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Type: Journal article
Title: Plasmin generation potential and recanalization in acute ischaemic stroke; an observational cohort study of stroke biobank samples
Author: Lillicrap, T.
Keragala, C.B.
Draxler, D.F.
Chan, J.
Ho, H.
Harman, S.
Niego, B.
Holliday, E.
Levi, C.R.
Garcia-Esperon, C.
Spratt, N.
Gyawali, P.
Bivard, A.
Parsons, M.W.
Montaner, J.
Bustamante, A.
Cadenas, I.F.
Cloud, G.
Maguire, J.M.
Lincz, L.
et al.
Citation: Frontiers in Neurology, 2020; 11:589628-1-589628-4
Publisher: Frontiers Media
Issue Date: 2020
ISSN: 1664-2295
Statement of
Thomas Lillicrap … Timothy Kleinig … Simon Koblar, Monica Anne Hamilton-Bruce … et al.
Abstract: Rationale: 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. Hypothesis: We hypothesize that individual patient plasmin potential, as measured by in vitro 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. Methods: 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 in-vitro 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. Outcomes: 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. Discussion: 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.
Keywords: Acute stroke therapy; fibrinolysis; rtPA; thrombolysis; plasmin; stroke; recanalization
Rights: Copyright © 2020 Lillicrap, Keragala, Draxler, Chan, Ho, Harman, Niego, Holliday, Levi, Garcia-Esperon, Spratt, Gyawali, Bivard, Parsons, Montaner, Bustamante, Cadenas, Cloud, Maguire, Lincz, Kleinig, Attia, Koblar, Hamilton-Bruce, Choi, Worrall and Medcalf. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI: 10.3389/fneur.2020.589628
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