PAI‐1 5G/5G genotype is an independent risk of intracranial hemorrhage in post‐lysis stroke patients

Abstract

Abstract Objective Thrombolysis 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. Methods Study 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). Results PAI‐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. Interpretation PAI‐1 5G/5G genotype is associated with a significant risk for developing ICH in post‐lysis stroke patients.