# Evaluation of Autoimmune FVIII Inhibitor Using Clot Waveform Analysis in Emicizumab-Treated Patients

## TL;DR

This study evaluates clot waveform analysis for diagnosing and monitoring autoimmune factor VIII deficiency in patients treated with emicizumab.

## Contribution

The study introduces clot waveform analysis as a potential diagnostic and monitoring tool for autoimmune factor VIII deficiency during emicizumab treatment.

## Key findings

- CWA-sTT reflects residual FVIII activity in patients with autoimmune FVIII deficiency.
- Emicizumab treatment was effective for major bleeding in patients with autoimmune FVIII deficiency.
- Anti-FVIII antibody activity can be measured using CWA-sTT even during emicizumab treatment.

## Abstract

Background/Objectives: Autoimmune factor VIII deficiency (AiFVIIID) is a rare disorder that causes severe bleeding. Emicizumab has recently been found to be effective in treating AiFVIIID; however, monitoring with standard coagulation tests presents challenges. Methods: Clot waveform analysis (CWA), which involves CWA-activated partial thromboplastin time (APTT), the CWA-small amount of tissue factor activation assay (sTF/FIXa), and clotting time using a small amount of thrombin (sTT), was used to both diagnose AiFVIIID and monitor emicizumab. Results: CWA-sTT reflects the residual FVIII activity in patients with AiFVIIID. Several tests were employed, including APTT, FVIII activity, CWA, mixing tests with normal plasma, FVIII inhibitor assays, and anti-FVIII antibody activity for the diagnosis of AiFVIID in three cases. However, the sensitivity of APTT reagents to AiFVIID differed between thrombocheck-APTT and APTT-SP. Emicizumab treatment was effective for major bleeding, and anti-FVIII antibody activity could be measured using CWA-sTT. Conclusions: The sensitivity of APTT reagents to AiFVIID varies. CWA-sTT may provide utility in the diagnosis of AiFVIIID. Emicizumab is useful for the treatment of AiFVIID, and anti-FVIII antibody activity can be measured even in patients treated with emicizumab.