Predicted coagulation potential using an in vitro simulated model of emicizumab prophylaxis and immune tolerance induction therapy in hemophilia A ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2021-02-26

AUTHORS

Yuto Nakajima, Hitoshi Tonegawa, Mariko Noguchi-Sasaki, Keiji Nogami

ABSTRACT

Emicizumab reduces bleeding in hemophilia A patients with inhibitor (HA-inh). A combination of immune tolerance induction therapy (ITI) and emicizumab prophylaxis may provide additional benefits, but coagulation potential during this treatment remains unknown. We assessed coagulation potentials in simulated ITI models in vitro using modified-clot waveform analysis. Factor (F)VIII-deficient plasma preincubated with anti-A2 and anti-C2 monoclonal antibodies was reacted with emicizumab (50 µg/mL) (emicizumab–HA–plasma), then spiking bypassing agents (BPAs): activated prothrombin complex concentrates (aPCC 1.3 IU/mL; 50 IU/kg), recombinant factor (rF)VIIa (2.2 µg/mL; 90 µg/kg), and FVIIa/FX (1.5 µg/mL; 60 µg/kg), and/or FVIII (100, 200 IU/dL). Coagulation potentials in emicizumab–HA–plasma (10 BU/mL) remained within the normal range when BPA and FVIII were both present. In emicizumab–HA–plasma (1 BU/mL) with BPA and FVIII (200 IU/dL), they were near or beyond the normal range, but those with a half concentration of rFVIIa based on the half-life in blood were within the normal range. In samples without inhibitor, coagulation potentials with combined BPA and FVIII were far beyond the normal range but with FVIII (100 IU/dL) and rFVIIa at half concentration they remained within the normal range. These results may provide information on the feasibility of concurrent ITI under emicizumab prophylaxis. More... »

PAGES

789-796

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-021-03108-8

DOI

http://dx.doi.org/10.1007/s12185-021-03108-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1135754256

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33635530


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