Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples
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...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2020.589628/full |
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| author | Thomas Lillicrap Thomas Lillicrap Charithani B. Keragala Dominik F. Draxler Dominik F. Draxler Dominik F. Draxler Jilly Chan Heidi Ho Stevi Harman Be'eri Niego Elizabeth Holliday Elizabeth Holliday Christopher R. Levi Christopher R. Levi Christopher R. Levi Carlos Garcia-Esperon Carlos Garcia-Esperon Neil Spratt Neil Spratt Prajwal Gyawali Prajwal Gyawali Andrew Bivard Andrew Bivard Andrew Bivard Mark W. Parsons Joan Montaner Joan Montaner Joan Montaner Alejandro Bustamante Israel Fernandez Cadenas Geoffrey Cloud Geoffrey Cloud Jane M. Maguire Lisa Lincz Lisa Lincz Lisa Lincz Timothy Kleinig Timothy Kleinig John Attia John Attia Simon Koblar Simon Koblar Monica Anne Hamilton-Bruce Monica Anne Hamilton-Bruce Philip Choi Philip Choi Bradford B. Worrall Bradford B. Worrall Robert L. Medcalf |
| author_facet | Thomas Lillicrap Thomas Lillicrap Charithani B. Keragala Dominik F. Draxler Dominik F. Draxler Dominik F. Draxler Jilly Chan Heidi Ho Stevi Harman Be'eri Niego Elizabeth Holliday Elizabeth Holliday Christopher R. Levi Christopher R. Levi Christopher R. Levi Carlos Garcia-Esperon Carlos Garcia-Esperon Neil Spratt Neil Spratt Prajwal Gyawali Prajwal Gyawali Andrew Bivard Andrew Bivard Andrew Bivard Mark W. Parsons Joan Montaner Joan Montaner Joan Montaner Alejandro Bustamante Israel Fernandez Cadenas Geoffrey Cloud Geoffrey Cloud Jane M. Maguire Lisa Lincz Lisa Lincz Lisa Lincz Timothy Kleinig Timothy Kleinig John Attia John Attia Simon Koblar Simon Koblar Monica Anne Hamilton-Bruce Monica Anne Hamilton-Bruce Philip Choi Philip Choi Bradford B. Worrall Bradford B. Worrall Robert L. Medcalf |
| author_sort | Thomas Lillicrap |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T15:45:34Z |
| format | Article |
| id | doaj.art-86906486acd54bac865705d696765ecb |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-19T15:45:34Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-86906486acd54bac865705d696765ecb2022-12-21T20:15:21ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-11-011110.3389/fneur.2020.589628589628Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank SamplesThomas Lillicrap0Thomas Lillicrap1Charithani B. Keragala2Dominik F. Draxler3Dominik F. Draxler4Dominik F. Draxler5Jilly Chan6Heidi Ho7Stevi Harman8Be'eri Niego9Elizabeth Holliday10Elizabeth Holliday11Christopher R. Levi12Christopher R. Levi13Christopher R. Levi14Carlos Garcia-Esperon15Carlos Garcia-Esperon16Neil Spratt17Neil Spratt18Prajwal Gyawali19Prajwal Gyawali20Andrew Bivard21Andrew Bivard22Andrew Bivard23Mark W. Parsons24Joan Montaner25Joan Montaner26Joan Montaner27Alejandro Bustamante28Israel Fernandez Cadenas29Geoffrey Cloud30Geoffrey Cloud31Jane M. Maguire32Lisa Lincz33Lisa Lincz34Lisa Lincz35Timothy Kleinig36Timothy Kleinig37John Attia38John Attia39Simon Koblar40Simon Koblar41Monica Anne Hamilton-Bruce42Monica Anne Hamilton-Bruce43Philip Choi44Philip Choi45Bradford B. Worrall46Bradford B. Worrall47Robert L. Medcalf48Department of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, AustraliaAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, AustraliaAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, AustraliaDepartment of Cardiology, University Hospital of Bern, Bern, SwitzerlandBern Centre for Precision Medicine, Bern, SwitzerlandAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, AustraliaAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, AustraliaAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, AustraliaAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, AustraliaDepartment of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, AustraliaDepartment of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, AustraliaSydney Partnership for Health, Education, Research and Enterprise, Sydney, NSW, AustraliaDepartment of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, AustraliaDepartment of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, AustraliaDepartment of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, AustraliaDepartment of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, AustraliaNeurology Department, Royal Melbourne Hospital, Melbourne, VIC, AustraliaSchool of Medicine, University of New South Wales, Sydney, NSW, AustraliaNeurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain0Stroke 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, Spain1Department of Neurology, Hospital Universitario Virgen Macarena, Seville, SpainNeurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain2Stroke Pharmacogenomics and Genetics Lab, Sant Pau Hospital Institute of Research, Barcelona, Spain3Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia4Department of Clinical Neuroscience, School of Nursing and Midwifery, Central Clinical School, Monash University, Melbourne, VIC, Australia5Department of Haematology, University of Technology Sydney, Sydney, NSW, AustraliaDepartment of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia6Haematology Department, Calvary Mater Newcastle, Waratah, NSW, Australia7Neurology Department, Royal Adelaide Hospital, Adelaide, SA, Australia8Adelaide Medical School, The University of Adelaide, Adelaide, SA, AustraliaDepartment of Neurology, John Hunter Hospital, Newcastle, NSW, AustraliaHunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia8Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia9Neurology, Central Adelaide Local Health Network, Adelaide, SA, Australia8Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia9Neurology, Central Adelaide Local Health Network, Adelaide, SA, Australia0Department of Neurosciences, Eastern Health, Melbourne, VIC, Australia1Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia2Department of Neurology, University of Virginia, Charlottesville, VA, United States3Department of Public Health Sciences, University of Virginia, Charlottesville, VA, United StatesAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC, AustraliaRationale: 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.https://www.frontiersin.org/articles/10.3389/fneur.2020.589628/fullacute stroke therapyfibrinolysisrtPAthrombolysisplasminstroke |
| spellingShingle | Thomas Lillicrap Thomas Lillicrap Charithani B. Keragala Dominik F. Draxler Dominik F. Draxler Dominik F. Draxler Jilly Chan Heidi Ho Stevi Harman Be'eri Niego Elizabeth Holliday Elizabeth Holliday Christopher R. Levi Christopher R. Levi Christopher R. Levi Carlos Garcia-Esperon Carlos Garcia-Esperon Neil Spratt Neil Spratt Prajwal Gyawali Prajwal Gyawali Andrew Bivard Andrew Bivard Andrew Bivard Mark W. Parsons Joan Montaner Joan Montaner Joan Montaner Alejandro Bustamante Israel Fernandez Cadenas Geoffrey Cloud Geoffrey Cloud Jane M. Maguire Lisa Lincz Lisa Lincz Lisa Lincz Timothy Kleinig Timothy Kleinig John Attia John Attia Simon Koblar Simon Koblar Monica Anne Hamilton-Bruce Monica Anne Hamilton-Bruce Philip Choi Philip Choi Bradford B. Worrall Bradford B. Worrall Robert L. Medcalf Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples Frontiers in Neurology acute stroke therapy fibrinolysis rtPA thrombolysis plasmin stroke |
| title | Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples |
| title_full | Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples |
| title_fullStr | Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples |
| title_full_unstemmed | Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples |
| title_short | Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples |
| title_sort | plasmin generation potential and recanalization in acute ischaemic stroke an observational cohort study of stroke biobank samples |
| topic | acute stroke therapy fibrinolysis rtPA thrombolysis plasmin stroke |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2020.589628/full |
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