Blood constituents and safety pharmacology

Abstract

The coagulation cascade consists of a complex network of interactions resulting in thrombin-mediated conversion of fibrinogen to fibrin, which is one major component of a thrombus. The coagulation cascade can be initiated either by the “exogenous pathway,” the release of thromboplastin (tissue factor) leading to activation of factor VII to the tissue factor/factor VIIa complex, or by the “endogenous pathway,” so-called contact activation leading via factors XII, XI, and IX to the assembly of the tenase complex consisting of activated factors VIII and IX and Ca2+on a phospholipid surface. Both complexes can activate factor X, which induces the formation of the prothrombinase complex consisting of factor Xa, factor Va, and Ca2+on a phospholipid’s surface. The latter leads to the activation of thrombin, which in turn cleaves fibrinogen to fibrin. The three coagulation tests (PT, APTT, and TT) allow differentiating between effects on the exogenous or endogenous pathway or on fibrin formation. The influence of compounds on the plasmatic blood coagulation is determined by measuring the coagulation parameters prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) ex vivo.