Restoration of the normal coagulation process: advances in therapies to antagonize heparin

Journal of Cardiovascular Pharmacology
M N D'Ambra

Abstract

A number of naturally occurring anticoagulants exist that preserve normal blood fluidity and limit blood clot formation to vascular injury sites, thus acting as regulators of hemostasis. The protein C/protein S pathway is one system that acts to modulate thrombin formation. The activation of protein C by thrombin is accelerated more than 1,000-fold at the endothelial surface by thrombomodulin localized on the endothelial cell. Activated protein C then binds to its co-factor, protein S, and the protein C/protein S complex exerts its antithrombotic function by inactivating the coagulation factors Va and VIIIa. Patients deficient in protein C and protein S may be particularly vulnerable to thrombotic events after cardiac surgery. In addition, several studies suggest that reductions in protein C and protein S concentrations, as well as thrombomodulin, occur during cardiopulmonary bypass (CPB). The possibility of a low anticoagulant potential when heparinization is reversed may be an important factor in the subsequent morbidity associated with thrombotic complications. Aprotinin is a serine protease inhibitor that in vitro binds competitively with the serine protease-activated protein C. However, aprotinin in the clinical setting ha...Continue Reading

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Citations

Nov 13, 2008·Internal and Emergency Medicine·Marcel Levi
Jun 21, 2011·Hämostaseologie·M LeviP W Kampuisen
Mar 2, 1999·British Journal of Haematology·D H Bevan
Jul 29, 1999·The Journal of Thoracic and Cardiovascular Surgery·O ShigetaT Mitsui
May 4, 2000·Journal of Cardiothoracic and Vascular Anesthesia·O KönerK Karaoğlu

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