Consensus Recommendations for Intramuscular COVID-19 Vaccination in Patients with Hemophilia

Abstract

Background Currently available coronavirus disease 2019 (COVID-19) vaccines are approved for intramuscular injection and efficacy may not be ensured when given subcutaneously. For years, subcutaneous vaccination was recommended in patients with hemophilia to avoid intramuscular bleeds. Therefore, recommendations for the application of COVID-19 vaccines are needed.

Methods The Delphi methodology was used to develop consensus recommendations. An initial list of recommendations was prepared by a steering committee and evaluated by 39 hemophilia experts. Consensus was defined as ≥75% agreement and strong consensus as ≥95% agreement, and agreement as a score ≥7 on a scale of 1 to 9. After four rounds, a final list of statements was compiled.

Recommendations Consensus was achieved that COVID-19 vaccines licensed only for intramuscular injection should be administered intramuscularly in hemophilia patients. Prophylactic factor replacement, given on the day of vaccination with a maximum interval between prophylaxis and vaccination of 24 hours (factor VIII and conventional factor IX concentrates) or 48 hours (half-life extended factor IX), should be provided in patients with moderate or severe hemophilia. Strong consensus was achieved that patients with mild hemophilia and residual factor activity greater than 10% with mild bleeding phenotype or patients on emicizumab usually do not need factor replacement before vaccination. Swelling, erythema, and hyperthermia after vaccination are not always signs of bleeding but should prompt consultation of a hemophilia care center. In case of injection-site hematoma, patients should receive replacement therapy until symptoms disappear.

Conclusions Consensus was achieved on recommendations for intramuscular COVID-19 vaccination after replacement therapy for hemophilia patients depending on disease severity.

Keywords

hemophilia - COVID-19 - vaccination - recommendation

Authors' Contributions

C.P., K.H., C.K., and A.T. developed the initial survey and the first set of recommendations. C.P. managed the consensus process and analyzed data. C.P. and A.T. wrote the final manuscript. All authors participated in the discussion of recommendations and Delphi results, reviewed the manuscript, and agreed with its final content.

