AUTHOR=Lillicrap Thomas , Keragala Charithani B. , Draxler Dominik F. , Chan Jilly , Ho Heidi , Harman Stevi , Niego Be'eri , Holliday Elizabeth , Levi Christopher R. , Garcia-Esperon Carlos , Spratt Neil , Gyawali Prajwal , Bivard Andrew , Parsons Mark W. , Montaner Joan , Bustamante Alejandro , Cadenas Israel Fernandez , Cloud Geoffrey , Maguire Jane M. , Lincz Lisa , Kleinig Timothy , Attia John , Koblar Simon , Hamilton-Bruce Monica Anne , Choi Philip , Worrall Bradford B. , Medcalf Robert L. 

TITLE=Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.589628

DOI=10.3389/fneur.2020.589628

ISSN=1664-2295

ABSTRACT=<p><bold>Rationale:</bold> More than half of patients who receive thrombolysis for acute ischaemic stroke fail to recanalize. Elucidating biological factors which predict recanalization could identify therapeutic targets for increasing thrombolysis success.</p><p><bold>Hypothesis:</bold> We hypothesize that individual patient plasmin potential, as measured by <italic>in vitro</italic> response to recombinant tissue-type plasminogen activator (rt-PA), is a biomarker of rt-PA response, and that patients with greater plasmin response are more likely to recanalize early.</p><p><bold>Methods:</bold> This study will use historical samples from the Barcelona Stroke Thrombolysis Biobank, comprised of 350 pre-thrombolysis plasma samples from ischaemic stroke patients who received serial transcranial-Doppler (TCD) measurements before and after thrombolysis. The plasmin potential of each patient will be measured using the level of plasmin-antiplasmin complex (PAP) generated after <italic>in-vitro</italic> addition of rt-PA. Levels of antiplasmin, plasminogen, t-PA activity, and PAI-1 activity will also be determined. Association between plasmin potential variables and time to recanalization [assessed on serial TCD using the thrombolysis in brain ischemia (TIBI) score] will be assessed using Cox proportional hazards models, adjusted for potential confounders.</p><p><bold>Outcomes:</bold> The primary outcome will be time to recanalization detected by TCD (defined as TIBI ≥4). Secondary outcomes will be recanalization within 6-h and recanalization and/or haemorrhagic transformation at 24-h. This analysis will utilize an expanded cohort including ~120 patients from the Targeting Optimal Thrombolysis Outcomes (TOTO) study.</p><p><bold>Discussion:</bold> If association between proteolytic response to rt-PA and recanalization is confirmed, future clinical treatment may customize thrombolytic therapy to maximize outcomes and minimize adverse effects for individual patients.</p>