CO073 | THROMBIN GENERATION PROFILE IN ELDERLY PATIENTS WITH ATRIAL FIBRILLATION: IMPACT OF ORAL ANTICOAGULANT TYPE

M. Di Gioia¹, M. Berteotti^1|2, G. Ciarrocca Taranta², F. Alfano^1|2, F. Crudele¹, F. Cesari¹, A.M. Gori^1|2, A. Rogolino¹, B. Giusti^1|2, R. Marcucci^1|2 | ¹Atherothrombotic Diseases, Careggi University Hospital, Firenze, Italy; ²Dep. of Experimental and Clinical Medicine, University of Florence, Italy

Background and Aims. Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of thromboembolic events. Oral anticoagulants, including direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), represent the cornerstone of treatment, with DOACs largely replacing VKAs due to a more favorable safety profile. Previous data from our group suggest differential effects of these therapies on hemostatic parameters. This study aimed to evaluate thrombin generation (TG) and fibrinolytic markers in AF patients, according to the type of oral anticoagulant, to better characterize their impact on the hemostatic profile.
Methods. STRAT-AF is a prospective, observational, single-center study enrolling patients aged >65 years with AF on oral anticoagulation. A total of 170 patients were included. Thrombin generation was assessed on platelet-poor plasma using calibrated automated thrombography (CAT) in the absence (TM−) and presence (TM+) of thrombomodulin. TG parameters included lag time, time to peak, peak thrombin, endogenous thrombin potential (ETP), and ETP ratio (ETP TM+/ETP TM−). Fibrinolytic markers included plasminogen activator inhibitor-1 (PAI-1) and clot lysis time (CLT).
Results. Mean age was 77.7±6.8 years; 34.7% were female, and 69.4% were on DOACs. Patients on dabigatran showed significantly prolonged lag time compared with factor Xa inhibitors and VKAs [19.7 vs 8.3 vs 8.3; p=0.008] and a longer time to peak compared with VKAs [31.5 vs 13.1; p=0.012]. The ETP ratio was higher in VKAs compared with both DOAC groups (p=0.004). CLT was significantly prolonged in patients on factor Xa inhibitors compared with VKAs and dabigatran [59.13 (45.35-75.58) vs 51.33 (41.60-58.96) vs 48.86 (42.66-59.31); p=0.026]. At multivariate analysis, age (OR 1.05; 95% CI 1.00-1.11; p=0.038), dabigatran therapy (OR 3.23; 95% CI 1.11-9.38; p=0.031) and statin use (OR 2.19; 95% CI 1.03-4.65; p=0.041) were identified as independent predictors for a prolonged lag time. Both factor Xa inhibitors (OR 0.388; 95% CI 0.183-0.820; p=0.013) and dabigatran (OR 0.332; 95% CI 0.134-0.820; p=0.017) were associated with lower ETP ratios compared to VKAs. Increasing age was inversely associated with a high ETP ratio (OR 0.937; 95% CI 0.891–0.986; p=0.013).
Conclusions. These findings provide evidence of the differential effects of DOACs and VKAs on the hemostatic profile of elderly AF patients. Overall, dabigatran causes prolonged TG kinetics, which is consistent with its mechanism as a direct thrombin inhibitor. Incorporating these parameters into existing risk assessment models could represent a valuable tool for a comprehensive characterization of the hemostatic profile in AF patients, potentially supporting more targeted therapeutic strategies.