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PRACTICE POINT

PODCAST

Diagnosis and management of typical, newly diagnosed primary immune

thrombocytopenia (ITP) of childhood

Posted: Oct 26 2018

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Principal author(s)

Jeremy N Friedman, Carolyn E Beck; Canadian Paediatric Society, Acute

Care Committee

Abstract

This practice point applies to children aged 90 days through 17 years who
have typical, newly diagnosed primary immune thrombocytopenia
(ITP). Current recommendations on management and information from
recent studies are summarized with the goal of decreasing variable practice
among providers and improving patient-centred care. Options for initially
managing young patients with ITP who experience bruising, petechiae or
occasional mild epistaxis not interfering with daily living include observation
without pharmacotherapy as a first-line option. When active therapy is
pursued, choices include the use of corticosteroids and IVIG. Children with
moderate or severe bleeding continue to require hospitalization and
treatment. Shared decision-making can enhance patient-centred care and
ensure that the families have a full understanding of the management
options available.

Keywords: Intracranial hemorrhage (ICH); Immune thrombocytopenia

(ITP); Intravenous immunoglobulin (IVIG); Shared decision-making (SDM)
The problem

Newly diagnosed primary immune thrombocytopenia (ITP) typically occurs

in healthy children and is characterized by immune-mediated destruction of
otherwise normal platelets. The cause of ITP is not usually known, but the
condition can be triggered by a viral infection or other immune
phenomenon. ITP affects approximately 5 in 100,000 children per year,
most commonly between age 2 to 5 years [1]. Typical natural history is self-
resolution within 6 months, which occurs in 75% to 80% of cases [2], with
some of the remaining children resolving within a year of diagnosis [3]. Most
children present with mild bruising and petechiae, but approximately 3%
present with more serious bleeding from the nose, mucosa or
gastrointestinal tract [4]. The most serious complication of ITP is intracranial
hemorrhage, which occurs in approximately 0.17% to 0.6% of cases [1][5][6].

Typical ITP can be diagnosed based on classic features of the patient’s

history, physical examination and laboratory investigation. Specific ‘red
flags’ should signal alternate diagnoses and warrant a hematology
consultation (Table 1). By definition, the platelet count in typical ITP is <100
x 109/L, but most cases have a platelet count of <20 x 109/L. In children with
typical features of ITP and no red flags, a bone marrow examination to rule
out leukemia is not necessary [2][7]. Secondary causes of ITP include drug-
induced, systemic lupus erythematosus and infections or immune-
deficiencies, and malignancy needs to be considered if red flags are
present. These causes need investigation in children who do not present
typically.

Table 1: ‘Red flags’ for alternate diagnoses

History

 Constitutional symptoms (fevers,

weight loss, night sweats)
 Bone pain
 Recurrent thrombocytopenia
 Poor treatment response
Physical examination

 Lymphadenopathy
 Hepatomegaly
 Splenomegaly
 Child is “unwell”
  Signs of chronic disease
Investigations

 Low Hb (unless mildly low and

explained by bleeding history)
 High mean corpuscular volume (MCV)
 Abnormal white blood cell (WBC)
and/or neutrophil count
 Abnormal cellular morphology on
smear

How best to manage cases of typical ITP in children remains unclear.

Pharmacological treatments increase the platelet count to reduce bleeding
or perceived bleeding risk. They are not curative, however, and side effects
as well as potential requirement for hospitalization must be considered.
While ITP guidelines in the U.K. [8] have recommended only treating
children with significant bleeding symptoms, this practice has not
traditionally been followed in North America [1][6].

Management options include observation without specific treatment or

active therapy with corticosteroids, intravenous immunoglobulin (IVIG) or
with anti-D immunoglobulin (anti-D) for Rh-positive children. Whether early
treatment affects the risk for life-threatening bleeding complications or for
developing chronic ITP is unclear [4][5][9][10].

This practice point summarizes the most recent recommendations from the
American Society of Hematology [2] and new information from recent
studies [1][6]. Guidance for decision-making is offered [11] with the goal of
decreasing variable practice among health care providers and enhancing
patient-centred management of this common childhood condition.
Treatment advice applies to children aged 90 days through 17 years who
have typical, newly diagnosed primary ITP (up to 3 months post-diagnosis).
This practice point does not address persistent, chronic or secondary
ITP [12].

