Edward Genton

Platelet Survival in Patients with Substitute Heart Valves

Abstract To determine the relation of thromboembolism to the presence of substitute heart valves platelet studies were performed in 55 patients. Average platelet survival was normal in patients wit...

Platelet Survival and Adhesiveness in Recurrent Venous Thrombosis

Abstract Of 28 patients with idiopathic recurrent venous thrombosis, platelet survival time was abnormally shortened in 18 and normal in 10, and platelet adhesiveness was increased in eight and normal in 20. Platelet survival time was normal in nine anticoagulant-responsive patients, but was significantly shortened in 15 patients who were refractory to anticoagulants or who had had arterial thrombosis. Platelet adhesiveness did not distinguish these patients, nor did it correlate with platelet survival time. Platelet-inhibitor therapy with sulfinpyrazone was effective in the control of thrombosis in seven patients with shortened platelet survival time, increasing platelet survival time and decreasing platelet adhesiveness. These results suggest that shortened platelet survival or increased platelet adhesiveness is present in a high proportion of patients with recurrent venous thrombosis. Platelet-inhibitor therapy may prove useful in such cases. (N Engl J Med 288:1148–1152, 1973)

Platelet Survival in Patients with Rheumatic Heart Disease

Abstract Platelet studies were carried out in patients with valvular heart disease to determine the correlation of results with thromboembolism. Platelet survival was normal in 11 patients with aor...

Drug Spotlight Program: Guidelines for Heparin Therapy

Abstract Thrombosis frequently complicates the course of patients, regardless of their primary disease, making it necessary that physicians, whatever their subspecialty discipline, understand the p...

Effects of Platelet Suppressant, Anticoagulant and Fibrinolytic Therapy in Patients with Recurrent Venous Thrombosis

Abstract Abnormalities of platelet survival time, fibrinogen survival time or fibrinolytic activity have been observed in patients with recurrent venous thrombosis. In the present study these measurements were undertaken in 41 patients with idiopathic recurrent venous thrombosis and repeated after treatment with sulfinpyrazone, ethylestrenol and phenformin or placebo. An additional 10 patients were studied before and after discontinuation of warfarin therapy. Platelet survival (autologous labelling with chromium-51) was shortened in 41 (80 percent); fibrinogen survival (autologous labelling with iodine-125) was shortened in 28 (55 per cent) and abnormal lytic activity (preocclusion and postvenous occlusion euglobulin lysis time) was present in 22 (43 per cent). All patients had at least one abnormal value, and two patients had abnormalities of all three measurements. The administration of sulfinpyrazone increased platelet survival (N = 14) but did not alter either fibrinogen survival or lytic activity. Lytic therapy (N = 7) decreased euglobulin lysis time but did not alter either platelet or fibrinogen survival, and placebo therapy (N = 11) did not alter any measurement. Discontinuation of warfarin therapy was associated with a decrease in fibrinogen survival (N = 10) but no alteration in platelet survival or lytic activity. During therapy (three months) with placebo, venous thrombosis occurred in four of 11 patients; with lytic agents, in three of seven; with sulfinpyrazone, in none of 14; and following discontinuation of warfarin therapy, in one of 10. Results suggest that abnormalities of platelet and fibrinogen survival, and of blood lytic activity are frequently observed in patients with recurrent venous thrombosis and that these measurements behave independently of each other. Platelet suppressant therapy appears to be superior to lytic therapy or to placebo therapy in preventing venous thrombosis in these patients.

Dose-related efficacy and bleeding complications of double-chain tissue plasminogen activator in acute myocardial infarction

Although the efficacy of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction has been demonstrated, little formal dose-ranging information is available. This study examined the use of duteplase, the double-chain rt-PA subsequently used in the Third International Study of Infarct Survival, in a multicenter trial of 267 patients with evolving acute myocardial infarction assigned to receive 1 of 6 weight-adjusted doses. The primary end point was infarct vessel patency after 90 minutes of drug infusion. Patency was defined as Thrombolysis in Myocardial Infarction trial grade 2 or 3 perfusion, and was determined by an independent core laboratory masked to treatment assignment. Patency was present in 48% of patients receiving the lowest dose range and 78% of those receiving the highest, with an association between thrombolytic dose and patency (p = 0.009). The frequency of serious bleeding complications also correlated with the total dose of rt-PA infused (p = 0.003). Bleeding complications were primarily related to instrumentation; blood loss requiring transfusion or otherwise deemed clinically significant occurred in 12% of patients (central nervous system hemorrhage occurred in 1.1%). Thus, higher doses of rt-PA are associated both with increased efficacy and increased risk of serious bleeding complications. Weight-adjusted dosing may provide an optimal risk-benefit ratio for thrombolysis during acute myocardial infarction.

Altered platelet function in patients with prosthetic mitral valves: Effects of sulfinpyrazone therapy

Platelet survival time and platelet adhesiveness and aggregation were examined in 16 patients with prosthetic mitral valves. Subsequently, nine patients were treated with sulfinpyrazone in doses of 400 mg and 800 mg/day, and the studies were repeated after a treatment period of 5 to 8 weeks. 51Chromium survival time was shortened in 15 of 16 patients, and the mean value for the entire group was 5.49 + 0.23 days (normal, 6.73 + 0.21 days; P < 0.001). Mean platelet adhesiveness in glass bead columns was 53 + 5% (normal, 30 to 60%). Platelet aggregation (turbidometric technic of Born) was normal. Treatment with 400 mg of sulfinpyrazone daily reduced platelet adhesiveness to 40 5% (P < 0.05), but effected no change in platelet survival time or platelet aggregation. Therapy with 800 mg of sulfinpyrazone daily corrected platelet survival time to normal, 6.68 + 0.57 days (P < 0.01), but it produced no further decrease in adhesiveness and no change in aggregation. It is concluded that platelet abnormalities regularly occur in patients with prosthetic mitral valves and may contribute to thromboembolism in this group. Platelet survival time is a more sensitive measure of altered platelet kinetics than platelet adhesiveness or platelet aggregation. Therapy with 800 mg of sulfinpyrazone per day corrects demonstrated abnormalities and may be useful for prevention of thromboembolism in patients with prosthetic mitral valves.