Abstract Number: PB0986
Meeting: ISTH 2020 Congress
Background: Emicizumab is used for the treatment of patients with severe haemophilia A with/without inhibitors. It is a bispecific antibody that mimics the properties of human FVIIIa activity by linking FIX and FX to activate FX.
Aims: To obtain results from plasma samples containing emicizumab in a multicentre exercise and identify any variability between different reagents and test methods.
Methods: Participants performed FVIII assays, according to their normal laboratory practice, on 3 plasma samples S19:10, S19:11 and S19:12. Sample S19:10 was obtained from a patient with severe Haemophilia A treated with emicizumab for 3 weeks. Sample S19:11 was constructed from in-vitro addition of emicizumab into FVIII deficient plasma to mimic a post treatment level. Sample S19:12 was a pool of FVIII deficient plasma with no emicizumab present. All plasma samples were buffered and lyophilised before distribution.
|Table 1||S19:10 FVIII 1-stage result||S19:11 FVIII 1-stage result||S19:12 FVIII 1-stage result|
|APTT Reagent||n||Median FVIII (IU/dL)||Median IU/dL (FVIII)||n||Median IU/dL (FVIII)|
|Siemens Actin FS||3||480.0||493.7||5||0.60|
|IL/Werfen Hemosil SynthasIL||6||687.6||764.9||6||0.40|
|Stago STA CK Prest||3||390.5||400||2||0.10|
|IL HemosIL APTT-SP||1||545.6||664.4||1||0.35|
|Grifols DG-APTT Synth||1||554.0||590||1||0.90|
[Table 1-Unmodified One-stage FVIII assay results]
Two centres used emicizumab specific calibrator material (r2 diagnostics) with the one-stage assay so results were in µg/ml rather than IU/dl surrogate FVIII activity. Results are shown below. No results were provided by participants for sample S19:12:· Siemens Actin FS = 60.9 (S19:10) and 73.1 (S19:11) *IL/Werfen Hemosil SynthasIL = 53.0 (S19:10) and 64.7 (S19:11)·
*Stago STA CK Prest = 54.1 (S19:10) and 62.1 (S19:11)*Results from same centre.
|Chromogenic Assay||Kit manufacturer||n||Median FVIII (IU/dL)||CV (%)||Median FVIII (IU/dL)||CV (%)||Median FVIII (IU/dL)||CV (%)|
|Chromogenic: bovine FIXa/FX||Siemens Bovine chromogenic||11||1.0||95.3||1.0||95.6||0.6||73.4|
|IL/Werfen Hemosil Electrochrome||1||2.4||–||2.8||–||0.7||–|
|Chromogenic: mixed human/bovine FIXa/FX||Technoclone||1||2.2||–||2.7||–||<1.0||–|
[Table 2-Chromogenic assays]
Chromogenic assaysThe FVIII results generated from the bovine chromogenic kits, Siemens and Coamatic, were nearly 2.5 fold lower than results from the IL/Werfen Hemosil Electrochrome kit.
Conclusions: This UK NEQAS BC exercise identified a large variety of assay methods and reagents used for monitoring emicizumab plasma samples. The widespread use of unmodified one stage FVIII assay s suggests the need for guidance on when to use which test method.
To cite this abstract in AMA style:Lowe A, Jennings I, Kitchen S, Kitchen D, Brown L, Munroe-Peart S, Walker I. Surrogate FVIII Activity in Patient and Constructed Plasma Samples Containing Emicizumab: A National External Quality Assurance Scheme for Blood Coagulation (UK NEQAS BC) Exercise [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/surrogate-fviii-activity-in-patient-and-constructed-plasma-samples-containing-emicizumab-a-national-external-quality-assurance-scheme-for-blood-coagulation-uk-neqas-bc-exercise/. Accessed November 30, 2021.
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