Blood coagulation and its alterations in hemorrhagic and thrombotic disorders.
Clinical observations have added to the understanding of basic mechanisms of blood coagulation and its alterations in certain hemorrhagic and thrombotic states. Much clinical evidence exists for concluding that the exposure of blood to tissue factor (thromboplastin) on tissue cells represents the key event initiating fibrin clot formation after tissue injury. This then results in the formation of activated factor VII (VIIa)-tissue factor complexes, which must activate both factor X and factor IX for normal hemostasis. I describe the possible clinical consequences of an aberrant function of the natural anticoagulants regulating blood coagulation--antithrombin, protein C, and tissue factor pathway inhibitor. Understanding the physiologic function of tissue factor pathway inhibitor can illuminate why hemophilic patients bleed, but many other questions remain. I briefly review the four causes for acquired disorders of the blood coagulation reactions--vitamin K deficiency, hepatocellular disease, antibodies to clotting factors, and disseminated intravascular coagulation--but limit my comments to the mechanisms that trigger the formation of antibodies to clotting factors and how these antibodies can deplete the blood of clotting factor activities. Finally, heparin is able to potentiate tissue factor pathway inhibitor function, which is a possible reason why the use of heparin but not warfarin can prevent the numerous thrombotic episodes of the Trousseau's syndrome.
Rapaport
S I
SI
Department of Medicine, University of California, School of Medicine, San Diego.
D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000266:history / Q000502:physiology; D006470:Hemorrhage / Q000097:blood*; D049673:History, 20th Century; D006801:Humans; D008074:Lipoproteins / Q000502:physiology; D011480:Protease Inhibitors; D013927:Thrombosis / Q000097:blood*
D001779:Blood Coagulation Factors; D008074:Lipoproteins; D011480:Protease Inhibitors; C051928:lipoprotein-associated coagulation inhibitor