A modified thrombin generation assay to evaluate the plasma coagulation potential in the presence of emicizumab, the bispecific antibody to ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2020-08-03

AUTHORS

Kenichi Ogiwara, Keiji Nogami, Naoki Matsumoto, Mariko Noguchi-Sasaki, Michinori Hirata, Tetsuhiro Soeda, Midori Shima

ABSTRACT

Emicizumab shortens activated partial thromboplastin time (aPTT) greater than Factor (F)VIII. Clot waveform analysis triggered by ellagic acid and tissue factor trigger (Elg/TF) provided a useful means of assessing emicizumab activity. Thrombin generation assays (TGA) using this trigger reagent might also overcome the difficulties associated with aPTT by emicizumab. To compare TGA triggered by Elg/TF and other reagents (FXIa, TF) for evaluating emicizumab activity. Emicizumab, FVIII, or FVIII-bypassing agents (BPAs) were incubated with FVIII-deficient plasmas prior to TGA initiated by Elg/TF (0.2 μM/0.5 pM), FXIa (5.21 pM), or TF (PPP-Reagent LOW®). Emicizumab, FVIII, or BPAs increased peak thrombin generation (peak-Th) dose-dependently using Elg/TF-trigger and the other triggers. Low responses were evident with FXIa-trigger and the enhanced effects remained below normal levels with Elg/TF-trigger. Experiments using FVIII with emicizumab demonstrated an additive effect on peak-Th using Elg/TF-trigger, and this effect appeared to be less at FVIII ≥ 40 IU/dl. BPAs with emicizumab appeared to mediate additive effects, although its effects were variable. Parameters of thrombin generation from BPAs and emicizumab with Elg/TF-trigger were improved to normal level compared to low TF-trigger. Elg/TF-TGA could evaluate global coagulation potential during emicizumab prophylaxis including concomitant therapy with FVIII or BPAs. More... »

PAGES

621-630

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12185-020-02959-x

DOI

http://dx.doi.org/10.1007/s12185-020-02959-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1129841268

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32748217


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