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The Role of Blood Platelets in Thrombosis in Relation to the Effects of Contraceptive Steroids on Platelet Function

  • R. J. Haslam

Abstract

Recent epidemiological studies (1,2) have shown that use of oral contraceptives of the combined progestin and estrogen type is associated with a considerably increased risk of venous thromboembolism and cerebral thrombosis, though an association between coronary thrombosis and contraceptive use has not yet been statistically proven. As the preparations used contain one of a wide variety of progestins combined with one of only two similar estrogens (ethynyl estradiol or mestranol), it is probable, if a causal relationship exists, that the harmful component is the estrogen. This conclusion is supported by reports that use of synthetic estrogens alone to suppress lactation (3) or in the treatment of carcinoma of the prostate (4) is associated with increased risk of venous thrombosis and pulmonary embolism. A wide range of both experimental and clinical studies have established the importance of blood platelets in both hemostasis and arterial thrombosis but, although there is considerable evidence for altered platelet function in venous thrombosis and in conditions predisposing thereto, platelets have often been ignored in this latter context. In an attempt to redress the balance this paper will be devoted mainly to an assessment of the possible roles for platelets in venous thrombosis and pulmonary embolism with particular emphasis on the effects of contraceptive steroids on platelet function.

Keywords

Oral Contraceptive Venous Thrombosis Platelet Function Blood Platelet Adenosine Diphosphate 
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.

