PB1168 - Correlations between concentrations and anticoagulant effects are different among direct oral anticoagulants administered to patients

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Yuta Fujimori, PhD

Clinical Laboratory Technician
Keio University Hospital
Shinjuku-ku, Tokyo, Japan

Co-Author(s)

MY

Masako Yamazaki

Project Assistant Professor
Chiba University
Chiba-shi, Chiba, Japan
TN

Terumichi Nakagawa

Clinical Laboratory Technician
Keio University Hospital
shinjuku-ku, Tokyo, Japan
TT

Takako Tamura

Clinical Laboratory Technician
Tokyo Women’s Medical University Hospital
Shnjuku-ku, Tokyo, Japan
MK

Maki Kondo

Clinical Laboratory Technician
Tokyo Women’s Medical University Hospital
Shinjuku-ku, Tokyo, Japan
MN

Masatoshi Nakamura

Doctoral Graduate Students
Kagoshima University
Kagoshima-shi, Kagoshima, Japan
YO

Yuki Obama

Doctoral Graduate Students
Kagoshima University
Kagoshima-shi, Kagoshima, Japan
KK

Kazuo Kitagawa

Professor
Tokyo Women’s Medical University
Shinjuku-ku, Tokyo, Japan
MI

Masahiro Ieko

Chief of Clinical Laboratory
Iwate Prefectural Chubu Hospital
Kitakami-shi, Iwate, Japan
TH

Teruto Hashiguchi

Professor
Kagoshima University
kagoshima, Kagoshima, Japan
MW

Masatoshi Wakui

Associate Professor
Keio University School of Medicine
shinjuku-ku, Tokyo, Japan

Background: Our multicenter study to assess the influence of direct oral anticoagulants (DOACs) on laboratory and clinical practice is ongoing, especially focusing on clot waveform analysis (CWA) based on prothrombin time (PT) and activated partial thromboplastin time (APTT) assays.

Aims: To assess correlations between drug concentrations versus anticoagulant effects represented by PT, APTT, and CWA parameters in patients on DOACs.

Methods: 232 plasma samples were collected from patients on dabigatran, apixaban, edoxaban, or rivaroxaban recruited at Tokyo Women’s Medical University Hospital, Tokyo, Japan. The plasma DOAC concentration measurement was based on dilute thrombin time for dabigatran or anti-activated factor X activity for apixaban, edoxaban, and rivaroxaban. PT and APTT assays as well as CWA were performed by using the automated coagulation analyzer, CN-6000 (Sysmex, Japan). The positive mode of clot waveforms was defined as the direction towards fibrin generation. Maximum value of the first derivative (Max1), maximum positive value of the second derivative (Maxp2), and maximum negative value of the second derivative (Maxn2) reflected the maximum coagulation velocity, acceleration, and deceleration, respectively. These CWA parameters were also adjusted by normalizing transmittance changes in clotting reaction curves.

Results: Samples from patients on edoxaban or rivaroxaban exhibited correlations between drug concentration versus PT, adjusted PT-CWA parameters, APTT, or adjusted APTT-CWA parameters. On the other hand, correlations between them were less or absent in samples from patients on dabigatran or apixaban. Non-adjusted PT-CWA or APTT-CWA parameters were not correlated with DOAC concentrations. In general, not only enzyme inhibitor concentrations but also substrate concentrations impact how inhibitory effects represented by IC50 appear. Differences in the degree of such impacts among DOACs might explain why correlations between drug concentrations versus anticoagulant effects vary.

Conclusion(s): The results suggest that the usability of drug concentrations to monitor and manage anticoagulation is different among DOACs.