Abstract TP023: Plasminogen Activator Inhibitor-1 Gene Polymorphism in Recurrent Ischemic Stroke Despite Anticoagulation: An Observational Study

Introduction: Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of fibrinolysis, acting as the primary inhibitor of tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Elevated PAI-1 levels increase the risk of thrombotic events by inhibiting endogenous fibrinolysis. The gene encoding PAI-1 has two different alleles 4G and 5G, which can lead to 3 genotypes: 4G/4G, 4G/5G and 5G/5G. The 4G allele increases gene expression and studies show 4G/4G to be associated with higher PAI-1 levels. We evaluated the distribution of 4G/5G polymorphism in patients who had recurrent ischemic strokes despite direct oral anticoagulant (DOAC) therapy. Methods: We conducted an observational study of 20 patients who developed ischemic stroke despite compliance with DOACs. Demographic and clinical data pertaining to comorbid conditions, and relevant laboratory tests were collected. All patients underwent a thrombophilia work up and PAI-1 gene testing. Data were analysed according to patient genotype to assess differences in clinical presentation, laboratory findings and treatment outcomes. Data analysis was performed using Microsoft Excel. Results: The relevant demographic and clinical data are shown in Table 1. Among the 20 patients, 5 (25%) had the 4G/4G genotype, 12 (60%) had the 4G/5G genotype, and 3 (15%) had the 5G/5G genotype of the PAI-1 gene. Fifteen patients (75%) were on Apixaban and 5 (25%) were on Rivaroxaban. Fifteen patients (75%) modified their antithrombotic therapy after recurrent ischemic stroke. This included 7 switching from a factor Xa inhibitor (FXa-I) to a direct thrombin inhibitor (DTI), 3 changing to a different FXa-I, 2 adding aspirin, 2 transitioning from FXa-I to warfarin, and 1 switching from FXa-I to DTI with aspirin. Four patients had recurrent strokes for the second time. Two (50%) of the patients had 4G/4G genotype, 1 (25%) 4G/5G and 1(25%) 5G/5G genotype. Conclusion: Our data shows that 2 out of 4 patients experienced recurrent strokes had the 4G/4G genotype. This trend suggests that the 4G/4G genotype may be linked to a higher thrombotic risk, which aligns with previous reports connecting this genotype to PAI-1 levels. Limitations include the small sample size and variable duration of follow-up, which may have prevented detection of recurrent events in patients with other genotypes. Larger, prospective studies are warranted to further clarify this association and guide more effective therapeutic strategies.