PB1112 - UK National External Quality Assessment Scheme for Blood Coagulation (UK NEQAS BC) Emicizumab programme, survey July 2022 results for modified one-stage assay and chromogenic assay.

Background: Emicizumab, a novel specific Haemophilia A therapy, is a bispecific monoclonal antibody that effectively performs the role of factor VIII in coagulation activation.

Aims: The NEQAS BC exercise in July 2022, was to gather data about low levels of detection for emicizumab in assays available to laboratories plus to mimic levels where non-compliance or an inhibitor to emicizumab may give clinical concern.

Methods: The samples distributed for this exercise included a FVIII deficient plasma spiked with emicizumab at approximately 21µg/ml (EMI 22:03) and normal plasma (EMI 22:04). Both samples were lyophilised Table 1 shows the data from 46 centres returning results.

Results: 91% centres used the R2 diagnostics calibrator with the other 9% preferring to use Hemlibra for calibration of modified one-stage assays.
Neither Emicizumab nor Hemlibra were used as calibrators for the chromogenic assay results obtained for sample EMI 22:03.
The data captured by modified one-stage assay for sample 22:04, containing no emicizumab gave a median emicizumab level 12.5 ug/ml, compared to the median FVIII level of 122iu/dL for all of the chromogenic assay results. Chromogenic assays or the unmodified one-stage assay should be used to measure normal plasma without emicizumab.

Conclusion(s): Clinically inhibitors to emicizumab would be a major concern for patients receiving treatment for Haemophilia A. However anecdotal evidence has highlighted that ongoing non-compliance to the treatment protocol for emicizumab may well explain emicizumab levels below the therapeutic window of 30-70 µg/ml.
The results of this exercise establish that FVIII deficient plasma spiked with Emicizumab, to a sub-therapeutic level of 21 µg/ml, can be measured by laboratory assays with a CV < 6.4%.