Haemostasis.
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.
Arnout
J
J
Centre for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O & N, 1, Box 911, Herestraat 49, 3000 Leuven, Belgium.
Hoylaerts
M F
MF
Lijnen
H R
HR
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000378:metabolism; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D038981:Receptors, Collagen / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; D010958:Plasminogen; D013925:Thromboplastin; D010960:Plasminogen Activators