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

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.

• Authors: István Szegedi, Attila Nagy, Edina G Székely, Katalin R Czuriga-Kovács, Ferenc Sarkady, Levente I Lánczi, Ervin Berényi, László Csiba, Zsuzsa Bagoly
• Journal: Annals of clinical and translational neurology (Ann Clin Transl Neurol) Vol. 6 Issue 11 Pg. 2240-2250 (11 2019) ISSN: 2328-9503 [Electronic] United States
• PMID: 31637872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

Chemical References

• Fibrinolytic Agents
• Plasminogen Activator Inhibitor 1
• SERPINE1 protein, human
• Tissue Plasminogen Activator

Topics

• Aged
• Female
• Fibrinolytic Agents (adverse effects)
• Genotype
• Humans
• Intracranial Hemorrhages (chemically induced, genetics)
• Male
• Middle Aged
• Plasminogen Activator Inhibitor 1 (genetics)
• Polymorphism, Genetic
• Risk Factors
• Stroke (drug therapy)
• Thrombolytic Therapy (adverse effects)
• Tissue Plasminogen Activator (adverse effects)