Do heparin fractions and heparinoids inhibit thrombin-catalyzed reactions in the absence of antithrombin III differently than crude heparin?
The study demonstrates that crude heparin is a more potent inhibitor of thrombin-catalyzed feedback reactions than low molecular weight fractions in the absence of antithrombin III, which may explain differences in antithrombotic and hemorrhagic properties.
The antithrombin-III-independent effect of heparin was studied in the following thrombin-catalyzed reactions: activation of purified plasma factor V and partially purified plasma factor VIII:C, generation of factor Va from the platelets and, in the presence of collagen, of the platelet procoagulant activity. Five heparin fractions and a heparinoid were compared to crude heparin. Crude heparin was a more potent inhibitor of these reactions than the fractions or the heparinoid. The inhibitory action of heparin (fractions) appeared to be the result of the formation of a complex between heparin and thrombin that alters the specificity of thrombin towards high molecular weight substrates. The inhibition of these thrombin-dependent feedback reactions in blood coagulation might be of importance in the mechanisms for the dissociation between the antithrombotic and hemorrhagic properties of low molecular weight heparins.
Baruch et al. (Tue,) studied this question.
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