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  • Title: Anticoagulant potential of synthetic and recombinant inhibitors of factor Xa and thrombin in vitro.
    Author: Hauptmann J, Kaiser B.
    Journal: Blood Coagul Fibrinolysis; 1993 Aug; 4(4):577-82. PubMed ID: 8218854.
    Abstract:
    The anticoagulant effects of thrombin inhibitors in vitro and ex vivo are well characterized. Inhibitors of factor Xa might also be effective as anticoagulants. We studied several synthetic, low-molecular-weight inhibitors with varying affinity to thrombin and factor Xa using three in vitro clot-based assays representative of the effects of thrombin added or generated via the intrinsic or extrinsic coagulation pathways. The recombinant selective thrombin and factor Xa inhibitors, hirudin and antistasin, were studied for comparison. The thrombin time assay is a measure of the antithrombin potential of a given inhibitor, while the activated partial thromboplastin time is influenced by inhibition of thrombin and/or of factor Xa in a similar manner. The prothrombin time assay was more sensitive to inhibition of factor Xa, as evidenced by the potent and selective inhibitor antistasin as well as for less potent and less selective synthetic inhibitors of factor Xa. Direct synthetic or recombinant inhibitors of factor Xa with Ki values in the submicromolar range were potent anticoagulants, approaching or exceeding the potency of hirudin in prolonging the prothrombin time and the activated partial thromboplastin time in vitro.
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