MMR vaccine and idiopathic thrombocytopaenic purpura
Open accessAbstract
AIMS: To estimate the relationship between idiopathic thrombocytopaenic purpura (ITP) and the measles, mumps and rubella (MMR) vaccination in children; calculating the relative risk estimate for ITP with in 6 weeks after MMR vaccination and the attributable risk of ITP within 6 weeks after MMR vaccination. METHODS: Using the General Practice Research Database we identified children with a first-time diagnosis of ITP from a base population of children aged less than 6 years between January 1988 and December 1999. After describing the characteristics of all the children identified with ITP, we focused on cases aged 13-24 months to perform a population-based, case-control analysis to estimate the relative risk of developing ITP within 6 weeks after MMR vaccination. We also calculated the risk of ITP attributable to the MMR vaccination. RESULTS: Sixty-three children with a first time diagnosis of ITP were identified; 23 cases were between 13 and 24 months old. The relative risk estimate for ITP within 6 weeks after MMR vaccination, compared to the combined group of unvaccinated children and children vaccinated with MMR more than 26 weeks previously was 6.3 (95% CI 1.3-30.1). The attributable risk of developing ITP within 6 weeks after MMR vaccination was estimated to be 1 in 25,000 vaccinations (95% confidence interval 21,300, 89,400). CONCLUSION: This study confirms the increased risk of ITP within 6 weeks after MMR vaccination. However, the attributable risk of ITP within 6 weeks after MMR vaccination is low.
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Lack of clarity over the vaccine exposure status of the controls made the results of the Black 2003 study difficult to interpret.
“Lack of clarity over the vaccine exposure status of the controls made the results of the Black 2003 study difficult to interpret.”
From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as Black 2003
The Case-control study section defines the controls’ MMR exposure categories, and Table 2 reports the number of controls in each category. The Discussion states that the authors were confident they had complete vaccine histories for all cases and controls, contrary to the claimed lack of clarity. (LLM, conf=0.89)
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Experimental — accuracy not yet measuredIn Black 2003, Bremner 2005, Bremner 2007, DeStefano 2004, Ma 2005, Mrozek-Budzyn 2010, Ray 2006, and Smeeth 2004, the risk of bias was moderate/unknown.
“Moderate/unknown risk of bias: eight studies (Black 2003; Bremner 2005; Bremner 2007; DeStefano 2004; Ma 2005; Mrozek-Budzyn 2010; Ray 2006; Smeeth 2004).”
From Vaccines for measles, mumps and rubella in children (2012) · cites this paper as Black 2003
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“10 of 4090 patients with HD developed ITP after a median of 23 months (3-57), including 6 in remission(58).”
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Demicheli, V., Rivetti, A., Debalini, M. G., & Di Pietrantonj, C. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004407.pub3 · Cited by 372 · see citing works
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“Thrombocytopenia has been demonstrated following the measles, mumps and rubella (MMR) vaccination, with Black et al (2003) estimating the relative risk for ITP within 6 weeks after MMR vaccination to be 6Æ3 [95% confidence interval (CI) 1Æ3– 30Æ1] and the attributable risk of developing ITP within…”
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Cines, D. B., Liebman, H. A., & Stasi, R. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2008.12.005 · Cited by 246 · see citing works
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“Total ITP cases, N 63 69 56 60 Gender, n (%) Male 33 (52) 31 (45) 30 (54) 29 (48) Female 30 (48) 38 (55) 26 (46) 31 (52) Platelet count at diagnosis (25th, 75th percentiles), per L 7000 (3000, 18 000) 8500 (3000, 18 500) 8000 (3000, 17 000) 7000 (4000, 16 000) Referral to hematologist, n (%) 52 (83) 51 (74) 48 (86) 48…”
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Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases
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“Moreover, seven children with MMR-unrelated ITP were subsequently vaccinated without disease relapses [77].”
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Glanz, J. M., McClure, D. L., XU, S., Hambidge, S. J., LEE, M., KOLCZAK, M. S., KLEINMAN, K. P., Mullooly, J. P., & France, E. K. (2006) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2005.11.012 · Cited by 117 · see citing works
“This investigation evaluates these traditional study designs as well as two newer designs in a simulated analysis of a known, rare, and acute vaccine reaction: idiopathic thrombocytopenic purpura (ITP) after measlesmumps-rubella (MMR) vaccination [1,2].”
