Abstract 2589: Temperature Dependence of Lysis with Tissue Plasminogen Activator, Eptifibatide, and Ultrasound

Introduction: Recombinant tissue plasminogen activator (rt-PA) is the only FDA approved thrombolytic therapy for acute ischemic stroke. Recent studies have shown hypothermia to be beneficial in patient outcome in stroke. However, rt-PA is less effective at temperatures less than 37°C. Interest in improving the lytic efficacy of rt-PA thrombolysis has led to the study of adjunctive therapies such as GP IIb-IIIa inhibitors like eptifibatide (Epf) and ultrasound (US) enhanced thrombolysis. However, the thrombolytic efficacy of combination therapy with rt-PA over a clinically applicable temperature range is unknown. Objective: The effects of temperature on the thrombolytic efficacy of combination rt-PA-driven thrombolysis were determined in an in-vitro human clot model. Methods: Human whole blood clots were made from blood obtained from volunteers, after local Institutional Review Board approval. Clots were made in 20-µL pipettes and placed in a water tank for microscopic visualization during treatment. Sample clots were exposed to human fresh-frozen plasma (hFFP) alone (Control); hFFP and rt-PA ([0.5 µg/ml]; “+rt-PA”); hFFP, rt-PA ([0.5 µg/ml]), and Epf ([0.63 µg/ml]; “+Epf”); and hFFP, rt-PA, Epf, and ultrasound supplied by a 2-MHz transcranial Doppler (TCD) unit (“+TCD”). Exposures were for 30 minutes at 30-37°C. Clot width was measured using a microscopic imaging technique and mean percent fractional clot loss (FCL) at 30 minutes was used to determine thrombolytic efficacy. Results: Each of 15 treatment groups had a minimum of 6 clots (range: 6-148) from 2 different donors (range: 2-21), for a total of 409 clots. At 37°C, FCLs for +rt-PA and +TCD groups were 44% (95% Confidence Interval: 37-52%) and 59% (54-64%) respectively (p Conclusion: Combination therapy using rt-PA, Epf, and 2-MHz US exhibits temperature dependence over a clinically applicable temperature range.