AI Article Synopsis

  • - Emicizumab is more effective than Factor (FVIII) in shortening activated partial thromboplastin time (aPTT) and its activity can be assessed using clot waveform analysis triggered by ellagic acid and tissue factor (Elg/TF).
  • - Thrombin generation assays (TGA) using Elg/TF showed that emicizumab, FVIII, and FVIII-bypassing agents enhanced thrombin generation in a dose-dependent manner, although responses were lower with FXIa-trigger.
  • - The combination of emicizumab and FVIII produced an additive effect on thrombin generation, particularly evident at lower FVIII concentrations, making Elg/TF-TGA a useful tool for evaluating coagulation

Article 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.

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

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