title: CHA2DS2-VASc and HAS-BLED scores and activated partial thromboplastin time for prediction of high plasma concentration of dabigatran at trough.
abstract: BACKGROUND
  Although 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.
  
  
  METHODS
  In the consecutive 48 patients with NVAF taking dabigatran at a daily dose of 220mg (n=32) or 300mg (n=16), we measured PDC using HEMOCLOT Thrombin Inhibitor assay and APTT ratio to control before (trough) and 2hours after taking dabigatran.
  
  
  RESULTS
  PDC was positively correlated with APTT ratio (R(2)=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.
  
  
  CONCLUSIONS
  This study provides an important clinical implication for identifying patients at high risk for major bleeding during dabigatran treatment in clinical practice.
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Shingen
authors.initials: S
authors.lastname: Owada
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Kinjo
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Taihei
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Advanced Management of Cardiac Arrhythmias, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Horiuchi
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Advanced Management of Cardiac Arrhythmias, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Cardiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. Electronic address: okumura@cc.hirosaki-u.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D000069604:Dabigatran; D004334:Drug Administration Schedule; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000517:prevention & control; D055815:Young Adult; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran
keywords: Activated partial thromboplastin time; CHA(2)DS(2)-VASc score; Dabigatran; HAS-BLED score