New research and guidance

In 2011, the American Society of Hematology (ASH) released a clinical

practice guideline on the evaluation and management of ITP [2]. For typical
ITP, the guideline suggested an approach aimed at achieving a platelet
count associated with adequate hemostasis (i.e., with no active bleeding,
specifically no epistaxis, menorrhagia or blood in stools), rather than
attaining an absolute number, while involving the patient and family in
treatment decisions. Most children with no bleeding or only mild bleeding
(petechiae and/or bruising; an estimated 77% of cases) can be managed
using observation alone, regardless of platelet count. This recommendation
aligned with international guidelines [13], and was based both on the relative
rarity of significant bleeding and lack of evidence that treatment decreases
risk for severe bleeding or for developing chronic ITP [4][5][9][10]. The
recommendation to move away from platelet count as a surrogate marker
for hemostasis and toward observation as the preferred management
option marked a shift from previous practice in North America.

Before publication of the 2011 guidelines, children hospitalized for typical,

newly diagnosed ITP in the United States usually received IVIG treatment
(i.e., in approximately 78% of cases) [6]. One recent study indicated poor
uptake of the guidelines. Out of 4,937 children with ITP, the number
receiving pharmacological treatment increased post-guideline (94.1%
versus 92.9%). Of note, only 14% of these children had documented
significant bleeding [1]. The tendency to actively treat ITP in the United
States contrasts with practice patterns in the U.K., where platelet-raising
treatment is used in only 16% of cases [14].

Recommendations

For children without active bleeding (described clinically in Table 2),

strongly consider observation as the first-line approach, with oral
corticosteroids or IVIG as second-line options. Involve the family in
management decisions and consider multiple factors, including the
individual’s bleeding risk (e.g., activity level), logistics (e.g., household
distance from hospital) and social issues (e.g., reliability of follow-up).
Shared decision-making should incorporate each family’s values and
preferences.

For children with moderate bleeding, active therapy continues to be

recommended. Treatment options include a single dose of IVIG (0.8 g/kg to
1.0 g/kg) or a short course of corticosteroids [15]. Intravenous anti-D immune
globulin (anti-D) can only be used in Rh-positive children and is generally
not considered as first-line therapy due to rare but serious adverse
effects [2].

For children with severe bleeding (e.g., prolonged epistaxis,

gastrointestinal bleeding or ICH; an estimated 3% of total cases),
immediate treatment in hospital with intravenous steroids and IVIG is
indicated. Tranexamic acid may help as an adjunct therapy at a dose of 25
mg/kg/dose administered 3 to 4 times per day (to a maximum of 1500 mg
per dose or 4500 to 6000 mg per day). Platelet transfusion is generally
contraindicated except for acute, life-threatening bleeds or in children
requiring immediate surgery.

Shared decision-making in children with ITP [11]

The relative rarity of severe bleeding with ITP makes it unlikely that future
trials will fully establish the risks and benefits of active treatment or alleviate
the decisional conflict that exists among providers and families considering
treatment options. Decisions remain preference-sensitive because the
benefits of any single option do not clearly outweigh potential risks. This
uncertainty provides an ideal opportunity for SDM, with discussions among
patients, parents and health care providers considering two or more
clinically reasonable options and paying explicit attention to family values
and preferences. Risk adversity, the desire for inpatient versus outpatient
management, and the risks and benefits of each option (e.g., degree of
comfort with blood products or corticosteroid side effects, and observation
versus active therapy) should be considered. Older children’s personal
goals relating to their participation in or return to regular activities after an
episode should also be accounted for. Clear, unbiased communication,
preferably using educational resources to inform families concerning the
pros and cons of management options (Table 3), is essential for effective
SDM.

Initial non-responders or early relapse

When pharmacotherapy is used, the goal is to raise platelet counts to a

level where hemodynamic stability is achieved. Some experts continue to
use a quantitative threshold (i.e., a platelet count >10 or 20 x 109/L) to
reduce risk for serious bleeding. For children who do not respond initially,
further treatment may involve switching to a different modality (e.g., from
IVIG to corticosteroids or vice-versa). Approximately one-third of children
who respond to treatment initially, regardless of type, will relapse, with
platelet counts falling below 20 x 109/L within 2 to 6 weeks. Retreatment
decisions should be based on similar criteria to those initially considered,
with modality depending on tolerance of and response to previous
treatment agents.

Supportive care and monitoring

All follow-up visits should include a physical examination, checking the

platelet count and anticipatory guidance around bleeding signs.
Appointments should be regularly scheduled until platelet counts have
recovered, with frequency of follow-up depending on the clinical scenario
and platelet count. When platelet counts remain low or there is evidence of
bleeding, patients must avoid contact sports and activities that may cause
injuries, especially to the head. Medications and complementary medicines
with anti-platelet activity (e.g., non-steroidal anti-inflammatories and some
herbal products) must also be avoided. Dentists and doctors should be
reminded of the condition at each visit. Collaboration among community
physicians, emergency department staff, hematologists and hospitalist
paediatricians is encouraged to build uniformity in evidence-based best
practice.

