title: The haemostatic balance -- Astrup revisited.
abstract: Prof. Tage Astrup first elaborated the notion that blood fluidity involved a balance between the tendency of blood to clot and for such clots to lyse. It would seem that, at that time, this haemostatic balance involved the notion that forming fibrin orchestrated its own destruction by stimulating fibrinolytic activity. In this review, we have clarified the detail of this balance and developed the thesis that Astrup's far-sighted balance notions involve a variety of control mechanisms. These involve the notion that thrombin, being at first sight a procoagulant, can also, in conjunction with thrombomodulin, act as a stimulus of anticoagulant activity by the generation of activated protein C. The thrombin-activatable fibrinolytic inhibitor (TAFI) is also involved in this balance since the generation of thrombin provokes the neutralisation of fibrinolysis by the TAFI pathway. The kallikrein/factor XII/urokinase pathway is discussed indicating yet another aspect of balance between the generation of coagulation and fibrinolysis. The overall theme of this review, apart from an insight into various aspects of the haemostatic balance, is that blood has a strong tendency to clot when tissue is damaged, and the intact vasculature requires major anticoagulant systems to prevent clots adhering to and stabilising in the vasculature.
authors.affiliation: National Institute for Biological Standards and Control, Potters Bar, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Gaffney
authors.forename: T A
authors.initials: TA
authors.lastname: Edgell
authors.forename: C M
authors.initials: CM
authors.lastname: Whitton
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D001778:Blood Coagulation Disorders / Q000097:blood*; D004211:Disseminated Intravascular Coagulation / Q000097:blood; D005174:Factor XII / Q000502:physiology; D005337:Fibrin / Q000096:biosynthesis; D005342:Fibrinolysis / Q000502:physiology; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D010974:Platelet Aggregation / Q000502:physiology; D011486:Protein C / Q000502:physiology; D013917:Thrombin / Q000096:biosynthesis; D019851:Thrombophilia / Q000097:blood
chemical_list: D011486:Protein C; D005174:Factor XII; D005337:Fibrin; D013917:Thrombin