P. C., and Sears, D. A., 1976, Studies on platelet plasma membranes. II. Charac­terization of surface proteins of rabbit platelets in vitro and during circulation in vivo using diazotized (1251). diiodosulfanilic acid as a label, J. Lab. Clin. Med. 88:247–260.PubMedGoogle Scholar
  26. George, J. N., Lyons, R. M., and Morgan, R. K., 1980a, Membrane changes associated with platelet activation, J. Clin. Invest. 66:1–9.CrossRefGoogle Scholar
  27. George, J. N., Lyons, R. M., and Morgan, R. K., 1980b, Membrane alterations caused by platelet aggregation and secretion, in: Platelets: Cellular Response Mechanisms and their Biological Significance (A. Rotman, F. A. Meyer, C. Gitler, and A. Silberberg, eds.), John Wiley and Sons, Ltd., Chichester, pp. 81–93.Google Scholar
  28. George, J. N., Thoi, L. L., and Morgan, R. K., 1981a, Quantitative analysis of platelet membrane glycoproteins: Effect of washing procedures and isolation of platelet density subpopulations, Thromb. Res. 23:69–77.CrossRefGoogle Scholar
  29. George, J. N., Reimann, T. A., Moake, J. L., Morgan, R. K., Cimo, P. L., and Sears, D. A., 1981b, Bemard-Soulier disease: A study of four patients and their parents, Br. J. Haematol. 48:459–467.CrossRefGoogle Scholar
  30. George, J. N., Thoi, L. L., McManus, L. M., and Reimann, T. A., 1982, Isolation of human platelet membrane microparticles from plasma and serum, Blood 60:834–840.PubMedGoogle Scholar
  31. George, J. N., Nurden, A. T., and Phillips, D. R., 1984, Molecular defects that cause abnormalities of platelet-vessel wall interactions, N. Engl. J. Med. 311:1084–1098.PubMedCrossRefGoogle Scholar
  32. Gimbrone, M. A., Aster, R. H., Cotran, R. S., Corkery, J., Jandl, J. H., and Folkman, J., 1969, Preservation of vascular integrity in organs perfused in vitro with a platelet-rich medium. Nature (London) 222:33–36.CrossRefGoogle Scholar
  33. Goldschmidt, B., Sarkadi, B., Gardos, G., and Matlary, A., 1974, Platelet production and survival in cyanotic congenital heart disease, Scand. J. Haematol. 13:110–115.PubMedCrossRefGoogle Scholar
  34. Hanson, S. R., and Harker, L. A., 1981, Survival of baboon platelets labeled with diazotized (125I)-iodosulfanilic acid: No effect of drugs that modify platelet behavior, Thromb. Res. 23:133–143.PubMedCrossRefGoogle Scholar
  35. Harker, L. A., and Finch, C. A., 1969, Thrombokinetics in man, J. Clin. Invest. 48:963–974.PubMedCrossRefGoogle Scholar
  36. Harker, L. A., Malpass, T. W., Branson, H. E., Hessel, E. A. II, and Slichter, S. J., 1980, Mechanism of abnormal bleeding in patients undergoing cardiopulmonary bypass: Acquired transient platelet dysfunction associated with selective a-granule release. Blood 56:824–834.PubMedGoogle Scholar
  37. Hellem, A. J., Borchgrevink, C. F., and Ames, S. B., 1961, The role of red cells in haemostasis: The relation between hematocrit, bleeding time, and platelet adhesiveness, Br. J. Haematol. 7:42–50.PubMedCrossRefGoogle Scholar
  38. Hillman, R. S., 1969, Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia, J. Clin. Invest. 48:443.PubMedCrossRefGoogle Scholar
  39. Hirsh, J., Glynn, M. F., and Mustard, J. F., 1968, The effect of platelet age on platelet adherence to collagen, J. Clin. Invest. 47:466–473.PubMedCrossRefGoogle Scholar
