Desirudin Reduces the Rate of Microvenous Thrombosis in a Rat Model

Abstract

In an effort to evaluate pharmacologic agents for optimal anticoagulant prophylaxis in patients undergoing free tissue transfer, we evaluated the efficacy of desirudin (Canyon Pharmaceuticals, Hunt Valley, MD), a recombinant hirudin that acts as a direct thrombin inhibitor, using a rat model of microvenous thrombosis. Randomized, blinded study using an in vivo rat model of microvenous failure. Thirty-two rats received either desirudin or saline in a randomized, blinded fashion 30 minutes prior to performance of a standardized thrombogenic procedure on rat femoral veins. Bleeding time, vessel patency, and presence of clot within the anastomosis were subsequently assessed. Appropriate statistical analyses were then performed. There was a significant increase in vessel patency in rats treated preoperatively with desirudin compared to controls receiving saline (96.9% vs. 53.1%, P < .001). In evaluating patent vessels for non-occluding clot, 41.2% of control rats had non-obstructive clot at the site of anastomosis, versus 3.2% of rats treated with desirudin (P = .002). Bleeding times were longer in desirudin-treated rats than those that received saline (7.17 +/- 3 minutes vs. 5.15 +/- 1.2 minutes, P = .027). The use of preoperative desirudin increases the rate of microvascular anastomotic patency, decreases the occurrence of non-occluding clot, and increases bleeding time in an in vivo rat model, indicating potential efficacy in patients undergoing microvascular free tissue transfer.