Skip to main content
ISTH 2024 Main banner
Back

Poster Networking

Coagulation Factors and Co-Factors

PB1111 - Usefulness of hybrid human-porcine factor VIII for emicizumab-treated patients with hemophilia A and inhibitors

Tuesday, June 25, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall
Background: Bypass hemostatic agents(BPAs) such as recombinant FVIIa are used for hemostatic management in patients with hemophilia A and inhibitors (PwHA-I) receiving emicizumab (Emi). However, there are almost no choice except BPAs. We have created hybrid human-porcine FVIII (hpFVIII) by recombining the A2 and C2 domains of human(h) FVIII with the homologous sequence of porcine (p)FVIII. We reported that hpFVIII improves coagulation potential of PwHA-I. (Mizumachi et al. ASH2022)

Aims: To investigate the effect of hpFVIII for Emi-treated PwHA-I.

Methods: HpFVIII mutant (2 nM) was added to plasmas in three Emi-treated PwHA-I (inhibitor titer 1.24 BU/mL, 5.67 BU/mL, 3.75 BU/mL, respectively) and commercially available FVIII-deficient plasmas spiked with Emi 50 μg/mL in the presence of human A2 (2.4 BU/mL) or A2C2 (5.8 BU/mL) inhibitor. Comprehensive coagulability was assessed using coagulation waveform analysis (CWA) (trigger; tissue factor and ellagic acid) and thrombin generation assay (TGA) (trigger; tissue factor); maximum coagulation rate (Ad|min1|) in CWA and peak thrombin (PeakTh) were used as coagulation parameters.

Results: Ad|min1| in FVIII-deficient plasmas spiked with emicizumab increased from 4.3±0.2 to 5.8±0.1 (Normal range: 7.1±0.6 nM), and Peak Th in them also increased from 86±13 nM to 122±23 nM (Normal range: 181±48 nM). The addition of hpFVIII to FVIII-deficient plasma spiked with Emi in the presence of A2 and A2C2 inhibitor increased Ad|min1| from 5.8±0.2 to 6.6±0.2 and PeakTh from 121±29 nM to 166±30 nM. The addition of hpFVIII to plasmas from PwHA-I during Emi administration increased Ad|min1| from 5.3±0.0 to 6.8±0.5 and PeakTh from 102±66 nM to 136±88 nM.

Conclusion(s): Our result suggested that hpFVIII could enhance coagulation potential in emicizumab-treated PwHA-I.