Clinical and Biological Activity of the Antiplatelet Agent Suloctidil in Treatment of Idiopathic Recurrent Vein Thrombosis (I.R.V.T.)

Summary

A double blind cross over study with suloctidil (Sulocton, Continental Pharma) and placebo was carried out for 6 months in 31. patients with idiopathic recurrent vein thrombosis. They were previously unsuccessfully treated with vitamin K antagonists (VKA) (18 patients) or acetylsalicylic acid (ASA) (13 patients) combined or not with a fibrinolysis activator (theophylline nicotinate).

Clinical features, ultrasonic venous flow and biological parameters were controlled monthly during the 6 month treatment. Relevant improvement of clinical, ultrasonic and biological parameters was only observed under suloctidil therapy: during placebo administration 12 patients developed new thrombotic events complicated in 2 by pulmonary embolism while none occurred under suloctidil therapy.

Key words

Idiopathic recurrent vein thrombosis - Suloctidil - Platelet retention and aggregation - Platelet release - PF₄ - Betathrom-boglobulin - Ultrasonic venous flow - Fibrinolysis activators

• References

• 1 Steele PP, Weily HS, Genton E. Platelet survival and adhesiveness in recurrent venous thrombosis. N Engl J Med 1973; 288: 1148-1152
• 2 Gallus AS, Hirsh J, Hull R, Van Aken WG. Diagnosis of venous thromboembolism. Semin Thromb Hemostas 1976; 2: 203-231
• 3 Wu KK, Barnes RW, Hoak JC. Platelet hyperaggregability in idiopathic recurrent deep vein thrombosis. Circulation 1976; 53: 687-691
• 4 Steele P, Ellis Jr J, Genton E. Effects of platelet suppressant, anticoagulant and fibrinolytic therapy in patients with recurrent venous thrombosis. Am J Med 1978; 64: 441-445
• 5 Clagett GP, Collins GJ. Platelets, thromboembolism and the clinical utility of antiplatelet drugs. Surg Gynecol Obstet 1978; 147: 257-279
• 6 Steele P. Trial of Dipyridamole-Aspirin in recurring venous thrombosis. Lancet 1980; 2: 1328-1329
• 7 Hume M, Sevitt S, Thomas DP. Venous thrombosis and pulmonary embolism. Harvard University Press Cambridge; Massachusets: 1970
• 8 Gallus AS, Walker IR, Hirsh J, Halasah G, Evans G. Platelet survival, fibrinolytic activity, antithrombin III level and fibrinogen survival in venous thromboembolism. Abst 209 Proc Vth Cong Int Soc Thromb Haemostas Paris 1975
• 9 Davies GC, Salzman EW. The treatment of venous thrombosis and pulmonary embolism. In: Venous and arterial thrombos. Ed. by Joist JH, Sherman LA. Grane and Stratton Inc.; 133-157 New York: 1978
• 10 Penner JA. Hypercoagulation and thrombosis. Med Clin N Am 1980; 64: 743-759
• 11 Hirsh J, Mc Bride JA. Increased platelet adhesiveness in recurrent venous thrombosis and pulmonary embolism. Br Med J 1965; 2: 797-799
• 12 Walsh PN. The possible role of platelet coagulant activities in the pathogenesis of venous thrombosis. Thrombos Diathes Haemorrh 1975; 33: 435-443
• 13 Abrahamsen AF. Platelet survival studies in man. Scand J Haematol 1968; (03) 7-53
• 14 Harker LA, Slichter SJ. Platelet and fibrinogen consumption in man. N Engl J Med 1972; 287: 999-1005
• 15 Smith JB, Ingerman C, Kocsis JJ. Formation of prostaglandins during the aggregation of human blood platelets. J Clin Invest 1973; 52: 965-969
• 16 Ganström E, Kindahl H, Samuelsson B. Radio-immunoassay f. TXB₂ . Ann Lett 1976; 9: 611-627
• 17 Pepper D. Measurement of platelet release reaction. In Thromboembolism. A new approach to therapy. Eds. Mitchel JRA, Domenet JG. 55-68 Acad Press; London: 1977
• 18 Smith RC, Duncanson J, Ruckley CV, Webber RV, Allan NC, Dawer J, Bolton AE, Hunter WM, Pepper DS, Cash JD. Betathromboglobulin and deep vein thrombosis. Thromb Haemostas 1978; 39: 338-346
• 19 Hirsh J. Blood tests for the diagnosis of venous and arterial thrombosis. Blood 1981; 57: 1-8
• 20 Hirsh J, Gallus AS. Hypercoagulability. In: Recent Advances in Haematology 2. Eds. Hoffbrand AV, Brain MC, Hirsh J. Churchill Livingstone, Edinburgh; London, New York: 1977: 431-451
• 21 Isacson S, Nilsson IM. Defective fibrinolysis in blood and vein walls in recurrent idiopathic venous thrombosis. Acta Chir Scand 1972; 138: 313-319
• 22 Nilsson IM. Phenformin and ethylestrenol in recurrent venous thrombosis. In Progress in Chemical Fibrinolysis and Thrombolysis. vol. 1 Eds. Davidson JF, Samama MM, Desnoyers PC. 1-12 Raven Press; New York: 1975
• 23 Browse NL, Gray L, Jarret PE, Morland M. Blood and vein wall fibrinolytic activity in health and vascular disease. Br Med J 1977; 1: 478-481
