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.
