Gabexate mesilate and heparin responsiveness in coronary patients

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.

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.

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.

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.