• 24 Ciavarella N, Schiavoni M, Parato M, Oreste A, Pilolli D, Ciccolella A, Coviello M. Defective fibrinolytic activity but normal prostacycline like activity in vein walls of patients with recurrent venous thrombosis. In: Progress in chemical fibrinolysis and thrombolysis. vol IV. Eds. Davidson JF. 115-123 Churchill Livingstone, Edinburgh; London, New York: 1979
• 25 Turpie AGG, Hirsh J. Platelet suppressant therapy. In venous and arterial thrombosis. Eds. Joist JH, Sherman LA. 339-358 Grane and Stratton Inc.; New York: 1978
• 26 Isacson S, Nilsson IM. Effect of treatment with combined phenformin and ethylestrenol on the coagulation and fibrinolytic systems. Scand J Haematol 1970; 7: 404-408
• 27 Jarret PEM, Morland M, Browse NL. Idiopathic recurrent superficial thrombophlebitis. Treatment with fibrinolytic enbrancement. Br Med J 1977; 1: 933-937
• 28 Bielawiec M, Mysliwiec M, Perzanowski A. Combined therapy with Phenformin plus Stanozolol in patients with occlusive arterial disease and recurrent venous thrombosis. In: Progress in Chemical fibrinolysis and thrombolysis. vol. 3 Eds. Davidson JF, Rowan RM, Samama MM, Denoy PC. 507-512 Raven Press; New York: 1978
• 29 de Gaetano G, Miragliotta G, Roncucci R, Lansen J, Lambelin G. Suloctidil: A novel inhibitor of platelet aggregation in human beings. Thromb Res 1976; 8: 361-371
• 30 Roba J, Bourgain R, Andries R, Claeys M, Van Opstal W, Lambelin G. Antagonism by suloctidil of arterial thrombus formation in rats. Thromb Res 1976; 9: 585-594
• 31 Mills DCB, Macfarlane DE. Depletion of platelet amine storage granules by the antithrombotic agent, suloctidil. Thromb Haemostas 1977; 38: 1010-1017
• 32 Gurewich V, Lipinski B. Evaluation of antithrombotic properties of suloctidil in comparision with aspirin and dipyridamole. Thromb Res 1976; 9: 101-108
• 33 Moriau M, Ferrant A. Antivitamines K et antiagrégants plaquettaires dans la prévention des thromboses. Acta Clin Belg 1977; 32: 409-421
• 34 Roba J, Claeys M, Roet R, Van Opstal W, Lambelin G. Erythrocyte membranes as a target for antithrombotic agents. Proc Xlth Int Cong Angiology, Prague. 1978: 96-98
• 35 Roncucci R, De Hertogh R, Dormandy JA, Doumont J, Gurewich V, Lambelin G, Lansen J, Rottiers R, Souridis E, Van Stalle F, Versee L. Effects of long-term treatment with suloctidil on blood viscosity, erythrocyte deformability and total fibrinogen plasma levels in diabetic patients. Arzneim Forsch 1979; 29: 682-684
• 36 Villa S, Cavenaghi AE, de Gaetano G. Suloctidil does not inhibit vascular prostacyclin activity in rats. Thromb Haemostas 1979; 42: 368
• 37 Bowie EJW, Owen OHA, Thompson JH, Didisheim P. A test of platelet adhesiveness. Mayo Clin Proc 1969; 44: 306-308
• 38 Born GVR, Cross MJ. The aggregation of blood platelets. J. Physiol 1963; 168: 178-195
• 39 Hurlet BirkJensen A, Legrand MonsieurA, Masure R. Analysis of heparin neutralizing assay conditions. Thromb Res 1978; 13: 609-614
• 40 Bolton AE, Ludlan CA, Moore S, Pepper DS, Cash JD. Three approaches to the radio-immunoassay of human beta-thromboglobulin. Br J Haematol 1976; 33: 233-238
• 41 Gram HC. A new method for determination of the fibrin percent in blood and plasma. J Biol Chem 1921; 49: 279-293
• 42 Vermylen C, Verstraete M. A simple method for the assay of factor VIII using 25 microliters of capillary blood. Br J Haematol 1968; 14: 241-245
• 43 Laurell CB. Antigen antibody crossed electrophoresis. Ann Biochem 1965; 10: 358-361
• 44 Macfarlane DE, Stibbe J, Kirby EP, Zucker HB, Grant RA, McPherson J. A method for assaying von Willebrand factor (Ristocetine cofactor). Thrombos Diathes Haemorrh 1975; 34: 306-310
• 45 Von Kaulla KN, Schulz RL. Method for the evaluation of human fibrinolysis. Studies with 2 combined technics. Am J Clin Pathol 1958; 29: 104-109
• 46 Buckell M. The effect of citrate on euglobulin methods of estimating fibrinolytic activity. J Clin Pathol 1958; 2: 403-410
• 47 Doyle DJ, Chesterman CN, Cade JF, McGready JR, Rennie GC, Morgan FJ. Plasma concentrations of platelet specific proteins correlated with platelet survival. Blood 1980; 55: 82-84
• 48 Moriau M, Ferrant A, Col-De Beys C, Hurlet A, Chalant C, Ponlot R, Jaumin P, Goenen M, Masure R, Lansen J, Roncucci R, Van Stalle F, Lambelin G. Suloctidil and platelet functions in man. 112 Abst Intern Confer on atherosclerosis. Milan 1977;
• 49 Moriau M, Roncucci R, Van Stalle F, Lambelin G. Effect of suloctidil in various forms of thromboembolic complications. 247 Abstract of Fifth International Congress on Thromboembolism. Bologne 1978;