Platelet Factor-4 Properties and Clinical Significance

  • M. B. Donati
  • M. Palester-Chlebowczyk
  • G. de Gaetano
  • J. Vermylen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 28)


In 1948, Conley and coworkers (2) observed that patients with thrombocytopenia had an increased sensitivity to heparin and suggested that platelets could counteract the anticoagulant effect of heparin. This observation was subsequently confirmed by other workers, who demonstrated that platelets contain a heparin-neutralizing substance (21, 42) referred to as Platelet Factor-4 (PF-4) (10); in 1957, Deutsch and coworkers (11) provided evidence that PF-4 is a real platelet and not a plasma factor adsorbed on the platelet surface. This factor was also shown to be different from the platelet thromboplastic factor (platelet factor-3) (43). Little is known, however, about the mechanism by which heparin is neutralized by platelets. The existence of weak “heparin-platelet” complexes has been suggested (31, 38), but direct evidence for such complexes still is lacking. Antiheparin activity of platelets was shown to be easily extracted from platelet homogenates with saline or buffer and to be insoluble in lipid solvents (11, 43).


Platelet Aggregation Idiopathic Thrombocytopenic Purpura Platelet Factor Release Reaction Aspirin Ingestion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Brown J. H., Mackey H. K., Riggilo D. A., A novel in vitro assay for antiinflammatory agents based on stabilization of erythrocytes. Proc. Soc. Exptl. Biol. Med., 125, 837, 1967.Google Scholar
  2. 2.
    Cowley C. L., Hartmann R. C., Lalley J. S., The relationship of heparin activity to platelet concentration Proc. Soc. Exptl. Biol. Med., 69, 284, 1948.Google Scholar
  3. 3.
    Day H. J., Stormorken K., Holmsen H., Subcellular localization of platelet factor 3 and platelet factor 4. Abstracts XII Congress Intern. Soc. Hemat., New York p. 172, 19Google Scholar
  4. 4.
    De Gaetano G., Discussion in: Acta Med. Scand., 1971, suppl. 525, p. 121.Google Scholar
  5. 5.
    De Gaetano G., Vermylen J., Verstraete M., Platelet aggregation by a specific human immunoglobulin preparation. Thromb. Diatli. haemorrh., 24, 419, 1970Google Scholar
  6. 6.
    De Gaetano G., Vermylen J., Verstraete M., Platelet aggregation by Thrombofax. Acta Univ. Carolinae Med., 1972, in press.Google Scholar
  7. 7.
    De Gaetano G., Vermylen J., Verstraete M., Platelet factor 3, I. Properties and clinical significance. This volume.Google Scholar
  8. 8.
    Deutsch E., Kain W. Studies on platelet factor 4, In: Henry Ford Hospital Intern. Symposium “Blood Platelets” 1960, p. 337.Google Scholar
  9. 9.
    Deutsch E., Lechner K., Platelet clotting factors. In “Biochemistry of Blood Platelets” edit, by Kowalski E. and Niewarowski S. Academic Press, London and New York, 1967, p. 23Google Scholar
  10. 10.
    Deutsch E., Johnson S. A., Seegers VI. H., Differentiation of certain platelet factors related to blood coagulation. Circ. Res., 3, 110, 1955.PubMedGoogle Scholar
  11. 11.
    Deutsch E., Wawersicii E., Franks G., Uber das Vorkommen eines Antiheparinfaktors in Thrombozyten und Geweben. I. Mitteilung Antiheparinaktivität der Thrombozyten. Thromb. Diath. haemorrh., 1, 3, 1957.Google Scholar
  12. 12.
    Donati M. B., Pales Terchlebowczyk M., De Gaetaito G., Vermylen J., Platelet factor 4. II. Methods of study This volume.Google Scholar
  13. 13.
    Eiber H. B., Danishefsky I., Heparin in blood. Proc. Soc. Exptl. Biol. Med., 94, 801, 1957.Google Scholar
