Prevention of Microvascular Thrombosis with Low-Dose Tissue Plasminogen Activator

Abstract

In a blind, randomized study, two groups, each of seven rabbits, were treated with either a very low dose of human melanoma cell line-derived tissue-type plasminogen activator (t-PA) or isotonic saline. t-PA (0.067 mg/kg of body weight) was administered intraaortically, 20 percent being given as a 30-second “bolus” infusion just prior to the reperfusion of intimectomized central ear arteries and the rest as a continuous infusion during the next 2 hours. Arteriotomic bleeding times, accumulations of 32P-labeled platelets, patency, and sizes of thrombus deposits 2 hours after reperfusion were recorded. To confirm the presence of tissue plasminogen activator in plasma, fibrinplate lysis assays of arterial plasma were performed immediately before and 1/2 hour and 2 hours after starting drug infusion. Arteriotomic bleeding times were similar in both groups. Transient “oozing” from wound edges occurred in 40 percent of rabbits treated with tissue plasminogen activator. Patency was significantly increased and thrombus deposits were smaller in the tissue plasminogen activator group. Plasma from animals treated with tissue plasminogen activator caused massive lysis of fibrin plates, whereas plasma from control animals caused little or no lysis. Platelet accumulations were very similar in both groups, indicating that occlusive thrombi mainly consisted of other elements than platelets (e.g., fibrin and red cells). Scanning electron microscopy showed normally adhering and aggregating platelets in both groups. This study shows that mild fibrinolytic stimulation with tissue plasminogen activator significantly improves patency in severely traumatized small-caliber arteries and indicates that such treatment may be one approach to prevent thrombosis at microvascular anastomotic sites.