%0 Journal Article
%A Lillicrap, Thomas
%A Keragala, Charithani B
%A Draxler, Dominik F
%A Chan, Jilly
%A Ho, Heidi
%A Harman, Stevi
%A Niego, Be'eri
%A Holliday, Elizabeth
%A Levi, Christopher R
%A Garcia-Esperon, Carlos
%A Spratt, Neil
%A Gyawali, Prajwal
%A Bivard, Andrew
%A Parsons, Mark W
%A Montaner, Joan
%A Bustamante, Alejandro
%A Fernandez-Cadenas, Israel 
%A Cloud, Geoffrey
%A Maguire, Jane M
%A Lincz, Lisa
%A Kleinig, Timothy
%A Attia, John
%A Koblar, Simon
%A Hamilton-Bruce, Monica Anne
%A Choi, Philip
%A Worrall, Bradford B
%A Medcalf, Robert L
%T Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples.
%D 2020
%@ 1664-2295
%U http://hdl.handle.net/10668/16648
%X 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.
%K acute stroke therapy
%K fibrinolysis
%K plasmin
%K recanalization
%K rtPA
%K stroke
%K thrombolysis
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