Download PDF
Thromb Haemost 1977; 38(04): 1085-1096
DOI: 10.1055/s-0038-1651925
Original Article
Schattauer GmbH

The Role of Platelets in the Pathogenesis of Thrombosis and Hemorrhage in Patients with Thrombocytosis

Peter N. Walsh
*   Specialized Center on Thrombosis Research, Philadelphia, Pennsylvania, U.S.A.
,
Scott Murphy
**   Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, U.S.A.
,
William E. Barry
***   Cardeza Foundation, Thomas Jefferson School of Medicine, Philadelphia, Pennsylvania, U.S.A.
› Author Affiliations
Further Information

Publication History

Publication Date:
04 July 2018 (online)

Also available at
    Permissions and Reprints

Summary

Some patients with thrombocytosis due to myeloproliferative diseases or other etiologies experience thromboembolic complications and others may bleed excessively. It seems unlikely that elevations in platelet count per se are a direct cause either of thrombosis or of hemorrhage. In an effort to ascertain whether variations in platelet function might determine whether an individual patient experiences thrombotic or hemorrhagic complications we have evaluated platelet function in 22patients with thrombocytosis due to a variety of etiologies. The results of platelet counts, bleeding time determinations, and studies of platelet aggregation were similar in patients with thrombosis, in patients with bleeding and in patients with neither complication. Therefore, detailed studies of platelet coagulant activities were carried out in 8patients. The results of platelet coagulant activity assays were normal in all 3patients with thrombocytosis and neither thrombotic nor bleeding complications and an additional 3patients with myeloproliferative diseases, normal platelet counts and no thrombohemorrhagic complications. In 2patients with thrombotic complications significant elevation of platelet coagulant activities concerned with the early phases of intrinsic coagulation were observed whereas in 2patients with severe hemorrhagic complications deficiences of either contact forming activity or collagen-induced coagulant activities were evident. This preliminary study suggests the possibility that variations in platelet coagulant activities concerned with the early stages of intrinsic coagulation may determine whether patients with thrombocytosis will experience bleeding or thrombotic complications.

 

