Pathophysiology and clinical aspects of fibrinolysis and inhibition of coagulation. Experimental and clinical studies with special reference to women on oral contraceptives and selected groups of thrombosis prone patients.
The primary aim of the haemostatic mechanism is to protect the vascular system and to keep it intact after injury in order to secure the function of tissues and organs. A second aim is to provide a matrix in wound healing and tissue repair. The regulation of this physiological mechanism is effected by a dynamic haemostatic balance comprising interactions between endothelial cells, thrombocytes, coagulation, and fibrinolysis. This balance determines the amount of fibrin layed down at a site of injury thereby influencing the progress of the reparative processes. Clinical experience has, as described, shown that the concept of a dynamic haemostatic balance, and the increase in knowledge about the mechanisms involved in its regulation, can be applied with success in the elucidation and treatment of cases of impaired haemostasis, or when during a disease instances of thrombosis or embolism arise, which otherwise would have been difficult to explain or to subject to rational treatment. The results obtained and the experiences gained have therefore substantiated the existence of such a balance. Disturbances in the regulation of the balance may cause the formation and deposition of too little fibrin at a site of injury resulting in impaired haemostasis, ultimately manifesting itself as a haemorrhagic disorder. Or, an enhanced formation or delayed resolution of fibrin may cause thrombosis. Therefore, in the acute clinical cases the balance may adequately be described as a thrombohaemorrhagic balance. These observations have in particular underscored the role of an impaired fibrinolysis or decreased inhibition of coagulation in the pathogenesis of thromboembolic disease. They suggest the existence of an antithrombotic potential, which might be reduced due to a decreased inhibition of coagulation and/or a decreased fibrinolysis. The major stages in the mechanisms of blood coagulation and fibrin resolution are now well elucidated. This has increased our understanding of the interplay between the activating and regulating factors by which the organism keeps the formation of fibrin under control. Effects of disturbances in the balance are illustrated by description of cases of haemorrhagic disorders or thrombosis, and the pathophysiological aspects are surveyed. The regulation of coagulation and fibrinolysis follows in both systems the same pattern. The active enzymes (thrombin and plasmin, respectively) are formed by activation of circulating proenzymes, and inhibitors (circulating or localized) exert their modifying influences at various stages of the total process.(ABSTRACT TRUNCATED AT 400 WORDS)
Jespersen
J
J
Department of Clinical Chemistry, Ribe County Hospital, Esbjerg, Denmark.
D020152:Antithrombin III Deficiency; D001777:Blood Coagulation / Q000187:drug effects; D003276:Contraceptives, Oral / Q000494:pharmacology*; D004198:Disease Susceptibility; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D010960:Plasminogen Activators / Q000502:physiology; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology
D003276:Contraceptives, Oral; D012739:Gonadal Steroid Hormones; D010960:Plasminogen Activators