title: Bleeding events and activated partial thromboplastin time with dabigatran in clinical practice.
abstract: BACKGROUND
  Dabigatran has demonstrated promising results for the prevention of strokes in patients with non-valvular atrial fibrillation (NVAF). However, there have been episodes of major bleeding, especially in elderly patients or those with renal dysfunction. The purpose of this study was to retrospectively examine the relationship between the bleeding events and activated partial thromboplastin time (APTT) values under dabigatran usage in the everyday clinical practice. Moreover, we investigated which factors would contribute to the APTT values.
  
  
  RESULTS
  A total of 139 NVAF patients (112 men, 65 ± 11 years) were included. We evaluated the influence of the putative etiological variables and the bleeding score, HAS-BLED score, on APTT values: age greater than 70 years, renal function, gender, dose of dabigatran, and the concomitant prescription of a P-glycoprotein inhibitor. There were 50 patients with an age of ≥ 70 years (36.0%). A P-glycoprotein inhibitor was administered in 18 patients. During the observation period (median 120 days) there was 1 episode of asymptomatic cerebral infarction. There were no intrinsic major bleeding events, however, 11 patients had minor hemorrhagic events. The results of the APTT measurements exhibited a variety of values both among inter- and intra-individuals. On multivariable analysis, significant associations were found between the following risk factors and the APTT values: creatinine clearance, dose of dabigatran, and concomitant use of a P-glycoprotein inhibitor. The minor bleeding events did not correlate with the APTT values, nor HAS-BLED score.
  
  
  CONCLUSIONS
  The APTT values became prolonged under dabigatran usage and exhibited a remarkable diversity. Although major bleeding did not occur unless APTT was prolonged excessively, minor bleeding arose irrespective of the APTT values even within the range of the APTT values not exceeding 80s.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan. mihoko_kawabata.cvm@tmd.ac.jp
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kawabata
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sasano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hachiya
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Yagishita
authors.forename: Koji
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masahito
authors.initials: M
authors.lastname: Suzuki
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hirao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000367:Age Factors; D000368:Aged; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D003404:Creatinine; D000069604:Dabigatran; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D003404:Creatinine; D000069604:Dabigatran
keywords: Anticoagulants; Atrial fibrillation; Thrombosis