Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Roche Products Ltd. Please contact Roche Drug Safety Centre by emailing welwyn.uk_dsc@roche.com or calling +44 (0)1707 367554.
Sustained levels of emicizumab concentration are maintained from week 5 onwards, so routine monitoring is not necessary.2
- Measurement of FVIII levels and FVIII inhibitors may be required when patients are receiving HEMLIBRA2
- Measurement of emicizumab concentration is recommended in patients with suspected anti-emicizumab antibodies2
HEMLIBRA affects intrinsic pathway clotting-based laboratory tests1,2
- Unlike FVIII, HEMLIBRA does not require activation by thrombin3,4
- The effect of HEMLIBRA on coagulation assays differs from FVIII, especially for assays based on intrinsic clotting1,2
Effects may persist for up to 6 months after the last dose of HEMLIBRA.1
Measuring FVIII activity is not required with HEMLIBRA due to its mechanism of action, please see PK and MOA
Supporting material:
Download: Laboratory assays and HEMLIBRA pdf
You will be prompted to log in or register before you are able to access this material.
Learn more about laboratory assays and HEMLIBRA
Below you will find three videos from a 2019 question and answer session with Dr Annette Bowyer, Lead Biomedical Scientist at Royal Hallamshire Hospital.
Why and how does HEMLIBRA affect coagulation tests in patients with haemophilia A?
Dr Bowyer explains:
- HEMLIBRA is a therapeutic bispecific monoclonal antibody that is not FVIII, but it mimics FVIII activity in the tenase complex. It does not need to be pre-activated by thrombin in the same way that native FVIII does, so it works as soon as it encounters FIXa or FX
- In patients receiving HEMLIBRA, the activated partial thromboplastin time (aPTT) is artificially shortened, often to below the bottom of the normal reference range
- Any coagulation tests that are based on the aPTT will be affected, and one-stage Factor assays will be erroneously raised, which could be misleading
Laboratory tests affected and not affected by HEMLIBRA1
Do not use tests affected by HEMLIBRA:1
- In patients receiving HEMLIBRA
- To monitor the activity of HEMLIBRA
- To determine dosing for Factor replacement or anticoagulation
- To measure FVIII inhibitor titres
Which tests may be used in patients receiving HEMLIBRA?
Dr Bowyer explains:
- It is possible to modify the one-stage aPTT-based FVIII assay to quantify the concentration of HEMLIBRA. This is achieved with a change in dilution to the one-stage assay and calibration with emicizumab-specific calibrators from r2 Diagnostics. This can then be used to measure the HEMLIBRA concentration in µg/ml
- Bovine-based chromogenic Bethesda assays should be used to measure FVIII activity and any concurrent FVIII therapy
Measuring FVIII activity, FVIII inhibitor levels and HEMLIBRA concentration in patients with haemophilia A1,5
To measure FVIII activity, use a chromogenic FVIII assay with bovine proteins. For FVIII inhibitor levels, use a chromogenic Bethesda assay with bovine proteins or ELISA for anti-FVIII antibody. To determine the HEMLIBRA concentration, use a modified one-stage FVIII assay, calibrated against emicizumab (r2 Diagnostics*).
*These calibrators and controls are registered with the Medicines and Healthcare products Regulatory Agency (MHRA) and are labelled with the Conformité Européenne (CE) mark. Reagents are available in the UK from Enzyme Research Laboratories.
How does HEMLIBRA impact coagulation tests in patients with FVIII inhibitors, and what assays should be used?
Dr Bowyer explains:
- HEMLIBRA remains active in the presence of FVIII inhibitors
- The presence of HEMLIBRA dramatically shortens the aPTT. One-stage aPTT-based Bethesda assays are therefore affected by HEMLIBRA, leading to false negative inhibitor titres
- Human chromogenic-based Bethesda assays are also sensitive to the presence of HEMLIBRA and may produce a false negative inhibitor titre
-
Biography, Dr Annette Bowyer, Lead Biomedical Scientist, Royal Hallamshire Hospital
Dr Bowyer is the lead biomedical scientist for the haemophilia assays section, in the department of coagulation at the Sheffield Haemophilia and Thrombosis Centre, a designated World Federation of Hemophilia (WFH) International Hemophilia Training Centre. She was awarded her PhD in cardiovascular science from the University of Sheffield with a thesis focusing on the laboratory diagnosis of mild haemophilia A.
With more than 15 years of experience in the diagnosis and monitoring of bleeding disorders, Dr Bowyer has a particular interest in laboratory issues surrounding extended half-life treatment products for haemophilia. Dr Bowyer has also published a review paper, entitled 'Laboratory issues in gene therapy and emicizumab' (Haemophilia, 2020).
Dr Bowyer is a fellow of the Institute of Biomedical Science and a member of the International Society on Thrombosis and Haemostasis (ISTH), the WFH and the UKHCDO laboratory working party.
h
For general information on laboratory assays in patients with haemophilia A, please see Haemophilia A and laboratory tests
h
ACT, activated clotting time; APC-R, activated protein C resistance; aPTT, activated partial thromboplastin time; CE, Conformité Européenne; ELISA, enzyme-linked immunosorbent assay; FVIII, Factor VIII; FIX, Factor IX; FIXa, activated Factor IX; FX, Factor X; ISTH, International Society on Thrombosis and Haemostasis; MHRA, Medicines and Healthcare products Regulatory Agency; PT, prothrombin time; TT, thrombin time; WFH, World Federation of Hemophilia.
h
References:
- HEMLIBRA Summary of Product Characteristics.
- Jenkins PV et al. Haemophilia 2020;26:151–5.
- Kitazawa T et al. Nat Med 2012;18:1570–4.
- Lenting PJ et al. Blood 2017;130:2463–8.
- Calhoon W et al. THSNA 2018 [Poster Presentation].
h
M-GB-00004694
Date of preparation: September 2021