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References

  1. 1.
    Inman, W.H.W. and Vessey, M.P.: Investigation of deaths from pulmonary, coronary and cerebral thrombosis and embolism in women of childbearing age. Brit. Med. J. 2:193 (1968).PubMedCrossRefGoogle Scholar
  2. 2.
    Vessey, M.P. and Doll, R.: Investigation of relation between use of oral contraceptives and thromboembolic disease. Brit. Med. J. 2:199 (1968).PubMedCrossRefGoogle Scholar
  3. 3.
    Daniel, D.G., Campbell, H. and Tumbull, A.C.: Puerperal thromboembolism and suppression of lactation. Lancet ii:287 (1967).Google Scholar
  4. 4.
    Veterans Administration Co-operative Urological Research Group: Treatment and survival of patients with cancer of the prostate. Sug. Gynecol. Obst. 124:1011 (1967).Google Scholar
  5. 5.
    Mustard, J.F.: Recent advances in molecular pathology:A review - Platelet aggregation, vascular injury and atherosclerosis Exp. Molec. Path. 1:366 (1967).CrossRefGoogle Scholar
  6. 6.
    Mustard, J.F.: Hemostasis and thrombosis. Seminars in Hematology 5:91 (1968).PubMedGoogle Scholar
  7. 7.
    Constantinides, P.: Plaque fissures in human coronary thrombosis. J. Atheroscler. Res. 6:1 (1966).CrossRefGoogle Scholar
  8. 8.
    Poole, J.C.F. and French, J.E.: Thrombosis. J. Atheroscler. Res. 1:251 (1961).PubMedCrossRefGoogle Scholar
  9. 9.
    Paterson, J.C.: Deep venous thrombosis. In Blood Vessels and Lymphatics. Abramson, D.I. (ed.) Academic Press, N.Y. p.688 (1962).Google Scholar
  10. 10.
    Spaet, T.H. and Zucker, M.B.: Mechanism of platelet plug formation and role of adenosine diphosphate. Amer. J. Physiol. 206:1297 (1964).Google Scholar
  11. 11.
    Baumgartner, H.R, Tranzer, J.P. and Studer, A.: An electron microscopic study of platelet thrombus formation in the rabbit with particular regard to 5-hydroxy-tryptamine release. Thromb. Diath. Haemorrh. 18:592 (1967).PubMedGoogle Scholar
  12. 12.
    Niewiarowski, S., Bankowski, E. and Rogowicka, I.: Studies on the absorption and activation of the Hageman factor (factor XII) by collagen and elastin. Thromb. Diath. Haemorrh. 14:387 (1965).PubMedGoogle Scholar
  13. 13.
    Hovig, T., Rowsell, H.C., Dodds, W.J., Jorgenson, L. and Mustard, J.F.: Experimental hemostasis in normal dogs and dogs with congenital disorders of blood coagulation. Blood 30:636 (1967).PubMedGoogle Scholar
  14. 14.
    Neistadt, A., Schwartz, R.W. and Schwartz, S.I.: Norethynodrel with mestranol and venous blood flow. J. Amer. Med. Assoc. 198:784 (1966).CrossRefGoogle Scholar
  15. 15.
    Goodrich, S.M. and Wood, J.E.: The effect of estradiol - 173 on peripheral venous distensibility and velocity of blood flow. Amer. J. Obst. Gynecol. 96:407 (1966).Google Scholar
  16. 16.
    Wessler, S.: Experimental coagulation thrombus. In Pathogenesis and Treatment of Thromboembolic Diseases. Thromb. Diath. Haemorrh. Suppl. 21:177 (1966).Google Scholar
  17. 17.
    Paterson, J.C. and McLachlin, J.: Precipitating factors in venous thrombosis. Surg. Gynecol. Obst. 98:96 (1954).Google Scholar
  18. 18.
    Robertson, H.R., Moore, J.R. and Mersereau, W.A.: Observations on thrombosis and endothelial repair following application of external pressure to veins. Canad. J. Surg. 3:5 (1959).PubMedGoogle Scholar
  19. Paterson, J.C.: personal communication, 1968.Google Scholar
  20. 20.
    Mustard, J.F., Murphy, E.A., Robinson, G.A., Rowsell, H.C., Ozge, A. and Crookston, J.H.: Blood platelet survival. Thromb. Diath. Haemorrh. Suppl. 13:245 (1964).Google Scholar
  21. 21.
    Abrahamsen, A.F.: Platelet survival studies in man. Scand. J. Haemat. Suppl. 3: (1968).Google Scholar
  22. 22.
    Adelson, E., Rheingold, J.J., Parker, O. Buenaventura, A. and Crosby, W.H.: Platelet and fibrinogen survival in normal and abnormal states of coagulation. Blood 17:267 (1961).PubMedGoogle Scholar
  23. 23.
    Murphy, E.A., and Mustard, J.F.: Coagulation tests and platelet economy in atherosclerotic and control subjects. Circulation 25:114 (1962).PubMedGoogle Scholar
  24. 24.
    Gorelick, M., Harkness, R.A., Ismail, A., Morse, W.I. and Shane, S.J.: Sex hormone metabolism and platelet economy in male survivors and myocardial infarction. Canad. Med. Assoc. J. 98:119 (1968).Google Scholar
  25. 25.
    O’Neill, B. and Firkin, B.: Platelet survival studies in coagulation disorders, thrombocythemia and conditions associated with atherosclerosis. J. Lab. Clin. Med. 64:188 (1964).PubMedGoogle Scholar
  26. 26.
    Wright, H.P.: Changes in adhesiveness of blood platelet following parturition and surgical operations. J. Path. Bact. 54:461 (1942).CrossRefGoogle Scholar
  27. 27.
    Hellem, A.J.: The adhesiveness of human blood platelets in vitro. Scand. J. Clin. Lab. Invest. 12: Suppl. 51 (1960).Google Scholar
  28. 28.
    Harrison, M.J.G. and Mitchell, J.R.A.: The influence of red blood cells on platelet adhesiveness. Lancet ii:1163 (1966).CrossRefGoogle Scholar
  29. 29.
