PB0085 - The evaluation of hemostatic abnormalities in congenital or acquired coagulation factor deficiency using a clot waveform.

Background: Regular prophylactic therapy, including emicizumab, for severe hemophilia or patients with FVIII inhibitors has spread. However, emicizumab is difficult to monitor, and extended half-life of factor VIII products (EHL-FVIII) may cause hypercoagulability. Tests have been developed for clot waveform analyses (CWAs) using activated partial thromboplastin time (APTT), small amounts of tissue factor FIX activation (sTF/FIXa) assays, and thrombin time (TT).

Aims: We aim to establish the clinical application of CWA in patients with severe bleeding with and without emicizumab.

Methods: The coagulation abilities were evaluated using the CWA-APTT, CWA-sTF/FIXa or CWA-TT in 8 of the FVIII concentrate products, emicizumab, and plasma from 50 patients with coagulation factor deficiency, 20 healthy volunteers.The APTT was measured using platelet-poor plasma (PPP) and APTT-SP (IL-Japan, Tokyo). The sTF/FIXa assay was performed using 2,000-fold diluted HemosIL RecombiPlasTin 2G (IL Japan, Tokyo) and platelet-rich plasma (PRP). The TT was performed using 0.2 IU thrombin and PRP or PPP. The ACL-TOP system (IL Japan) was used to obtain the peak time (PT) and peak height (PH) of fibrin formation (FF) and the first derivative (1stD) and second derivative (2ndD) curves, referred to as the FFT and FFH, 1stDPT and 1stDPH, and 2ndDPT and 2ndDPH, respectively.

Results: The CWA-APTT revealed markedly decreased PHs in patients with severe hemophilia A and patients with FVIII inhibitors, with the 1stDPH in patients with FVIII inhibitors being extremely low. The CWA-TT using a small amount of thrombin was able to reflect thrombin burst and proved useful for evaluating the FVIII activity independent of the presence of emicizumab. The CWA-sTF/FIXa detected hypercoagulability in hemophilic patients treated with EHL-FVIII and was useful for evaluating the efficacy of activated FVII.

Conclusion(s): CWAs are useful for monitoring the clotting activity in patients with congenital or acquired coagulation factor deficiency treated with FVIII products or bypass therapy.