Relationship between plasma dabigatran concentration and activated partial thromboplastin time in Japanese patients with non-valvular atrial fibrillation.
BACKGROUND
Activated partial thromboplastin time (aPTT) is recommended for monitoring anticoagulant activity in dabigatran-treated patients; however, there are limited data in Japanese patients. To clarify the relationship between plasma dabigatran concentration and aPTT, we analyzed plasma dabigatran concentration and aPTT at various time points following administration of oral dabigatran in a Japanese hospital.


METHODS
We enrolled 149 patients (316 blood samples) with non-valvular atrial fibrillation (NVAF) who were taking dabigatran. Patients had a mean age of 66.6±10.0 years (range: 35-84) and 66% were men. Plasma dabigatran concentrations and aPTT were measured using the Hemoclot(®) direct thrombin inhibitor assay and Thrombocheck aPTT-SLA(®), respectively. Samples were classified into eight groups according to elapsed times in hours since oral administration of dabigatran.


RESULTS
Significantly higher dabigatran concentrations were observed in samples obtained from patients with low creatinine clearance (CLCr) (CLCr<50 mL/min). Dabigatran concentrations and aPTT were highest in the 4-h post-administration range. Additionally, there was a significant correlation between plasma dabigatran concentrations and aPTT (y=0.063x+32.596, r (2)=0.648, p<0.001). However, when plasma dabigatran concentrations were 200 ng/mL or higher, the correlation was lower (y=0.040x+38.034 and r (2)=0.180); these results were evaluated by a quadratic curve, resulting in an increased correlation (r (2)=0.668).


CONCLUSIONS
There was a significant correlation between plasma dabigatran concentrations and aPTT. Additionally, in daily clinical practice in Japan, plasma dabigatran concentrations and aPTT reached a peak in the 4-h post administration range. Considering the pharmacokinetics of dabigatran, aPTT can be used as an index for risk screening for excess dabigatran concentrations in Japanese patients with NVAF.
Department of Laboratory Medicine, Tenri Hospital, Tenri, Japan.
Daiki
D
Shimomura
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Yoshihisa
Y
Nakagawa
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Hirokazu
H
Kondo
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Toshihiro
T
Tamura
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Masashi
M
Amano
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Yukiko
Y
Hayama
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Naoaki
N
Onishi
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Yodo
Y
Tamaki
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Makoto
M
Miyake
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Kazuaki
K
Kaitani
Department of Cardiology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara 632-8552, Japan.
Chisato
C
Izumi
Tenri Institute of Medical Research, Tenri, Japan.
Masahiko
M
Hayashida
Department of Laboratory Medicine, Tenri Hospital, Tenri, Japan.
Aya
A
Fukuda
Department of Laboratory Medicine, Tenri Hospital, Tenri, Japan.
Fumihiko
F
Nakamura
Division of Laboratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Seiji
S
Kawano
Anticoagulants; Dabigatran; Non-valvular atrial fibrillation; aPTT