Abstract T MP20: A Rapid Clot Lysis Assay to Predict Response to IV rt-PA in Stroke
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.
Author Disclosures: I.Y. Sazonova: Research Grant; Modest; EDCLOT grant (Genentech, CA) to JAS and IYS, BBDI award (GRU) to JAS and IYS, and R21-NS072318-01 award to IYS. F. Janes: None. J.L. Waller: None. J.E. Brittain: None. G. Gigli: None. R. Giacomello: None. D.C. Hess: Honoraria; Modest; has received honoraria from Vindico CME. Ownership Interest; Modest; cofounder of REACH Health Inc, has cofounder’s equity and is on the REACH Health Inc Board of Directors. Consultant/Advisory Board; Modest; serves on a Pfizer Data and Safety Monitoring Board an Adjudication Committee for CoVance. J.A. Switzer: Research Grant; Significant; Research grants for Genentech on Telestroke Networks. Consultant/Advisory Board; Modest; REACH Health, Inc.. Other; Significant; Georgia Regents Medical Center employs Dr Switzer and the hospital provides contracted telehealth services to hospitals in Georgia and South Carolina for telestroke.
- © 2014 by American Heart Association, Inc.