Publikationsverlauf

Eingereicht: 14. Februar 2021

Angenommen: 25. Februar 2021

Artikel online veröffentlicht:
15. April 2021

• References

• 1 Yang J, Zheng Y, Gou X. et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis 2020; 94: 91-95
• 2 Fathi M, Vakili K, Sayehmiri F. et al. The prognostic value of comorbidity for the severity of COVID-19: a systematic review and meta-analysis study. PLoS One 2021; 16 (02) e0246190
• 3 Langer F, Kluge S, Klamroth R, Oldenburg J. Coagulopathy in Covid-19 and its implication for safe and efficacious thromboprophylaxis. Hamostaseologie 2020; 40 (03) 264-269
• 4 Libster R, Pérez Marc G, Wappner D. et al; Fundación INFANT–COVID-19 Group. Early high-titer plasma therapy to prevent severe Covid-19 in older adults. N Engl J Med 2021; 384 (07) 610-618
• 5 Weinreich DM, Sivapalasingam S, Norton T. et al. Trial Investigators. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med 2021; 384 (03) 238-251
• 6 Goldman JD, Lye DCB, Hui DS. et al; GS-US-540-5773 Investigators. Remdesivir for 5 or 10 days in patients with severe Covid-19. N Engl J Med 2020; 383 (19) 1827-1837
• 7 Kalil AC, Patterson TF, Mehta AK. et al; ACTT-2 Study Group Members, ACCT-2 Study Group Members. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med 2021; 384 (09) 795-807
• 8 Mitjà O, Corbacho-Monné M, Ubals M. et al. BCN-PEP-CoV-2 Research Group. A cluster-randomized trial of hydroxychloroquine for prevention of COVID-19. N Engl J Med 2021; 384 (05) 417-427
• 9 Horby P, Lim WS, Emberson JR. et al. Dexamethasone in hospitalized patients with COVID-19—preliminary report. N Engl J Med 2020
• 10 Stone JH, Frigault MJ, Serling-Boyd NJ. et al; BACC Bay Tocilizumab Trial Investigators. Efficacy of tocilizumab in patients hospitalized with COVID-19. N Engl J Med 2020; 383 (24) 2333-2344
• 11 Fachgruppe COVRIIN Am Robert-Koch-Institut. Medikamentöse Therapie bei COVID-19 mit Bewertung durch die Fachgruppe COVRIIN am Robert-Koch-Institut 2020 [cited February 6, 2020]. Accessed March 10, 2021 at: https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/COVRIIN_Dok/Therapieuebersicht.pdf?__blob=publicationFile
• 12 Baden LR, El Sahly HM, Essink B. et al. COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021; 384 (05) 403-416
• 13 Polack FP, Thomas SJ, Kitchin N. et al; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383 (27) 2603-2615
• 14 Voysey M, Clemens SAC, Madhi SA. et al; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021; 397 (10269): 99-111
• 15 Logunov DY, Dolzhikova IV, Shcheblyakov DV. et al; Gam-COVID-Vac Vaccine Trial Group. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 2021; 397 (10275, Suppl 1): 671-681
• 16 Sadoff J, Le Gars M, Shukarev G. et al. Interim results of a phase 1-2a trial of Ad26.COV2.S Covid-19 vaccine. N Engl J Med 2021
• 17 Murphy MK, Black NA, Lamping DL. et al. Consensus development methods, and their use in clinical guideline development. Health Technol Assess 1998; 2 (03) i-iv , 1–88
• 18 Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs 2000; 32 (04) 1008-1015
• 19 Cuhls K. Die Delphi-Methode – eine Einführung. In: Niederberger M, Renn O. eds. Delphi-Verfahren in den Sozial- und Gesundheitswissenschaften. Wiesbaden: Springer Fachmedien Wiesbaden; 2019: 3-31
• 20 Srivastava A, Santagostino E, Dougall A. et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia 2020; (26, Suppl 6): 1-158
• 21 CDC/NCIRD. ACIP General Best Guidance for Immunization - Special Situations [cited February 1, 2021]. Accessed March 10, 2021 at: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/special-situations.html
• 22 Robert Koch-Institut. Impfen bei Blutungsneigung. Accessed March 10, 2021 at: https://www.rki.de/DE/Content/Infekt/Impfen/Stichwortliste/G/Injektionsort_Tabelle.pdf?__blob=publicationFile
• 23 Santagostino E, Riva A, Cesaro S. et al; the HEVA Study Group. Consensus statements on vaccination in patients with haemophilia—results from the Italian haemophilia and vaccinations (HEVA) project. Haemophilia 2019; 25 (04) 656-667
• 24 Pfrepper C, Krause M, Sigl-Kraetzig M, Königs C, Wendisch J, Olivieri M. Vaccination in patients with haemophilia-Results from an online survey among haemophilia treatment centres in Germany. Haemophilia 2019; 25 (04) e304-e306
• 25 COVID-19 vaccination guidance for people with bleeding disorders [cited January 26, 2021]. Accessed March 10, 2021 at: https://news.wfh.org/covid-19-vaccination-guidance-for-people-with-bleeding-disorders/
• 26 Carpenter SL, Soucie JM, Presley RJ. et al; Hemophilia Treatment Center Network Investigators. Hepatitis B vaccination is effective by subcutaneous route in children with bleeding disorders: a universal data collection database analysis. Haemophilia 2015; 21 (01) e39-e43
• 27 Hochart A, Falaise C, Huguenin Y, Meunier S. Intramuscular vaccination of haemophiliacs: Is it really a risk for bleeding?. Haemophilia 2019; 25 (05) e322-e323
• 28 Lenting PJ. Laboratory monitoring of hemophilia A treatments: new challenges. Blood Adv 2020; 4 (09) 2111-2118
• 29 Holstein K, Albisetti M, Bidlingmaier C. et al; ‘Ständige Kommission Hämophilie’ (Haemophilia board) of the German, Swiss Austrian Society for Thrombosis Haemostasis Research (GTH). Practical guidance of the GTH Haemophilia Board on the use of emicizumab in patients with haemophilia A. Hamostaseologie 2020; 40 (05) 561-571
• 30 Matzinger P. The danger model: a renewed sense of self. Science 2002; 296 (5566): 301-305
• 31 Lövgren KM, Søndergaard H, Skov S, Wiinberg B. Non-genetic risk factors in haemophilia A inhibitor management - the danger theory and the use of animal models. Haemophilia 2016; 22 (05) 657-666
• 32 Platokouki H, Fischer K, Gouw SC. et al. Vaccinations are not associated with inhibitor development in boys with severe haemophilia A. Haemophilia 2018; 24 (02) 283-290
• 33 Lai JD, Moorehead PC, Sponagle K. et al. Concurrent influenza vaccination reduces anti-FVIII antibody responses in murine hemophilia A. Blood 2016; 127 (26) 3439-3449
• 34 Wagner N, Assmus F, Arendt G. et al. Impfen bei Immundefizienz. Bundesgesundheitsbl 2019; 62 (04) 494-515
• 35 Aktualisierte Empfehlungen zur COVID-19 Schutzimpfung bei Patienten mit Blut- und Krebserkrankungen [cited January 24, 2021]. Accessed March 10, 2021 at: https://www.dgho.de/publikationen/stellungnahmen/gute-aerztliche-praxis/coronavirus/covid-19-vakzine-20210107.pdf
• 36 Chung JY, Thone MN, Kwon YJ. COVID-19 vaccines: the status and perspectives in delivery points of view. Adv Drug Deliv Rev 2020; 170: 1-25