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

Lillicrap, T; Keragala, CB; Draxler, DF; Chan, J; Ho, H; Harman, S; Niego, B; Holliday, E; Levi, CR; Garcia-Esperon, C; Spratt, N; Gyawali, P; Bivard, A; Parsons, MW; Montaner, J; Bustamante, A; Cadenas, IF; Cloud, G; Maguire, JM; Lincz, L; Kleinig, T; Attia, J; Koblar, S; Hamilton-Bruce, MA; Choi, P; Worrall, BB; Medcalf, RL

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

Lillicrap, T Keragala, CB Draxler, DF Chan, J Ho, H Harman, S Niego, B Holliday, E Levi, CR Garcia-Esperon, C Spratt, N Gyawali, P Bivard, A Parsons, MW Montaner, J Bustamante, A Cadenas, IF Cloud, G Maguire, JM Lincz, L Kleinig, T Attia, J Koblar, S Hamilton-Bruce, MA Choi, P Worrall, BB Medcalf, RL

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Publisher:: Frontiers Media SA
Publication Type:: Journal Article
Citation:: Frontiers in neurology, 2020, 11, pp. 589628-589628
Issue Date:: 2020-01

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Field	Value	Language
dc.contributor.author	Lillicrap, T
dc.contributor.author	Keragala, CB
dc.contributor.author	Draxler, DF
dc.contributor.author	Chan, J
dc.contributor.author	Ho, H
dc.contributor.author	Harman, S
dc.contributor.author	Niego, B
dc.contributor.author	Holliday, E
dc.contributor.author	Levi, CR
dc.contributor.author	Garcia-Esperon, C
dc.contributor.author	Spratt, N
dc.contributor.author	Gyawali, P
dc.contributor.author	Bivard, A
dc.contributor.author	Parsons, MW
dc.contributor.author	Montaner, J
dc.contributor.author	Bustamante, A
dc.contributor.author	Cadenas, IF
dc.contributor.author	Cloud, G
dc.contributor.author	Maguire, JM
dc.contributor.author	Lincz, L
dc.contributor.author	Kleinig, T
dc.contributor.author	Attia, J
dc.contributor.author	Koblar, S
dc.contributor.author	Hamilton-Bruce, MA
dc.contributor.author	Choi, P
dc.contributor.author	Worrall, BB
dc.contributor.author	Medcalf, RL
dc.date.accessioned	2020-12-09T05:09:07Z
dc.date.available	2020-09-25
dc.date.available	2020-12-09T05:09:07Z
dc.date.issued	2020-01
dc.identifier.citation	Frontiers in neurology, 2020, 11, pp. 589628-589628
dc.identifier.issn	1664-2295
dc.identifier.issn	1664-2295
dc.identifier.uri	http://hdl.handle.net/10453/144597
dc.description.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.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	Frontiers Media SA
dc.relation	http://purl.org/au-research/grants/nhmrc/1085550
dc.relation.ispartof	Frontiers in neurology
dc.relation.isbasedon	10.3389/fneur.2020.589628
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences, 1109 Neurosciences, 1701 Psychology
dc.title	Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke; an Observational Cohort Study of Stroke Biobank Samples.
dc.type	Journal Article
utslib.citation.volume	11
utslib.location.activity	Switzerland
utslib.for	1103 Clinical Sciences
utslib.for	1109 Neurosciences
utslib.for	1701 Psychology
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-12-09T05:08:59Z
pubs.publication-status	Published
pubs.volume	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.

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http://hdl.handle.net/10453/144597