From the World Federation of Hemophilia Medical Advisory Board (MAB)* and the WFH Coagulation Product Safety, Supply, and Access (CPSSA) Committee**:
*MAB members: Greig Blamey, Ampaiwan Chuansumrit, Saliou Diop, Vincent Dumez, Magdy El Ekiaby, Cedric Hermans, Alfonso Iorio, Radoslaw Kaczmarek, Kate Khair, Steve Kitchen, Barbara Konkle, Ed Kuebler, Declan Noone, Flora Peyvandi, Steven Pipe, Jeff Stonebraker, Graeme Ting, Alain Weill, and Glenn F. Pierce, Chair
**CPSSAC members: Magdy El Ekiaby, Dan Hart, Marion Koerper, Mike Makris, Brian O’Mahony, David Page, Flora Peyvandi, Glenn Pierce, Thomas Sannié, Uwe Schlenkrich, Mark Skinner, Alok Srivastava, Craig Upshaw, and Radoslaw Kaczmarek, Chair
For people with hemophilia (PWH) currently treated with standard or extended recombinant half-life FVIII or FIX concentrates, FEIBA, FVIIa, or emicizumab:
- No reason to change the recommended treatment regimen
- No reason to fear at this stage a shortage of treatment supplies, manufacturing issues or interruption in the supply chain
- Contact hemophilia treatment centres (HTC) if stock at home or at hospital is limited
- If you treat at home, do not order more replacement products than reasonably needed. However, a few extra doses for home use are prudent in case of any delivery delays or disruptions.
For PWH treated with plasma-derived FVIII/FIX
- Viral inactivation and elimination procedures employed are sufficient to destroy lipid-enveloped viruses like SARS-CoV-21
- Not recommended to switch product
- No supply disruptions in plasma-derived product supplies have been detected to date. The primary concern is a decrease in plasma collections at the front end of the plasma-derived product production at this stage.2,3
- Blood and plasma donation continue to be a safe process, and the need for plasma donations is a great as ever. The support of current and new donors remains critical to maintain an adequate supply of blood and plasma during the pandemic.
- All HTCs and blood and plasma collection centres are reminded to follow guidelines to protect both personnel and donors to prevent the spread of SARS-CoV-2 through human-to-human contact via respiratory droplets, as well as fomites.4
- For PWH treated with other blood-derived products which are not virally inactivated (e.g., cryoprecipitate, platelets),treatment decisions should be based on clinical risk/benefit analysis balancing the safety of not treating a bleeding event and any residual risk of acquiring another infection.
For PWH currently in clinical trials (excluding post-marketing trials)5
- Contact your HTC to discuss the implications of the pandemic
- Ensure availability of study drugs and that the treatment is not interrupted
- Discuss modalities of follow-up/monitoring with an HTC study team. Remote follow-up visits are strongly encouraged unless an investigational product has to be administered and face to face monitoring is needed to prevent dangerous side effects.
- For PWH who recently received a gene therapy product (<12 months after infusion), scheduled liver function testing should remain a priority for safety and efficacy purposes.
- Do not discontinue or switch treatment if you are currently receiving a clinical trial treatment unless directed to do so by the study team.
For PWH who are scheduled to be soon enrolled in a trial testing a new treatment5
- Postponement of enrollment should be discussed with the study team
- Many medical centres have banned initiation of new clinical trials so as to not distract medical resources needed to deal with the pandemic
Specific measures to reduce exposure of SARS-CoV-2, the virus that causes COVID-19 in PWH with hemophilia
- All measures to reduce exposure to persons with COVID-19 should be proactively promoted in all PWH with comorbidities (cardiovascular disease, hypertension, obesity, diabetes, HIV, old age), or on steroids or other powerful immunosuppressant drugs.6,7
- Exposure to everyone, including lower risk individuals and children, is the single most important precaution to avoid infection. Sheltering in place and social distancing are the most important tools to use.
- Minimize the need to visit health care professionals in hospitals or offices. Non-urgent care and elective surgeries should be postponed.
