Abstract
ObjectiveThrombolysis by recombinant tissue plasminogen activator (rt‐PA) is the main pharmacological therapy in acute ischemic stroke (IS); however, it is only effective in a subset of patients. Here we aimed to investigate the role of plasminogen activator inhibitor‐1 (PAI‐1), an effective inhibitor of t‐PA, and its major polymorphism (PAI‐1 4G/5G) in therapy outcome.MethodsStudy population included 131 consecutive IS patients who all underwent thrombolysis. Blood samples were taken on admission, 1 and 24 h after rt‐PA infusion. PAI‐1 activity and antigen levels were measured from all blood samples and the PAI‐1 4G/5G polymorphism was determined. Clinical data including NIHSS were registered on admission and day 1. ASPECTS was assessed using CT images taken before and 24 h after thrombolysis. Intracranial hemorrhage (ICH) was classified according to ECASS II. Long‐term outcome was defined 90 days post‐event by the modified Rankin Scale (mRS).ResultsPAI‐1 activity levels dropped transiently after thrombolysis, while PAI‐1 antigen levels remained unchanged. PAI‐1 4G/5G polymorphism had no effect on PAI‐1 levels and did not influence stroke severity. PAI‐1 activity/antigen levels as measured on admission were significantly elevated in patients with worse 24 h ASPECTS (<7). Logistic regression analysis including age, sex, NIHSS on admission, BMI, history of arterial hypertension, and hyperlipidemia conferred a significant, independent risk for developing ICH in the presence of 5G/5G genotype (OR:4.75, 95%CI:1.18–19.06). PAI‐1 levels and PAI‐1 4G/5G polymorphism had no influence on long‐term outcomes.InterpretationPAI‐1 5G/5G genotype is associated with a significant risk for developing ICH in post‐lysis stroke patients.
Highlights
Ischemic stroke (IS) is a common vascular disease with high morbidity and mortality.[1]
Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association
As compared to admission plasminogen activator inhibitor-1 (PAI-1) activity levels, a highly significant reduction was observed; the median value of PAI-1 activity was below the lower limit of the reference interval when measured immediately after thrombolysis (PAI-1 activity on admission: median: 2.34, IQR: 1.46–5.17 U/mL; immediately after thrombolysis: median: 0.94, IQR: 0.73–1.18 U/mL)
Summary
Ischemic stroke (IS) is a common vascular disease with high morbidity and mortality.[1]. The relative benefit of i.v. t-PA is unquestionable for selected patients with acute IS, in a large proportion of patients neurological improvement fails and about 6–8% develop hemorrhagic transformation after thrombolysis as a side effect.[5] In order to improve safety and outcome of i.v. rt-PA therapy, there is a growing interest in finding new biomarkers as potential a 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
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