ESPID REPORTS AND REVIEWS

Thrombocytosis and Infections in Childhood

Valerio Cecinati, MD,* Letizia Brescia, MD,* and Susanna Esposito, MD

I n both children and adults, thrombocytosis

is usually defined as a platelet count of
counts in children with RT due to infections
mainly peak in the second week and return to

1,000 109/L
0 12 y (9 mo)
more than 450 109/L.1 As there are many

23 (74%)
normal values within a median of 3 to 4
weeks and always within 3 months.3,4

Denton
primary and secondary causes, as well as

et al10

n.a.
n.a.
n.a.
n.a.
n.a.
31

14

false or spurious conditions mimicking
thrombocytosis, establishing the cause re-
quires considering clinical features and he-
matologic parameters. Pediatric primary
thrombocytosis is very rare, but reactive
0
The platelets are generally small with
a normal mean platelet volume. A bone mar-
row aspirate is not usually required for RT;
however, if one is performed because of
diagnostic uncertainty, it shows megakaryo-

800 109/L
thrombocytosis (RT) can be frequently ob- cytic hyperplasia and a normal mature and

57 (77%)
0 14 y (n.a.)
served in children with infections, iron defi- left-shifted megakaryocyte morphology. The

OShea
et al9

n.a.
ciency, tissue damage, hemolysis, autoim- megakaryocytes have a normal interstitial

74

17
14
6
4
16

mune diseases, malignancies, and other
causes of an acute-phase response.1 The in-
cidence of secondary forms due to infections
is significantly higher in childhood than in
0
distribution without clustering, and reticulin
levels are typically not increased.
Many reports indicate that bacterial
infections are more frequently associated

600 109/L
0 14 y (10 mo)
adulthood, and infections are the main cause with childhood RT than viral infections. Re-

308 (67%)
Mastubara
of pediatric RT, with reported incidence spiratory tract infections are the most com-

et al8

n.a.
rates ranging from 37% to 78%.2 This wide mon, followed by gastrointestinal and uri-

456

182
55
21
4
57

range may be explained by the cutoff platelet
count, the study population (in-patients, out-
patients, or both), and the median age of the
enrolled subjects.
0
nary tract infections5; however, RT may also
be encountered in children with meningitis,
tuberculosis, and human immunodeficiency
virus infection.3,6 RT is a frequent finding in

500 109/L
children with lower respiratory tract infec-

157 (64%)
0 18 y (n.a.)
ETIOPATHOGENESIS tions, especially in the presence of pleural

Yadav
et al6

n.a.
247

81
28
8
17
23

In pediatric patients with infections,
RT is due to increased megakaryopoiesis and
thrombopoiesis, which can be stimulated up
to 10-fold. Under these conditions, platelet
production is altered and may be regulated
by various cytokines, such as interleukin
0
effusions or empyema. It has recently been
reported that Mycoplasma pneumoniae in-
fections may sometimes appear with RT as a
hematological manifestation, although this
infection has mainly been associated with
800 109/L
thrombocytopenia.7 Table 1 summarizes the 0 13 y (13 mo)
27 (75%)
TABLE 1. Characteristics of RT Caused by Infections in Children

(IL-)1 alpha, IL-8, IL-6, and tumor necrosis findings of some of the main pediatric stud-
et al4
Vora

518
n.a.
n.a.
n.a.
n.a.
n.a.
factor.3 IL-6 plays a major direct and indirect ies of RT during infections.
36

role by stimulating megakaryopoiesis or he-
patic thrombopoietin (TPO) production. In
the first week of stimulation, when the plate-
let count is still normal, circulating TPO
0
There is no agreement as to whether
platelet counts are prognostic of the outcome
of pediatric infections, although a recent
study has found that thrombocytotic patients
900 109/L
0 16 y (9 mo)

concentrations peak on day 4 2 days and

25 (27%)

with lower respiratory tract infections have a

then gradually decrease. In the second or more severe clinical evolution than patients
et al3
Chan

310
94

8
5
1
9
2

third week, when platelet counts peak, TPO
concentrations are back in the normal range.
Furthermore, TPO concentrations usually
correlate with those of C-reactive protein and
IL-6 levels.3 This explains why platelet
without RT, which suggests that increased
platelet counts in the second week of illness
may be a marker of the severity of pediatric
lower respiratory tract infections.11 The find-
ings of a study of the clinical significance of
Thromboembolic and thrombohemorrhagic

RT in children with urinary tract infections

RT indicates thrombocytosis; n.a., not available.