  • References

  • 1 Adams T, Schutz L, Goldberg L. 1974; Platelet function abnormalities in the myeloproliferative disorders. Scandinavian Journal of Haematology 13: 215.
    PubMedGoogle Scholar
  • 2 Barbui T, Battista R, Dini E. 1973; Spontaneous platelet aggregation in myeloproliferative disorders. Acta Haematologica 50: 25.
    CrossrefPubMedGoogle Scholar
  • 3 Bensinger T. A, Logue G. L, Rundles R. W. 1970; Hemorrhagic thrombocythemia; control of postsplenectomy thrombocytosis with melphalan. Blood 36: 61.
    PubMedGoogle Scholar
  • 4 Berger S, Aledort L. M, Gilbert H. S, Hanson J. P, Wasserman L. R. 1973; Abnormalities of platelet function in patients with polycythemia vera. Cancer Research 33: 2683.
    PubMedGoogle Scholar
  • 5 Bigelow F. S. 1954; Serotonin activity in blood: Measurements in normal subjects and in patients with thrombocythemia hemorrhagica and other hemorrhagic states. Journal of Laboratory and Clinical Medicine 43: 759.
    PubMedGoogle Scholar
  • 6 Boughton B. J, Corbett W. E. N, Ginsburg A. D. 1977; Myeloproliferative disorders: a paradox of in-vivo and in-vitro platelet function. Journal of Clinical Pathology 30: 228.
    CrossrefPubMedGoogle Scholar
  • 7 Brecher G, Cronkite E. P. 1950; Morphology and enumeration of human blood platelets. Journal of Applied Physiology 3: 365.
    CrossrefPubMedGoogle Scholar
  • 8 Brodsky I, Ross E. M, Petkov G, Kahn S. B. 1972; b Platelet and fibrinogen kinetics with [75Se]-Selenomethionine in patients with myeloproliferative disorders. British Journal of Haematology 22: 179.
    CrossrefPubMedGoogle Scholar
  • 9 Brodsky I, Kahn S. B, Ross E. M, Petkov G. 1972; a Platelet and fibrinogen kinetics in the chronic myeloproliferative disorders. Cancer 30: 1444.
    CrossrefPubMedGoogle Scholar
  • 10 Cardamone J. M, Edson J. R, McArthur J. R, Jacob H. S. 1972; Abnormalities of platelet function in myeloproliferative disorders. Journal of the American Medical Association 221: 270.
    CrossrefPubMedGoogle Scholar
  • 11 Cohen I, Djaldetti M, Karp M, De Vries A. 1966; Thrombocytosis with impaired platelet adhesiveness and platelet factor 3 availability. New Istanbul Contributions to the Clinical Sciences 9: 20.
    PubMedGoogle Scholar
  • 12 Dawson A. A, Ogston D. 1970; The influence of the platelet count on the incidence of thrombotic and haemorrhagic complications in polycythemia vera. Postgraduate Medical Journal 46: 76.
    CrossrefPubMedGoogle Scholar
  • 13 Didisheim P, Bunting D. 1966; Abnormal platelet function in myelofibrosis. The American Journal of Clinical Pathology 45: 566.
    PubMedGoogle Scholar
  • 14 Drummond A. H, Gordon J. L. 1974; A rapid, sensitive microassay for platelet 5-HT. Thrombosis et Diathesis Haemorrhagica 31: 366.
    PubMedGoogle Scholar
  • 15 Epstein E, Goedel A. 1934; Hämorrhagische Thrombocythämie bei vasculärer Schrumpfmilz. Virchows Archiv 292: 233.
    CrossrefPubMedGoogle Scholar
  • 16 Gilbert H. S. 1975; Definition, clinical features and diagnosis of polycythaemia vera. Clinics in Haematology 4: 263.
    PubMedGoogle Scholar
  • 17 Ginsburg A. D. 1974. Thrombocytosis and thrombocythemia. In: Physiological Pharmacology. Vol. V. Blood. (eds.) Root W. S, Berlin N. I. Academic Press; New York: 199-235.
    Google Scholar
  • 18 Ginsburg A. D. 1975; Platelet function in patients with high platelet counts. Annals of Internal Medicine 82: 506.
    CrossrefPubMedGoogle Scholar
  • 19 Gunz F. W. 1960; Hemorrhagic thrombocythemia: A critical review. Blood 15: 706.
    PubMedGoogle Scholar
  • 20 Gunz F. W. 1972. Essential thrombocythemia, Chapter 83. In: Hematology. (eds.) Williams W. J, Beutler E, Erslev A. J, Rundles R. W. McGraw-Hill Book Co.; New York: 704.
    Google Scholar
  • 21 Hardistry R. M, Wolff H. H. 1955; Haemorrhagic thrombocythaemia: a clinical and laboratory study. British Journal of Haematology 1: 390.
    CrossrefPubMedGoogle Scholar
  • 22 Harker L. A, Finch C. A. 1969; Thrombokinetics in man. Journal of Clinical Investigation 48: 963.
    CrossrefPubMedGoogle Scholar
  • 23 Hirsh J, Dacie J. V. 1966; Persistent postsplenectomy thrombocytosis and thromboembolism: a consequence of continuing anaemia. British Journal of Haematology 12: 44.
    CrossrefPubMedGoogle Scholar
  • 24 Holmsen H, Østvold A.-C, Day H. J. 1973; Behavior of endogenous and newly absorbed serotonin in the platelet release reaction. Biochemical Pharmacology 22: 2599.
    CrossrefPubMedGoogle Scholar
  • 25 Inceman S, Tangun Y. 1972; Platelet defects in the myeloproliferative disorders. Annals of the New York Academy of Science 201: 251.
    CrossrefPubMedGoogle Scholar
  • 26 Kutti J, Weinfeld A. 1971; Platelet survival in active polycythaemia vera with reference to the haematocrit level. Scandinavian Journal of Haematology 8: 405.
    PubMedGoogle Scholar
  • 27 Laszlo J. 1975; Myeloproliferative disorders (MPD): myelofibrosis, myelosclerosis, extramedullary hematopoiesis, undifferentiated MPD and hemorrhagic thrombocythemia. Seminars in Hematology 12: 409.
    PubMedGoogle Scholar
  • 28 Martinez J, Shapiro S. S, Holburn R. R. 1973; Metabolism of human prothrombin and fibrinogen in patients with thrombocytosis secondary to myeloproliferative states. Blood 42: 35.