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“…associated with an increased risk of ITP within 6 weeks after vaccination, although less frequently compared with that after natural measles or rubella virus infection (Jonville-Bera et al, 1996; Miller et al, 2001; Black et al, 2003; Jadavji et al, 2003; Rajantie et al, 2007; France et al, 2008).”
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“In most cases, it is mild and presents with only bruising and petechiae.(17) Platelet counts are higher than in the case of non-vaccine-associated ITP (> 20,000 × 10(9)/L in 33–19% of patients).”
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“The only relevant data come from 65 children who developed ITP after an initial MMR vaccination; upon receipt of a second MMR vaccine, none developed a recurrence.(3,4,7) After the fatal vaccine reaction, many of the patients in the Massachusetts General Hospital ITP Center had great trepidation about receiving any of…”
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POSTVACCINATION THROMBOCYTOPENIA IN CANADA
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“3 times and had a risk of one ITP case in a mean of 25,000 doses [30].”
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Bennett, C. M., & Tarantino, M. D. (2009) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2009.08.002 · Cited by 20 · see citing works
“The risk of ITP is increased in children after immunization with measles, mumps, and rubella (MMR) vaccine.(25,26) In the vast majority of children with ITP, no specific infection can be documented.”
BackgroundDo childhood vaccines cause thrombocytopenia?
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“A data linkage study (10) examining the second dose of MMR did not find any increased risk of thrombocytopenia.”
BackgroundResultInfluentialVaccination and Risk of Childhood IgA Vasculitis
Piram, M., Chiappe, S. G., Madhi, F., Ulinski, T., & Mahr, A. (2018) · PEDIATRICS · doi:10.1542/peds.2018-0841 · Cited by 18 · see citing works
Stowe, J., Andrews, N. J., & Miller, E. (2019) · CNS Drugs · doi:10.1007/s40263-019-00670-y · Cited by 18 · see citing works
Martins, R. D. M., Camacho, L. A. B., Marcovistz, R., de Noronha, T. G., Maia, M. D. L. S., dos Santos, E. M., Barbosa, G. G., da Silva, A. M. V., de Souza, P. C. N. F., Lemos, M. C. F., et al. (2008) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762008000700014 · Cited by 18 · see citing works
“…has been shown with measles vaccines and measles-containing vaccines (Farrington et al. 1995, Jonville-Béra et al. 1996, Miller et al. 2001, Black et al. 2003, Jadavji et al. 2003, Jefferson et al. 2004, France et al. 2008), whereas for the hepatitis B vaccine there are only indications of…”
BackgroundMaure, C. G., Elango, V., BLACK, S. B., Pérez-Vilar, S., Castro, J. L., Bravo‐Alcántara, P., Molina-León, H. F., Weibel, D. M., Sturkenboom, M., ZUBER, P. L. F., et al. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.07.085 · Cited by 17 · see citing works
Update on side effects from common vaccines
Song, B. J., & Katial, R. K. (2004) · Current Allergy and Asthma Reports · doi:10.1007/s11882-004-0010-8 · Cited by 17 · see citing works
Ho, W., Lee, C.-C., Chen, C.-J., Lu, M., Hu, F., Jou, S., Lin, D., & Lin, K. (2012) · Journal of Pediatric Hematology/Oncology · doi:10.1097/mph.0b013e3182282548 · Cited by 16 · see citing works
“%) patients >10 years of age at the onset of ITP.”
