Recent studies in patients with acute coronary syndromes have shown significant reduction in the progression of coronary thrombosis using a regimen consisting of low-dose aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. Pathophysiologically, acute coronary syndromes and free tissue transfer are similar in that both involve endothelial damage and clot formation. Using a well-described thrombogenic model in rats, the authors investigated whether this same drug regimen could successfully prevent microsurgical anastomotic thrombosis.
Using a randomized, controlled, blinded experimental design, thrombogenic anastomoses were performed on 30 rat femoral arteries and 29 veins (n = 59). Prior to vessel clamp, each rat received one of three treatment regimens intravenously. Regimen 1 consisted of aspirin (10 mg/kg), heparin (120 units/kg), and tirofiban (1 mg/kg). Regimen 2 contained only aspirin and heparin, and regimen 3 contained isotonic saline (control). The vessels were assessed for patency using the milking test at 5, 15, 30, and 120 min post reperfusion, then harvested for microscopic analysis. Patency rates among treatment groups were analyzed for significant difference using the Fisher's exact test.
Regimen 1 had a patency rate of 100% in both arteries (n = 10) and veins (n = 9) at each time interval. Regimen 2 had an arterial patency rate (n = 10) of 100% at 5 min, 70% at 15 min, then increased to 80% at 20 and 120 min. Venous patency rates for regimen 2 (n = 10) were 90% at 5 and 10 min, and 70% thereafter. Regimen 3 had an arterial patency rate (n = 10) of 60% at 5 min and 40% thereafter, whereas venous patency rates (n = 10) decreased from 80% at 5 min to 20% by 120 min. Regimen 1 significantly increased patency rates compared to control at 30 and 120 min in veins, and at 15, 30, and 120 min in arteries (p < 0.01). The only statistical difference between regimen 2 and control was in venous patency at 120 min (p < 0.04). Regimen 1 had a 10% hematoma rate, whereas none developed with regimens 2 or 3. Microscopic analysis revealed significantly decreased anastomotic thrombus formation in both regimens 1 and 2 compared to control (p < 0.004).
Prophylactic treatment using a regimen of aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban significantly increased patency and decreased thrombus formation in rat femoral arteries and veins after thrombogenic anastomoses. Further study in humans is warranted to determine the role of glycoprotein IIb/IIIa inhibitors in microsurgery.
