doi:10.1111/jpc.

13627

VIEWPOINT

Lessons in the diagnosis and management of immune

thrombocytopenic purpura in children
Catherine Cole
Department of Paediatric, Adolescent Haematology and Oncology, Princess Margaret Hospital for Children, Perth, Western Australia, Australia

In 2012, I wrote a rapid update on childhood immune thrombo- is a specialised test best ordered by an academic haematologist (Figs
cytopenic purpura (ITP) published in this journal.1 Several evol- 2, 3).
ving issues lead me to provide some further lessons, including: Lesson 2: Liaising with the laboratory haematologist
1 How to make a diagnosis of ITP. regarding the blood film is essential.
2 Why it is very important not to treat non-bleeders with ITP.
3 When to consider use of the new thrombopoietic agents.
Why It Is Important Not to Treat ITP
It is now widely accepted that children with ITP who are not
How to Make a Diagnosis of ITP bleeding should not be treated as the natural history will not be
altered.3 Treatment of those with troublesome bleeding is recom-
The diagnosis of ITP remains one of exclusion and requires taking
mended because the risk of serious haemorrhage (intracranial
a history (ITP frequently follows a viral infection or, less com-
bleeding) can be predicted by mucosal bleeding.
monly, routine immunisation), including family history; perform-
A short course of corticosteroids (e.g. prednisolone 2–4 mg/kg/
ing a physical examination, which should be normal apart from
day × 4 days with ranitidine) could be considered simple, cheap
bruising and petechiae; and haematologist review of the periph-
and relatively non-toxic therapy, which will result in a temporary
eral blood film showing no abnormalities apart from thrombocy-
rise in platelet count and amelioration of bruising and petechiae
topenia. ITP is more common in young children than in
in most patients. However, the platelet response will be short
teenagers, in whom associated autoimmune disorders such as
lived, 2–3 weeks, and bruising and petechiae will recur associated
systemic lupus erythematosus should be considered, especially in
with recurrent profound thrombocytopenia. If corticosteroids
girls and in certain ethnic populations, including Asians and
have been prescribed initially, it is difficult to avoid prescribing
many of the indigenous populations of Oceania. These patients
on representation as parents will expect this. Before too long, the
frequently have lymphopenia. Consider requesting an erythro-
child will be Cushingoid from repeated courses of corticosteroids.
cyte sedimentation rate (Fig. 1).
Lesson 1: Consider a detailed history, including ethnic-
ity, age and family history.
Making a diagnosis of ITP is easiest when there is severe throm-
bocytopenia, <20 and often <10 × 109/L, as milder thrombocytope-
nia may be seen as part of the inherited thrombocytopenias.2 Large
platelets seen on the blood film are in keeping with ITP; however,
recent genetic studies have highlighted the need for the considera-
tion of inherited macrothrombocytopenias, especially the MYH9
disorders, which are autosomal dominant and associated with deaf-
ness, cataracts and renal failure. These associated features can be
ameliorated if addressed early, and diagnosing these inherited
macrothrombocytopenias also avoids unnecessary ITP treatments.
Historically, these patients have not been diagnosed until early
adulthood, and many have been labelled chronic ITP and have
received several lines of therapy, including chronic corticosteroids,
intravenous immunoglobulin and rituximab, or have undergone
splenectomy. Genetic diagnosis of the inherited thrombocytopenias

Correspondence: Professor Catherine Cole, Department of Paediatric,
Adolescent Haematology and Oncology, Princess Margaret Hospital for
Children, GPO Box D184, Perth, WA 6001, Australia. Fax: +61 89340
8384; email: catherine.cole@health.wa.gov.au
Conflict of interest: None declared.
Accepted for publication 9 May 2017.
Fig. 1 The figure depicts a 15-year-old girl with haemoglobin 138 g/L;
white cell count 2.8 × 109/L, neutrophils 1.34 × 109/L and lympho-
cytes 1.01 × 109/L; platelet count 13 × 109/L; erythrocyte sedimenta-
tion rate 30 mm/hr, c-reactive protein 17; alanine aminotransferase
267 U/L; lactate dehydrogenase 1040 U/L. Indications of lymphopenia
and raised erythrocyte sedimentation rate. First presentation of
systemic lupus erythematosus.