BackgroundInfluentialIdiopathic thrombocytopenic purpura in childhood: Twenty years of experience in a single center
Stiakaki, E., Perdikogianni, C., Thomou, C., Markaki, E., Katzilakis, N., Tsirigotaki, M., & Kalmanti, M. (2012) · Pediatrics International · doi:10.1111/j.1442-200x.2012.03606.x · Cited by 16 · see citing works
Weißer, K., Barth, I., & Keller‐Stanislawski, B. (2009) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-009-0961-y · Cited by 15 · see citing works
Frequently asked questions on seven rare adverse events following immunization
D’Alò, G. L., Zorzoli, E., Capanna, A., Gervasi, G., Terracciano, E., Zaratti, L., & Franco, E. (2016) · Journal of preventive medicine and hygiene · doi:10.15167/2421-4248/jpmh2017.58.1.659 · Cited by 14 · see citing works
“VI-ITP that occurs after MMR vaccination has an onset within 6 weeks of vaccine administration and presents with a higher platelet count than ITP after natural infection [127] and with clinical manifestations such as petechiae of moderate severity [128], although rarely there have been reports of gastrointestinal (GI)…”
BackgroundBravo‐Alcántara, P., Pérez-Vilar, S., Molina-León, H. F., Sturkenboom, M., BLACK, S. B., ZUBER, P. L. F., Maure, C. G., Castro, J. L., Castellano, V. E., Chiarvetti, L., et al. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.04.069 · Cited by 15 · see citing works
Immune thrombocytopenia purpura flare post COVID-19 vaccine
Ali, E., Al-maharmeh, Q., Rozi, W., Habib, M. B., Abdallah, A., Abdulgayoom, M., & Yassin, M. A. (2021) · Annals of Medicine and Surgery · doi:10.1016/j.amsu.2021.103164 · Cited by 13 · see citing works
Uaprasert, N., Panrong, K., Tungjitviboonkun, S., Dussadee, K., Decharatanachart, P., Kaveevorayan, P., Shoosanglertwijit, R., Watanaboonyongcharoen, P., Bunworasate, U., & Rojnuckarin, P. (2021) · Blood Coagulation & Fibrinolysis · doi:10.1097/mbc.0000000000001082 · Cited by 12 · see citing works
Immunization Rates at the School Entry in 2012
Weigel, M., Bruns, R., Weitmann, K., & Hoffmann, W. U. (2014) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2014.0788 · Cited by 12 · see citing works
Severe Immune Thrombocytopenia after COVID-19 Vaccination: Two Case Reports and a Literature Review
Shonai, T., Kimura, F., & Watanabe, J. (2022) · Internal Medicine · doi:10.2169/internalmedicine.9177-21 · Cited by 11 · see citing works
“Although the attributable risk is low (1 in 25,000 after MMR vaccination), the relative risk of ITP after MMR vaccination is high (16).”
BackgroundIs MMR immunisation safe in chronic Idiopathic thrombocytopenic purpura?
Bibby, A. C., Farrell, A., Cummins, M., & Erlewyn‐Lajeunesse, M. (2008) · Archives of Disease in Childhood · doi:10.1136/adc.2007.132340 · Cited by 11 · see citing works
Real‐world, single‐center experience of SARS‐CoV‐2 vaccination in immune thrombocytopenia
Woolley, P., Tailor, A., Shah, R., Westwood, J., & Scully, M. (2022) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15704 · Cited by 10 · see citing works
MMR vaccine - how effective and how safe?
(2003) · Drug and Therapeutics Bulletin · doi:10.1136/dtb.2003.41425 · Cited by 10 · see citing works
Evidencias científicas disponibles sobre la seguridad de las vacunas
Picazo, J. J., Fernández, J. A., Axpe, J. M. A., Ordóñez, D. B., Gurrea, A. B., José, X. B., Díez‐Domingo, J., Romo, F. G., Matos, T. H.-S., Ruíz-Contreras, J., et al. (2011) · Vacunas · doi:10.1016/s1576-9887(11)70002-4 · Cited by 9 · see citing works
Liao, P., Teng, C. J., & Chou, C. (2021) · Vaccines · doi:10.3390/vaccines9121486 · Cited by 9 · see citing works
Jacobs, J. W., Booth, G. S., Guarente, J., Schlafer, D., Zheng, L., & Adkins, B. D. (2022) · British Journal of Haematology · doi:10.1111/bjh.18627 · Cited by 9 · see citing works
“87 46 g/L (17 g/L) Hepatitis B (15) DTP/DTaP/DT (12) H.”