TABLE 2: Classification of bleeding and management options

Severity [2] No or mild bleeding Moderate bleeding Severe bleeding

Proportion of (77%) (20%) (3%)

cases [4]

Clinical  No bleeding; or (at  More severe skin  Bleeding episodes

most) bruising, manifestations, with (epistaxis, melena,
description petechiae or some mucosal lesions menorrhagia and/or
occasional, mild and more intracranial hemorrhage)
epistaxis troublesome epistaxis requiring hospital
 No or very little or menorrhagia admission
interference with
daily living
 May include non-
oozing petechiae
on oral mucosa or
resolved mild
epistaxis
Management  Observation  Corticosteroids (e.g.,  Non life-threatening (see
 Corticosteroids prednisone) Moderate bleeding)
options (e.g., prednisone)  IVIG  Life-threatening: IV
 IVIG methylprednisolone + IVIG
+ platelet transfusion +/-
tranexamic acid
Data drawn from references [2][4] IVIG Intravenous immunoglobulin IV intravenous

TABLE 3: Comparison of therapeutic options

Observation* Glucocorticoids IVIG

Dose N/A Oral prednisone or 0.8 g/kg to 1
dexamethasone (steroids g/kg
may be given IV)
Single dose
Dose regimes vary:
prednisone 4 mg/kg/day Consider
orally (divided twice to four measuring
times daily) for 4 days (to a baseline IG
maximum 150 levels for
mg/day) [15]without taper, children <1 year
versus 2 mg/kg/day of age or when
orally for 1 to 2 weeks, with an immune
tapering dose deficiency is
suspected
No evidence to support a
longer versus brief course [4]
Side-effects Longer period Mood changes Headache
and of activity (aseptic
disadvantages restriction [2] Increased appetite, weight meningitis)

Anxiety while Gastritis (consider use of Nausea,

awaiting stomach protectant) vomiting
platelet
recovery [2] Hypertension (with a longer Fever
course)
Rash
Poor taste may affect
tolerance Hemolysis
(rare)

Requires IV
placement and
(at minimum) a
one-day stay in
hospital
Cost Outpatient Outpatient management Hospital
management admission
No IV required
No medication Expensive
cost Inexpensive
Action 75% to 80% Effective in up to 72% to Effective in
will improve 88% of cases [2] >80% of
within 6 cases [2]
months [2] Increase in platelets,
usually within 48 h Increase in
Will take longer platelets usually
for platelet within 24 h;
count to rise peak response
at 2 to 7 days [2]

Should be used
if more rapid
increase is
required [10]
*Only recommended in cases with no or mild bleeding

Data drawn from reference [2][4][10][15] IVIG Intravenous immunoglobulin IV intravenous N/A
not applicable

Recommended resources

SickKids Hospital (updated December 2012). Immune thrombocytopenia

(ITP): What happens after
diagnosis: http://www.aboutkidshealth.ca/En/HealthAZ/ConditionsandDisea
ses/blooddisorders/Pages/ITP-what-happens-after-diagnosis.aspx
Centre hospitalier universitaire Sainte-Justine, Services d’hématologie et
de pédiatrie (July 2013 version). Protocole de prise en charge des
thrombopénies immunes aiguës, nouvellement diagnostiquées, au CHU
Sainte-Justine: http://www.urgencehsj.ca/wp-
content/uploads/thrombop%C3%A9nie.pdf

Acknowledgements

This practice point was reviewed by the Community Paediatrics Committee

and the Emergency Medicine and Hospital Paediatrics Sections of the
Canadian Paediatric Society. It was also reviewed by representatives of the
Canadian Paediatric Thrombosis and Hemostasis Network, with our
thanks.

CANADIAN PAEDIATIC SOCIETY ACUTE CARE COMMITTEE

Members: Carolyn Beck MD, Laurel Chauvin-Kimoff MD (Chair), Kimberly

Dow MD (Board Representative), Catherine Farrell MD (past member),
Jeremy Friedman MD (past member), Evelyne D. Trottier MD, Kristina
Krmpotic MD, Kyle McKenzie MD

Liaisons: Kevin Chan MD, CPS Paediatric Emergency Medicine Section;

Marie-Joëlle Doré-Bergeron MD, CPS Hospital Paediatrics Section

Principal authors: Jeremy N Friedman MD, Carolyn E Beck MD

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American Society of Hematology. The American Society of
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Disclaimer: The recommendations in this position statement do not

indicate an exclusive course of treatment or procedure to be followed.
Variations, taking into account individual circumstances, may be
appropriate. Internet addresses are current at time of publication.

Last updated: Oct 29 2018

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