Journal of Paediatrics and Child Health (2017) 1

© 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians)
Immune thrombocytopenic purpura in childhood
Fig. 2 The figure depicts a 10-year-old boy with haemoglobin 107 g/L;
white cell count 7.0 × 109/L; platelet count 2 × 109/L. Manual platelet
count 30 × 109/L, with many large platelets on the blood film. Bone marrow
shows increased megakaryocytes with hyperlobated and dysmorphic
forms. Diagnosis: Congenital macrothrombocytopenia.
Children who are refractory to steroids are eligible for treatment
with intravenous immunoglobulin, but this requires intravenous
access and exposes the child to a blood product, albeit a virally
inactivated product. The subgroup of children who go on to have
chronic ITP (~10% will still have thrombocytopenia > 12
months) and are referred to a haematologist will then be told
that they should not have been treated at all!
Lesson 3: Only treat ITP for bleeding. It is helpful to
measure platelet counts as infrequently as possible as the
platelet number is not used as a trigger for treatment.
When to Consider Use of the New
Thrombomimetic Agents
Thrombopoietin (TPO) receptor agonists now have therapeutic
goods authority-approved indications and are included on the
pharmaceutical benefits scheme as second-line therapy in ITP.4–6
The first-generation agents were associated with the development
of anti-thromopoietin antibodies and thrombocytopenia and did
not make it to market. The second-generation agents share no
homology with native TPO, and antibody formation has not
occurred. There are two agents: romiplostim is administered sub-
cutaneously and has an indication only in adults. Eltrombopag, a
smaller molecule, is orally bioavailable and has an indication for
patients aged >1 year. Both indications are post-splenectomy
unless splenectomy is contraindicated
It is essential to consider these agents to be palliative as the
platelet count will fall to baseline in at least 70% of patients once
the drug is stopped. Hence, beginning these expensive agents
with limited long-term data is of concern if undertaken outside a
clinical trial. Known side effects of eltrombopag include reversible
elevation of liver enzymes, requiring monitoring. Additionally,
there is an increase in thromboembolic events compared with
placebo; so, if used, the lowest efficacious dose is recommended,
2 Journal of Paediatrics and Child Health (2017)
© 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians)
C Cole
Fig. 3 The figure depicts an 8-year-old boy requiring surgery with a mater-
nal history of May Hegglin anomaly and haemoglobin 124 g/L; white cell
count 7.3 × 109/L; platelet count 6 × 109/L. Manual platelet count was
60 × 109/L, and Dohle-like bodies were seen in neutrophils. Diagnosis:
MYH9-related disorder.
and the treatment plan should include weaning with a view to
cessation. Bone marrow fibrosis should be assessed annually.
Long-term toxicity is unknown.
Recently in Europe and the USA, the need for prior splenec-
tomy was removed from the indication, and it is likely that
Australia will also amend the indication. On cost-effective
grounds alone, these expensive agents fail in comparison with
laparoscopic splenectomy, with appropriate immunisations and
penicillin prophylaxis, yet there is understandable reticence for
splenectomy in the first decade of life as well as a human ten-
dency to consider newer therapies to be superior to older treat-
ments. Splenectomy remains efficacious in chronic ITP, and long-
term safety is established.
Lesson 4: Thrombomimetic agents should be considered
palliative treatments.
Perhaps, the most important lesson is to remember that as ITP
remains a diagnosis of exclusion, the diagnosis should be regu-
larly reconsidered. Family history is not static but evolves over
time and should be taken repeatedly. Patients who are refractory
to therapy may be candidates for newer thrombopoietic agents,
but the very refractoriness should be a reminder to revisit the
diagnosis, especially as testing for rare, inherited thrombocytope-
nias becomes routinely available.
Lesson 5: Haematologists managing children with
chronic ITP should reconsider the diagnosis regularly.
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