CO070 | PLASMIN GENERATION AND ITS INTERPLAY WITH COAGULATION AND FIBRINOLYSIS IN ATRIAL FIBRILLATION: IMPACT OF ANTICOAGULANT THERAPY

G. Ciarrocca Taranta¹, F. Alfano¹, M. Di Gioia², M. Berteotti^1|2, E. Lotti², F. Cesari², A. Rogolino², F.A. Barbuto¹, A. M Gori^1|2, E. Sticchi^1|2, B. Giusti^1|2, R. Marcucci^1|2 | ¹Dep of Experimental and Clinical Medicine, University of Florence, Italy; ²Atherothrombotic Diseases, Careggi University Hospital, Firenze, Italy

Background and Aims. Atrial fibrillation (AF) is one of the most common cardiac arrhythmias in clinical practice. Evidence shows an impaired balance between clot formation and fibrinolysis in AF, characterized by a prothrombotic and hypofibrinolytic state with dysregulated plasmin generation. This study aimed to evaluate plasmin generation (PG) and its relationships with markers of fibrinolysis (clot lysis time, CLT) and coagulation (thrombin generation, TG) in patients with AF.
Methods. The STRAT-AF study, an observational prospective study, enrolled 180 AF patients referred for anticoagulant management. A total of 159 with complete laboratory data were included in the final analysis. Among them, 31.5% were treated with vitamin K antagonists (VKA) and 68.5% with direct oral anticoagulants (DOAC). Citrated whole blood was centrifuged (4000 x g, 15 min), with an additional centrifugation step for TG assays; PG and TG were measured using a fluorometer (Fluoroscan Ascent). Parameters included lag time, time to peak (ttPeak), peak, and endogenous plasmin or thrombin potential (EPP/ETP). CLT was assessed in the presence of tissue factor and tPA, monitoring absorbance at 405 nm.
Results. Non-parametric analysis showed a significant positive association between PG lag time and CLT (rho = 0.163; p = 0.043). Conversely, significant negative correlations were found between both EPP (rho = −0.207; p = 0.010) and PG peak (rho = −0.178; p = 0.027). Significant correlations were also observed between PG and TG: PG lag time correlated with TG lag time (rho = 0.300; p < 0.001) and TG ttPeak (rho = 0.254; p = 0.001); PG ttPeak correlated with TG lag time (rho = 0.229; p = 0.004); and PG and TG ttPeak values were also associated (rho = 0.195; p = 0.014). When stratified by anticoagulant therapy, DOAC-treated patients showed longer PG lag time [9.15 (4.30–32.57) vs 8.15 (3.3–14.52); p = 0.171] and significantly longer PG ttPeak [18.85 (1.07–37.67) vs 12.95 (6.52–19.65); p = 0.008] compared with VKA-treated patients. Among DOACs, dabigatran was associated with significantly higher lag time, peak, and ttPeak values compared with other DOACs. In logistic regression analysis, after the adjustment for age, sex, CHA2DS2-VASc, and type of anticoagulant therapy, reduced plasmin generation, as reflected by lower ETP-PG and peak-PG, was associated with the occurrence of non-lacunar infarction at 1-year follow-up [OR (95% CI): 0.17 (0.05-0.61, p=0.007].
Conclusions. These findings highlight a close interplay between fibrinolysis and coagulation in AF. Delayed plasmin generation is associated with a hypofibrinolytic state, while increased plasmin activity promotes faster clot lysis. Anticoagulant therapy influences fibrinolytic profiles, with DOACs—particularly dabigatran—associated with delayed plasmin activation compared with VKAs. Overall, both anticoagulant type and fibrinolytic balance contribute to the hemostatic profile in AF and may favor the formation of more stable, lysis-resistant thrombi, as suggested by the inverse association between non-lacunar infarcts and plasmin generation.