Clopidogrel Use for Reducing the Rate of Thrombosis in a Rat Model of Microarterial Anastomosis

OBJECTIVES: The national success rate for microvascular free tissue transfer is around 94%. However, in cases of failure, which is most often due to thrombosis in the vascular pedicle, the morbidity can be significant. Microvascular surgeons have used various pharmacologic agents to reduce thrombosis rates; however, none have been ideal. We examined the effects of clopidogrel bisulfate (Plavix), a member of the relatively new class of antiplatelet agents, on the rate of arterial thrombosis in a rat model. DESIGN: Prospective randomized, blinded. SETTING: Tertiary care academic medical center. SUBJECTS: Male Sprague-Dawley rats weighing between 350 and 400 g. INTERVENTION: Clopidogrel or placebo via gavage. After waiting 2 hours for absorption and activation, the "tuck" model of microvascular anastomosis was performed on both femoral arteries. Arteries were transected after 3 hours and patency was assessed. MAIN OUTCOME MEASURES: Bleeding time was obtained by determining the time to clot after removal of 2 mm from the tail tip. Vessel patency was assessed after 3 hours in the clopidogrel-treated and control groups. RESULTS: Of 33 arteries, 19 (58%) in the control group developed complete thrombosis by the end of the period compared with only 6 (19%) of 32 arteries in the group that received clopidogrel. Chi(2) analysis revealed this to be significant (P = .001). The mean (SD) bleeding time in the control group was 158 (44) seconds compared with 233 (48) seconds in the clopidogrel group. CONCLUSIONS: Clopidogrel significantly reduced the rate of arterial thrombosis in a rat model of microvascular repair. The average bleeding time in the clopidogrel group was prolonged, suggesting that absorption and activation occurred. These preliminary data suggest a potential role for clopidogrel in select high-risk patients undergoing microvascular free tissue transfer.