2. ARTICLE
The Risk of Immune Thrombocytopenic Purpura After
Vaccination in Children and Adolescents
AUTHORS: Sean T. O’Leary, MD, MPH,a,b,c Jason M. Glanz, WHAT’S KNOWN ON THIS SUBJECT: Studies on vaccine safety are
PhD,c David L. McClure, PhD,c Aysha Akhtar, MD, MPH,d crucial to the ongoing success of our national immunization
Matthew F. Daley, MD,a,c Cynthia Nakasato, MD,e Roger program. ITP has a known association with MMR in young
Baxter, MD,f Robert L. Davis, MD, MPH,g Hector S. Izurieta, children, occurring in 1 in 40 000 doses. The risk after other
MD, MPH,d Tracy A. Lieu, MD, MPH,h,i and Robert Ball, MD, childhood vaccines is unknown.
MPH, Scmd
aDepartment of Pediatrics, University of Colorado Anschutz
WHAT THIS STUDY ADDS: This study found no increased risk of
Medical Campus, Aurora, Colorado; bChildren’s Outcomes
ITP after vaccines other than MMR in young children, confirmed
Research Program, Children’s Hospital Colorado, Aurora,
Colorado; cInstitute for Health Research, Kaiser Permanente an association of ITP with MMR, and also found that ITP may occur
Colorado, Denver, Colorado; dCenter for Biologics Evaluation and after certain other vaccines in older children.
Research, Food and Drug Administration, Rockville, Maryland;
eCenter for Health Research Hawaii, Kaiser Permanente Hawaii,
Honolulu, Hawaii; fKaiser Permanente Vaccine Study Center,
Oakland, California; gCenter for Health Research Southeast,
Kaiser Permanente of Georgia, Atlanta, Georgia; hCenter for Child
Health Care Studies, Department of Ambulatory Care and
Prevention, Harvard Pilgrim Health Care Institute, Boston,
abstract
Massachusetts; and iDivision of General Pediatrics, Children’s BACKGROUND: The risk of immune thrombocytopenic purpura (ITP)
Hospital Boston, Massachusetts after childhood vaccines other than measles-mumps-rubella vaccine
KEY WORDS (MMR) is unknown.
immune thrombocytopenia purpura, children, vaccines, adverse
reactions, thrombocytopenia
METHODS: Using data from 5 managed care organizations for 2000 to
2009, we identified a cohort of 1.8 million children ages 6 weeks to 17
ABBREVIATIONS
CI—confidence interval years. Potential ITP cases were identified by using diagnostic codes and
DTaP—diphtheria-tetanus-acellular pertussis vaccine platelet counts. All cases were verified by chart review. Incidence rate
HBV—hepatitis B virus vaccine ratios were calculated comparing the risk of ITP in risk (1 to 42 days
Hep A—hepatitis A vaccine
Hib—Haemophilus influenzae type b vaccine after vaccination) and control periods.
HPV—human papilloma virus vaccine RESULTS: There were 197 chart-confirmed ITP cases out of 1.8 million
IPV—inactivated poliovirus vaccine
IRR—incident rate ratio
children in the cohort. There was no elevated risk of ITP after any vaccine
ITP—immune thrombocytopenic purpura in early childhood other than MMR in the 12- to 19-month age group. There
MCV—meningococcal conjugate vaccine was a significantly elevated risk of ITP after hepatitis A vaccine at 7 to 17
MMR—measles-mumps-rubella vaccine
years of age, and for varicella vaccine and tetanus-diphtheria-acellular
MMRV—measles-mumps-rubella-varicella vaccine
PCV—pneumococcal conjugate vaccine pertussis vaccine at 11 to 17 years of age. For hepatitis A, varicella,
RV—rotavirus vaccine and tetanus-diphtheria-acellular pertussis vaccines, elevated risks were
Tdap—tetanus-diphtheria-acellular pertussis vaccine based on one to two vaccine-exposed cases. Most cases were acute
TIV—trivalent influenza vaccine
VAR—varicella vaccine and mild with no long-term sequelae.
