Excessive Prolongation of Coagulation Time During Treatment with Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation

Abstract Background Conventional coagulation assays have poor sensitivity and specificity for assessing the anticoagulant effect of direct oral anticoagulants (DOACs). This study aimed to evaluate the causes and consequences of the excessive prolongation of coagulation time in patients with nonvalvular atrial fibrillation who receive DOACs. Methods We retrospectively analyzed 1,521 patients (age, 66±12 years). The PT and APTT were averaged if they were measured more than twice depending on the respective DOAC and dosage across individuals. Excessive coagulation time prolongation was defined as PT or APTT of >2 standard deviations over the median for each DOAC. Results In all, 1,913 DOAC cases were found. Excessive prolongation, which was noted in 88 patients (5.8%), was found to be significantly associated with inappropriately high DOAC dosage and body weight (≤60 kg). During follow-up (median, 8.9 months), thromboembolisms developed in 10 patients (0.66%) and bleeding events in 85 (5.6%). Bleeding events were significantly higher in patients with excessive prolongation (EP group) than in those without (p = 0.013). Of the 53 patients in EP group, 15 (28%) were positive for anti-phospholipid antibodies, 6 (11%) had inappropriately high prescription dosages, 4 (8%) had coagulation factor deficiencies, and 3 (6%) had severe liver dysfunction. Conclusions Bleeding event rates were remarkably higher in patients receiving DOACs that caused excessive prolongation of PT or APTT. Thus, following the current guidelines and administering recommended dose of DOACs are fundamentally important. Patients with body weight of