- Paracetamol (acetaminophen) reduces fever without inhibiting the inflammatory response needed for fighting coronavirus and is recommended for persons with bleeding disorders
- Paracetamol (acetaminophen) should not exceed 60mg/kg/day or 3g/day, since it causes liver damage at higher doses
- Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) are usually not advised in PWH with bleeding disorders because they may increase bleeding though inhibition of platelet function. In addition, in particular ibuprofen has been suggested to either make COVID-19 worse or enhance risk of infection with SARS-CoV-2 due to upregulation of the entry receptor, angiotensin converting enzyme 2. However, the evidence supporting this is limited at this time.8,10
- Remember, specific hygienic measures, such as regular hand washing with soap, not touching one’s face, not aerosolizing a cough, and maintaining at least 2 metres (6 feet) distance from other people are key to preventing coronavirus transmission.
Specific measures in case of hospital admission of a bleeding disorders patient with COVID-19 infection
- Good liaison between the hospital where patient is admitted and the HTC
- Arrange replacement therapy / secure venous access.
- Inform team in case of treatment with emicizumab (risk of mis-management and mis-interpretation of hemostasis laboratory tests by unfamiliar health professionals).11
- Inform if you are part of an ongoing experimental treatment with rebalancing agents (anti-TFPI and fitusiran) and you have a risk of thrombosis or other clotting system imbalances, or you’ve undergone a recent treatment with gene therapy. If so, liaise with HTC.
- If you have COVID-19 infection, some clinicians suggest prophylactic therapy and maintaining higher clotting factor levels as a precaution against bleeding into lungs from potentially severe damage inflicted by SARS-CoV-2 and severe coughing/nose blowing creating increased blood pressure in brain that might lead to bleeding. There are case reports providing evidence to support this statement.
The news is changing daily. We will update WFH information as needed,
- Busch M, LM Katz, H Shan.Webinar: Update on the COVID-19 Coronavirus Outbreak: Blood Collection and Safety Implications. ISBT Education. 03/04/20. https://educaisbtweb.org/isbt/2020/covid-19/289245/michael.busch.louis.m.katz.26.hua.shan.webinar.update.on.the.covid-19.html?f=menu%3D8%2Abrowseby%3D8%2Asortby%3D2%2Alabel%3D19776. Accessed 19 March 2020.
- Novel Coronavirus Disease (COVID-19) Resources. https://www.pptaglobal.org/23-advocacy/access-to-care/1057-covid-19. Accessed 19 March 2020.
- New Coronavirus (SARS-CoV-2) and the Safety Margins of Plasma Protein Therapies. https://www.pptaglobal.org/media-and-information/ppta-statements/1055-2019-novel-coronavirus-2019-ncov-and-plasma-protein-therapies. Accessed 19 March 2020.
- van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17. DOI: 1056/NEJMc2004973.
- FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-pandemic. Accessed 19 March 2020.
- Zhou F, T Yu, R Du. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. Published online March 9, 2020. DOI: https://doi.org/10.1016/S0140-6736(20)30566-3.
- Fang L, G Karakiulakis, M Roth. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020. Published Online March 11, 2020 DOI:https://doi.org/10.1016/S2213-2600(20)30116-8
- EMA gives advice on the use of non-steroidal anti-inflammatories for COVID-19. https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19. Accessed 19 March 2020.
- Voiriot G, Q Philippot, A Elabbadi , C Elbim4, Martin Chalumeau, M Fartoukh. Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients. J. Clin. Med. 2019, 8, 786; doi:10.3390/jcm8060786
- Legras A, B Giraudeau, A-P Jonville-Bera, et al. A multicentre case-control study of nonsteroidal anti-inflammatory drugs as a risk factor for severe sepsis and septic shock. Critical Care 2009, 13:R43 (doi:10.1186/cc7766).
- Adamkewicz JI, DC Chen, I Paz-Priel. Effects and Interferences of Emicizumab, a Humanised Bispecific Antibody Mimicking Activated Factor VIII Cofactor Function, on Coagulation Assays. Thromb Haemost 2019; 119(07): 1084-1093. DOI: 10.1055/s-0039-1688687
Websites of interest
https://www.cdc.gov Centers for Disease Control and Prevention (US)
https://www.who.int/emergencies/diseases/novel-coronavirus-2019 and https://www.who.int/health-topics/coronavirus World Health Organization
https://www.ecdc.europa.eu/en/novel-coronavirus-china EU Center for Disease Prevention and Control
https://www.nih.gov/health-information/coronavirus National Institutes of Health
https://www.worldometers.info/coronavirus/ global data
https://www.nejm.org/coronavirus New England Journal of Medicine summaries
https://www.pptaglobal.org/23-advocacy/access-to-care/1057-covid-19 Plasma protein therapeutics association
https://www.isbtweb.org/ International Society of Blood Transfusion