www.pediatrics.org/cgi/doi/10.1542/peds.2011-1111 CONCLUSIONS: ITP is unlikely after early childhood vaccines other than
doi:10.1542/peds.2011-1111 MMR. Because of the small number of exposed cases and potential
Accepted for publication Oct 6, 2011 confounding, the possible association of ITP with hepatitis A, varicella,
and tetanus-diphtheria-acellular pertussis vaccines in older children
(Continued on last page) requires further investigation. Pediatrics 2012;129:1–8
PEDIATRICS Volume 129, Number 2, February 2012 1
Downloaded from pediatrics.aappublications.org by guest on January 17, 2012
3. Immune thrombocytopenic purpura Colorado, Kaiser Permanente Hawaii, of resolution, exposure to medications,
(ITP)was firstdescribedaftera wild-type Kaiser Permanente Georgia, Kaiser Per- sequelae, treatment, medically attended
measles virus infection in 1952.1 In 1966, manente Northern California, and Har- illnesswithin6weeksbeforeITPdiagnosis,
Oski and Naiman reported thrombocy- vard Vanguard Medical Associates) by and medical setting of the diagnosis.
topenia after a live attenuated measles using data from the years 2000 to 2009,
vaccine.2 Since then, the association of with Kaiser Permanente Colorado as the Confirmation of ITP Cases Using
live attenuated measles-mumps-rubella lead site. The study was a retrospective Medical Record Review
(MMR) vaccine and ITP has been well es- cohort study, with 1.8 million children For the confirmatory chart review, a
tablished.3–11 ITP is known to occur after enrolled in the cohort. We included chil- case was defined as a child aged 6
many types of infections, including nu- dren in the cohort who had been vacci- weeks to 18 years with a platelet count
merous vaccine-preventable diseases.12–18 nated while actively enrolled in their of ,50 000/mL, with normal red and
In approximately two-thirds of ITP cases, respective health plans. The institu- white blood cell indices, and the pres-
there is a history of a preceding in- tional review board of each study site ence of clinical signs and symptoms
fectious illness in the days to weeks be- approved the study. of ITP, such as petechiae, significant
fore ITP onset.19 A subset of these children bruising, or spontaneous bleeding. A
will have an identifiable virus, such as Ascertainment of Cases of ITP case was excluded if, in the 6 weeks
Epstein-Barr virus, varicella zoster virus, before diagnosis, the child was exposed
influenza virus, or HIV.16 Because vaccines Electronic Identification of Possible to a platelet-depleting medication (such
are designed to induce an immune re- Cases as antiepileptics and sulfonamide anti-
sponse that mimics natural infection to Initial identification of possible cases biotics) or infected with wild-type vari-
produce immunologic protection, it is was conducted at the lead site by using cella or Epstein-Barr virus. Patients with
theoretically possible that vaccines be- electronic databases, with the analyst no signs or symptoms of ITP, whose low
sides MMR could trigger ITP. In addition, blinded to vaccination status. We re- platelet counts were found incidentally
there have been case reports of ITP after viewed the electronic data to exclude on complete blood count screening, were
other childhood vaccines, including hep- cases of thrombocytopenia from other excluded. Children with probable sepsis
atitis B vaccine (HBV), diphtheria-tetanus- known conditions by using the Inter- or meningitis were also excluded. The
pertussis vaccine (DTP), and hepatitis A national Classification of Diseases, Ninth ITP resolution date, determined by med-
vaccine (Hep A).20–25 However, the risk Revision (ICD-9) diagnosis codes (such ical chart review, was defined as the
of ITP after childhood vaccines other as neonatal thrombocytopenia, aplastic date of the first platelet count of .100
than MMR is currently unknown. anemia, disseminated intravascular co- 000/mL with no evidence of a drop in
Known rare severe complications of ITP agulation, acquired hemolytic anemia, platelet count in subsequent months. A
include intracranial hemorrhage and se- chronic liver disease, or malignancy). We case with no follow-up platelet count
vere bleeding.26–29 Case reports and case then identified children ,18 years of .100 000/mL was considered acute if
series have described severe adverse age with either two platelet counts of there was other evidence in the medi-
events after MMR-associated ITP.4,7,11,30 ,50 000/mL in a 6-week period or one cal record of ITP resolution. For this
The risk of severe outcomes of ITP after platelet count of ,50 000/mL and an study, we defined chronic ITP as throm-
MMR vaccination is thought to be quite associated ICD-9 code of 287.0 to 287.9, bocytopenia lasting .6 months, consis-
low, but few studies have examined se- inclusive, within 6 weeks of the low tent with the definitions used in the
vere complications as an outcome.9 platelet count (see Appendix for specific literature at the time.31,32 Since the time
ICD-9 codes). this study was designed and conducted,
Using a large population from five man-
an expert panel has recommended a
aged care organizations, we sought to Abstraction of Medical Records definition of chronic ITP as lasting .12
ascertain (1) the risk of ITP in children 6
For the remaining possible cases that months33; this definition cannot be
weeks to 18 years of age afterall vaccines
were not excluded electronically, applied to the current study, because
routinely administered during childhood
medical records were photocopied, medical record abstraction information
and (2) the risk of serious complications
deidentified at participating sites, is not available for .12 months after
of ITP after vaccination in children.
