Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Jun 2013
ReviewClotting activation and hyperfibrinolysis in cirrhosis: implication for bleeding and thrombosis.
Hyperfibrinolysis may be detected in patients with cirrhosis, particularly in case of severe liver failure. Hyperfibrinolysis is usually associated with prolonged global tests of clotting activation, which are then dependent on impaired synthesis of clotting factors by liver cells. The term "coagulopathy" has therefore been coined to indicate the existence of hyperfibrinolysis and blood hypocoagulation in cirrhosis, and, for a long time, these changes have been believed to facilitate bleeding. ⋯ The support of these findings by more recent data allows a redefinition of the overall clotting picture, in particular hyperfibrinolysis, in cirrhosis. Thus, this review analyzes prevalence and clinical impact of hyperfibrinolysis in cirrhosis, focusing in particular on whether it is primary or secondary to clotting activation. Furthermore, we focused such changes in the context of more recent data showing an association between cirrhosis and thrombosis.
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Sepsis, defined as infection-induced systemic inflammatory response syndrome, invariably leads to hemostatic abnormalities ranging from insignificant coagulopathy to disseminated intravascular coagulation (DIC). The inflammation-induced activation of coagulation, the downregulation of physiologic anticoagulant pathways, and impairment of fibrinolysis play a pivotal role in the pathogenesis of microvascular fibrin thrombosis and multiple organ dysfunction syndrome (MODS) in DIC associated with sepsis. The balance between tissue plasminogen activator and plasminogen activator inhibitor-1 mainly regulates fibrinolytic activity. ⋯ Evidence indicates that physical entrapment of bacteria by fibrin at the site of infection may limit their capacity to disseminate into nearby tissues, organs, and systemic circulation. Under this circumstance, impairment of fibrinolysis has protective role in the host defense. Given the protective and pathologic potential of fibrinolysis during sepsis, therapeutics that control DIC as a systemic syndrome, while maintaining the host defense at the infectious foci, are required for the protection against both the development of MODS and for the host defense mechanisms.