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Effects of emicizumab on APTT, one-stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors.
Haemophilia. 2020 May; 26(3):536-542.H

Abstract

INTRODUCTION

Emicizumab (Hemlibra, Roche-Chugai) is a recombinant humanized bispecific IgG4 antibody which mimics some of the actions of activated factor VIII (FVIIIa) by binding to factor X (FX) and activated factor IX (FIXa) to activate FX.

AIM

To evaluate the effect of emicizumab on the APTT, standard one-stage APTT-based FVIII activity assay (sOSA) using plasma calibrators, modified OSA (mOSA) using r2 Diagnostics emicizumab specific calibrator and chromogenic FVIII assays. Tests were performed on plasma artificially spiked with emicizumab and from four severe haemophilia A (SHA) patients treated with emicizumab.

METHOD

APTT in spiked plasma was performed with 13 APTT reagents and in SHA patients with 5 reagents. OSA in spiked plasma was performed with 9 APTT reagents, 7 APTT reagents were used for OSA in SHA patients and six chromogenic substrate assays (CSA) were performed.

RESULTS

In SHA, APTTs normalized after the first dose of emicizumab. At weeks 32/36 of treatment, the mean sOSA FVIII:C ranged from 2.47 IU/mL (Synthasil) to greater than 7.00 IU/mL with all other reagents. mOSA ranged from 59.8 µg/mL (Synthasil) to 74.5 µg/mL (APTT SP). Bovine CSA did not recover any FVIII:C activity. Hyphen Biomed human CSA, demonstrated FVIII activity when calibrated against a plasma calibrator.

CONCLUSION

The APTT was significantly shortened in the presence of emicizumab. sOSA FVIII:C levels were erroneously high, and it is not recommended that these be performed. Quantification of emicizumab concentration was possible by mOSA. Human CSA was sensitive to emicizumab and surrogate FVIII:C activity could be determined. Bovine CSA were insensitive to emicizumab and could not be used to quantify emicizumab concentration.

Authors+Show Affiliations

Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK.Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK.Department of Coagulation, Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32249990

Citation

Bowyer, Annette, et al. "Effects of Emicizumab On APTT, One-stage and Chromogenic Assays of Factor VIII in Artificially Spiked Plasma and in Samples From Haemophilia a Patients With Inhibitors." Haemophilia : the Official Journal of the World Federation of Hemophilia, vol. 26, no. 3, 2020, pp. 536-542.
Bowyer A, Kitchen S, Maclean R. Effects of emicizumab on APTT, one-stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors. Haemophilia. 2020;26(3):536-542.
Bowyer, A., Kitchen, S., & Maclean, R. (2020). Effects of emicizumab on APTT, one-stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors. Haemophilia : the Official Journal of the World Federation of Hemophilia, 26(3), 536-542. https://doi.org/10.1111/hae.13990
Bowyer A, Kitchen S, Maclean R. Effects of Emicizumab On APTT, One-stage and Chromogenic Assays of Factor VIII in Artificially Spiked Plasma and in Samples From Haemophilia a Patients With Inhibitors. Haemophilia. 2020;26(3):536-542. PubMed PMID: 32249990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of emicizumab on APTT, one-stage and chromogenic assays of factor VIII in artificially spiked plasma and in samples from haemophilia A patients with inhibitors. AU - Bowyer,Annette, AU - Kitchen,Steve, AU - Maclean,Rhona, Y1 - 2020/04/06/ PY - 2019/11/04/received PY - 2020/02/26/revised PY - 2020/03/17/accepted PY - 2020/4/7/pubmed PY - 2020/12/15/medline PY - 2020/4/7/entrez KW - APTT KW - chromogenic KW - emicizumab KW - factor VIII KW - haemophilia A KW - one-stage SP - 536 EP - 542 JF - Haemophilia : the official journal of the World Federation of Hemophilia JO - Haemophilia VL - 26 IS - 3 N2 - INTRODUCTION: Emicizumab (Hemlibra, Roche-Chugai) is a recombinant humanized bispecific IgG4 antibody which mimics some of the actions of activated factor VIII (FVIIIa) by binding to factor X (FX) and activated factor IX (FIXa) to activate FX. AIM: To evaluate the effect of emicizumab on the APTT, standard one-stage APTT-based FVIII activity assay (sOSA) using plasma calibrators, modified OSA (mOSA) using r2 Diagnostics emicizumab specific calibrator and chromogenic FVIII assays. Tests were performed on plasma artificially spiked with emicizumab and from four severe haemophilia A (SHA) patients treated with emicizumab. METHOD: APTT in spiked plasma was performed with 13 APTT reagents and in SHA patients with 5 reagents. OSA in spiked plasma was performed with 9 APTT reagents, 7 APTT reagents were used for OSA in SHA patients and six chromogenic substrate assays (CSA) were performed. RESULTS: In SHA, APTTs normalized after the first dose of emicizumab. At weeks 32/36 of treatment, the mean sOSA FVIII:C ranged from 2.47 IU/mL (Synthasil) to greater than 7.00 IU/mL with all other reagents. mOSA ranged from 59.8 µg/mL (Synthasil) to 74.5 µg/mL (APTT SP). Bovine CSA did not recover any FVIII:C activity. Hyphen Biomed human CSA, demonstrated FVIII activity when calibrated against a plasma calibrator. CONCLUSION: The APTT was significantly shortened in the presence of emicizumab. sOSA FVIII:C levels were erroneously high, and it is not recommended that these be performed. Quantification of emicizumab concentration was possible by mOSA. Human CSA was sensitive to emicizumab and surrogate FVIII:C activity could be determined. Bovine CSA were insensitive to emicizumab and could not be used to quantify emicizumab concentration. SN - 1365-2516 UR - https://www.unboundmedicine.com/medline/citation/32249990/Effects_of_emicizumab_on_APTT_one_stage_and_chromogenic_assays_of_factor_VIII_in_artificially_spiked_plasma_and_in_samples_from_haemophilia_A_patients_with_inhibitors_ L2 - https://doi.org/10.1111/hae.13990 DB - PRIME DP - Unbound Medicine ER -