and sent to the lead site. Trained medical the onset date. A pediatrician (S.T.O.)
abstractors blinded to vaccination status blinded to vaccination status indepen-
METHODS used a standardized paper-based instru- dently reviewed all charts to confirm
This investigation was conducted in five ment to collect the following: date of di- the onset date, assign case status, and
health care systems (Kaiser Permanente agnosis, symptoms, platelet counts, date assign the ITP resolution date.
2 O’LEARY et al
Downloaded from pediatrics.aappublications.org by guest on January 17, 2012
4. ARTICLE
“Serious adverse events” were defined administered simultaneously with MMR laboratory error (n = 14), ITP as an in-
as having any of the following: intracra- or MMRV, because MMR has been highly cidental finding (n = 12), completely
nial hemorrhage, bleeding requiring associatedwithITPinpreviousstudies,3–11 missing medical records (n = 10), and
hospitalization, bleeding requiring and the measles, mumps, and rubella recurrence of ITP (n = 7).
transfusion of packed red blood cells components in MMRV are identical to
or platelets, or death. those used in MMR. IRRs were calculated Cases of Immune
for each vaccine for the age groups Thrombocytopenic Purpura
Analytic Methods shown in Table 2. Age groups were se-
Table 1 shows the characteristics of all
lected based on when the majority of
We used self-controlled case series chart-confirmed cases of ITP (n = 197).
each vaccine was given, with the ex-
(SCCS) methods to examine the risk of Cases were spread across all age
ception of trivalent influenza vaccine
ITP after childhood vaccines. The SCCS ranges with similar numbers of cases
(TIV), live attenuated influenza vaccine
method uses exposed and unexposed among boys and girls. Most cases (93%)
(LAIV), and Hep A, which are given over
person-time to calculate incident rate received hematology consultation, and
a broader age range. For varicella vac-
ratios (IRRs) with each case acting as its half the children diagnosed with ITP
cine (VAR), 12 to 23 months was chosen
own control.34,35 Exposure in this con- had an acute illness in the previous 6
instead of 12 to 19 months to be able
text means exposure to a vaccine in weeks. The majority of cases of ITP in
to examine it separately from MMR, be-
a prespecified time window preceding younger children were classified as
cause most of the doses of VAR in the 12-
the onset of ITP. The SCCS method has acute, whereas over one-third in the 11-
to 19-month age group had been given
been shown to be a valid alternative to 17-year-old age group were chronic.
simultaneously with MMR. The risk
to traditional cohort and case-control Of 38 total cases exposed to vaccines
of ITP attributable to vaccine exposure
designs.36 in a 1- to 42-day risk window, 31 (81%)
was calculated as the difference be-
For each child, follow-up time was were acute, 6 (16%) were chronic, and
tween the incidence rates of exposed
limited to the 365 days before and after 1 (3%) was unknown. Of 159 unexposed
and unexposed children for each
vaccination. We defined the exposed cases, 125 (79%) were acute, 31 (19%)
vaccine in the childhood series. For
period as 1 to 42 days after vaccination were chronic, and 3 (2%) were un-
TIV and LAIV, exposures and case
for all vaccines. The unexposed period known. All cases were included in the
dates were limited to the September
was defined as the time before and IRR calculations. There was no seasonal
to December influenza vaccination
after the exposed period within 365 distribution of cases (P = .94).37
season.