  40. Hoffman, R., Mazur, E., Bruno, E., and Floyd, V., 1981, Assay of an activity in the serum of patients with disorders of thrombopoiesis that stimulates formation of megakaryocytic colonies, N. Engl. J. Med. 305:533–538.PubMedCrossRefGoogle Scholar
  41. Hohnsen, H., and Dangelmaier, C. A., 1981, Evidence that the platelet plasma membrane is impermeable to calcium and magnesium complexes of A23187. A23187-induced secretion is inhibited by Mg2+ and Ca2+, and requires aggregation and active cyclooxygenase, J. Biol. Chem. 256:10449–10452.Google Scholar
  42. Jaffe, E. A., Hoyer, L. W., and Nachman, R. L., 1974, Synthesis of von Willebrand factor by cultured human endothelial cells, Proc. Natl Acad. Sci. U.S.A. 71:1906–1909.PubMedCrossRefGoogle Scholar
  43. Jaffe, E. A., Ruggiero, J. T., Leung, L. L. K., Doyle, M. J., McKeown-Longo, P. J., and Mosher, D. F., 1983, Cultured human fibroblasts synthesize and secrete thrombospondin and incorporate it into extra­cellular matrix, Proc. Natl. Acad. Sci. U.S.A. 80:998–1002.PubMedCrossRefGoogle Scholar
  44. Kallinikos-Maniatis, A., 1969, Megakaryocytes and platelets in central venous and arterial blood. Acta Haematol. 42:330–335.PubMedCrossRefGoogle Scholar
  45. Karpatkin, S., 1972, Platelet senescence, Annu. Rev. Med. 23:101–128.PubMedCrossRefGoogle Scholar
  46. Kaufman, R. M., Airo, R., Pollack, S., Crosby, W. H., and Dobemeck, R., 1965a, Origin of pulmonary megakaryocytes. Blood 25:767–775.Google Scholar
  47. Kaufman, R. M., Airo, R., Pollack, S., and Crosby, W. H., 1965b, Circulating megakaryocytes and platelet release in the lung, Blood 26:720–731.Google Scholar
  48. Kay, M. M. B., 1981, Isolation of the phagocytosis-inducing IgG-binding antigen on senescent somatic cells. Nature (London) 289:491–494.CrossRefGoogle Scholar
  49. Kelton, J. G., and Denomme, G., 1982, The quantitation of platelet-associated IgG on cohorts of platelets separated from healthy individuals by bouyant density centrifugation. Blood 60:136–139.PubMedGoogle Scholar
  50. Kinlough-Rathbone, R. L., Mustard, J. F., Perry, D. W., Dejana, E., Cazenave, J.-P., Packham, M. A., and Harfenist, E. J., 1983a, Factors influencing the deaggregation of human and rabbit platelets, Thromb. Haemostasis 49:162–167.Google Scholar
  51. Kinlough-Rathbone, R. L., Mustard, J. F., Packham, M. A., and Harfenist, E. F., 1983b, Factors influenc­ing the deaggregation of chymotrypsin-treated human platelets aggregated by fibrinogen, Thromb. Haemostasis 49:196–198. ,Google Scholar
  52. Kitchens, C. S., 1977, Amelioration of endothelial abnormalities by prednisone in experimental throm­bocytopenia in the rabbit, J. Clin. Invest. 60:1129–1134.PubMedCrossRefGoogle Scholar
  53. Levin, J., and Bessman, J. D., 1983, The inverse relation between platelet volume and platelet number. Abnormalities in hematologic disease and evidence that platelet size does not correlate with platelet age, J. Lab. Clin. Med. 101:295–307.PubMedGoogle Scholar
  54. Levine, S. P., and Krentz, L. S., 1977, Development of a radioimmunoassay for human platelet factor 4, Thromb. Res. 11:673–686.PubMedCrossRefGoogle Scholar
  55. Lichtman, M. A., Chamberlain, J. K., Simon, W., and Santillo, P. A., 1978, Parasinusoidal location of megakaryocytes in the marrow: A determinant of platelet release. Am. J. Hermatol. 4:303–312.CrossRefGoogle Scholar
