Beyond prothrombin time and activated partial thromboplastin time: coagulation in vivo-an illustrated review

The steps that initiate coagulation in vivo are different from the components of prothrombin time (PT) and activated partial thromboplastin time (aPTT). The reactions of PT and aPTT are kept separate by the addition of high concentrations of tissue factor (for PT) or silica (for aPTT). In vivo, these reactions blend together as an initiation phase followed by a propagation phase. The initiation phase produces small quantities of thrombin, while much larger amounts of thrombin are generated by the propagation phase. Formation of a visible clot occurs when less than 4% of the total thrombin is generated. Although the contact pathway is essential for the aPTT reaction, this set of reactions does not play a role in normal hemostasis in vivo but does appear to be important in pathologic thrombosis and inflammation. The hemostatic pathways are controlled in vivo by the antithrombin system, tissue factor pathway inhibitor, and the protein C and protein S complexes. Platelets and endothelial cells are an essential component of hemostasis. In the presence of thrombin and vessel wall damage, platelets are activated, and they adhere to the bleeding site and aggregate releasing other mediators for further platelet aggregation.