days of follow-up before or after vac-
cination. We compared the incidence of Risk of Immune Thrombocytopenic
ITP during the 42 days after vaccination RESULTS Purpura After Vaccines
(exposed period) with the incidence of A total of 1.8 million children received a The risk of ITP after vaccination by
ITP during the unexposed period. Day total of 15 million vaccine doses during vaccine and age group is shown in
0 (the day of vaccination) was excluded, the study period. Using electronic data- Table 2. None of the routine childhood
because any cases occurring at this time bases, among the 1.8 million children vaccines given in the first year of life
were most likely coincidental. Because who received one or more vaccines, we was significantly associated with an in-
a child with ITP cannot become a new identified 696 potential cases of ITP. Of creased risk of ITP. For vaccines rou-
case until the current illness resolves, these, we excluded 248 based on the tinely administered at 12 to 19 months of
patients diagnosed with ITP did not presence of chronic conditions known to age, there was a significant association
contribute person-time from the date of cause thrombocytopenia, leaving a total of ITP with MMR (IRR, 5.48, 95% confi-
ITP onset to the date of resolution. For of 448 possible cases for chart review. dence interval [CI] 1.61, 18.64). For other
each vaccine, person-time was counted Afterchartreview, an additional251were vaccines commonly given in this age
only during the age when the vaccine is excluded for the following reasons: range (VAR, diphtheria-tetanus-acellular
licensed for use. For example, for MMR, alternative hematologic or oncologic pertussis vaccine [DTaP], pneumococcal
person-time before 12 months of age did diagnoses (n = 94), acute exclusionary conjugate vaccine [PCV], inactivated
not contribute to the calculation. illness such as probable sepsis or poliovirus vaccine [IPV], Haemophilus
For vaccines other than MMR and meningitis (n = 46), ITP in which an influenza type b vaccine [Hib], and
measles-mumps-rubella-varicella vac- onset date could not be determined HepA), there was no increased risk of
cine (MMRV), IRRs were calculated only from the medical record (n = 40), med- ITP (calculated when not given simul-
when the other vaccines were not ications known to cause ITP (n = 28), taneously with MMR or MMRV). There
PEDIATRICS Volume 129, Number 2, February 2012 3
Downloaded from pediatrics.aappublications.org by guest on January 17, 2012
5. TABLE 1 Characteristics of Medical Record Validated Cases of Immune Thrombocytopenic children having an event that required
Purpura (n = 197)
transfusion.
