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  • Title: Influence of thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 gene polymorphisms on tissue-type plasminogen activator-induced recanalization in ischemic stroke patients.
    Author: Fernandez-Cadenas I, Alvarez-Sabin J, Ribo M, Rubiera M, Mendioroz M, Molina CA, Rosell A, Montaner J.
    Journal: J Thromb Haemost; 2007 Sep; 5(9):1862-8. PubMed ID: 17723126.
    Abstract:
    OBJECTIVE: Endogenous resistance to tissue-type plasminogen activator (t-PA) might decrease the benefit of thrombolysis-induced recanalization. Thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) are fibrinolysis inhibitors. TAFI removes residues from partially degraded fibrin that in turn eliminates plasminogen binding sites; PAI-1 directly inhibits the activity of t-PA. We aimed to study whether the presence of two common functional polymorphisms of the TAFI and PAI-1 genes influence rates of recanalization of the middle cerebral artery (MCA) among t-PA-treated stroke patients. METHODS AND RESULTS: TAFI and PAI-1 polymorphism determinations were performed by restriction fragment length polymorphism mapping and conventional sequencing in 139 patients with strokes involving the MCA and who received t-PA within 3 h. Recanalization was diagnosed by means of transcranial Doppler. No association was found between PAI-1 4 G/5 G polymorphism and recanalization rate. Dyslipidemia and TAFI Thr325Ile polymorphism were the main variables associated with recanalization resistance by the end of t-PA infusion: odds ratio (OR) 4.1 [95% confidence interval (95% CI) 1.6-10.8, P = 0.003] and OR 5.6 (95% CI 1.2-20, P = 0.031), respectively. The combination of the two polymorphisms doubled the risk of absence of recanalization: OR 11.1 (95% CI 1.4-89.8, P = 0.025). CONCLUSIONS: Polymorphic fibrinolysis inhibitor genes influence t-PA-induced recanalization resistance in ischemic stroke patients, especially when coexisting in the same patient. Efforts to individualize thrombolytic treatments are required.
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