were similar, and the authors suggested that

From the *Department of Biomedicine of Evolutive a high platelet count may indicate the site
Age, University of Bari, Bari, Italy; and Depart-
No. patients with infections (%)

and severity of infection (upper rather than

ment of Maternal and Pediatric Sciences, Universita
degli Studi di Milano, Fondazione IRCCS Ca
lower urinary tract infection) and the type of
Type of infection, number

Granda Ospedale Maggiore Policlinico, Milan, Italy. organism (Gram positive rather than Gram
Gastrointestinal tract
Age range (median age)

Address for correspondence: Susanna Esposito, MD, negative). Consequently, in addition to

No. enrolled children
Platelet count cutoff

Department of Maternal and Pediatric Sciences, acute-phase blood markers and renal imag-
Time to recovery, d
Respiratory tract

complications

Universita degli Studi di Milano, Fondazione

ing, platelet counts may be both diagnosti-
Urinary tract

IRCCS Ca Granda Ospedale Maggiore Poli-

cally and prognostically useful in the man-
Meningitis

clinico, Via Commenda 9, 20122 Milano, Italy.

E-mail: susanna.esposito@unimi.it. agement of pediatric urinary infections.5
Other

The authors have no funding or conflicts of interest to
disclose.
Copyright 2012 by Lippincott Williams & Wilkins
ISSN: 0891-3668/12/3101-0080
DOI: 10.1097/INF.0b013e318241f47a
Conversely, other authors have found that
platelet counts do not correlate with out-
comes, disease activity, or the severity of the
infections.12,13 Kilpi et al found RT in 49%

80 | www.pidj.com The Pediatric Infectious Disease Journal Volume 31, Number 1, January 2012
The Pediatric Infectious Disease Journal Volume 31, Number 1, January 2012
of 311 children with bacterial meningitis
after the first week of treatment, and that it
had no influence on the neurologic outcome
of the surviving patients, thus demonstrating
that the patients who died developed throm-
bocytopenia rather than RT.13
Moreover, some studies have shown
that RT can also occur during antibiotic
treatment for pediatric infections. It may
appear as a laboratory side effect after
treatment with carbapenems (ie, imipenem/
cilastatin, meropenem) and cephalosporins
(ie, ceftriaxone and ceftazidime) in the
case of neonatal and childhood central ner-
vous system or respiratory tract infection,
and it has an incidence of nearly 10% in
treated patients.14 It has also been reported
that there is an association between RT and
the use of antifungal therapy for childhood
candidemia.15
The occurrence of childhood RT is
age dependent: the highest incidence is
found among neonates (particularly prema-
ture babies) and infants aged up to 24
months, which gradually decreases up to the
age of 10 years. Mastubara et al studied 456
Japanese thrombocytotic children, more than
80% of whom were aged less than 2 years
and only 3% were aged 8 to 10 years.8
Similar results have been reported by OShea
2012 Lippincott Williams & Wilkins
et al, who found that the majority of Euro-
pean children with RT due to infections are
less than 2 years old.9
TREATMENT
As thromboembolic events have not
been reported in children with RT secondary
to infections, treatment with platelet aggre-
gation inhibitors is not required even when
the platelet count is high (ie, 1000 109/
L).10 It is important to remember that a
conservative approach is recommended and
treatment should be aimed at the underlying
infection and not the platelet count.
REFERENCES
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165177.
3. Chan KW, et al. Thrombocytosis in childhood: a
survey of 94 patients. Pediatrics. 1989;84:1064
1067.
4. Vora AJ, et al. Secondary thrombocytosis. Arch
Dis Child. 1993;68:88 90.
5. Garoufi A, et al. Reactive thrombocytosis in chil-
dren with upper urinary tract infections. Acta
Paediatr. 2001;90:448 449.
ESPID Reports and Reviews
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thrombocytosis. Indian J Pediatr. 2010;77:643
647.
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662 666.
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incidence and etiology of childhood thrombocy-
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9. OShea J, et al. Thrombocytosis in childhood.
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10. Denton A, et al. Extreme thrombocytosis in ad-
missions to paediatric intensive care: no require-
ment for treatment. Arch Dis Child. 2007;92:
515516.
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patients is associated with severe lower respira-
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755759.
12. Indolfi G, et al. Incidence and clinical signifi-
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acquired infections. Platelets. 2008;19:409 414.
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penia in childhood bacterial meningitis. Pediatr
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14. Grubbauer HM, et al. Ceftriaxone monotherapy
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