Chromogenic Factor VIII

Coagulation

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Description

Factor VIII (FVIII) is an essential coagulation protein. A reduction or absence of FVIII results causes the X-linked bleeding disorder, haemophilia A. A reduction in FVIII may also be observed in patients with von Willebrand disease (VWD). FVIII activity (FVIII:C) may be measured by one-stage clotting, two-stage clotting or chromogenic assays.

The chromogenic FVIII assay was first introduced in the 1980s. Activated FVIII (FVIIIa), along with FIXa, is a cofactor which activates FX to FXa in the tenase complex of coagulation. The concentration of FVIII(a) is made the rate limiting step in the assay and FXa is generated is proportional to this. The FXa generated cleaves a specific chromophore and the resultant change in optical density is measured at 405nm.

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Indications

The measurement of factor VIII activity (FVIII:C) in plasma. This assay will be performed as part of an investigation into a prolonged APTT, investigation of a bleeding disorder or to monitor replacement FVIII therapy (both standard and extended half-life) in patients with haemophilia A and VWD.

Approximately one third of patients with the mild form of haemophilia A with demonstrate significantly different FVIII:C when measured by one-stage FVIII compared to the two-stage or chromogenic FVIII. This is known as assay discrepancy. Half of patients with assay discrepancy will have a two-fold or lower one-stage FVIII than two-stage or chromogenic FVIII and approximately half will have a two-fold or lower two-stage or chromogenic FVIII than one-stage FVIII. There is a genetic link to both versions of FVIII assay discrepancy.

Hemlibra is a bispecific antibody which mimics the action of FVIII and is licensed for the treatment of some Haemophilia A patients. Chromogenic FVIII assays are also used in the presence of Hemlibra (emicizumab). A chromogenic FVIII assay which contains human FIXa and FX is sensitive to emicizumab and can be used to indicate the presence of the drug. A chromogenic FVIII:C assay which contains bovine FIXa is insensitive to emicizumab and can be used to monitor any additional FVIII therapy given to the patient.

The Sheffield Coagulation department offers both human and bovine chromogenic assays. Routine investigations are performed with the human chromogenic assay. The bovine chromogenic assay is available for the testing of patients treated with emicizumab.

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Sample Type

Plasma (Citrate Blue) x 2

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Reference Range

Adult reference range is indicated on the report

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Turnaround Time

Within 2 weeks (or on demand)

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Testing Frequency

Daily (available out of core hours)

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References

Bowyer AE, Duncan EM, Antovic JP. Role of chromogenic assays in haemophilia A and B diagnosis. Haemophilia. 2018;24(4):578–583. doi:10.1111/hae.13520.

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See Also

von Willebrand Disease Screen
FVIII complex
One-stage Factor Assay
Two-stage Factor VIII
Factor VIII Inhibitor Assay

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