  56. Luthra, M. G., Friedman, J. M., and Sears, D. A., 1979, Studies of density fractions of normal human erythrocytes labeled with iron-59 in vivo, J. Lab. Clin. Med. 94:879–895.Google Scholar
  57. Lutz, H. U., and Fehr, J., 1979, Total sialic content of glycophorins during senescence of human red blood cells, J. Biol. Chem. 254:11177–11180.PubMedGoogle Scholar
  58. Martin, J. F., Trowbridge, E. A., Salmon, G. L., and Salter, D. N., 1982, The relationship between platelet and megakaryocyte volumes, Thromb. Res. 28:447–459.PubMedCrossRefGoogle Scholar
  59. Martin, J. F., Shaw, T., Heggie, J., and Penington, D. G., 1983, Measurement of the density of human platelets and its relationship to volume, Br. J. Haematol. 54:337–352.PubMedCrossRefGoogle Scholar
  60. Massini, P., and Lüscher, E. F., 1971, The induction of the release reaction in human platelets by close cell contact, Thromb. Diath. Haemorrh. 25:13–20.PubMedGoogle Scholar
  61. Massini, P., Naf, U., and Lüscher, E. F., 1982, Clot retraction does not require calcium ions and depends on continuous contractile activity, Thromb. Res. 27:751–756.PubMedCrossRefGoogle Scholar
  62. Mazur, E., Hoffman, R., and Bruno, E., 1981, Regulation of human megakaryocytopoiesis, J. Clin. Invest. 68:733–741.PubMedCrossRefGoogle Scholar
  63. McEver, R. P., Baenziger, N. L., and Majerus, P. W., 1980, Isolation and quantitation of the platelet membrane glycoprotein deficient in thrombasthenia using a monoclonal hybridoma antibody, J. Clin. Invest. 66:1311–1318.PubMedCrossRefGoogle Scholar
  64. McEver, R. P., Bennett, E. M., and Martin, M. N., 1983, Identification of two structurally and functionally distinct sites on human platelet membrane glycoprotein Ilb-IIIa using monoclonal antibodies, 7. Biol. Chem. 258:5269–5275.Google Scholar
  65. Mezzano, D., Hwang, K., Catalano, P., and Aster, R. H., 1981, Evidence that platelet buoyant density, but not size, correlates with platelet age in man. Am. J. Hematol. 11:61–76.PubMedCrossRefGoogle Scholar
  66. Mollison, P. ,L., 1983, Blood Transfusion in Clinical Medicine, 7th ed., Blackwell, Oxford, pp. 468–473.Google Scholar
  67. Mosher, D. F., 1980, Fibronectin, Prog. Hemost. Thromb. 5:111–151.PubMedGoogle Scholar
  68. Mustard, J. F., Packham, M. A., Kinlough-Rathbone, R. L., Perry, D. W., and Regoeczi, E., 1978, Fibrinogen and ADP-induced platelet aggregation. Blood 52:453–466.PubMedGoogle Scholar
  69. Nachman, R. L., Levine, R. F., Jaffe, E. A., 1977, Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes, J. Clin. Invest. 60:914–921.PubMedCrossRefGoogle Scholar
  70. Nurden, A. T., Dupuis, D., Pidard, D., Kieffer, N., Kunicki, T. J., and Cartron, J. P., 1982, Surface modifications in the platelets of a patient with β-N-acetyl-D-galactosamine residues, the Tn syndrome, J. Clin. Invest. 70:1281–1291.PubMedCrossRefGoogle Scholar
  71. Nugent, D., Berglund, L., and Bernstein, L, 1984, Platelet senescence antigen recognized by human Imonoclonal autoantibody. Blood 64:89a.Google Scholar
  72. Paulus, J. M., 1975, Platelet size in man, Blood 46:321–336.PubMedGoogle Scholar
  73. Pederson, N. T., 1978, Occurrence of megakaryocytes in various vessels and their retention in the pulmonary capillaries in man, Scand. J. Haematol. 21:369–375.pCrossRefGoogle Scholar
