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. 1978 Apr;61(4):1102–1106. doi: 10.1172/JCI109010

Thrombin generation and secretion of platelet Factor 4 during blood clotting.

M A Shuman, S P Levine
PMCID: PMC372628  PMID: 207723

Abstract

We have studied the platelet release reaction and thrombin generation during the spontaneous clotting of whole blood in vitro. Both thrombin formation and secretion of platelet Factor 4 were detected at least 12 min before clotting (clotting time, 22--26 min). Initially, at low thrombin concentrations (2--5 ng/ml), there is a small increase in plasma platelet Factor 4 (less than 1% of the amount present in serum). This is followed by a gradual increase in both platelet Factor 4 and thrombin concentrations over a 12 to 20-min interval. Finally, 5 min 5 before clotting, there is a rapid increase in both thrombin generation and platelet secretion. Thus, we have shown that the release of platelet Factor 4 is a prolonged reactoin and the extent to which it occurs parallel thrombin generation. It is only when thrombin concentrations are high (45--90) ng/ml)--during the period of clot formation--that the major part of platelet Factor 4 secretion occurs. Release of platelet Factor 4, like fibrin formation, occurs in the last step of in vitro coagulation.

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Selected References

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

  1. Broekman M. J., Handin R. I., Cohen P. Distribution of fibrinogen, and platelet factors 4 and XIII in subcellular fractions of human platelets. Br J Haematol. 1975 Sep;31(1):51–55. doi: 10.1111/j.1365-2141.1975.tb00831.x. [DOI] [PubMed] [Google Scholar]
  2. Da Prada M., Jakábová M., Lüscher E. F., Pletscher A., Richards J. G. Subcellular localization of the heparin-neutralizing factor in blood platelets. J Physiol. 1976 May;257(2):495–502. doi: 10.1113/jphysiol.1976.sp011380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davey M. G., Lüscher E. F. Actions of thrombin and other coagulant and proteolytic enzymes on blood platelets. Nature. 1967 Dec 2;216(5118):857–858. doi: 10.1038/216857a0. [DOI] [PubMed] [Google Scholar]
  4. Detwiler T. C., Feinman R. D. Kinetics of the thrombin-induced release of calcium (II) by platelets. Biochemistry. 1973 Jan 16;12(2):282–289. doi: 10.1021/bi00726a017. [DOI] [PubMed] [Google Scholar]
  5. Fenton J. W., 2nd, Fasco M. J., Stackrow A. B. Human thrombins. Production, evaluation, and properties of alpha-thrombin. J Biol Chem. 1977 Jun 10;252(11):3587–3598. [PubMed] [Google Scholar]
  6. Ganguly P. Binding of thrombin to human platelets. Nature. 1974 Feb 1;247(5439):306–307. doi: 10.1038/247306a0. [DOI] [PubMed] [Google Scholar]
  7. Holmsen H., Setkowsky C. A., Lages B., Day H. J., Weiss H. J., Scrutton M. C. Content and thrombin-induced release of acid hydrolases in gel-filtered platelets from patients with storage pool disease. Blood. 1975 Jul;46(1):131–142. [PubMed] [Google Scholar]
  8. Levine S. P., Krentz L. S. Development of a radioimmunoassay for human platelet factor 4. Thromb Res. 1977 Nov;11(5):673–686. doi: 10.1016/0049-3848(77)90025-1. [DOI] [PubMed] [Google Scholar]
  9. Levine S. P., Wohl H. Human platelet factor 4: Purification and characterization by affinity chromatography. Purification of human platelet factor 4. J Biol Chem. 1976 Jan 25;251(2):324–328. [PubMed] [Google Scholar]
  10. Marciniak E. Factor-Xa inactivation by antithrombin. 3. Evidence for biological stabilization of factor Xa by factor V-phospholipid complex. Br J Haematol. 1973 Mar;24(3):391–400. doi: 10.1111/j.1365-2141.1973.tb01662.x. [DOI] [PubMed] [Google Scholar]
  11. Marcus A. J. Recent advances in platelet lipid metabolism research. Ann N Y Acad Sci. 1972 Oct 27;201:102–108. doi: 10.1111/j.1749-6632.1972.tb16291.x. [DOI] [PubMed] [Google Scholar]
  12. Martin B. M., Wasiewski W. W., Fenton J. W., 2nd, Detwiler T. C. Equilibrium binding of thrombin to platelets. Biochemistry. 1976 Nov 2;15(22):4886–4893. doi: 10.1021/bi00667a021. [DOI] [PubMed] [Google Scholar]
  13. Miletich J. P., Jackson C. M., Majerus P. W. Interaction of coagulation factor Xa with human platelets. Proc Natl Acad Sci U S A. 1977 Sep;74(9):4033–4036. doi: 10.1073/pnas.74.9.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Osterud B., Rapaport S. I., Lavine K. K. Factor V activity of platelets: evidence for an activated factor V molecule and for a platelet activator. Blood. 1977 May;49(5):819–834. [PubMed] [Google Scholar]
  15. Shuman M. A., Majerus P. W. The measurement of thrombin in clotting blood by radioimmunoassay. J Clin Invest. 1976 Nov;58(5):1249–1258. doi: 10.1172/JCI108579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shuman M. A., Majerus P. W. The perturbation of thrombin binding to human platelets by anions. J Clin Invest. 1975 Oct;56(4):945–950. doi: 10.1172/JCI108174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shuman M. A., Tollefsen D. M., Majerus P. W. The binding of human and bovine thrombin to human platelets. Blood. 1976 Jan;47(1):43–54. [PubMed] [Google Scholar]
  18. Tollefsen D. M., Feagler J. R., Majerus P. W. The binding of thrombin to the surface of human platelets. J Biol Chem. 1974 Apr 25;249(8):2646–2651. [PubMed] [Google Scholar]
  19. Walsh P. N., Gagnatelli G. Platelet antiheparin activity: storage site and release mechanism. Blood. 1974 Aug;44(2):157–168. [PubMed] [Google Scholar]
  20. Yin E. T. Effect of heparin on the neutralization of factor Xa and thrombin by the plasma alpha-2-globulin inhibitor. Thromb Diath Haemorrh. 1975 Feb 28;33(1):43–50. [PubMed] [Google Scholar]

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