PAI-1 5G/5G genotype is an independent risk of intracranial hemorrhage in post-lysis stroke patients.
Aged
Female
Fibrinolytic Agents
/ adverse effects
Genotype
Humans
Intracranial Hemorrhages
/ chemically induced
Male
Middle Aged
Plasminogen Activator Inhibitor 1
/ genetics
Polymorphism, Genetic
Risk Factors
Stroke
/ drug therapy
Thrombolytic Therapy
/ adverse effects
Tissue Plasminogen Activator
/ adverse effects
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
04
04
2019
revised:
13
08
2019
accepted:
22
09
2019
pubmed:
23
10
2019
medline:
22
9
2020
entrez:
23
10
2019
Statut:
ppublish
Résumé
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. 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). 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. PAI-1 5G/5G genotype is associated with a significant risk for developing ICH in post-lysis stroke patients.
Identifiants
pubmed: 31637872
doi: 10.1002/acn3.50923
pmc: PMC6856768
doi:
Substances chimiques
Fibrinolytic Agents
0
Plasminogen Activator Inhibitor 1
0
SERPINE1 protein, human
0
Tissue Plasminogen Activator
EC 3.4.21.68
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2240-2250Subventions
Organisme : National Research, Development and Innovation Fund
ID : FK128582
Pays : International
Organisme : National Research, Development and Innovation Fund
ID : K120042
Pays : International
Organisme : Hungarian Academy of Sciences
ID : MTA-DE Cerebrovascular and Neurodegenerative Resea
Pays : International
Organisme : European Regional Fund
ID : GINOP-2.3.2-15-2016-00043
Pays : International
Organisme : European Regional Fund
ID : GINOP-2.3.2-15-2016-00048
Pays : International
Informations de copyright
© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
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