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The influence of cefamandole and vancomycin used for prophylaxis on the warfarin anticoagulation response in 60 cardiac valve replacement patients during the postoperative period is presented. Patients were divided into two groups, hyper-responders prothrombin time (PT) greater than or equal to 32 sec, 48 hr after the initial warfarin dose (GrIHR), or normal responders PT less than 32 sec (GrIINR). Fifteen patients (25%) were in GrIHR (PT 44.3 +/- 10.5) and 45 in GrIINR (21 +/- 5). Fourteen of the 15 GrIHR patients received cefamandole and 1 of the 15 GrIHR patients received vancomycin p less than 0.05, as prophylaxis. Warfarin sensitivity was assessed using a warfarin dose index (WDI) calculated in the initial postoperative period (WDIINT) and at discharge (WDIDIS). GrIHR patients had greater WDIINT and WDIDIS compared to GrIINR p less than 0.001. Baseline prothrombin time measured 8 hours prior to start of warfarin therapy (PTBL), was linearly correlated to the WDIINT with r = 0.8, p less than 0.001 in cefamandole patients only. The data suggests that cefamandole increases warfarin sensitivity early in the postoperative course of oral anticoagulation therapy, which may lead to excessively high prothrombin times with the possibility for serious bleeding.