Fibrinogen mediated activation of platelet aggregation and thromboxane A2 release: pathological implications in vascular disease.

D P Mikhailidis, M A Barradas, A Maris, J Y Jeremy, P Dandona

The effect of a human fibrinogen preparation on in vitro platelet aggregation was assessed. Platelets were obtained from healthy volunteers. Human fibrinogen induced platelet aggregation in 65% of platelet rich plasma samples and enhanced submaximal platelet aggregation induced by heparin or by several conventional agonists in all samples. Aggregation induced by fibrinogen alone was reversed by the in vitro addition of human albumin. Fibrinogen induced aggregation was associated with the release of the vasoconstrictor, thromboxane A2. Preincubation with indomethacin inhibited both the aggregation and the release of thromboxane A2. Fibrinogen had no effect on in vitro vascular prostaglandin I2 synthesis (rat aortic rings) during a 60 minute incubation. The observed effects of fibrinogen on platelet function may be relevant to clinical conditions in which hyperaggregability of platelets is associated with hyperfibrinogenemia and thrombosis.

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