Factor VIII Inhibitors (one-stage, chromogenic, porcine)

Coagulation

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Description

20-50% of patients with congenital haemophilia A develop anti-factor VIII alloantibodies (inhibitors) when treated with FVIII replacement therapy. Regular monitoring of inhibitor levels (titre) is required for patients with, or at risk of, inhibitor development. The inhibitor titre is measured in Bethesda units (BU) with 1 BU being defined as the titre of inhibitor which will inhibit 50% of total FVIII activity. This is usually performed by a one-stage Bethesda inhibitor assay. A heat treatment step can also be included to remove any FVIII form the plasma prior to assay if necessary.

Haemophilia A patients treated with Hemlibra (emicizumab) will also require regular monitoring of inhibitor levels. Emicizumab interferes with one-stage Bethesda inhibitor assays causing a false negative or lower inhibitor titre. A Bovine chromogenic inhibitor assay is insensitive to the presence of emicizumab so is necessary for inhibitor measurement in the presence of emicizumab.

Rarely, autoantibodies to FVIII can develop in previously unaffected people in the disorder acquired haemophilia A (AHA). This is a condition, usually in the elderly, which presents with bruising and bleeding, a prolonged APTT, reduced FVIII and positive FVIII inhibitor assay. One of the treatments for AHA is recombinant porcine FVIII however in some patients there is cross-reactivity between the anti-human antibodies and the porcine FVIII. A porcine inhibitor assay can be used to measure any cross-reacting antibodies.

The Sheffield Coagulation department can perform each of these assays.

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Sample Type

Plasma (Citrate Blue) x 2.

FVIII:C level is also required for analysis of FVIII inhibitor with the exception of porcine inhibitors. This can be provided by the referring laboratory or performed in Sheffield.

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Reference Range

Negative inhibitor titre is normal.

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Turnaround Time

Within 2 weeks

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Testing Frequency

Weekly or as required. Available outside core hours.

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External Notes

Samples must be received before 2pm for same day analysis. Prior arrangement with haematology SPR and laboratory is required for urgent requests.

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References

Verbruggen B et al (1995). The Nijmegen modification of the bethesda assay for FVIII:C inhibitors: improved specificity and reliability. Thromb Haemost. 73, 247-51
Kruse-Jarres R, Kempton CL, Baudo F, et al. Acquired hemophilia A: Updated review of evidence and treatment guidance. Am J Hematol. 2017;92(7):695–705. doi:10.1002/ajh.24777
Jenkins PV, Bowyer AE, Burgess C et al (2020). Laboratory coagulation tests and emicizumab treatment A United Kingdom Haemophilia Centre Doctors' Organisation guideline. Haemophilia, 26(1), 151-155

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Please note: the above information is subject to change and we endeavour to keep this website up to date wherever necessary.