Age Groups Total
The negative findings from this study
6 wk to 11 mo 12–23 mo 24–59 mo 5–10 y 11–17 y are important. In the 12- to 19-month
Total ITP cases, n 17 30 63 55 32 197 age group (and 12–23 months for Hep A
Male, % 77 50 47 44 56 51
Platelet count at diagnosis in thousands/mL, 13 9 12 7 10 10
and VAR), age groups when ITP is rel-
mean atively common, we found no increased
Hematology consultation, % 94 80 91 96 100 93 risk of ITP for VAR, Hep A, DTaP, IPV, Hib,
Nonexclusionary acute illnessa within 6 wk 77 60 50 39 44 50
or PCV. The elevated IRR for MMRV
before diagnosis, %
Nonexclusionary medicationb within 6 wk 29 13 20 20 25 21 in this age group is not surprising,
before diagnosis, % because the measles, mumps, and ru-
Nonexclusionary acute illnessa at 29 33 17 25 13 22 bella components in MMRV are essen-
presentation, %
Diagnosis type, % tially identical to MMR. The finding that
Acute 94 83 8 80 59 79 the IRR for MMRV does not appear to be
Chronic 6 17 16 16 38 19 elevated beyond that of MMR is reas-
Unknown 0 0 2 4 3 2
For acute cases, mean time to resolution 22 21 45 41 36 36 suring given the recently reported
in days twofold increased risk of febrile sei-
Serious adverse events, % 0 0 2 5 6 3 zures for MMRV compared with MMR
ITP, immune thrombocytopenic purpura. and VAR given separately.38 The confir-
a Exclusionary acute illnesses included Epstein-Barr virus, varicella, sepsis/possible sepsis, bacteremia
b Exclusionary medications included sulfa drugs and antiepileptics such as valproic acid and carbamazepine; nonexclu- matory finding that MMR is associated
sionary medication means that the case was exposed to a medication, but that medication is not known to cause throm- with ITP helps validate the other find-
bocytopenia
ings of our current study, both positive
and negative. While we found several
elevated IRRs that approached statis-
were 1.9 cases of ITP per 100 000 doses Distribution of Cases tical significance in older children,
of MMR. Figure 1 shows the distribution of cases such as human papilloma virus vaccine
The risk of ITP after Hep A, VAR, and by week in the risk period after vacci- (HPV), TIV, and meningococcal conju-
tetanus-diphtheria-acellular pertussis nation for vaccines for which there gate vaccine (MCV), estimates in older
vaccine (Tdap) was significantly ele- were statistically significantly elevated children are less stable because there
vated in three discrete age categories IRRs during the exposed postvaccination are fewer cases of ITP on which to
as shown in Table 2. For Hep A and Tdap, period. perform analyses.
elevated IRRs were based on two vaccine- The findings related to Hep A, Tdap,
exposed cases, whereas, for VAR, there DISCUSSION and VAR should be considered as
was one vaccine-exposed case.
In this large multisite study of 1.8 million hypothesis-generating rather than as
children, we examined the risk of ITP conclusive evidence that these vaccines
Serious Adverse Events after all childhood vaccines. Our rate are associated with ITP. Our study used
Six of the 197 chart-reviewed cases of ratio estimates were based on medical self-controlled case series analyses, an
ITP had serious adverse events. All of the chart-confirmed cases of ITP. We did not effective method for studying rare ad-
subjects with serious adverse events find an increased risk of ITP for any of verse events after vaccines.34–36 How-
developed bleeding requiring hospi- the commonly given childhood vaccines ever, the events in our analysis were
talization and/or transfusion, and none other than MMR in younger children, an very rare, and since we looked at many
had any known long-term complications. important finding given that the di- possible associations, there is the pos-
There were no deaths. Of the 6 cases of agnosis of ITP is most common in the 1- sibility that significant associations
serious adverse events, only one was to 3-year age group. We also present could surface by chance alone. This is
a vaccine-exposed case, a 4-year-old important new data showing an asso- particularly true in older children and
girl who developed ITP complicated by ciation of ITP with Hep A, Tdap, and VAR in adolescents. ITP is much more common
hematochezia and hematuria requir- older children. In addition, we provide in the 1- to 3-year age group than in
ing a packed red blood cell trans- data showing that serious sequelae af- infants ,1 year or in persons .6 years
fusion 4 weeks after receiving DTaP, ter vaccine-associated ITP are rare, with of age.39 Therefore, in the 1- to 3-year
MMR, and IPV. only one child of 1.8 million vaccinated age groups, there are ample cases
4 O’LEARY et al
Downloaded from pediatrics.aappublications.org by guest on January 17, 2012
6. ARTICLE
TABLE 2 The Risk of Idiopathic Thrombocytopenic Purpura in the 1 to 42 Days After Vaccination, contributing person-time to both the
for Vaccines Routinely Administered During Childhood and Adolescencea
exposed and unexposed denominators,
Vaccine (age group) IRR 95% CI P Exposed Cases, n Unexposed Cases, n creating more stable estimates of risk
6 wk to 11 mo2 compared with older children where,
Hib 0.53 0.14 1.94 .33 3 10
RV —b — — — 1 0
because of the more pronounced rarity
DTaP — — — — 0 7 of ITP, there may be fewer cases con-
IPV — — — — 0 7 tributing unexposed person-time. Re-
HBV — — — — 0 7
PCV 0.58 0.15 2.18 .42 3 9
garding biologic plausibility, it is also
6 to 23 mo unclear why these vaccines would trig-
TIV 2.69 0.81 8.88 .11 5 7 ger ITP in older age groups but not in
12 to 19 mo
MMR 5.48 1.61 18.64 .006 6 5
younger ones. So, although it is impor-
MMRV 2.87 0.78 10.56 .11 4 6 tant to consider that the findings
DTaP 1 0.21 4.81 .99 2 8 showing an elevated risk of ITP after Hep
Hib 0.75 0.16 3.63 .72 2 9
A, VAR, and Tdap in older children may
HBV — — — — 0 2
PCV 0.72 0.14 3.97 .70 2 8 be real, these results must be interpreted
12 to 23 mo with caution.
