When the continuity of the vascular endothelium is disrupted, platelets and
fibrin seal off the defect. Haemostatic processes are classified as primary (mainly involving platelets) and secondary (mainly related to
fibrin formation or blood coagulation). When the
blood clot is no longer required for haemostasis, the fibrinolytic system will dissolve it. The pivotal
ligand for initial platelet recruitment to injured vessel wall components is
von Willebrand factor (vWF), a multimeric
protein present in the subendothelium and in plasma, where it is conformationally activated by shear forces. Adhering activated platelets recruit additional platelets, which are in turn activated and form a platelet aggregate. Coagulation is initiated by a reaction, activating factors IX and X. Once critical amounts of
factor Xa are generated,
thrombin generation is initiated and soluble
fibrinogen is converted into insoluble
fibrin. Excessive
thrombin generation is prevented via inhibition by
antithrombin and also via downregulation of its further generation by activation of the
protein C pathway. Activation of the fibrinolytic system results from conversion of the
proenzyme plasminogen into the active
serine proteinase plasmin by tissue-type or
urokinase-type
plasminogen activators.
Plasmin digests the
fibrin component of a
blood clot. Inhibition of the fibrinolytic system occurs at the level of the
plasminogen activator (by
plasminogen activator inhibitors) or at the level of
plasmin (by alpha2-antiplasmin). Together, these physiological processes act to maintain normal functioning blood vessels and a non-thrombotic state.