    Hellem, A.J., Odegaard, A.E. and Skalhegg, B.A.: Investigations on adenosine diphosphate (ADP) induced platelet adhesiveness vitro. I. The ADP-platelet reaction in various experimental conditions. Thromb. Diath. Haemorrh. 10:61 (1963).PubMedGoogle Scholar
  30. 30.
    Bobek, K. and Cepelak, V.: Laboratory diagnosis of venous thrombosis. Acta Med. Scand. 160:121 (1958).PubMedCrossRefGoogle Scholar
  31. 31.
    Hume, M. and Chan, Y.K.: Examination of the blood in the presence of venous thrombosis. J. Amer. Med. Assoc. 200747 (1967).CrossRefGoogle Scholar
  32. 32.
    Hirsh, J. and McBride, J.A.: Increased platelet adhesiveness in recurrent venous thrombosis and pulmonary embolism. Brit. Med. J. 2:797 (1965).PubMedCrossRefGoogle Scholar
  33. 33.
    Bygdeman, S., Eliasson, R. and Johnson, S.R.: Relationship between post-operative changes in adenosine diphosphate induced platelet adhesiveness and venous thrombosis. Lancet i:1301 (1966).CrossRefGoogle Scholar
  34. 34.
    Bennett, P.N.: Post-operative changes in platelet adhesiveness. J. Clin. Path. 20:708 (1967).PubMedCrossRefGoogle Scholar
  35. 35.
    Hirsh, J., Glynn, M.F. and Mustard, J.F.: The effect of platelet age on platelet adherence to collagen. J. Clin. Invest. 47:466 (1968).PubMedCrossRefGoogle Scholar
  36. Evans, G. and Mustard, J.F.: Platelet-surface reaction and thrombosis. Surgery 64:273 (1968).PubMedGoogle Scholar
  37. 36.
    Caspary, E.A. and Peberdy, M.: Oral contraception and blood platelet adhesiveness. Lancet i: 1142 (1965).CrossRefGoogle Scholar
  38. 37.
    Hilden, M., Amris, C.J. and Starup, J.: The haemostatic mechanism in oral contraception. Acta. Obst. Gynecol. Scand. 46: 562 (1967).CrossRefGoogle Scholar
  39. 38.
    Elkeles, R.S., Hampton, J.R. and Mitchell, J.R.A.: Effect of oestrogens and human platelet behavior. Lancet ii:315 (1968).CrossRefGoogle Scholar
  40. 39.
    Bom, G.V.R.: Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194:927 (1962).Google Scholar
  41. 40.
    O’Brien, J.R., Heywood, J.B. and Heady, J.A.: The quantitation of platelet aggregation induced by four compounds: a study in relation to myocardial infarction. Throirib. Diath. Haemorrh. 16:752 (1966).Google Scholar
  42. 41.
    Emmons, P.R. and Mitchell, J.R.A.: Post-operative changes in platelet clumping activity. Lancet i:71 (1965).CrossRefGoogle Scholar
  43. 42.
    Hampton, J.R. and Mitchell, J.R.A.: Effect of aggregating agents on platelet electrophoretic behavior. Brit. Med. J. 1:1074 (1966).PubMedCrossRefGoogle Scholar
  44. 43.
    Hampton, J.R. and Mitchell, J.R.A.: A transferable factor causing abnormal platelet behavior in vascular disease. Lancet ii:764 (1966).CrossRefGoogle Scholar
  45. 44.
    Grottum, K.A.: Influence of aggregating agents on electrophoretic mobility of blood platelets from healthy individuals and from patients with cardiovascular diseases. Lancet i:1406 (1968).CrossRefGoogle Scholar
  46. 45.
    Bolton, C.H., Hampton, J.R. and Mitchell, J.R.A.: Effect of oral contraceptive agents on platelets and plasma phospholipids. Lancet i:1336 (1968).CrossRefGoogle Scholar
  47. 46.
    Thomas, D.P., Gurewich, V. and Stuart, R.K.: Epinephrine potentiation of platelet aggregation: its effect on death from experimental pulmonary embolism. J. Lab. Clin. Med. 71:955 (1968).PubMedGoogle Scholar
  48. 47.
    Aurell, M., Cramer, K. and Rybo, G.: Serum lipids and lipoproteins during long term administration of an oral contraceptive. Lancet i:291 (1966).CrossRefGoogle Scholar
  49. Wynn, V. Doar, J.W.H. and Mills, G.L.: Some effects of an oral contraceptive on serum lipid and lipoprotein levels. Lancet ii:720 (1966).Google Scholar
  50. 48.
    Laron, Z. and Kowadlo-Silbergeld, A.: Fat mobilizing effect of oestrogens. Acta Endocr. 48:125 (1965).PubMedGoogle Scholar
  51. 49.
    Wynn, V. and Doar, J.W.H.: Some effects of oral contraceptives on carbohydrate metabolism. Lancet ii:715 (1966).CrossRefGoogle Scholar
  52. 50.
    Hoak, J.C., Poole, J.C.F. and Robinson, D.S.: Thrombosis associated with the mobilization of fatty acids. Amer. J. Path. 43:987 (1963).PubMedGoogle Scholar
  53. 51.
    Jacobson, P.: Spontaneous hemorrhage; clinical entity, with special reference to epistaxis. Arch. Otolaryng. 59:523 (1954).CrossRefGoogle Scholar
  54. 52.
    Carre, I.J., Campbell, S., Nicholl, B. and Carson, N.A.J.: Prolonged bleeding time and A.H.G. deficiency. A case treated with oestrogens. Brit. Med. J. 2:682 (1961).Google Scholar
  55. 53.
    Akman, N., Bayrak, G., Berkarda, B. and Ulutin, O.N.: The effect of oestradiol succinate on in vivo platelet adhesion. New Istanbul Contrib. Clin. Sci. 8:106 (1965).Google Scholar
  56. Gorelick, M.M. and Read, H.C.: Effect of estrogen- progestin compounds on platelet-surface reactions and coagulation factors in bleeding disorders. Reported to Canad. Soc. Clin. Invest. 1968.Google Scholar

Copyright information

© Plenum Press, New York 1969

Authors and Affiliations

  • R. J. Haslam
    • 1
  1. 1.Department of PathologyMcMaster UniversityHamiltonCanada

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