Frontiers in Neurology (Nov 2020)
Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples
- 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
Affiliations
- Thomas Lillicrap
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- Thomas Lillicrap
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Charithani B. Keragala
- Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
- Dominik F. Draxler
- Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
- Dominik F. Draxler
- Department of Cardiology, University Hospital of Bern, Bern, Switzerland
- Dominik F. Draxler
- Bern Centre for Precision Medicine, Bern, Switzerland
- Jilly Chan
- Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
- Heidi Ho
- Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
- Stevi Harman
- Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
- Be'eri Niego
- Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
- Elizabeth Holliday
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- Elizabeth Holliday
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Christopher R. Levi
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- Christopher R. Levi
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Christopher R. Levi
- Sydney Partnership for Health, Education, Research and Enterprise, Sydney, NSW, Australia
- Carlos Garcia-Esperon
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- Carlos Garcia-Esperon
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Neil Spratt
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- Neil Spratt
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Prajwal Gyawali
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- Prajwal Gyawali
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Andrew Bivard
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- Andrew Bivard
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Andrew Bivard
- Neurology Department, Royal Melbourne Hospital, Melbourne, VIC, Australia
- Mark W. Parsons
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Joan Montaner
- Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain
- Joan Montaner
- 0Stroke 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
- Joan Montaner
- 1Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain
- Alejandro Bustamante
- Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain
- Israel Fernandez Cadenas
- 2Stroke Pharmacogenomics and Genetics Lab, Sant Pau Hospital Institute of Research, Barcelona, Spain
- Geoffrey Cloud
- 3Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia
- Geoffrey Cloud
- 4Department of Clinical Neuroscience, School of Nursing and Midwifery, Central Clinical School, Monash University, Melbourne, VIC, Australia
- Jane M. Maguire
- 5Department of Haematology, University of Technology Sydney, Sydney, NSW, Australia
- Lisa Lincz
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- Lisa Lincz
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Lisa Lincz
- 6Haematology Department, Calvary Mater Newcastle, Waratah, NSW, Australia
- Timothy Kleinig
- 7Neurology Department, Royal Adelaide Hospital, Adelaide, SA, Australia
- Timothy Kleinig
- 8Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- John Attia
- Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
- John Attia
- Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
- Simon Koblar
- 8Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Simon Koblar
- 9Neurology, Central Adelaide Local Health Network, Adelaide, SA, Australia
- Monica Anne Hamilton-Bruce
- 8Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
- Monica Anne Hamilton-Bruce
- 9Neurology, Central Adelaide Local Health Network, Adelaide, SA, Australia
- Philip Choi
- 0Department of Neurosciences, Eastern Health, Melbourne, VIC, Australia
- Philip Choi
- 1Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
- Bradford B. Worrall
- 2Department of Neurology, University of Virginia, Charlottesville, VA, United States
- Bradford B. Worrall
- 3Department of Public Health Sciences, University of Virginia, Charlottesville, VA, United States
- Robert L. Medcalf
- Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia
- DOI
- https://doi.org/10.3389/fneur.2020.589628
- Journal volume & issue
-
Vol. 11
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.
Keywords