VAR — — — — 0 8
Hep A 0.22 0.03 1.82 .16 1 11 Reports of ITP in association with vac-
2 to 6 y cines other than MMR are uncommon,
TIV 1.86 0.41 8.38 .42 3 7 and most previous information on ITP
Hep A 1.14 0.34 3.86 .83 4 27
4 to 6 y after vaccines other than MMR has
MMR 3.06 0.42 22.30 .27 2 7 come from vaccine adverse-event sur-
MMRV — — — — 0 5 veillance systems. Specifically relating
VAR 4.39 0.46 41.65 .20 1 5
DTaP 2.57 0.53 12.37 .24 2 12 to the findings in our present study of an
IPV 1.37 0.23 8.32 .73 2 12 increased risk with Hep A, Tdap, and
7 to 17 y VAR, there have been three published
Hep A 23.14 3.59 149.30 .001 2 3
TIV 5.95 0.54 65.96 .15 2 2
reports of ITP after whole-cell DTP
11 to 17 y vaccine20,40 and one after DT vaccine,40
VAR 12.14 1.10 133.96 .04 1 2 but no published case reports of ITP
MMR — — — — 0 1
HPV 9.71 0.87 108.92 .07 1 2
after Hep A, VAR, or Tdap. Regarding
MCV 6.02 0.64 56.18 .12 1 4 cases of ITP reported from surveillance
Tdap 20.29 3.12 131.83 .002 2 3 systems, as opposed to published case
a For vaccines other than MMR and MMRV, relative risks are shown only for vaccines when not given in conjunction with MMR
reports, a study from Canada based on
or MMRV; LAIV is not shown, because there are no vaccine-exposed cases in any age category.
b Vaccines for which there are either no exposed or unexposed cases will have no IRR or CI reported. an active surveillance system for vac-
cine adverse events reported 28 cases
of ITP after DTP or DTaP vaccine com-
pared with 77 reported after MMR, with
only 10 reports after VAR (and no
reports after Hep A, because children
do not routinely receive Hep A in Can-
ada).41 In a recently published report
from the US Vaccine Adverse Events
Reporting System (VAERS), although
there were 478 reports of ITP after
MMR alone or in combination with
other vaccines, there were 47 cases
reported after VAR, 32 after Hep A, and
only 8 after Tdap.42 It is important to
recognize that reports from surveil-
FIGURE 1
Distribution of cases of immune thrombocytopenic purpura, date of onset in relation to timing of receipt lance systems are subject to reporting
of vaccine (week 0), for vaccines with statistically significantly elevated incident rate ratios. bias, and so providers may overreport
PEDIATRICS Volume 129, Number 2, February 2012 5
Downloaded from pediatrics.aappublications.org by guest on January 17, 2012
7. ITP after MMR because there is a known in a large network of managed care found no increased risk for most of the
association. organizations with a large sample size vaccines in the childhood series, an un-
The characteristics of our vaccine- and all cases were confirmed by med- surprising finding of an increased risk of
associated ITP cases are important to ical record review. However, although ITP after MMR, and, less expected, we also
consider. The vast majority of our cases the sample size was large, ITP is a rare found possible increased risk of ITP for
were acute and mild. In addition, we had disease; therefore, the number of con- Hep A, VAR, and Tdap in older children.