  74. Policy, M. J., Leung, L. L. K., Clark, F. Y., and Nachman, R. L., 1981, Thrombin-induced platelet membrane glycoprotein lib and Ilia complex formation: An electron microscope study, J. Exp. Med. 154:1058–1068.CrossRefGoogle Scholar
  75. Quesenberry, P., and Levitt, L., 1979, Hematopoietic stem cells, N. Engl. J. Med. 301:755–760, 819, 868–872.PubMedCrossRefGoogle Scholar
  76. Rabellino, E. M., Levene, R. B., Leung, L. L. K., and Nachman, R. L., 1981, Human megakaryocytes. II. Expression of platelet proteins in early marrow megakaryocytes, J. Exp. Med. 154:88–100.PubMedCrossRefGoogle Scholar
  77. Rand, M. L., 1982, Studies of changes in rabbit platelets as they age in vivo, Ph.D. Thesis, University of Toronto.Google Scholar
  78. Rand, M. L., Packham, M. A., and Mustard, J. F., 1983, Survival of density subpopulations of rabbit: Use of 51Cr-or IIIIn-labeled platelets to measure survival of least dense and most dense platelets concurrently. Blood 61:362–367.PubMedGoogle Scholar
  79. Reimers, H. J., Kinlough-Rathbone, R. L., Cazenave, J. P., Senyi, A. F., Hirsh, J., Packham, M. A., and Mustard, J. F., 1976, In vitro and in vivo function of thrombin-treated platelets, Thrombos. Haemo. 35:151–166.Google Scholar
  80. Ryo, R., Nakeff, A., Huang, S. S., Ginsberg, M., and Deuel, T. F., 1983, New synthesis of a platelet specific protein: Platelet factor 4 synthesis in a megakaryocyte-enriched rabbit bone marrow culture system, J. Cell Biol. 96:515–520.PubMedCrossRefGoogle Scholar
  81. Savage, B., Kotze, H. F., Hanson, S. R., and Harker, L. A., 1983, Platelet density increases with platelet aging in baboons, Circulation 68(Suppl III):318a.Google Scholar
  82. Shaklai, M., and Tavassoli, M., 1978, Demarcation membrane system in the rat megakaryocyte and the mechanism of platelet formation: A membrane reorganization process, J. Ultrastruct. Res. 62:270–285.PubMedCrossRefGoogle Scholar
  83. Shepro, D., Sweetman, H. E., and Hechtman, H. B., 1980, Experimental thrombocytopenia and capillary ultrastructure, Blood 56:937–939.PubMedGoogle Scholar
  84. Shulman, N. R., Watkins, S. P., Jr., Itscoitz, S. B., and Students, A. B., 1968, Evidence that the spleen retains the youngest and most hemostatically effective platelets. Trans. Assoc. Am. Physicians 81:302–313.PubMedGoogle Scholar
  85. Solum, N. O., Olsen, T. M., Gogstad, G. O., Hägen, I., and Brosstad, F., 1983, Demonstration of a new glycoprotein Ib-related component in platelet extracts prepared in the presence of leupeptin, Biochim. Biophys. Acta 729:53–61.PubMedCrossRefGoogle Scholar
  86. Stenberg, P. E., Shuman, M. A., Levine, S. P., and Bainton, D. F., 1984, Redistribution of alpha-granules and their contents in thrombin-stimulated platelets, J. Cell Biol. 98:748–760.PubMedCrossRefGoogle Scholar
  87. Suda, T., Suda, J., and Ogawa, M., 1983, Single-cell origin of mouse hematopoietic colonies expressing multiple lineages in various combinations, Proc. Soc. Nad. Acad. Sci. U.S.A. 80:6689–6693.CrossRefGoogle Scholar
  88. Tabilio, A., Rosa, J. P., Testa, U., Kieffer, N., Nurden, A. T., Del Carizo, M. C., Breton-Gorius, J., and Vainchenker, W., 1984, Expression platelet membrane glycoproteins and a-granule proteins by a human erythroleukemia cell line (HEL), EMBO J. 3:453–459.PubMedGoogle Scholar
