Abstract
Introduction: Despite adequate heparinization, significant thrombin formation, as measured by molecular hemostatic markers, occurs during CPB. [1] The presence of thrombin not only promotes fibrin generation and possibly a consumptive coagulopathy, but also activates fibrinolysis. It has been proposed that dilution of antithrombin III (ATIII) during CPB plays a contributory role. [2] We hypothesized that supplementation of AT-III to normal physiologic levels would decrease thrombin generation and possibly reduce perioperative bleeding. Methods: Twenty patients undergoing cardiac surgery were randomized for this double-blind, placebo-controlled study. Ten patients received ATIII supplementation (50U/kg) by an intravenous infusion prior to incision, and 10 patients received placebo. Heparin and protamine administration were per protocol in both groups. Blood samples were obtained preoperatively, each hour while on CPB, and 1, 3, and 24 hrs after completion of CPB. Samples were analyzed for ATIII concentration, thrombin-antithrombin complex (TAT), and D-dimers. Results: As expected, significantly higher perioperative concentrations of ATIII were observed in the treatment group. However, no statistically significant differences in TAT or D-dimer concentrations were observed between the groups. In addition, no statistically significant differences in heparin administration, postoperative blood loss, patient demographics, AXC time, or CPB time were evident between the two groups. Discussion: Despite statistically significant increases in ATIII concentrations measured in the treatment group, we observed no significant differences in thrombin generation (TAT), fibrinolytic activity (D-dimers), or postoperative blood loss between the groups. These results suggest that preoperative supplementation of ATIII to physiologic plasma concentrations does not affect thrombin generation or blood loss associated with cardiac surgery.
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