no vaccine-exposed cases that went on firmed ITP cases was relatively low. In Additional studies are needed to better
to develop serious permanent compli- addition, it is difficult to examine the explore these possible associations.
cations. Our findings are consistent with risk of ITP after vaccines routinely given
previous studies of vaccine-associated with MMR, a vaccine known to be as- ACKNOWLEDGMENTS
ITP in this regard. ITP after vaccination sociated with ITP. As discussed, the This publication was supported by
may have a similar clinical course as study was also limited by the method- a subcontract from Kaiser Permanente
ITP from other causes. Studies on the ologies currently available for examining with funds provided by the Food and
genetics of ITP are ongoing, but it is rare adverse events. Drug Administration. Its contents are
thought that there is likely a genetic Vaccine safety is a priority of national solely the responsibility of the authors
predisposition asin other immune-related immunizationpolicy,andstudiesdesigned and do not necessarily represent the of-
diseases, such as insulin-dependent to investigate vaccine adverse events are ficial views of Kaiser Permanente or the
diabetes mellitus.43 crucial to the ongoing success of our Food and Drug Administration.
There are several strengths and limi- national immunization program. In our The authors thank Jo Ann Shoup at the
tations in this study. It is the first study to present study, we have used the best Institute for Health Research at Kaiser
examine in a systematic way the risk of available science to help define the risk of Permanente Colorado and Melisa Rett,
ITP after vaccines other than MMR. In a rare and usually benign vaccine adverse MPH, at the Harvard Pilgrim Health Care
addition, the study was performed event, ITP, after all childhood vaccines. We Institute for project management.
REFERENCES
1. Fisher OD, Kraszewski TM. Thrombocyto- pharmacovigilance centres and Pasteur- 14. Ozsoylu S, Kanra G, Savas G. Thrombocyto-
penic purpura following measles. Arch Dis Mérieux Sérums et Vaccins. Pediatr Infect penic purpura related to rubella infection.
Child. 1952;27(132):144–146 Dis J. 1996;15(1):44–48 Pediatrics. 1978;62(4):567–569
2. Oski FA, Naiman JL. Effect of live measles 8. Kiefaber RW. Thrombocytopenic purpura 15. Polat A, Inan M, Cakaloz I, Karakus YT. A
vaccine on the platelet count. N Engl J Med. after measles vaccination. N Engl J Med. case of symptomatic idiopathic thrombo-
1966;275(7):352–356 1981;305(4):225 cytopenic purpura during mumps. Pediatr
3. Autret E, Jonville-Béra AP, Galy-Eyraud C, 9. Mantadakis E, Farmaki E, Buchanan GR. Hematol Oncol. 2005;22(3):215–218
Hessel L. Thrombocytopenic purpura after Thrombocytopenic purpura after measles- 16. Rand M. Virus associated idiopathic throm-
isolated or combined vaccination against mumps-rubella vaccination: a systematic bocytopenic purpura. Transfus Sci. 1998;19
measles, mumps and rubella [in French]. review of the literature and guidance for (3):253–259
Therapie. 1996;51(6):677–680 management. J Pediatr. 2010;156(4):623– 17. Yeager A. Varicella associated thrombocy-
4. Beeler J, Varricchio F, Wise R. Thrombocy- 628 topenia: clues to the etiology of childhood
topenia after immunization with measles 10. Miller E, Waight P, Farrington CP, Andrews idiopathic thrombocytopenic purpura. Johns
vaccines: review of the vaccine adverse N, Stowe J, Taylor B. Idiopathic thrombo- Hopkins Med J. 1980;146:270–274
events reporting system (1990 to 1994). cytopenic purpura and MMR vaccine. Arch 18. Yenicesu I, Yetgin S, Ozyürek E, Aslan D.
