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Effect of emicizumab on global coagulation assays for plasma supplemented with apixaban or argatroban

  • Armando TripodiEmail author
  • Veena Chantarangkul
  • Lidia Padovan
  • Marigrazia Clerici
  • Erica Scalambrino
  • Flora Peyvandi
Article
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Abstract

Emicizumab is a bi-specific humanized monoclonal antibody mimicking the factor (F) VIII cofactor activity in mediating the activation of FX by FIXa. Recent observations showed that emicizumab when added to pooled normal plasma (PNP), hemophilic plasma or PNP added with unfractionated heparin is able to interfere with coagulation assays. To further explore the mechanisms of assay interference we investigated the effect of emicizumab on global coagulation assays for the PNP added with two direct oral anticoagulants, apixaban or argatroban. Aliquots of PNP were added with purified apixaban or argatroban at a concentration of 500 ng/mL and emicizumab at concentrations ranging from 0 to 100 µg/mL. Plasma samples were then tested for the activated partial thromboplastin time (APTT) and for thrombin generation (the latter for the apixaban plasma only). Emicizumab at a 25–50 µg/mL shortened the APTT of the PNP with or without apixaban or argatroban. The extent of correction was greater for the apixaban or argatroban plasma and amounted to 35% or 42%, respectively. The parameters of thrombin generation (lag-time and time-to-peak) for the PNP supplemented with apixaban were shortened by 30% or 25%, respectively and the endogenous thrombin potential and the peak-thrombin were marginally affected. Emicizumab attenuates in vitro the anticoagulant activity of the PNP induced by apixaban or argatroban as documented by the correction of prolonged APTT and velocity of thrombin generation (i.e., lag-time and time-to-peak). Whether the above effects have any relevance in vivo is unknown.

Keywords

Direct oral anticoagulants Hemophilia Factor VIII Thrombin generation Activated partial thromboplastin time 

Notes

Author contributions

AT conceived the study. VC supervised preparation of test plasmas and laboratory testing. AT wrote the manuscript. MC, LP and ES, tested samples. FP and all the other authors reviewed data and revised the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoAngelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi VillaMilanItaly
  2. 2.Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanItaly

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