Abstract T MP20: A Rapid Clot Lysis Assay to Predict Response to IV rt-PA in Stroke

Abstract

Background: The cornerstone of acute stroke therapy is intravenous rt-PA, with the goal of rapid thrombolysis and restoration of blood flow. Unfortunately, less than half of patients treated have a favorable outcome. Since recanalization is closely correlated with the clinical response, endogenous resistance to rt-PA may inhibit thrombolysis and neurologic improvement. The primary objective of this research study was to evaluate whether an in vitro clot lysis assay and thrombolytic biomarkers could predict response to IV rt-PA in acute ischemic stroke patients Methods: Ischemic stroke patients who received IV rt-PA were recruited from two sites (Augusta, GA and Udine, Italy). Blood samples were collected prior to rt-PA administration and a favorable clinical response to rt-PA was specified as an NIHSS score of two or less at 24 hours. The time required for 50% platelet-poor clot lysis (C50%) was measured by an in vitro turbidimetric assay. The endogenous major fibrinolytic inhibitors (tissue plasminogen inhibitor, PAI-1; and α2-antiplasmin, α2-AP), D-dimer, fibrinogen and pro-thrombin time (PT), were assessed and correlated with clinical outcome. Results: We enrolled 54 rt-PA recipients (63±15 years; 72% male, and 85% white). The mean NIHSS was 11.2±5.1 at admission and 8.2±8.1 at 24 hours; 36% of patients had a favorable clinical response. There was a moderate reduction in C50% among patients with a favorable clinical outcome compared to those with an unfavorable outcome (669.5±46.3 vs. 704.7±91.6; p=0.075). There was no significant difference in PT (13.6±0.8 sec vs. 13.8±1.2 sec; p=0.444), PAI-1(28.2±34.1 pg/mL vs. 19.8±25.9 pg/mL; p=0.321), α2-AP (85.1±7.2 % vs. 88.8±10.1 %; p=0.153), D-dimer (269.5±232.2 ng/mL vs. 368.2±444.6 ng/mL; p=0.303) or fibrinogen (318.1±71.4 mg/dL vs. 343.0±173.1 mg/dL; p=0.465) levels between subjects with favorable and unfavorable response to rt-PA. Summary: Lack of response to IV rt-PA in stroke patients may reflect endogenous resistance to fibrinolysis reflected by prolonged clot lysis in vitro. The utility of clot lysis to predict rt-PA unresponsiveness should be tested in a larger clinical study.