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
| Autor: | Annette E. Bowyer, Steve Kitchen, Rhona Maclean |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Fviii activity
Haemophilia A 030204 cardiovascular system & hematology Antibodies Monoclonal Humanized Hemophilia A Hemostatics law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law Antibodies Bispecific Medicine Humans Genetics (clinical) Emicizumab Chromatography Factor VIII biology business.industry Chromogenic Factor X One stage Hematology General Medicine medicine.disease chemistry biology.protein Recombinant DNA Partial Thromboplastin Time Antibody business circulatory and respiratory physiology 030215 immunology |
| Zdroj: | Haemophilia : the official journal of the World Federation of HemophiliaREFERENCES. 26(3) |
| ISSN: | 1365-2516 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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