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Título: | Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples |
Autor: | Lillicrap, Thomas; Keragala, Charithani B.; Draxler, Dominik F.; Chan, Jilly; Ho, Heidi; Harman, Stevi; Niego, Be'eri; Holliday, Elizabeth; Levi, Christopher R.; García-Esperon, Carlos; Spratt, Neil; Gyawali, Prajwal; Bivard, Andrew; Parsons, Michael W.; Montaner, Joan CSIC ORCID; Bustamante, Alejandro; Fernández-Cadenas, Israel; Cloud, Geoffrey; Maguire, Jane; Lincz, Lisa; Kleinig, Timothy; Attia, John; Koblar, Simon; Hamilton-Bruce, Monica Anne; Choi, Philip; Worrall, Bradford B.; Medcalf, Robert L. | Palabras clave: | Acute stroke therapy Fibrinolysis rtPA Thrombolysis Plasmin Stroke Recanalization |
Fecha de publicación: | 3-nov-2020 | Editor: | Frontiers Media | Citación: | Frontiers in Neurology 11: 589628 (2020) | Resumen: | [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. |
Versión del editor: | http://doi.org/10.3389/fneur.2020.589628 | URI: | http://hdl.handle.net/10261/236523 | DOI: | 10.3389/fneur.2020.589628 | Identificadores: | doi: 10.3389/fneur.2020.589628 e-issn: 1664-2295 |
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