Demonstration of background rates of three conditions of interest for vaccine safety surveillance
Wormsbecker, A. E., Johnson, C., Bourns, L., Harris, T. M., Crowcroft, N. S., & Deeks, S. L. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210833 · Cited by 8 · see citing works
Recurrent immune thrombocytopenia following different vaccines
Morin, E., & Sadarangani, M. (2019) · BMJ Case Reports · doi:10.1136/bcr-2019-231260 · Cited by 8 · see citing works
Gaunt, E. R., & Mabbott, N. A. (2021) · Immunotherapy Advances · doi:10.1093/immadv/ltab019 · Cited by 8 · see citing works
“The bestevidenced association is that of the live measles, mumps and rubella vaccines with thrombocytopenic outcome reported to occur in 1 in 21,000 to 1 in 40,000 vaccine recipients [49, 50].”
A Case of Immune Thrombocytopenic Purpura After Rabies Vaccination
Fulbright, J. M., Williams, S. E., & Pahud, B. A. (2015) · Journal of Pediatric Hematology/Oncology · doi:10.1097/mph.0000000000000388 · Cited by 8 · see citing works
Meyer, O. G. J. (2013) · doi:10.2217/ebo.12.293 · Cited by 8 · see citing works
Lloyd, P. C., Smith, E. R., Gruber, J. F., Ondari, M., Wong, H., Hu, M., Clarke, T. C., McEvoy, R., Amend, K. L., Beachler, D. C., et al. (2025) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.70151 · Cited by 7 · see citing works
Bias and estimation under misspecification of the risk period in self‐controlled case series studies
Campos, L. F., Şentürk, D., Chen, Y., & Nguyen, D. V. (2017) · Stat · doi:10.1002/sta4.166 · Cited by 6 · see citing works
“The SCCS method has been used to examine the relationship between rare vaccine reactions, such as idiopathic thrombocytopenic purpura (ITP) after measles–mumps–rubella (MMR) vaccination (Miller et al., 2001; Black et al., 2003).”
MethodCommunicating About Immunizations
Loehr, J. (2020) · Primary Care Clinics in Office Practice · doi:10.1016/j.pop.2020.05.010 · Cited by 6 · see citing works
Vaccinations and Autoimmune Diseases
Salemi, S., & D’Amelio, R. (2010) · International Reviews of Immunology · doi:10.3109/08830181003792795 · Cited by 6 · see citing works
Type 1 immune‐mediated polyarthritis in dogs and lack of a temporal relationship to vaccination
Idowu, O. A., & Heading, K. L. (2017) · Journal of Small Animal Practice · doi:10.1111/jsap.12774 · Cited by 6 · see citing works
Immune thrombocytopenia in a 68‐year‐old woman after COVID‐19 vaccination
Kenney, A., & Adhikari, A. (2021) · Clinical Case Reports · doi:10.1002/ccr3.4689 · Cited by 6 · see citing works
Kemmeren, J. M., van der Maas, N., & de Melker, H. E. (2010) · European Journal of Pediatrics · doi:10.1007/s00431-010-1294-4 · Cited by 6 · see citing works
Pharmacoepidemiologic Studies of Vaccine Safety
Chen, R. T., Glanz, J. M., & Vellozzi, C. J. (2012) · Pharmacoepidemiology · doi:10.1002/9781119959946.ch26 · Cited by 6 · see citing works
COVID-19 vaccination and immune thrombocytopenia: Cause for vigilance, but not panic
Al-Samkari, H. T. (2023) · Research and Practice in Thrombosis and Haemostasis · doi:10.1016/j.rpth.2023.100039 · Cited by 5 · see citing works
“There may be an association with de novo ITP in the 6 weeks following the measles, mumps, and rubella (MMR) vaccine in toddlers [5], but in a study evaluating children who developed ITP after receiving MMR, none had a recurrence after a subsequent dose of MMR vaccine [6].”
BackgroundAssociation between Helicobacter pylori infection and platelet count in mice
Fukuda, T., Asou, E., Nogi, K., Yasuda, M., & Gotō, K. (2018) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.18-0004 · Cited by 5 · see citing works
“Autoimmune manifestations, including ITP, have been reported following vaccination against several infectious agents, including measles, mumps, and rubella, Pneumococcus, Haemophilus influenza type B, hepatitis B virus, and varicella-zoster virus [4, 8, 17, 21].”