Pediatr Infect Dis J. 1996;15(1):88–90 Dis Child. 2001;84(3):227–229 Virus-associated immune thrombocytope-
5. Black C, Kaye JA, Jick H. MMR vaccine and 11. Nieminen U, Peltola H, Syrjälä MT, Mäkipernaa nic purpura in childhood. Pediatr Hematol
idiopathic thrombocytopaenic purpura. Br A, Kekomäki R. Acute thrombocytope- Oncol. 2002;19(6):433–437
J Clin Pharmacol. 2003;55(1):107–111 nic purpura following measles, mumps 19. Blanchette V, Bolton-Maggs P. Childhood im-
6. France EK, Glanz J, Xu S, et al; Vaccine and rubella vaccination. A report on 23 mune thrombocytopenic purpura: diagnosis
Safety Datalink Team. Risk of immune patients. Acta Paediatr. 1993;82(3):267– and management. Hematol Oncol Clin North
thrombocytopenic purpura after measles- 270 Am. 2010;24(1):249–273
mumps-rubella immunization in children. 12. Hudson JB, Weinstein L, Chang TW. Throm- 20. Arya LS, Ghai OP, Saraya AK. Thrombocyto-
Pediatrics. 2008;121(3). Available at: www. bocytopenic purpura in measles. J Pediatr. penic purpura following DPT vaccination.
pediatrics.org/cgi/content/full/121/3/e687 1956;48(1):48–56 Pediatr Hematol Oncol. 1993;10(4):381–383
7. Jonville-Béra AP, Autret E, Galy-Eyraud C, 13. Morse EE, Zinkham WH, Jackson DP. Throm- 21. Neau D, Bonnet F, Michaud M, et al. Immune
Hessel L. Thrombocytopenic purpura after bocytopenic purpura following rubella in- thrombocytopenic purpura after recombinant
measles, mumps and rubella vaccination: fection in children and adults. Arch Intern hepatitis B vaccine: retrospective study of sev-
a retrospective survey by the French regional Med. 1966;117(4):573–579 en cases. Scand J Infect Dis. 1998;30(2):115–118
6 O’LEARY et al
Downloaded from pediatrics.aappublications.org by guest on January 17, 2012
9. APPENDIX 1 International Classification of APPENDIX 2 Positive Predictive Value of International Classification of Diseases, Ninth Revision
Diseases, Ninth Revision (ICD- (ICD-9) Diagnosis Codes and Platelets Counts in Predicting a Confirmed Cases of
9) Diagnosis Codes Used in Immune Thrombocytopenic Purpura upon Chart Review
Electronic Database Search
Platelet Counts Diagnosis Code Group ITP Case PPV, %
ICD-9 Code Category
Yes No
287.0 Allergic purpura
287.1 Qualitative platelet defects Years 2000–2004a
287.2 Other nonthrombocytopenic purpura 1 count ,50K and 287.31 ITP 0 0 —
287.3 Primary thrombocytopeniaa 1 count ,50K and Other TP codeb 50 70 41.7
287.4 Secondary thrombocytopeniab 2 counts ,50K and No code 2 15 11.8
287.5 Thrombocytopenia, unspecified Total 52 85 38.0
287.8 Other specified hemorrhagic conditions Years 2005–2008
287.9 Unspecified hemorrhagic conditions 1 count ,50K and 287.31 ITP 90 24 78.9
a
1 count ,50K and Other TP codeb 63 113 35.8
Includes primary thrombocytopenia, unspecified
2 counts ,50K and No code 1 20 4.8
(287.30), immune (idiopathic) thrombocytopenic purpura
(ITP) (287.31), other primary thrombocytopenia (287.39)
Total 154 157 49.5
and congenital and hereditary thrombocytopenias. PPV, positive predictive value; TP, thrombocytopenic purpura; ITP, immune thrombocytopenic purpura.
b Includes thrombocytopenia caused by dilution, drugs, a Immune thrombocytopenic purpura (287.31) was not routinely used until 2005.
extracorporeal circulation of the blood, and platelet b 287, 287.0, 287.1, 287.2, 287.3 287.30, 287.39, 287.4, 287.5, 287.8, 287.9.
alloimmunization.
8 O’LEARY et al
Downloaded from pediatrics.aappublications.org by guest on January 17, 2012
