Thrombodynamics of Microvascular Repairs: Effects of Antithrombotic Therapy on Platelets and Fibrin

Abstract

To evaluate the hypothesis that platelets and fibrin differentially accrue at microvascular anastomoses in arteries versus veins and under different pharmacologic conditions. We evaluated mouse arterial and venous anastomoses with intravital fluorescence imaging, using fluorophore-labeled platelets and anti-fibrin antibodies to measure the extent of thrombus component development in the intraluminal anastomotic site. We evaluated systemic heparin or eptifibatide (platelet aggregation inhibitor) to determine their relative influences on thrombus composition. Platelets accumulated rapidly in both arterial and venous repairs, and then fell in number after 10 to 30 minutes of reflow. Fibrin had a relatively steady development over 60 minutes in veins, with a more variable increase in arteries. Heparin reduced platelet accumulation in arteries and fibrin development in veins. Eptifibatide reduced platelets in both arteries and veins and had an apparent effect on lowering the amount of fibrin in veins. These findings show that platelets have a rapid, transient response, whereas fibrin has a slower, more sustained accrual in both arterial and venous anastomoses. Furthermore, inhibition of either coagulation or platelet aggregation can influence presumably non-targeted components of thrombosis in vascular repairs of both arteries and veins. Preventing replantation failure using antithrombotic therapies requires a better understanding of the effect of each pharmacologic compound on the various aspects of thrombogenesis.