Vitamin K antagonists favourably modulate fibrin clot properties in patients with atrial fibrillation as early as after 3 days of treatment: Relation to coagulation factors and thrombin generation

Introduction: Atrial fibrillation (AF) increases the risk of thromboembolism that is reduced by vitamin K antagonists (VKAs). We sought to investigate changes in plasma fibrin clot phenotype at the onset of oral anticoagulation. Materials and methods: Forty consecutive AF patients (aged 45-83 years, CHA2DS2-VASc score 3.0 +/- 1.5) who started therapy with warfarin or acenocoumarol were studied. Plasma fibrin clot permeability (K-s), clot lysis time (CLT), along with clotting factors (F), thrombin generation (TG) profiles and protein C (PC) levels were determined on days 3, 5, 7, 28 and 56 +/- 1 since the first dose. Results: AF patients had 16% highermedian of K-s and 15% lower median of CLT as early as on day 3 of VKA therapy compared with the baseline (both p < 0.001), reaching the plateau values on day 7 and 5, respectively. Higher Ks values on days 1 and 3 were found in AF patients with further stable anticoagulation (both p < 0.05). Moreover, FIX explained 32% of the total variability in Ks. Multivariate analysis adjusted for potential confounders including time as a predictor showed that vitamin K-dependent (VKD) factors, PC and TG parameters were the predictors of Ks (all p < 0.0001), while only the lag phase of TG and thrombin peak predicted CLT (both p < 0.05) in AF patients. Regression analysis of time-series showed however, that CLT was also predicted by VKD factors and PC (all p < 0.05). Conclusions: Plasma fibrin clot properties in AF patients are favourably modified as early as after 3 days of VKA administration, which might contribute to antithrombotic effectiveness. (C) 2015 Elsevier Ltd. All rights reserved.