Abstract Number: PB0342
Meeting: ISTH 2020 Congress
Background: Emicizumab, a humanized bispecific antibody for haemophilia A (HA) treatment, is well known to affect the activated partial thromboplastin time (aPTT) making not reliable all the aPTT-based tests (one-stage assay and Bethesda assay for measuring FVIII inhibitor titre). The use of chromogenic assay with bovine regents (insensitive to Emicizumab) or preventive neutralization of the drug are mandatory in order to avoid misinterpretation of the results.
Aims: To evaluate the effect of Emicizumab Neutralizing Antibodies (anti-Emi) by comparing the results obtained with aPTT-based and chromogenic assays on samples from HA patients treated with Emicizumab.
Methods: Twenty-five plasma samples of HA patients without FVIII inhibitor were analysed for aPTT and FVIII:C activity; FVIII inhibitor titre was measured using Nijmegen-Bethesda assay on 10 samples of HA patients. FVIII:C activity and inhibitor titre were measured both with the one-stage (Actin FS – Siemens, Germany) and the chromogenic assay (with bovine regents, Siemens). Emicizumab concentration was measured by using a modified one-stage assay calibrated with a specific Calibrator (r2 Diagnostics Inc., US). All the tests were performed on Sysmex CS-2400 (Sysmex, Kobe, Japan) before and after the addition (1:20) of a mixture of two anti-idiotype monoclonal antibodies neutralising Emicizumab (Chugai Pharmceutical, Japan).
Results: Emicizumab concentration measured after the neutralization was < 5 µg/mL in all the samples.
The table reports the results [mean (range)] obtained on the 25 plasma samples without FVIII inhibitor
Inhibitor titre was < 0.5 UB in almost all the 10 samples when measured with the one-stage before Emicizumab neutralization. A good correlation (r=0.996) was found between inhibitor titre measured with chromogenic assay and with one-stage assay after neutralization.
Conclusions: These preliminary results showed the efficacy of the anti-Emi that could be used in the laboratory monitoring of HA patients treated with Emicizumab when the one-stage is the only available assay.
|Before neutralization||After neutralization|
|Emicizumb (μg/mL)||61.9 (36.4-99.2)||0.3 (0.3-1.1)|
|aPTT (sec)||20.25 (18.4-25.7)||> 70|
|one-stage FVIII:C (IU/dL)||> 480||0.25 (0.2-0.3)|
|chromogenic FVIII:C (IU/dL)||< 3.3||–|
[Results of patients without FVIII inhibitor]
To cite this abstract in AMA style:Novembrino C, Boscolo-Anzoletti M, Rossi F, Mancuso E, Shinohara S, Peyvandi F. Evaluation of the Effect Emicizumab Neutralizing Antibodies on aPTT Clotting-based Tests Results in Patients Treated with Emicizumab [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/evaluation-of-the-effect-emicizumab-neutralizing-antibodies-on-aptt-clotting-based-tests-results-in-patients-treated-with-emicizumab/. Accessed January 28, 2022.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/evaluation-of-the-effect-emicizumab-neutralizing-antibodies-on-aptt-clotting-based-tests-results-in-patients-treated-with-emicizumab/