Additive effect on the global clotting function in moderate/mild hemophilia A by addition of emicizumab, evaluated by clot waveform analysis
ISTH Academy. Nakajima Y. Jul 9, 2019; 264388; PB1197 Topic: FVIII/IX Basic and Laboratory
Yuto Nakajima
Yuto Nakajima
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Additive Effect on the Global Clotting Function in Moderate/Mild Hemophilia A by Addition of Emicizumab, Evaluated by Clot Waveform Analysis

Y. Nakajima1, K. Nogami1, K. Yada1, S. Furukawa1, M. Noguchi2, K. Hirata2, M. Shima1
1Nara Medical University, Kashihara, Japan, 2Chugai Pharmaceutical Co., Ltd, Product Research, Kamakura, Japan

Main Topic: Coagulation and Anticoagulation
Category: FVIII/IX Basic and Laboratory

Background: Emicizumab prophylaxis markedly decreases bleeding events in severe-type patients with hemophilia A (PwHA) irrespective of FVIII inhibitors. The hemostatic effect of emicizumab for patients with mild/moderate HA (PwMHA) has not been reported, however.
Aims: To evaluate the additive effect by spiking emicizumab on global clotting function of PwMHA.
Methods: We tested 16 plasma samples obtained from PwMHA (6 moderate and 10 mild patients), and FVIII-deficient plasmas mixed with various concentrations of rFVIII (0-40 IU/dl) as contrived standard plasma. We evaluated the coagulation function in these samples after by spiking emicizumab (0, 50, 100 µg/ml) with clot waveform analysis using tissue factor and ellagic acid as triggers. An adjusted-|min1| (Ad|min1|), representing the maximum velocity of coagulation reaction adjusted to minimize the influence of fibrinogen, was used for quantative assessment.
Results: The mean value of Ad|min1| in the contrived plasma (rFVIII:C 0, 5, 40 IU dL-1) was 3.60 ± 0.07/min, 3.99 ± 0.02/min and 5.81 ± 0.01/min in the absence of emicizumab, respectively, whilst that increased to 4.61±0.02/min, 4.81±0.02/min and 6.19±0.02/min by spiking emicizumab (100µg/ml). According to the increase rate of them (28%, 20% and 7%, respectively) and each level of FVIII:C, dose-response standard curve was obtained. In plasmas of moderate and mild patients, Ad|min1| was 4.31 ± 0.33/min and 5.01 ± 0.43/min without emicizumab and increased to 5.31±0.56/min (+23%) and 5.71±0.47/min (+14%) by spiking emicizumab (100µg/ml), respectively. Emicizumab improved coagulation function of all MHA cases, although some individual differences were observed. The increase rate of Ad|min1| in 4 moderate cases was 40%, 43%, 46% and 62% and that in 3 moderate and 1 mild cases was 213%, 230%, 193% and 170% of increase value of corresponding FVIII:C calculate by standard curve. However, there was no significant difference in the increase rate between others.
Conclusions: Emicizumab could enhance the coagulation function for PwMHA.

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