There has been considerable discussion in the hemophilia community regarding the optimal protocol for the administration of vaccines to individuals with bleeding disorders. Speculation that vaccines may induce the development of inhibitors to factor concentrates are not substantiated1. The MASAC Vaccine Working Group has reviewed the available literature, online and in print, and has developed the following recommendations.
1. Centers for Disease Control and Prevention (CDC) Guidelines
It is highly recommended (See MASAC Recommendation #218, page 5, Section G.1 and G.2)1 that patients with bleeding disorders continue to follow the American Academy of Pediatrics’ and CDC’s vaccine recommendation route and schedule for their age. These recommendations can be found on the CDC website as follows:
- Infant Schedule Age (0-6yrs):
- Child Schedule Age (7-18 yrs):
- Adult Schedule Age (19 yrs and older):
- Travel Recommendations:
- Special Groups:
2. Protocol for Administration of Vaccines
MASAC recommends that when giving immunizations, the following procedures may be considered:
- A fine-gauge needle (23 gauge or smaller caliber) be used.2
- Firm pressure should be applied to the site for at least 2 minutes without rubbing.2
- The patient and/or caregiver should be informed that there is risk of hematoma development at the injection site.2 Patients with hemophilia depending on their factor level, may consider use of therapy to prevent hematoma formation, in consultation with their hemophilia treatment center.
- Anticipatory guidance should be given regarding when to call the physician or HTC regarding any adverse reactions such as hematoma, fever, warmth, redness.2
- For pain/fever relief 2, avoid aspirin and NSAIDS (such as ibuprofen, naproxen sodium) because of the potential risk of bleeding. Acetaminophen is a safe alternative, but should be used with caution, especially in individuals at risk for liver disease.
- If the patient is receiving prophylaxis treatment for hemophilia, vaccination may be administered within 24 hours of Standard or Extended half-life FVIII or Standard half-life FIX concentrate and within 48 hours of administration of Extended half-life FIX concentrate, to decrease the risk of developing a hematoma.3-4 For patients with a basal FVIII or FIX level above 10%, no hemostatic precautions may be required.5
- Patients on Emicizumab prophylaxis may not require additional treatment prior to vaccinations.3-5
- Patients with Type 1 or 2 Willebrand disease (VWD), depending on their baseline von Willebrand factor (VWF) activity levels, may consider use of therapy to prevent hematoma formation, in consultation with their hemophilia treatment center. Patients with Type 3 VWD should consider a VWF-containing infusion prior to vaccination.5
- All rare bleeding disorder patients (including those with thrombocytopenia and/or platelet function disorders) should be vaccinated with the above general precautions.
- Patients on Vitamin K antagonists should have prothrombin time testing performed within 72 hours prior to injection to determine international normalized ratio (INR); if results are stable and within the therapeutic range, they can be vaccinated intramuscularly. No data are available in patients on DOACs/NOACs.6
3. Vaccines that can be given subcutaneously
There is considerable variation regarding vaccine route of administration (IM vs SQ) among HTC providers (reference CDC data). Many vaccines have not undergone rigorous investigation to demonstrate that SQ administration is as effective as IM administration. Whether or not the potential reduction in intramuscular hematomas from SQ administration outweighs any potential reduction in vaccine efficacy is not known. The vaccines (single vaccines, not in combination with other vaccines) that have been tested and demonstrated to be effective when administered either IM or SQ include:
A. Pneumococcal polysaccharide (PPSV)7
B. Polio, inactivated (IPV)7
C. Hepatitis A8
D. Hepatitis B9-11
4. The safety, efficacy, and optimal protocols for administration of other existing, and existing and emerging vaccines will be evaluated by MASAC on an ongoing basis.
5. Live vaccines should not be administered in patients receiving high dose steroid or immune-modulating drugs as a part of immune tolerance therapies or gene therapy protocols.12
- Platokouki H, Fischer K, Gouw SC, Rafowicz A, Carcao M, Kenet G, Liesner R, Kurnik K, Rivard GE, van den Berg HM. Vaccinations are not associated with inhibitor development in boys with severe haemophilia A. Haemophilia. 2018 Mar;24(2):283-290.
- MASAC recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders Revised October 2013. MASAC Document #218.
- Tiede A, Leise H, Horneff S, Oldenburg J, Halimeh S, Heller C, Königs C, Holstein K, Pfrepper C. Safety of intramuscular COVID-19 vaccination in patients with haemophilia. Haemophilia. 2022 Sep;28(5):687-693. doi: 10.1111/hae.14586. Epub 2022 May 13. PMID: 35561276; PMCID: PMC9348084.
- Pfrepper C, Holstein K, Königs C, Heller C, Krause M, Olivieri M, Bidlingmaier C, Sigl-Kraetzig M, Wendisch J, Halimeh S, Horneff S, Richter H, Wieland I, Klamroth R, Oldenburg J, Tiede A; Hemophilia Board of the German, Austrian, Swiss Society on Thrombosis Hemostasis Research (GTH). Consensus Recommendations for Intramuscular COVID-19 Vaccination in Patients with Hemophilia. Hamostaseologie. 2021 Jun;41(3):190-196. doi: 10.1055/a-1401-2691. Epub 2021 Apr 15. PMID: 33860513.
- Guidance from the World Federation of Hemophilia (WFH), European Association for Haemophilia and Allied Disorders (EAHAD), European Haemophilia Consortium (EHC), and U.S. National Hemophilia Foundation (NHF).
- Caldeira D, Rodrigues BS, Alves M, Pinto FJ, Ferreira JJ. Low risk of haematomas with intramuscular vaccines in anticoagulated patients: a systematic review with meta-analysis. Thromb J. 2022 Feb 16;20(1):9.
- Immunization Action Coalition, www.immunize.org, www.vaccineinformation.org, http://www.immunize.org/catg.d/p3085.pdf.
- Ragni MV, Lusher JM, Koerper MA, Manco-Johnson M, Krouse DS. Safety and immunogenicity of subcutaneous hepatitis A vaccine in children with haemophilia. Haemophilia 2000; 6(2): 98-103.
- Gazengel C, Courouce AM, Torchet MF, Kremp O, Brangier J, Brechot C, Degos F. Use of HBV vaccine in hemophiliacs. Scand J Haematol 1984; 40: 323-8.
- Janco RL. Immunogenicity of subcutaneous hepatitis B vaccine in hemophiliacs. J Pediatr 1985; 107: 316.
- Zanetti AR, AR, Mannucci PM, Tanzi E, Moroni GA, De Paschale M, Morfini M, Carnelli V, Tirindelli MC, De Biasi R, Ciavarella N, et al. Hepatitis B vaccination of 113 hemophiliacs: lower antibody response in anti-LAV/HTLV-III-positive patients. Am J Hematol, 1986; 23: 339- 45.
- Golli T, Kastrin A, Pokorn M, Rener-Primec Z. Immunosuppression and immunization: Vaccination in pediatric patients with neuromuscular diseases treated with steroids or immune-modulating drugs. Eur J Paediatr Neurol. 2021 Nov;35:158-164.