CHA2DS2-VASc and HAS-BLED scores and activated partial thromboplastin time for prediction of high plasma concentration of dabigatran at trough

• High plasma dabigatran concentration (PDC) at trough is a high risk for bleeding.
• Dabigatran prolongs the APTT, and PDC positively correlates with APTT.
• High scores of CHA2DS2-VASc and HAS-BLED are related to high PDC at trough.
• These risk scores combined with APTT are useful for predicting high trough PDC.

IntroductionAlthough dabigatran, an oral direct thrombin inhibitor, does not require routine monitoring, high plasma concentration of dabigatran (PDC) at trough level is shown to be a high risk for bleeding in patients with nonvalvular atrial fibrillation (NVAF). As dabigatran prolongs the activated partial thromboplastin time (APTT), we examined relationships of PDC at trough with APTT and clinical features to identify patients at high risk for major bleeding during dabigatran treatment.Materials and MethodsIn the consecutive 48 patients with NVAF taking dabigatran at a daily dose of 220 mg (n = 32) or 300 mg (n = 16), we measured PDC using HEMOCLOT Thrombin Inhibitor assay and APTT ratio to control before (trough) and 2 hours after taking dabigatran.ResultsPDC was positively correlated with APTT ratio (R2 = 0.64, p < 0.0001). Using this regression equation and values of median trough PDC 116 (46.7-269) ng/mL observed in patients with major bleeding in the RE-LY trial, we calculated the expected value of APTT ratio corresponding to the 10th percentile of trough PDC (46.7). It was 1.20. There was a significant increase in trough PDC with increasing CHA2DS2-VASc score (p = 0.01) and with increasing HAS-BLED score (p = 0.01), especially in CHA2DS2-VASc score ≥ 4 and in HAS-BLED score ≥ 3, respectively. The highest trough PDC was obtained in patient group with CHA2DS2-VASc score ≥ 4, HAS-BLED score ≥ 3, or creatinine clearance ≤ 80, each combined with trough APTT ratio ≥ 1.20.ConclusionsThis study provides an important clinical implication for identifying patients at high risk for major bleeding during dabigatran treatment in clinical practice.