  89. Tavassoli, M., 1980, Megakaryocyte-platelet axis and the process of platelet formation and release, Blood 55:537–545.PubMedGoogle Scholar
  90. Tavassoli, M., and Aoki, M., 1981, Migration of entire megakaryocytes through the marrow-blood barrier, Br. J. Haematol. 48:25–29.PubMedCrossRefGoogle Scholar
  91. Thiagarajan, P., Shapiro, S. S., De Marco, L., Levine, E., and Yalcin, A., 1983, Monoclonal and polyclonal antibodies to human platelet membrane glycoprotein Ilia detect a related protein in human endothelial cells, Clin. Res. 31:485A.Google Scholar
  92. Thompson, C. B., Love, D. G., Quinn, P. G., and Valeri, C. R., 1983, Platelet size does not correlate with platelet age, Blood 62:487–494.PubMedGoogle Scholar
  93. Trowbridge, E. A., Martin, J. F., and Slater, D. N., 1982, Evidence for a theory of physical fragmentation of megakaryocytes, implying that all platelets are produced in the pulmonary circulation, Thromb. Res. 28:461–475.PubMedCrossRefGoogle Scholar
  94. Turitto, V. T., 1982, Blood viscosity, mass transport, and thrombogenesis. Prog. Hemost. Thromb. 6:139–177.PubMedGoogle Scholar
  95. Turitto, V. T., and Weiss, H. J., 1980, Red blood cells: Their dual role in thrombus formation. Science 207:541–543.PubMedCrossRefGoogle Scholar
  96. Tuszynski, G. P., Komecki, E., Ciemiewski, C., Knight, L. C., Koshy, A., Srivastava, S., Newiarowski, S., and Walsh, P. N., 1984, Association of fibrin with the platelet cytoskeleton, J. Biol. Chem. 259:5247–5254.PubMedGoogle Scholar
  97. Vainchenker, W., Guichard, J., Deschamps, J. F., Bouguet, J., Titeux, M., Chapman, J., McMichael, A. J., and Breton-Gorius, J., 1982, Megakaryocyte cultures in the chronic phase and in the blast crisis of chronic myeloid leukaemia: Studies on the differentiation of the megakaryocte progenitors and on the maturation of megakaryocytes in vitro, Br. J. Haematol. 51:131–146.CrossRefGoogle Scholar
  98. Van Oost, B. A., van Hien-Hagg, I., Timmermans, A. P. M., and Sixma, J. J., 1983, The effect of thrombin on the density distribution of blood platelets: Detection of activated platelets in the circulation, Blood 62:433–438.PubMedGoogle Scholar
  99. Van Oost, B. A., Timmermans, A. P. M., and Suxma, J. J., 1984, Evidence that platelet density depends on the a-granule content in platelets. Blood 63:482–485.PubMedGoogle Scholar
  100. Weiss, L., 1974, A scanning electron microscopic study of the spleen. Blood 43:665–691.PubMedGoogle Scholar
  101. Williams, N., and Levine, R. F., 1982, The origin, development and regulation of megakaryocytes, Br. J. Haematol 52:173–180.PubMedCrossRefGoogle Scholar
  102. Wright, H. P., 1942, Changes in the adhesiveness of blood platelets following parturition and surgical operations, J. Pathol. Bacteriol. 54:461–468.CrossRefGoogle Scholar
  103. Zucker-Franklin, D., and Petursson, S., 1984, Thrombocytopoiesis-analysis by membrane tracer and freeze-fracture studies on fresh human and cultured mouse megakaryocytes, J. Cell Biol. 99:390–402.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • James N. George
    • 1
  1. 1.Division of Hematology, Department of MedicineUniversity of Texas Health Science Center at San AntonioSan AntonioUSA

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