BackgroundInfluentialLevi, M., Donzellini, M., Varone, O., Sala, A., Bechini, A., Boccalini, S., & Bonanni, P. (2015) · Journal of preventive medicine and hygiene · doi:10.15167/2421-4248/jpmh2014.55.4.455 · Cited by 5 · see citing works
“One of the two cases of thrombocytopenic purpura that were registered can be put in causal correlation with the MMRV vaccine, since it occurred after co-administration with this vaccine, and while there is no evidence of an increased risk in children following immunization with MCC [23], idiopathic thrombocytopenic pu…”
BackgroundIdiopathic thrombocytopenic purpura following measles–rubella‐conjugated vaccine
Kitazawa, J., OHTANI, K., Shiotani, M., Satoh, A., Sugimoto, K., Nomura, Y., & 青山, 隆. (2007) · Pediatrics International · doi:10.1111/j.1442-200x.2007.02458.x · Cited by 5 · see citing works
Subacute sclerosing panencephalitis and immune thrombocytopenia: More than a coincidence?
Öncel, I. H., Saltık, S., & Anlar, B. (2017) · Medical Hypotheses · doi:10.1016/j.mehy.2017.12.028 · Cited by 4 · see citing works
Pharmacoepidemiologic Studies of Vaccine Safety
Chen, R. T., Glanz, J. M., & Shimabukuro, T. T. (2019) · Pharmacoepidemiology · doi:10.1002/9781119413431.ch20 · Cited by 4 · see citing works
Presenting signs and clinical outcome in dogs with metaphyseal osteopathy: 39 cases (2009–2018)
Robertson, A., Black, V., Villedieu, E., Clarke, K. E., Faux, I., Major, A. C., & Adamantos, S. E. (2022) · Journal of Small Animal Practice · doi:10.1111/jsap.13554 · Cited by 3 · see citing works
“It has been suggested that vaccination can act as a trigger for the development of immune-mediated conditions in people, such as immune-mediated thrombocytopaenia (ITP) (Black et al. 2003).”
BackgroundImmune thrombocytopenia in infants: a retrospective study with comparison to toddlers
Lee, A. C.-W. (2023) · Singapore Medical Journal · doi:10.4103/singaporemedj.smj-2021-184 · Cited by 3 · see citing works
“[21] The major limitation in this study is a potential referral bias.”
COVID ‐19‐induced immune thrombocytopenia management approach: A case report and literature review
Alahwal, H. M., Alsharif, M., Alsharif, M., Almohammadi, A. T., Al-Marzouki, A. F., Barefah, A., Bahashwan, S., Radhwi, O., & Damanhouri, G. A. (2024) · Clinical Case Reports · doi:10.1002/ccr3.9070 · Cited by 3 · see citing works
Vaccine Case–Population: A New Method for Vaccine Safety Surveillance
Théophile, H., Moore, N. D., Robinson, P., Bégaud, B., & Pariente, A. (2016) · Drug Safety · doi:10.1007/s40264-016-0449-2 · Cited by 3 · see citing works
- Authors
- Black, C., Kaye, J. A., & Jick, H.
- Affiliations
- Boston University (US)
- Corresponding author
- Black, Corri
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2003-01
- Volume
- 55
- Issue
- 1
- Pages
- 107-111
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC1884189
- OpenAlex
- W1486224385
- Cited by
- 137
- References
- 14
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 2 · 2022: 10 · 2021: 17 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- AstraZeneca
- GlaxoSmithKline
- Novartis Farmacéutica
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Surgery › Heparin-Induced Thrombocytopenia and Thrombosis
- Keywords
- MMR vaccine, measles-mumps-rubella vaccination, vaccine adverse events, children, relative risk, attributable risk
- MeSH terms
- Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Risk Factors, Case-Control Studies, Purpura, Thrombocytopenic, Idiopathic, Measles-Mumps-Rubella Vaccine
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