VPB1118 - Application of prothrombin time clot waveform analysis to assessment of in vitro effects of anticoagulants on normal plasma

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Yuta Fujimori

Clinical Laboratory Technician
Keio University Hospital
Tokyo, Tokyo, Japan

Co-Author(s)

MW

Masatoshi Wakui

associate professor
Department of Laboratory Medicine, Keio University School of Medicine
Shinjuku, Tokyo, Japan
YO

Yuko Ozaki

Clinical Laboratory Technician
Clinical Laboratory, Keio University Hospital
Tokyo, Tokyo, Japan
EO

Emiri Osada

Clinical Laboratory Technician
Clinical Laboratory, Keio University Hospital
Tokyo, Tokyo, Japan
SO

Shusaku Oka

Clinical Laboratory Technician
Clinical Laboratory, Keio University Hospital
Tokyo, Tokyo, Japan
YK

Yoshino Kondo

Clinical Laboratory Technician
Clinical Laboratory
Tokyo, Tokyo, Japan
TN

Terumichi Nakagawa

Clinical Laboratory Technician
Clinical Laboratory, Keio University Hospital
Tokyo, Tokyo, Japan
SN

Shoko Nakamura

Clinical Laboratory Technician
Clinical Laboratory, Keio University Hospital
Tokyo, Tokyo, Japan
HK

Hisako Katagiri

Clinical Laboratory Technician
Clinical Laboratory, Keio University Hospital
Shinjuku, Tokyo, Japan
MM

Mitsuru Murata

professor
Department of Laboratory Medicine, Keio University School of Medicine
Shinjuku, Tokyo, Japan

Background: Clot waveform analysis (CWA) has been reported to extend the interpretation of clotting time measurement. We have reported the usability of activated partial prothrombin time (APTT) measurement-based clot waveform analysis (APTT-CWA) for assessment of effects of various anticoagulants. Although prothrombin time (PT) measurement is also available for CWA, the usability of PT-CWA for assessment of anticoagulant effects remains to be evaluated.

Aims: To evaluate the usability of PT-CWA for the assessment of pharmacological characteristics of various anticoagulants.

Methods: Samples were prepared by spiking plasma with each of three antithrombin-dependent (unfractionated heparin, low-molecular-weight heparin, and fondaparinux) and seven antithrombin-independent anticoagulants (rivaroxaban, apixaban, edoxaban, dabigatran, argatroban, hirudin, and bivalirudin). PT measurement and PT-CWA were performed using RecombiPlasTin 2G (Werfen, Spain) and automated blood coagulation analyzers, CN6000 (Sysmex, Japan). To compensate influence of fibrinogen on CWA parameters (maximum coagulation velocity, acceleration, and deacceleration), adjustment was performed according to the changes in transmittance of the optical system presenting clotting reaction curves. Both adjusted and non-adjusted CWA parameters were used in the present study.

Results: PT and the adjusted or non-adjusted PT-CWA parameters were hardly changed by antithrombin-dependent anticoagulants. While antithrombin-independent anticoagulants also exhibited dose-dependent PT prolongation, dose-dependent decreases were observed in adjusted but not non-adjusted PT-CWA parameters. Rivaroxaban and bivalirudin exhibited rebounding elevation of adjusted PT-CWA parameters at the highest concentration tested. These features were different from those observed in APTT-CWA for the same drug, which have been reported previously. In addition, as suggested by the similarity in observations between rivaroxaban and bivalirudin, pharmacological categorization did not necessarily correspond to dose-dependent changes in PT-CWA parameters.

Conclusion(s): CWA should be interpreted in consideration of the differences in dose-dependent anticoagulant effects between the intrinsic and extrinsic pathways. How best to use adjusted and non-adjusted CWA parameters differently would be a concern to be addressed.