  14. 14.
    Farbiszewski R., Lipinski B., Niewiarowski S., Poplawski A., Hypercoagulability and thrombocytopenia after platelet factor 4 infusion into rabbits. Experientia, 24, 578, 1968.PubMedCrossRefGoogle Scholar
  15. 15.
    Farbiszewski R., Loewiarowski S., Worowski K., Lipinski B., Release of platelet factor 4 in vivo during intravascular coagulation and in thrombotic states. Thromb. Diath. haemorrh., 19, 578, 1968.PubMedGoogle Scholar
  16. 16.
    Harada K., Zucker M. B., Simultaneous development of platelet factor 4 activity and release of 14c-serotonin. Thromb. Diath. haemorrh., 25, 41, 1971PubMedGoogle Scholar
  17. 17.
    Holger-Madseit T., Reduction of heparin activity by plasma globulin in patients with increasing heparin resistance. Acta heamat., 27, 157, 1962.CrossRefGoogle Scholar
  18. 18.
    Holmsm H., Day H. J., Storkmorken H., The platelet release reaction. Scand. J. Haemat., suppl. 8, 1969.Google Scholar
  19. 19.
    Jaques L. B., Momhouse F. C., Stewart M. A method for determination of heparin blood. J. Physiol., 109, 41, 1949.PubMedGoogle Scholar
  20. 20.
    Jürgens R., Die Blutplättchen und ihre Bedeutung für Blutungsneigung und Thrombusbildung. Dtsch. med. Wschr., 77, 1265, 1952.CrossRefGoogle Scholar
  21. 21.
    Kubisz P., Sultan Y., Delobel J., Caen J., Mesure de la libération du facteur plaquettaire 4 (FP4) dans thrombopathies constitutionelles et acquises. Rev. Europ. Etudes Clin. Biol., 15, 698, 1970.Google Scholar
  22. 22.
    Lipihski B., Worowski K., Detection of soluble fibrin monomer complexes in human plasma by means of protamine sulphate test. Thromb. Diath. haemorrh., 20, 44, 1968.Google Scholar
  23. 23.
    Lipinski B., Worowski K., Jeljaszewicz J., Niewiarowski S., Rejniak L., Participation of soluble fibrin monomer complexes and platelet factor 4 in the generalized Schwartzman reaction. Thromb. Diath. haemorrh., 20, 285, 1968.PubMedGoogle Scholar
  24. 24.
    Louis J., Salmon J., Etude du syndrome de coagulation intravasculaire secondaire aux réactions anaphylactiques du lapin. Rôle du facteur 4 plaquettaire. Comptes rendus des séances de la Société de Biologie, 163, 2778, 1969.Google Scholar
  25. 25.
    Luscher E. F., Die Biochemie der Gerinnungsfaktoren der Thrombozyten. Fourth International Congress of Biochemistry Vienna, Pergamon Press, 1958, p. 75.Google Scholar
  26. 26.
    Marr J., Barboriak J. J., Johnson S. A., Relationship of appearance of adenosine diphosphate, fibrin formation and platelet aggregation in the haemostatic plug in vivo. Nature, 205, 259, 1965.PubMedCrossRefGoogle Scholar
  27. 27.
    Niewiarowski S., Farbiszewski R., Poplawski A., Neutralization of antithrombin VI (fibrinogen degradation products) with platelet antiheparin factor (platelet factor 4) Thromb. Diath. haemorrh., 14, 490, 1965.Google Scholar
  28. 28.
    Niewiarowski S., Lipinski B., Farbiszewski R., Poplawski A., The release of platelet factor 4 during platelet aggregation and the possible significance of this reaction in hemostasis. Experientia, 24, 343, 1968.PubMedCrossRefGoogle Scholar
  29. 29.
    Niewiarowski S. Poplawski A., Lipinski B., Farbiszewski R., The release of platelet clotting factors during aggregation and viscous metamorphosis. Exp. Biol. Med., 3, 121, 1968.Google Scholar
  30. 30.
    Niewiarowski S., Thomas D. P., Platelet factor 4 and adenosine diphosphate release during human platelet aggregation. Nature, 222, 1269, 1969.PubMedCrossRefGoogle Scholar
