Authors: FERNANDEZ-CADENAS, I.; ALVAREZ-SABIN, J.; RIBO, M.; RUBIERA, M.; MENDIOROZ, M.; MOLINA, C. A.; ROSELL, A.; MONTANER, J.

Source: Journal of Thrombosis and Haemostasis, Volume 5, Number 9, September 2007 , pp. 1862-1868(7)

Publisher: Wiley-Blackwell

Abstract:

Summary. 

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.

Keywords: plasminogen activator inhibitor-1; polymorphism; stroke; thrombin-activatable fibrinolysis inhibitor; thrombolysis; tissue-type plasminogen activator

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1538-7836.2007.02665.x

Publication date: 2007-09-01

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• In this Subject: Allergy & Immunology
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