VPB0209 - Usefulness of the human-factor based chromogenic substrate assay for evaluating coagulability of Emicizumab

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Tomoko Yamaguchi, MD

Staff physician
Tokyo Medical University
Shinjukuku, Tokyo, Japan

Co-Author(s)

KS

Keiko Shinozawa

Assistant Professor
Department of Laboratory Medicine, Tokyo Medical University
Shinjuku-ku, Tokyo, Japan
HI

Hiroshi Inaba

Assistant Professor
Department of Laboratory Medicine, Tokyo Medical University
Shinjuku-ku, Tokyo, Japan
AM

Ayano Mitsuhashi

Researcher
Tokyo Medical University
Shinjukuku, Tokyo, Japan
YH

Yuko Harada

Staff Physician
Tokyo Medical University
Shinjukuku, Tokyo, Japan
RM

Ryui Miyashita

Staff Physician
Tokyo Medical University
Shinjukuku, Tokyo, Japan
YK

Yoshiko Kamikubo

Staff Physician
Tokyo Medical University
Shinjukuku, Tokyo, Japan
AI

Akito Ichiki

Staff Physician
Tokyo Medical University
Shinjukuku, Tokyo, Japan
YC

Yushi Chikasawa

Physician
Tokyo Medical University
Tokyo, Tokyo, Japan
MB

Masato Bingo

Assistant Professor
Department of Laboratory Medicine, Tokyo Medical University
Shinjuku-ku, Tokyo, Japan
RS

Ryoko Sekiya

Staff Physician
Tokyo Medical University
Shinjukuku, Tokyo, Japan
TM

Takashi Muramatsu

associate professor/lecturer
Tokyo Medical University
Shinjukuku, Tokyo, Japan
MY

Mihoko Yotsumoto

associate professor/lecturer
Tokyo Medical University
Shinjukuku Nishishinjuku, Tokyo, Japan
TH

Takeshi Hagiwara

Associate Professor
Department of Laboratory Medicine, Tokyo Medical University
Shinjuku-ku, Tokyo, Japan
KA

Kagehiro Amano

Professor
Department of Laboratory Medicine, Tokyo Medical University
Tokyo, Tokyo, Japan
SN

Satoru Nagatoishi

Specially Appointed Associate Professor
The Institute of Medical Science, The University of Tokyo
Minatoku, Tokyo, Japan
KT

Kohei Tsumoto

Professor
The Institute of Medical Science, The University of Tokyo
Minatoku, Tokyo, Japan
EK

Ei Kinai

Professor
Department of Laboratory Medicine, Tokyo Medical University
Shinjuku-ku, Tokyo, Japan

Background: Emicizumab is a bispecific antibody mimicking activated factor VIII (FVIII) and increasingly used because of its practicality. In patients receiving emicizumab, since activated partial thromboplastin time (aPTT) is excessively shortened, it is an urgent issue to establish an appropriate and easy-to-access coagulation assay.

Aims: The aim of this study is to assess the usefulness of the human factor-based chromogenic substrate assay (hCSA) with reference to the thrombin generation assay (TGA), the established coagulation assay for emicizumab.

Methods: The coagulability of spiked emicizumab and recombinant FVIII (rFVIII) were measured and compared among TGA using extrinsic and intrinsic pathway triggers, hCSA, one-stage clotting assay (OSA), and clot waveform analysis (CWA). We also investigated the additive effect of 340 nM emicizumab in combination with rFVIII by measuring in the same assays.

Results: Both the peak thrombin by TGA and FXa generation by hCSA consistently showed a linear relationship between emicizumab and rFVIII concentration in wide range of emicizumab concentration (10-2000 nM). While TGA showed a plateau in higher emicizumab concentration, hCSA did not at any concentration. FVIII-equivalent activity of emicizumab in hCSA can be approximated by halving to that in TGA triggered by the extrinsic pathway reagent (27.3 IU/dL vs. 13.9 IU/dL) in steady state (340 nM) of emicizumab. The additive effect in combination of 340 nM of emicizumab plus rFVIII gradually diminished at higher range of rFVIII in TGA, hCSA and CWA.

Conclusion(s): Reported FVIII activity of emicizumab in hCSA can be easily approximated to TGA, and the additive effect of FVIII on emicizumab is diminished in higher doses of FVIII. For clinical applicability of hCSA, further investigation is needed.
This research was supported by Chugai Pharmaceutical Co., Ltd, and emicizumab used in this study was provided by Chugai Pharmaceutical.