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Antiplatelet drugs and generation of thrombin in clotting blood
A Szczeklik, M Krzanowski, P Gora and J Radwan
Department of Medicine, Copernicus Academy of Medicine, Cracow, Poland.
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.
Volume 80,
Issue 8,
pp. 2006-2011,
10/15/1992
Copyright © 1992 by The American Society of Hematology
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