[Thrombin: antithrombotic properties and pharmacological consequences].
During the last few years, the availability of endothelial cell cultures isolated from different vascular regions contributed to a significant increase in understanding the complex pro- and antithrombotic mechanisms in our circulatory system. The most important key enzyme is thrombin. Due to its haemostatic properties this serin protease catalyzes fibrin formation, activation of factors V, VIII and XIII as well as irreversible platelet aggregation. These processes may occur even within the circulatory system in case of endothelial stimulation (e. g. by inflammation mediators) for expression of binding sites for factors IX, IXa, X, Xa, von Willebrand protein and PAF. Thus not only catalytically activated coagulatory cascades, but also enhanced cooperation of platelets and granulocytes will occur. Paradoxically, in low intravascular concentration, thrombin, in combination with a healthy endothelial layer, may be the critical factor for the inhibition of thromboses. Respective antithrombogenic properties will mainly affect pre-venous microvascular circulation. In detail, they include thrombin-induced endothelial formation of antiaggregatory autacoids from platelet release products, anticoagulatory activation of protein C and absorption of active coagulation factors at endothelial heparan/ATIII complexes as well as release of profibrinolytic plasminogen activator of endothelial origin. The understanding of these complex regulatory functions enables not only a critical evaluation of actually discussed haemostasiologic risk factors (enhanced platelet reactivity, high concentrations of factor VII, VIII, fibrinogen, PAI, ATIII), but also the development of new pharmacologic strategies for prevention of thrombosis.
Chirurgische Klinik und Poliklinik, Klinikum der Universität München-Grosshadern, Marchioninistr. 15, 81377 München.
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D000991:Antithrombins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005337:Fibrin / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D013917:Thrombin / Q000502:physiology*; D013927:Thrombosis / Q000517:prevention & control
D000991:Antithrombins; D001779:Blood Coagulation Factors; D005337:Fibrin; D013917:Thrombin