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Dan Med Bull. 1988 Feb;35(1):1-33.

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.

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  • 1Department of Clinical Chemistry, Ribe County Hospital, Esbjerg, Denmark.


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)


A detailed review of the dynamic processes of coagulation and fibrinolysis precedes a discussion of clinical applications, especially for users of oral contraception and others with antithrombin-III disorders. Coagulation and fibrinolysis are both initiated by activation of circulating pro-enzymes, namely thrombin and plasmin. Both of these have circulating and local inhibitors that modify stages of the clotting and fibrinolytic processes. The circulating system, also called the intrinsic coagulation system, can be regarded as an amplification system related to the extrinsic, or cellular system. Antithrombin-III (AT-III) is a specific plasma protein that inhibits coagulation at the step (after platelets aggregate) of fibrin formation. At-III can be measured immunologically, or functionally by its ability to bind thrombin in the presence of heparin. Familial AT-III deficiencies incur a risk of venous thrombosis, and may be total or partial, depending on the type of genetic defect. Affected individuals may be treated with vitamin-K antagonists, anabolic steroids, or subcutaneous, low-dose heparin. Episodes of thrombosis may also represent acquired AT-III deficiency, such as in pregnancy, abortion, post-surgery, or disseminated intravascular coagulation. The approximately 10% decrease in AT-III seen in women taking estrogen-containing oral contraceptives is within normal limits. The oral route is significant, as AT-III is a protein made by the liver. This fall is not of any physiological significance, since the plasma euglobulin fibrinolytic system is also increased. Some pill users with AT-III deficiency or other thrombosis-prone conditions, however, may be at risk of increased thrombosis.

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