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Hanet_45971000_2012.pdf
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- Abstract
- FXII, called Hageman factor, was first identifîed in a patient that had the particularity to show a prolonged aPTT while routine test and do not suffer from any bleeding disorder but died from a pulmonary embolism. Research about FXII then emerged. The intrinsic pathway does not seem important for normal hemostasis. Indeed, when an injury occurs, the extrinsic pathway of coagulation virtually handles the whole thrombin/fibrin formation process. The intrinsic pathway is then activated in a FXII-independent pathway to sustain thrombin formation. Tissue factor would be the main physiological activator while FXII seems to help thrombus stability because it enables propagation and growth of the thrombus. Inhibition of FXII might be useful to treat any thrombotic diseases. To assess the importance of FXII inhibition, tests were launched using FXIFA mice. Results clearly show a protective effect against thrombus formation in FeCh, ligation of aorta and the carotid, pulmonary embolism and ischémie brain injury tests. However, there are already many anticoagulant drugs on the market. Inhibition of FXII seems to be a better therapy as the benefit-risks balance is positive with limited risks of hemorrhage condition compared with the other drugs. FXII might be an idéal target for safer therapy for patients in a near future. Pharmacologically inhibiting FXII could provide safer anticoagulation in prévention of venous and arterial thrombosis events without any bleeding disorders.