Relation between dabigatran concentration, as assessed using the direct thrombin inhibitor assay, and activated clotting time/activated partial thromboplastin time in patients with atrial fibrillation.
Dabigatran is a direct thrombin inhibitor that has been approved for preventing stroke in patients with atrial fibrillation. In this study, we aimed to assess the associations between the dabigatran concentration (calculated through plasma-diluted thrombin time, as assessed using the Hemoclot assay) and the activated partial thromboplastin time (aPTT) and activated clotting time (ACT). We recruited 137 patients with atrial fibrillation who were receiving a normal dose of dabigatran (300 mg/d) or a reduced dose of dabigatran (220 mg/d, usually administered to patients who were elderly, had moderate renal dysfunction, or who were also receiving verapamil). We then assessed the aPTT, ACT, and Hemoclot results of the patients and calculated the plasma dabigatran concentration. The mean plasma concentration of dabigatran was 127 ± 88 ng/ml, although no significant differences in dabigatran concentration, ACT, or aPTT were observed when we compared the 2 doses of dabigatran (300 or 220 mg/d). The dabigatran concentration was within the therapeutic levels in most patients, although a high value (>300 ng/ml) was observed in several patients, which indicated a high risk of bleeding. The dabigatran concentration was strongly and positively correlated with ACT and aPTT (r = 0.87, p <0.001; and r = 0.76, p <0.001; respectively). Multivariate analysis revealed that verapamil use was independently associated with elevated dabigatran concentrations (p <0.001). Therefore, ACT and aPTT may be useful for bedside assessment of the anticoagulant activity of dabigatran, and verapamil use may be a risk factor for elevated dabigatran concentrations.
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan; Department of Cardiovascular Medicine, Hokkaido University, Sapporo, Japan. Electronic address: kenji.okubo@gmail.com.
Kenji
K
Okubo
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Taishi
T
Kuwahara
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Katsumasa
K
Takagi
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Masateru
M
Takigawa
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Jun
J
Nakajima
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Yuji
Y
Watari
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Emiko
E
Nakashima
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Kazuya
K
Yamao
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Tadashi
T
Fujino
Department of Cardiovascular Medicine, Hokkaido University, Sapporo, Japan.
Hiroyuki
H
Tsutsui
Cardiovascular Center, Yokosuka Kyosai Hospital, Yokosuka, Japan.
Atsushi
A
Takahashi
D000368:Aged; D000991:Antithrombins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001777:Blood Coagulation; D000069604:Dabigatran; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D012307:Risk Factors; D013918:Thrombin Time; D015091:beta-Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran