Role of Fibrinogen Levels and Factor XIII V34L Polymorphism in Thrombolytic Therapy in Stroke Patients

Abstract

Background and Purpose— The identification of genetic and environmental factors that could improve the benefit/risk ratio of thrombolytic therapy in patients with ischemic stroke is crucial. Methods— We studied the role in the efficacy and side-adverse effects of thrombolytic therapy in stroke of 2 factors involved in the structure and stability of fibrin clot: fibrinogen levels and factor XIII (FXIII) V34L, a common and functional polymorphism. Our study enrolled 200 consecutive patients with stroke who received intravenous recombinant tissue plasminogen activator. Results— Patients with FXIII V/V genotype and low fibrinogen (<3.6 g/L) displayed the best clinical outcome. In contrast, carriers of the L34 variant and high fibrinogen levels showed almost no clinical response. Moreover, patients with high fibrinogen levels at admission displayed higher mortality than patients with lower fibrinogen levels (22.6% versus 9.7%, P =0.027; OR=2.72). The FXIII V34L polymorphism also associated with mortality: 20.0% of L34 carriers but 9.1% of patients with V/V genotype died after thrombolytic therapy ( P =0.034; OR=2.50). The deleterious effect of this variant seemed to be exacerbated by high levels of fibrinogen, supporting the role of fibrinogen levels in determining the hemostatic consequences of the FXIII polymorphism. Conclusions— Our study identifies 2 markers involved in fibrin formation associated with the efficacy of thrombolytic therapy and early mortality rates in patients with ischemic stroke. These markers could be useful to identify patients with stroke suitable for a safe thrombolytic therapy.