PB0118 - Comparison of Clot Waveform Analysis with or without Adjustment between Activated Partial Thromboplastin Time and Prothrombin Time Assays to Assess In Vitro Effects of Direct Oral Anticoagulants

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

YF

YUTA FUJIMORI, PhD

Clinical Laboratory Technologist
Keio University Hospital
Shinagawa-ku, Tokyo, Japan

Co-Author(s)

MW

Masatoshi Wakui

Associate Professor
Keio University
Shinjuku-ku, Tokyo, Japan
YO

Yuko Ozaki

Clinical Laboratory Technologist
Keio Univesity Hospital
Shinjuku-ku, Tokyo, Japan
EO

Emiri Osada

Clinical Laboratory Technologist
Keio University Hospital
Shinjuku-ku, Tokyo, Japan
SO

Shusaku Oka

Clinical Laboratory Technologist
Keio University Hospital
Shinjuku-ku, Tokyo, Japan
Konomi Igarashi

Clinical Laboratory Technologist
Keio University Hospital
Nakano-Ku, Tokyo, Japan
YK

Yoshino Kondo

Clinical Laboratory Technologist
Keio University Hospital
Shinjuku-ku, Tokyo, Japan
TN

Terumichi Nakagawa

Clinical Laboratory Technologist
Keio Univerisy Hospital
Shinjuku-ku, Tokyo, Japan
SN

Shoko Nakamura

Clinical Laboratory Technologist
Keio University Hospital
Shinjuku-ku, Tokyo, Japan
HY

Hiromitsu Yokota

Manager
Keio University Hospital
Shinjuku-ku, Tokyo, Japan
HM

Hiromichi Matsushita

Professor
Keio University
Shinjuku-ku, Tokyo, Japan

Background: Clot waveform analysis (CWA) has been reported to enhance the interpretation of clotting time measurement. We presented the usability of PT-CWA for assessment of anticoagulant effects.

Aims: This study aimed to compare CWA with or without adjustment using the changes in transmittance of the optical system between APTT and PT assays for better understanding how to apply CWA to evaluation of the effects of direct oral anticoagulants (DOACs).

Methods: Samples were prepared by spiking plasma with rivaroxaban, apixaban, edoxaban, or dabigatran. CWA was performed by using automated blood coagulation analyzers, CN6000 (Sysmex, Japan). To compensate the influence of fibrinogen on CWA parameters, adjustment was done by unifying the maximum changes in transmittance in clotting reaction curves. Both adjusted and non-adjusted CWA parameters were utilized.

Results: Adjusted PT-CWA parameter values exhibited dose-dependent decrease. In non-adjusted PT-CWA, they unexpectedly rose at low drug concentrations but declined at high concentrations. On the other hand, in both adjusted and non-adjusted APTT-CWA, they showed dose-dependent decrease. Adjusted but not non-adjusted CWA parameters were applicable to Hill plot analysis. All DOACs exhibited Hill coefficients exceeding 1.5 for most adjusted CWA parameters, indicating positively cooperative effects in PT-CWA. This was inconsistent with findings from APTT-CWA, in which three activated coagulation factor X inhibitors, rivaroxaban, apixaban, and edoxaban exhibited Hill coefficients being around 1.0 or less. The observed differences between PT-CWA and APTT-CWA suggest the involvement of thrombin positive feedback in the expression of DOAC effects.

Conclusion(s): Dose-dependent changes at low DOAC concentrations differed between adjusted and non-adjusted PT-CWA parameters, in contrast to APTT-CWA parameters. The cooperativity of DOAC effects observed through PT-CWA differed from that observed through APTT-CWA. To interpret CWA results, it is crucial to consider the differences in dose-dependent effects of DOACs between the intrinsic and extrinsic coagulation pathways.