RT Journal Article
T1 Plasmin Generation Potential and Recanalization in Acute Ischaemic Stroke  an Observational Cohort Study of Stroke Biobank Samples.
A1 Lillicrap, Thomas
A1 Keragala, Charithani B
A1 Draxler, Dominik F
A1 Chan, Jilly
A1 Ho, Heidi
A1 Harman, Stevi
A1 Niego, Be'eri
A1 Holliday, Elizabeth
A1 Levi, Christopher R
A1 Garcia-Esperon, Carlos
A1 Spratt, Neil
A1 Gyawali, Prajwal
A1 Bivard, Andrew
A1 Parsons, Mark W
A1 Montaner, Joan
A1 Bustamante, Alejandro
A1 Cadenas, Israel Fernandez
A1 Cloud, Geoffrey
A1 Maguire, Jane M
A1 Lincz, Lisa
A1 Kleinig, Timothy
A1 Attia, John
A1 Koblar, Simon
A1 Hamilton-Bruce, Monica Anne
A1 Choi, Philip
A1 Worrall, Bradford B
A1 Medcalf, Robert L
K1 acute stroke therapy
K1 fibrinolysis
K1 plasmin
K1 recanalization
K1 rtPA
K1 stroke
K1 thrombolysis
AB 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.
SN 1664-2295
YR 2020
FD 2020-11-03
LK https://hdl.handle.net/10668/27599
UL https://hdl.handle.net/10668/27599
LA en
DS RISalud
RD Apr 7, 2025