Topically applied recombinant tissue plasminogen activator for the treatment of venous ulcers. Preliminary report

Abstract

Background: Increasing evidence suggests that fibrin deposition is an important pathogenic component of venous ulceration and that fibrin removal could accelerate ulcer healing.

Objective: We sought to determine whether topical application of recombinant tissue plasminogen activator (tPA) compounded in 1% hyaluronate acid (HA) can be used safely in venous ulcers and whether it can accelerate healing.

Methods: Twelve patients were randomized in a double-blind fashion in three sequential groups of four subjects each, so as to receive daily topical application of either placebo (HA alone, one patient) or tPA/HA (three patients) at escalating doses of 0.25, 0.5, and 1.0 mg/ml of tPA for 4 weeks.

Results: No safety problems occurred, and we found a close direct correlation between mean ulcer reepithelialization, fibrin removal, and the dose of topically applied tPA (r = 0.991).

Conclusion: In this first study to examine its usefulness, topically applied tPA appears to be a safe and promising agent for treating venous ulcers.