fibrinopeptide-a and ozagrel

Platelets participate in formation of thrombin through secretion of coagulation factors and by providing a catalytic surface on which prothrombinase complex is assembled. We studied the effects of four antiplatelet drugs on thrombin formation in healthy volunteers. Thrombin generation was monitored both in vitro--in recalcified plasma--and ex vivo--in blood emerging from a standardized skin microvasculature injury, which also served to determine bleeding time. A mathematical model has been developed to describe the latter reaction. It is based on estimation of the rate of increase in fibrinopeptide A (FPA), a specific marker of thrombin activity, in blood emerging from skin incisions. Two hours after the ingestion of 500 mg of aspirin, thrombin formation became significantly impaired both in vitro and ex vivo. In contrast, 2 hours after the oral administration of placebo, indomethacin 50 mg, or OKY-046 (a thromboxane synthase inhibitor) 400 mg, thrombinogenesis remained unaltered. Ticlopidine, studied either 3 hours after 500 mg oral administration, or after 5 days of intake at a daily dose of 500 mg, had no effect on thrombin generation. Thus, aspirin, contrary to other antiplatelet drugs, depresses thrombin formation in clotting blood, a phenomenon that might be of clinical relevance. It is suggested that aspirin exerts this effect by acetylating prothrombin and/or macromolecules of platelet membrane.

Topics: Adult; Aspirin; Blood Coagulation; Female; Fibrinopeptide A; Humans; In Vitro Techniques; Indomethacin; Kinetics; Male; Mathematics; Methacrylates; Middle Aged; Models, Biological; Platelet Aggregation Inhibitors; Skin; Thrombin; Thromboxane-A Synthase; Ticlopidine

The present study was designed to examine the effects of sodium ozagrel on hemostatic markers and cerebral blood flow in lacunar infarction. Ten cases of lacunar infarction in which sodium ozagrel was given (administered group), 10 cases of lacunar infarction in which sodium ozagrel was not given (nonadministered group), and 10 age-matched controls in which cerebrovascular diseases were absent but risk factors were similar to those of the patients (control group) were studied. Intravenous infusion of 80 mg of sodium ozagrel was done twice a day for 2 weeks. Platelet factor 4, beta-thromboglobulin, and fibrinopeptide A were significantly higher in the administered and nonadministered groups than in the control group at the time of admission. Platelet factor 4, beta-thromboglobulin, fibrinopeptide A, and thromboxane B2 were decreased significantly by the administration of sodium ozagrel. The blood flow in the cerebral cortex was significantly lower in the administered and nonadministered groups than in the control group. The blood flows around the infarcted area, in the cerebral cortex, and in the cerebral white matter were significantly increased by the administration of sodium ozagrel. Sodium ozagrel is considered to decrease platelet aggregation and increase cerebral blood flow by decreasing thromboxane A2, which has a platelet-aggregating and a vasoconstricting action. Sodium ozagrel is considered to be effective in the acute phase of lacunar infarction.

Topics: Aged; beta-Thromboglobulin; Cerebral Infarction; Cerebrovascular Circulation; Enzyme Inhibitors; Fibrinopeptide A; Hemostasis; Humans; Magnetic Resonance Angiography; Methacrylates; Middle Aged; Platelet Factor 4; Thromboxane-A Synthase