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Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples.
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.
Afiliación
  • Lillicrap T; Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
  • Keragala CB; Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
  • Draxler DF; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.
  • Chan J; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.
  • Ho H; Department of Cardiology, University Hospital of Bern, Bern, Switzerland.
  • Harman S; Bern Centre for Precision Medicine, Bern, Switzerland.
  • Niego B; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.
  • Holliday E; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.
  • Levi CR; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.
  • Garcia-Esperon C; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.
  • Spratt N; Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
  • Gyawali P; Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
  • Bivard A; Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
  • Parsons MW; Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
  • Montaner J; Sydney Partnership for Health, Education, Research and Enterprise, Sydney, NSW, Australia.
  • Bustamante A; Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
  • Cadenas IF; Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
  • Cloud G; Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
  • Maguire JM; Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
  • Lincz L; Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
  • Kleinig T; Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
  • Attia J; Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
  • Koblar S; Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
  • Hamilton-Bruce MA; Neurology Department, Royal Melbourne Hospital, Melbourne, VIC, Australia.
  • Choi P; School of Medicine, University of New South Wales, Sydney, NSW, Australia.
  • Worrall BB; Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
  • Medcalf RL; Stroke Research Program, Institute of Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas (Spanish National Research Agency), University of Seville, Seville, Spain.
Front Neurol ; 11: 589628, 2020.
Article en En | MEDLINE | ID: mdl-33224099
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Front Neurol Año: 2020 Tipo del documento: Article País de afiliación: Australia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Front Neurol Año: 2020 Tipo del documento: Article País de afiliación: Australia
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