Prevention of microsurgical anastomotic thrombosis using aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban.
BACKGROUND
Recent clinical trials involving patients with acute coronary syndromes have demonstrated significant reduction in the progression of coronary artery thrombosis using a regimen of aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. Acute coronary syndromes and free tissue transfer are similar pathophysiologically in that they both involve endothelial injury, thrombosis, and ischemia. In this study, the authors investigate tirofiban, combined with aspirin and heparin, for the prevention of microsurgical anastomotic thrombosis in a thrombogenic rat model.


METHODS
Using a randomized, controlled, double-blind experimental design, 80 thrombogenic anastomoses were performed on rat femoral arteries (n = 40) and veins (n = 40). Preoperatively, each rat received one of four treatment regimens: aspirin and heparin (regimen 1), aspirin and heparin plus tirofiban (regimen 2), tirofiban alone (regimen 3), or isotonic saline (control) (regimen 4). Vessels were assessed for patency at 5, 15, 30, and 120 minutes after reperfusion and then harvested for microscopic analysis.


RESULTS
At 120 minutes after reperfusion, regimen 1 had an arterial and venous patency rate of 80 percent and 70 percent, respectively, whereas the vessel patency rate for regimen 2 was 100 percent. The difference between regimens 1 and 2 was not statistically significant. Regimens 3 and 4 had vessel patency rates of 40 percent or less. The aspirin/heparin and aspirin/heparin/tirofiban groups both demonstrated significantly improved vessel patency and significantly less thrombotic occlusion compared with controls.


CONCLUSIONS
Combination therapy with aspirin, heparin, and tirofiban significantly increases arterial and venous patency and decreases anastomotic thrombus formation in thrombogenic anastomoses in rats. The role of glycoprotein IIb/IIIa inhibitors in microsurgery warrants further investigation.
Chung
Thomas L
TL
Baltimore, Md. From the Division of Plastic and Reconstructive Surgery, University of Maryland Medical Center, and Department of Anatomy and Neurobiology, University of Maryland School of Medicine.
Pumplin
David W
DW
Holton
Luther H
LH
Taylor
Jesse A
JA
Rodriguez
Eduardo D
ED
Silverman
Ronald P
RP
D000714:Anastomosis, Surgical; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006493:Heparin / Q000627:therapeutic use*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000503:physiopathology / Q000517:prevention & control*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014654:Vascular Patency
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D006493:Heparin; D000077466:Tirofiban; D001241:Aspirin