Accumulation of risk factors enhances the prothrombotic state in atrial fibrillation

Background The present study was conducted to investigate the relation between the accumulation of the risk factors of thromboembolism and the levels of hemostatic markers in patients with nonvalvular atrial fibrillation (NVAF). Methods Five hundred ninety-one NVAF patients and 129 control subjects were categorized into low, moderate or high risk of thromboembolism, according to CHADS2 index. One point each was given to patients with advanced age (≥ 75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with CHADS2 score of 0, 1 or 2, and ≥ 3 were classified as low, moderate and high risk, respectively. Levels of hemostatic markers (platelet factor 4, β-thromboglobulin, prothrombin fragment F1 + 2 and D-dimer) were determined. Results Of 591 patients with NVAF, 302 were treated with warfarin (mean international normalized ratio 1.88). D-dimer levels increased as the risk level increased irrespective of warfarin use. Particularly, NVAF patients without receiving warfarin (n = 289) had significantly higher D-dimer levels than control patients (e.g., for high risk patients, 175 ± 144 vs 75 ± 87 ng/ml, p < 0.001), while NVAF patients receiving warfarin had intermediate levels (136 ± 156 ng/ml). F1 + 2 levels increased as the risk level increased, and were significantly suppressed by warfarin. Levels of markers of platelet activation (platelet factor 4 and β-thromboglobulin) were increased in NVAF patients but not affected by the risk level. Conclusion Coagulation and fibrinolytic activity is increased along with the accumulation of the risk factors of thromboembolism in NVAF patients.