Inhibition of thrombin-catalyzed reactions in blood coagulation and platelet activation by heparin fractions in the absence of antithrombin III.
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.
D000990:Antithrombin III / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000502:physiology; D005165:Factor V / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D015943:Factor Va; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D005246:Feedback; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001779:Blood Coagulation Factors; C049426:platelet procoagulant factor; D015943:Factor Va; D000990:Antithrombin III; D005165:Factor V; D005169:Factor VIII; D005170:Factor X; D006493:Heparin; D003094:Collagen; D013917:Thrombin; D015951:Factor Xa