Prevention of Microvascular Thrombosis with Short-Term Infusion of Human Tissue-Type Plasminogen Activator

Abstract

A locally active thrombolytic agent, human tissue-type plasminogen activator (t-PA), given over a finite time period (24 hours) by local infusion, maintains long-term microvascular patency (7 days) in a proven thrombosis model using an arterial inversion graft in the rabbit model. Thirteen rabbits in the control group and 16 rabbits in the experimental group underwent an arterial inversion graft followed by continuous infusion (24 hours) with human tissue-type plasminogen activator (experimental) or normal saline (control). No significant clinical bleeding or alteration of coagulation parameters was noted in hematologic studies in both experimental and control groups. Scanning electron microscopy of the postoperative human tissue-type plasminogen activator-perfused arteries suggests an interaction of the human tissue-type plasminogen activator with specific platelet receptors in reversing microvascular thrombosis by decreasing or preventing further platelet aggregation and adhesion. Human tissue-type plasminogen activator infused locally for a finite period (24 hours) allows adequate time for platelet metamorphosis to occur in converting a thrombogenic to a nonthrombogenic vessel surface. The clinical ramifications in preventing or reversing microvascular thrombosis in free-tissue transfers and replantation surgery are apparent. Further study in this area will enhance our understanding of the pathogenesis and prevention of microvascular thrombosis.