Clinical management support: Known interference between Hemlibra (emicizumab injection) and lab assays used to diagnose coagulopathy / DIC caused by COVID-19 infection

Clinical management support: Known interference between Hemlibra® (emicizumab injection) and lab assays used to diagnose coagulopathy / DIC caused by COVID-19 infection - Recalls and safety alerts
Starting date:
April 17, 2020
Posting date:
April 17, 2020
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Biologic/vaccine
Source of recall:
Health Canada
Issue:
Important Safety Information
Audience:
Healthcare Professionals
Identification number:
RA-72779

Last updated:

2020-04-17

Health Canada posts safety alerts, public health advisories, press releases and other notices from industry as aservice to health professionals, consumers, and other interested parties. Although Health Canada authorizestherapeutic products, Health Canada does not endorse either the product or the company. Any questions regardingproduct information should be discussed with your health professional. 

This is duplicated text of a letter from Hoffmann-La Roche Limited. Originally issued on April 10, 2020.

Contact the company for a copy of any references, attachments or enclosures.

Clinical management support: Known interference between Hemlibra® (emicizumab injection) and lab assays used to diagnose coagulopathy / DIC caused by COVID-19 infection

April 10, 2020

We are reaching out to you to remind you about Hemlibra® (emicizumab injection) and its known interaction with certain laboratory assays. Some of these assays may be relevant to some patients that are receiving Hemlibra and become infected with the novel coronavirus that causes COVID-19. Given that the physicians and laboratories treating COVID-19 patients may not be familiar with Hemlibra, we want you to be prepared to share this information in cases where it is relevant. The information below supplements the list of coagulation assays in the Product Monograph that may or may not be affected by Hemlibra: https://www.rochecanada.com/PMs/Hemlibra/Hemlibra_PM_E.pdf

COVID-19 is caused by a novel coronavirus, therefore its effects on people with Hemophilia A is not well understood. Patients with severe COVID-19 infection, with or without hemophilia, may develop a COVID-19 associated coagulopathy resembling disseminated intravascular coagulation (DIC) as the condition progresses.

Importantly, Hemlibra is known to interfere with one-stage clotting assays, some of which are used to diagnose and monitor patients with DIC. The following table lists common coagulation assays that may be used to diagnose, monitor and manage patients with COVID-19 associated coagulopathy, and indicates whether these assays are affected by Hemlibra, and potential alternatives where applicable.

Analyte / Assay Assay interference with Hemlibra? Alternatives
aPTT Yes (overestimates coagulation potential of Hemlibra) For heparin monitoring: anti-Xa assay
PT Yes (weak effect) No mitigation required (small effect)
D-Dimer No
Fibrinogen: Clauss method No
Fibrinogen: derived Yes (weak effect) No mitigation required (small effect); or use Clauss method
Protein C: chromogenic No
Protein C: aPTT-based Yes (overestimate coagulation potential of Hemlibra) Chromogenic protein C assay
Antithrombin activity No
Anti-Xa activity No

FVIII activity: aPTT-based

Yes (overestimate coagulation potential of Hemlibra) Chromogenic FVIII assay (see below guidance)

FVIII activity: chromogenic bovine reagents

No Does not detect Hemlibra, but allows measurement of endogenous or infused FVIII activity

FVIII activity: chromogenic

human reagents

No Responsive to Hemlibra, but may overestimate clinical hemostatic potential of Hemlibra

1) For additional information on effects and interferences of Hemlibra on coagulation assays, please refer to Adamkewicz, et al. Thromb Haemost 2019;119:1084-1093.

2) Please consult the Product Monograph for further information

While this information is known within the hemophilia community, if a patient on Hemlibra seeks treatment due to symptoms of COVID-19 infection, we recommend the above table or information is communicated proactively to the treating healthcare provider, to ensure they are aware of this information and to remind them to consult the Product Monograph. The long half-life (~30 days) of Hemlibra should also be taken into consideration in the context of clinical management.  Please consult the Product Monograph in all cases.

Additional Pharmacovigilance Reporting Request

Patient safety is Roche's highest priority. At this time, the interaction between Hemlibra and the coagulopathy secondary to COVID-19 infection is unknown. We are committed to obtaining as much information as possible. We are closely monitoring the evolving COVID-19 situation and reviewing any information regarding COVID-19 infections in patients receiving Hemlibra as it becomes available.

We encourage reporting of all confirmed/suspected cases of COVID-19 in patients receiving Hemlibra through the reporting contact information provided below.

Please be prepared to provide as many details as possible, including COVID-19 specific details such as:

  • Patient demographics
  • COVID-19 diagnostic test results 
  • Coagulation laboratory test results (D-dimer, platelets, PT/INR, fibrinogen, etc.), if applicable and imaging results as appropriate if thrombotic complications are suspected
  • Concurrent or recent use of medications that may have an impact on hemostasis (e.g. replacement factor, FFP, low-molecular weight heparin, etc.)
  • Assessment of causality
  • Contact details to conduct follow up, as needed

You may find these additional resources useful: 

        - Public Health Agency of Canada COVID-19 Information Site

        - ISTH COVID-19 Resource center

        - WFH COVID-19 guidance

If you have Hemlibra-related medical inquiries, please contact our Medical Information team:

Serious Warnings and Precautions Box

The following serious adverse reactions have been reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving Hemlibra prophylaxis.

  • Thrombotic microangiopathy (TMA)
  • Thromboembolism

Discontinue aPCC at least 24 hours before starting Hemlibra and avoid use of aPCC during Hemlibra treatment unless no other treatment options/alternatives are available.  If aPCC is indicated in a patient receiving Hemlibra prophylaxis, the initial dose should not exceed 50 U/kg. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of Hemlibra if symptoms occur (see Warnings and Precautions [8] in the Product Monograph).

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