Factor XI and XII as antithrombotic targets

Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants...

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Bibliographic Details
Published in:Current opinion in hematology Vol. 18; no. 5; p. 349
Main Authors: Müller, Felicitas, Gailani, David, Renné, Thomas
Format: Journal Article
Language:English
Published: United States 01.09.2011
Subjects:
Animals
Anticoagulants - pharmacology
Anticoagulants - therapeutic use
Blood Coagulation - drug effects
Blood Coagulation - physiology
Factor XI - antagonists & inhibitors
Factor XI - metabolism
Factor XI Deficiency - blood
Factor XI Deficiency - drug therapy
Factor XI Deficiency - metabolism
Factor XII - antagonists & inhibitors
Factor XII - metabolism
Factor XII Deficiency - blood
Factor XII Deficiency - drug therapy
Factor XII Deficiency - metabolism
Hemostasis - drug effects
Hemostasis - physiology
Humans
Thrombosis - drug therapy
Thrombosis - metabolism
ISSN:1531-7048, 1531-7048
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Summary:Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding. Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis). Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII-factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk.
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ISSN:1531-7048
1531-7048
DOI:10.1097/MOH.0b013e3283497e61