Platelet Aggregation by Thimerosal

Summary

Thimerosal, a sulphydryl inhibitor, induces aggregation of normal platelet rich plasma over a wide range of concentrations. Low doses induce a monophasic response preceded by a lag phase, high doses produce an immediate biphasic response.

Thimerosal induces platelet aggregation through its binding by sulphydryl groups.

Thimerosal induced aggregation is not mediated by ADP, it is not influenced by fibrinogen, von Willebrand factor, calcium, and magnesium ions of the medium.

Thimerosal induced platelet aggregation is normal in patients affected by thrombocyto-pathia (defect of ADP release) but not in patients affected by Glanzmann’s thrombasthenia. Mercaptopropionglycine, a substance which tends to preserve SH groups, inhibits platelet aggregation induced by thimerosal, thrombin, collagen, and ADP.

A mechanism is proposed for thimerosal induced aggregation and the role of SH groups also in ADP, thrombin and collagen induced aggregation is indicated.

• References

• 1 Alendorf L. M, Troup S. B, Weed R. I. 1974; Inhibition of sulphydryl dependent platelet functions by penetrating and non penetrating analogues of parachloromercurbenzene. Blood 43: 121.
• 2 Al-Mondhtry H, Spaet T. H. 1970; Inhibition of platelet adhesion to collagen by sulphydryl inhibitors Proceedings of the Society for Experimental. Biology and Medicine 135: 878.
• 3 Ando Y, Steiner M, Baldini M. 1974; Effect of storage on sulphydryl and disulphide groups of human platelets. Blood 43: 121.
• 4 Bettex-Gallant M, Lüscher E. F. 1965; Thrombostenin, the contractile protein from blood platelets and its relation to other contractile protein from blood platelets Adv. Prot. Chem 20: 1.
• 5 Born G. V. R. 1963; The aggregation of blood platelets. Journal of Physiology 168: 178.
• 6 De Gaetano G, Vermylen J, Verstraete M. 1971; Dissociation between platelet factor 3 availability and platelet aggregation. Acta Medica Scandinavica Suppl. 525-99
• 7 Fantl P, Ebbels L, Nelson J. F. 1951; The presence of thiol groups in thrombocytes and their significance in the contraction of fibrin gel British Journal of Experimental. Pathology 32: 538.
• 8 Harrison M. J. G, Emmons P. R, Mitchell J. R. A. 1966; The effect of sulphydryl and enzyme inhibitors on platelet aggregation in vitro Thrombosis et Diathesis. Haemorrhagica 16: 122.
• 9 Haslam R. J. 1964; Role of adenosine diphosphate in the aggregation of human blood platelets by thrombin and by fatty acids. Nature 202: 765.
• 10 Holmsen H, Day H. j, Stormorken H. 1969; The blood platelet release reaction Scandinavian. Journal of Haematology Suppl. 8: 1.
• 11 Nachman R. L, Ferris B. 1974; Binding of adenosine diphosphate by isolated membrane from human platelets. Journal of Biological Chemistry 249: 704
• 12 Robinson C. W, Mason R. G, Wagner R. H. 1963; Effect of sulphydryl inhibitors on platelet agglutinability. Proceedings of the Society for Experimental Biology and Medicine 113: 857.
• 13 Sinakos Z, Caen J. P. 1967; Platelet aggregation in mammalian. A comparative study Thrombosis et Diathesis Haemorrhagica 17: 99.
• 14 Walsh P. N. 1972; Albumin density gradient separation and washing of platelets and the study of platelet coagulant activies. British Journal Haematology 22: 205.
• 15 Zucker M. B, Peterson J. 1968; Inhibition of adenosine diphosphate-induced secondary aggregation and other platelet functions by acetylsalicylie acid ingestion. Proceedings of the Society for Experimental Biology and Medicine 127: 547.