    PubMedGoogle Scholar
  • 29 Mason Jr J. E, De Vita V. T, Canellos G. P. 1974; Thrombocytosis in chronic granulocytic leukemia: incidence and clinical significance. Blood 44: 438.
    PubMedGoogle Scholar
  • 30 McClure P. D, Ingram G. I. C, Stacey R. S, Glass U. H, Matchett M. O. 1966; Platelet function test in thrombocythaemia and thrombocytosis. British Journal of Haematology 12: 478.
    CrossrefPubMedGoogle Scholar
  • 31 Milstone J. H. 1964; Thrombokinase as prime activator of prothrombin: historical perspectives and present status. Federation Proceedings 23: 742.
    PubMedGoogle Scholar
  • 32 Monto R. W, Griest W. D, Szilagyi D. E. 1952; Essential thrombophilia. Archives of Internal Medicine 90: 54.
    CrossrefPubMedGoogle Scholar
  • 33 Neemeh J. A, Bowie E. J. W, Thompson Fr J. H, Didisheim P, Owen Jr C. A. 1972; Quantitation of platelet aggregation in myeloproliferative disorders. American Journal of Clinical Pathology 57: 336.
    CrossrefPubMedGoogle Scholar
  • 34 Nygaard K. K, Brown G. E. 1937; Essential thrombophilia. Archives of Internal Medicine 59: 83.
    PubMedGoogle Scholar
  • 35 Ozer F. L, Truax W. E, Miesch D. C, Levin W. C. 1960; Primary hemorrhagic thrombocythemia. American Journal of Medicine 28: 807.
    CrossrefPubMedGoogle Scholar
  • 36 Preston F. E, Emmanuel I. G, Winfield D. A, Malia R. G. 1974; Essential thrombocythaemia and peripheral gangrene. British Medical Journal 3: 548.
    CrossrefPubMedGoogle Scholar
  • 37 Rigby P. G, Leavell B. S. 1960; Polycythemia vera. Archives of Internal Medicine 5: 100.
    PubMedGoogle Scholar
  • 38 Spaet T. H, Lejnieks I, Gaynor E, Goldstein M. L. 1969; Defective platelets in essential thrombocythemia. Archives of Internal Medicine 124: 135.
    CrossrefPubMedGoogle Scholar
  • 39 Takácsi-Nagy L, Gráf F. 1975; Definition, clinical features and diagnosis of myelofibrosis. Clinics in Haematology 4: 291.
    PubMedGoogle Scholar
  • 40 Taylor D. D, Senhauser D. A, Cavazos F. 1968; Thrombocytopathy associated with nonleukemic megakaryocytic myelosis. Functional and fine structure observations of the abnormal platelets. The American Journal of Clinical Pathology 49: 662.
    PubMedGoogle Scholar
  • 41 Vreeken J, Van Aken W. G. 1971; Spontaneous aggregation of blood platelets as a cause of idiopathic thrombosis and recurrent painful toes and fingers. Lancet II: 1394.
    PubMedGoogle Scholar
  • 42 Walsh P. N. 1972; a Albumin density gradient separation and washing of platelets and the study of platelet coagulant activities. British Journal of Haematology 22: 205.
    CrossrefPubMedGoogle Scholar
  • 43 Walsh P. N. 1972; b The effect of dilution of plasma on coagulation. The significance of the dilution – activation phenomenon for the study of platelet coagulant activities. British Journal of Haematology 22: 219.
    CrossrefPubMedGoogle Scholar
  • 44 Walsh P. N. 1972; c The role of platelets in the contact phase of blood coagulation. British Journal of Haematology 22: 237.
    CrossrefPubMedGoogle Scholar
  • 45 Walsh P. N. 1972; d The effects of collagen and kaolin on the intrinsic coagulant activity of platelets. Evidence for an alternative pathway in intrinsic coagulation not requiring factor XII. British Journal of Haematology 22: 393.
    CrossrefPubMedGoogle Scholar
  • 46 Walsh P. N. 1972; e Platelet coagulant activities in thrombasthenia. British Journal of Haematology 23: 553.
    CrossrefPubMedGoogle Scholar
  • 47 Walsh P. N, Biggs R. 1972; The role of platelets in intrinsic factor-Xa formation. British Journal of Haematology 22: 743.
    CrossrefPubMedGoogle Scholar
  • 48 Walsh P. N, Mills D. C. B, Pareti F. I, Stewart G. J, Macfarlane D. E, Johnson M. E, Egan J. J. 1975; Hereditary giant platelet syndrome. Absence of collagen-induced coagulant activity and deficiency of factor-XI binding to platelets. British Journal of Haematology 29: 639.
    CrossrefPubMedGoogle Scholar
  • 49 Walsh P. N, Pareti F. I, Corbett J. J. 1976; Platelet coagulant activities and serum lipids in transient cerebral ischemia. New England Journal of Medicine 295: 854.
    CrossrefPubMedGoogle Scholar
  • 50 Walsh P. N, Mills D. C. B, White J. G. 1977; Metabolism and function of human platelets washed by albumin density gradient separation. British Journal of Haematology 36: 285.
    PubMedGoogle Scholar
  • 51 Wasserman L. R, Gilbert H. S. 1963; Surgery in polycythemia vera. The New England Journal of Medicine 269: 1226.
    CrossrefPubMedGoogle Scholar
  • 52 Wasserman L. R, Gilbert H. S. 1966; Complications of polycythemia vera. Seminars in Hematology 3: 199.
    PubMedGoogle Scholar
  • 53 Weinfeld A, Branehög I, Kutti J. 1975; Platelets in the myeloproliferative syndrome. Clinics in Haematology 4: 373.
    PubMedGoogle Scholar
  • 54 Zahavi J, Marder V. J. 1974; Acquired “Storage pool disease” of platelets associated with circulating antiplatelet antibodies. The American Journal of Medicine 56: 883.
    CrossrefPubMedGoogle Scholar
  • 55 Zucker S, Mielke C. H. 1972; Classification of thrombocytosis based on platelet function tests: correlation with hemorrhagic and thrombotic complications. The Journal of Laboratory and Clinical Medicine 80: 385.
    PubMedGoogle Scholar