Natural viral infections such as influenza, varicella, measles, mumps and rubella are associated with immune thrombocytopenic purpura (ITP). Thus, influenza, varicella, measles, mumps and rubella vaccines prevent ITP by protecting against natural infection. Measles-containing vaccines can very rarely cause ITP within 6 weeks of vaccination in children. However, these vaccines prevent many more cases of ITP than they cause. Influenza vaccines do not cause ITP. Other vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause ITP.
Rates of ITP after MMR vaccination have been estimated at 1-3 cases per 100,000 doses [1-3]. However, this is significantly lower than rates of ITP after natural infection otherwise prevented by the vaccine; the incidence of ITP after natural rubella infection is an estimated 1 per 3,000, and incidence after natural measles infection is estimated to be even higher .
The 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), found no relevant studies of quality in the literature assessing an association between ITP and diphtheria, tetanus, pertussis and varicella vaccines, since the only applicable studies available used passive surveillance systems and therefore lacked an unvaccinated comparison group .
Studies published since this report have consistently shown an increased risk of thrombocytopenic purpura in children within 6 weeks of measles-containing vaccination [1, 2, 5, 6]. However, several studies published since this report have found no association between influenza vaccines and ITP [7-9], and early childhood vaccines other than MMR or MMRV (ProQuad) have not been shown to cause ITP [1, 2]. One study examining the safety of trivalent inactivated seasonal influenza vaccination in pregnant women reported a null association with thrombocytopenia . A VSD study of 438,487 live births between 2007 and 2013 found slightly decreased rates of venous thromboembolic events and thrombocytopenia among pregnant women receiving Tdap vaccination . A retrospective observational study of California infants found no cases of ITP during the 30-day risk interval after 46,486 doses of DTaP-IPV/Hib vaccine administered .
Proposed Biological Mechanism
ITP has been associated with natural viral infections such as influenza, varicella, measles, mumps and rubella [2, 13]. Patients with ITP have antibodies to platelets. Measles virus has an affinity for platelets and measles vaccine results in a transient decrease in platelet counts in the first few days following vaccination. ITP occurs later, within the first 6 weeks following vaccination. The most likely pathogenesis for ITP involves altered immune processing of the measles virus-platelet aggregations and induction of anti-platelet antibodies . The IOM found only weak mechanistic evidence for an association between ITP and varicella vaccine, even when considering knowledge about the natural infection, as the only post-vaccination case documented provided little evidence beyond recurrence of symptoms after vaccine re-challenge . The IOM also concluded that there was no mechanistic evidence for an association between ITP and diphtheria, tetanus or pertussis vaccines .
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