Effect of heparin and low molecular weight heparins on thrombin-induced blood platelet activation in the absence of antithrombin III

The antithrombin III independent effect of crude heparin, 2 heparin fractions and a heparinoid on in vitro thrombin-induced [human] platelet activation was investigated. Thrombin-induced platelet factor Va generation and thrombin plus collagen-induced platelet prothrombin converting activity were tested. Crude heparin was a more potent inhibitor of these reactions than the fractions or the heparinoid. The inhibitory action of the heparins was found to be the result of a direct effect on thrombin and not of an effect either on platelet activation functions or on the assembly or functioning of the prothrombinase complex. Probably this heparin inhibition is due to the masking of secondary macromolecular substrate binding sites on the thrombin molecule. No correlation was found between IC50 [median inhibitory concentration] values and the antithrombin III-dependent antithrombin specific activities of the heparins. This supports the notion that heparin properties, other than their affinity for antithrombin III, may contribute to the action of this drug in blood coagulation.