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

Article


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., ..., Medcalf, Robert L.. 2020. "Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples." Frontiers in Neurology. 11, pp. 1-4. https://doi.org/10.3389/fneur.2020.589628
Article Title

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

ERA Journal ID123670
Article CategoryArticle
AuthorsLillicrap, Thomas (Author), Keragala, Charithani B. (Author), Draxler, Dominik F. (Author), Chan, Jilly (Author), Ho, Heidi (Author), Harman, Stevi (Author), Niego, Be’eri (Author), Holliday, Elizabeth (Author), Levi, Christopher R. (Author), Garcia-Esperon, Carlos (Author), Spratt, Neil (Author), Gyawali, Prajwal (Author), Bivard, Andrew (Author), Parsons, Mark W. (Author), Montaner, Joan (Author), Bustamante, Alejandro (Author), Cadenas, Israel Fernandez (Author), Cloud, Geoffrey (Author), Maguire, Jane M. (Author), Lincz, Lisa (Author), Kleinig, Timothy (Author), Attia, John (Author), Koblar, Simon (Author), Hamilton-Bruce, Monica Anne (Author), Choi, Philip (Author), Worrall, Bradford B. (Author) and Medcalf, Robert L. (Author)
Journal TitleFrontiers in Neurology
Journal Citation11, pp. 1-4
Article Number589628
Number of Pages4
Year2020
Place of PublicationSwitzerland
ISSN1664-2295
Digital Object Identifier (DOI)https://doi.org/10.3389/fneur.2020.589628
Web Address (URL)https://www.frontiersin.org/articles/10.3389/fneur.2020.589628/full
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.

Keywordsacute stroke therapy, fibrinolysis, rtPA, thrombolysis, plasmin, stroke, recanalization
Contains Sensitive ContentDoes not contain sensitive content
ANZSRC Field of Research 2020320905. Neurology and neuromuscular diseases
320102. Haematology
Byline AffiliationsUniversity of Newcastle
Monash University
School of Health and Wellbeing
University of New South Wales
University of Seville, Spain
Vall d'Hebron Institute of Research, Spain
Sant Pau Hospital Institute of Research, Spain
University of Technology Sydney
University of Adelaide
University of Virginia, United States
Institution of OriginUniversity of Southern Queensland
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