  31. 31.
    Nilsson I. M., Wmckert A., Demonstration of a heparin-like anticoagulant in normal blood. I. Human blood. Acta Med. Scand., suppl. 150, 297, 1955.Google Scholar
  32. 32.
    O’Brien J. R., Effect of salicylates on human platelets. Lancet, 1, 779, 1968.PubMedCrossRefGoogle Scholar
  33. 33.
    O’brien J. R., Finch W., Clark E., Platelet-bound and soluble platelet factor 4: effects of aggregating agents, of aggregation, and of aspirin. Proc. Soc. Exptl. Biol. Med., 134, 1128, 1970.Google Scholar
  34. 34.
    Pepper D. S., Moore S., Cash J. D., Preliminary studies on the isolation and characterization of human platelet anti-heparin activity (platelet factor 4). Abstract 2nd Congress International Society or Thrombosis and Haemostasis, Oslo, 244, 1971.Google Scholar
  35. 35.
    Poplawski A., Hiwiarowski S., Dissociation of platelet antiheparin factor (platelet factor 4) and lipoprotein lipase inhibitor. Biochim. Biophys. Acta, 90, 403, 1964.CrossRefGoogle Scholar
  36. 36.
    Poplawski A., Prokopowicz J., Hewiarowski S., Antiheparin activity in subcellular fraction of human granulocytes. Thromb. Diath. haemorrh., 21, 170, 1969.PubMedGoogle Scholar
  37. 37.
    Rapaport S. I., Ames S. B., Antiheparin activity of erythrocyte hemolysate. Proc. Soc. Exptl. Biol. Med., 95, 158, 1957.Google Scholar
  38. 38.
    Rapaport S. I., Ames S. B., Clotting factor assays on plasma from patients receiving intra-muscular or subcutaneous heparin. Amer. J. Med. Scien., 234, 678, 1957.CrossRefGoogle Scholar
  39. 39.
    Solum N. O., Platelet aggregation during fibrin polymerization. Scand. J. clin. Lab. Invest., 18, 577, 1966.PubMedCrossRefGoogle Scholar
  40. 40.
    Stewart G. J., Niewiarowski S., Aggregation of fibrinogen and its degradation products by basic proteins. An electron microscope study. Thromb. Diath. haemorrh., 25, 566, 1971.PubMedGoogle Scholar
  41. 41.
    Tamka K., Ilzuka Y., Suppression of enzyme release from isolated rat liver lysosomes by non-steroidal anti-inflammatory drugs. Biochem. Pharmacol., 17, 2023, 1960.Google Scholar
  42. 42.
    Vait Creveld S., Paulssen M. M., Significance of clotting factors in blood platelets in normal and pathological conditions. Lancet, 2, 242, 1951.CrossRefGoogle Scholar
  43. 43.
    Vaedeedriessche R., Separation of the thromboplastic activity and the heparin-neutralizing auction of thrombocytes. Acta Med. Scand., 165, 217, 1959.Google Scholar
  44. 44.
    Vermylm J., Dotrsmont G., Donati M. B., De Gaetauo G., Michielsen P., Pharmacological modification of urinary excretion of fibrinogenlike material in glomerulonephritis. Scand. J. Haemat., suppl. 13, p. 365, 1971.Google Scholar
  45. 45.
    Verstraete M., Platelet factors. Thromb. Diath. haernorrh., suppl. 20, 397, 1966.Google Scholar
  46. 46.
    Wegrzynonicz Z., Personal communication.Google Scholar
  47. 47.
    Youssef A., Barkhan P., Release of platelet factor 4 by adenosine diphosphate and other platelet aggregating agents. Brit. Med. J., 1, 746, 1968.PubMedCrossRefGoogle Scholar
  48. 48.
    Youssef A. H., Barkhan P., Inhibition by aspirin of release of antiheparin activity from human platelets. Brit. Med. J., 3, 394, 1969.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1972

Authors and Affiliations

  • M. B. Donati
    • 1
  • M. Palester-Chlebowczyk
    • 1
  • G. de Gaetano
    • 1
  • J. Vermylen
    • 1
  1. 1.Laboratory of Blood CoagulationUniversity of LeuvenBelgium

Personalised recommendations