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eISSN: 1643-3750

Gabexate mesilate and heparin responsiveness in coronary patients

Marco Ranucci

Med Sci Monit 2004; 10(3): PI40-43

ID: 11610

Published: 2004-03-01


Background:     Heparin responsiveness in patients undergoing coronary operations changes depending on many individual factors. Reduced sensitivity to heparin is a common feature and may determine a difficult intraoperative anticoagulation. The aim of this study was to determine the effectiveness of a novel serine proteases inhibitor (gabexate mesilate) in increasing heparin responsiveness.
Material/Methods:     20 patients undergoing coronary operations with cardiopulmonary bypass were studied with respect to their heparin responsiveness. This was measured using individual dose/response tests with a heparin monitoring system before and after a 10-minute intravenous infusion of 2 mg·kg–1·h–1 of gabexate mesilate, a direct inhibitor of factor Xa, thrombin, kallikrein, and other serine proteases. The complete test was performed before initiating the surgical maneuvers.
Results:     At each heparin concentration, gabexate mesilate produced a significant prolongation of the kaolin-activated clotting time. The heparin responsiveness (seconds·IU–1·ml–1) in terms of activated clotting time significantly (p=0.007) increased from the baseline of 68.1±13.8 to 74.7±16.1 during infusion, and the heparin loading dose (IU/kg) required to reach the target activated clotting time of 480 seconds significantly (p=0.009) decreased from the baseline of 290±82.3 to 260±77.6 during gabexate mesilate infusion.
Conclusions:     Gabexate mesilate significantly increases individual heparin responsiveness in coronary patients. Its use in the treatment of patients with a reduced sensitivity to heparin may support or replace the conventional therapeutic approach based on fresh frozen plasma or purified antithrombin.

Keywords: Aged, Antithrombins - metabolism, Bleeding Time, Blood Coagulation, Coronary Disease - drug therapy, Factor Xa - antagonists & inhibitors, Female, Gabexate - pharmacology, Heparin - metabolism, Heparin - pharmacology, Humans, Kallikreins - antagonists & inhibitors, Male, Middle Aged, Serine Proteinase Inhibitors - pharmacology, Thrombin - antagonists & inhibitors, Time Factors, Aged, Antithrombins - metabolism, Bleeding Time, Blood Coagulation, Coronary Disease - drug therapy, Factor Xa - antagonists & inhibitors, Female, Gabexate - pharmacology, Heparin - pharmacology, Humans, Kallikreins - antagonists & inhibitors, Male, Middle Aged, Serine Proteinase Inhibitors - pharmacology, Thrombin - antagonists & inhibitors, Time Factors



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