Idiopathic thrombocytopaenic purpura

General paediatrics, Haem/Oncology

or ITP for short. Mostly primary school age children – rare under 2yrs.

80% of children with ITP will recover spontaneously within 6–8 weeks.

Diagnosis

Diagnosis by exclusion, because lots of causes of low platelets. Can occur at any age, but in neonates maternal ITP or alloimmune thrombocytopenia more likely.

In acute ITP:

  • Short history: purpura/bruising appear over 24–48 hr.
  • No patterning, and not tender. Often in mouth (cf trauma).
  • Platelet count usually less than 10–20/fl but may be 0 (with few symptoms or signs!)
  • Children with counts above 20 rarely show any symptoms cf other causes.

May follow an acute viral infection or within 6 weeks of immunisation esp MMR (1 in 24 000 risk).

(The CSM recommend that children who develop MMR associated ITP should have serology checked and a second dose given if not fully immune – rubella associated ITP is a bigger problem than MMR associated ITP!).

ITP associated with Varicella needs special caution: occasionally more complex coagulation disorders viz antibodies against proteins S +/or C.

Differential diagnosis

A chronic history, with symptoms developing over weeks or months, is possible in ITP but suggests something else. See bruising – beware non-accidental injury (NAI) and meningococcal disease: children with infection usually have other features and non-accidental injury does not present with generalized purpura.

Special diagnostic considerations in older children

  • Children over the age of 10 more likely to have a chronic course.
  • Consider other autoimmune diseases esp systemic lupus erythematosus (SLE) and antiphospholipid syndrome

Investigations

  • Full blood count and film.
  • Coagulation screening. Only necessary if there is a possibility of meningococcal infection, other features suggestive of an inherited bleeding disorder, or a suspicion of NAI.
  • Group and save in case needs treatment/transfusion later.
  • (Antiplatelet antibodies do not assist in the diagnosis)
  • Bone marrow aspiration. Normal bone marrow excludes some causes of thrombocytopenia but does not explain peripheral destruction. Consider if therapy is considered (esp steroids), in the presence of atypical clinical features or if no response to treatment.

Management: general measures

Classify clinically and not by platelet count, because even with severe thrombocytopenia (less than 10 /fl) clinical symptoms usually “mild”. Equally, pronounced skin purpura and bruising, however extensive, do not indicate a serious bleeding risk on their own and serious complications are probably rarer than sometimes quoted.

  • Two UK national surveys of children with ITP have demonstrated that only 4% of children with ITP have serious symptoms such as severe epistaxis or GI bleeding.
  • Several studies have confirmed that the incidence of intracranial haemorrhage (ICH) is 0.1–0.5% (cf 1- 3% as widely quoted) – only 2 UK cases, complete recovery in both.
  • Impossible to predict which children will develop an ICH – ?other predisposing factors eg underlying vascular anomaly. ICH has occurred in children who have been treated.
  • The severity of bleeding at any given time, esp at presentation, does not predict the risk of subsequent episodes of serious bleeding.
  • Children who continue to be severely thrombocytopenic with significant bleeding symptoms are very rare – refer to a specialist centre for management.

Treatment: Watch and Wait policy

  • More than 80% of children with acute ITP will not have significant bleeding symptoms (brief mucosal bleeding only) and will not need treatment to raise count. It is essential that the parents, and child where able, have an explanation that this is usually a self-limiting benign disorder.
  • Hospital admission should be reserved for children with clinically important bleeding (severe epistaxis, i.e. lasting more than 30 min with heavy bleeding, GI bleeding, etc.). Tranexamic acid can be useful.
  • Advise parents to watch for other signs of bleeding and give contact name and 24 h telephone number; as far as possible, avoid contact sports or activities with high risk of trauma or head injury. Hard with toddlers! Avoid immunisations. Helmet on bike/scooter!
  • Other activities can be continued as normal, and the child should be encouraged to continue schooling on the basis that ITP is a disorder that may last some weeks or months.
  • Repeat count within the first 7-10 d to check that there is no evidence of a serious marrow disorder emerging, eg aplasia.
  • Otherwise repeat platelet counts weekly or as clinically indicated by a change of symptoms (beware excessive family focus on numbers). While purpura still present, count is likely to be less than 20 /fl.
  • Minimise interference with schooling – deal with lifestyle limitation issues. “Most parents and patients can live quite comfortably with petechiae and low platelets awaiting spontaneous remission, providing their physician can!” (Dickerhoff, 1994).

Specific treatment to raise the platelet count

Several therapies raise the count faster than no treatment. However, all have significant side effects and none alters the underlying pathology nor increases the chance of complete remission. These strategies are appropriate for children with severe bleeding symptoms.

Recommendation: If a child has mucous membrane bleeding and more extensive cutaneous symptoms, high dose prednisolone 4 mg/kg/d is effective (Grade A recommendation, Level Ib evidence). It can be given as a very short course (maximum 4 d). There are no direct comparisons of low dose (1–2 mg/kg/d) with high dose therapy. If lower doses of 1–2 mg/kg/d are used the treatment should be given for no longer than 14 days, irrespective of response.

Other steroid regimens:

  • High dose methyl prednisolone (HDMP). This has been used as an alternative to IVIg because it is cheaper and effective.
  • Pulsed high dose dexamethasone. This treatment appears to be less effective in children than in adults in producing long-term remission, but may be useful as a temporary measure.

Intravenous immunoglobulin is effective and seems to work more quickly cf steroids (mean 2 days to achieve plt count of 50 cf 4 days). Works by binding to spleen receptors, reducing platelet destruction. Expensive and invasive, reserve for emergency treatment of patients who do not remit or respond to steroids and who have active bleeding. It is an appropriate treatment to enable essential surgery or dental extractions. IVIg is a pooled blood product, the risks of which must be explained to patients. It has significant side effects (75% of children, esp severe headache).

Recommendation: IVIg can raise the platelet count rapidly, but should be reserved for emergency treatment of serious bleeding symptoms or in children undergoing procedures likely to induce blood loss. It is effective given as a single dose of 0.8 g /kg (Evidence level Ib, Grade A recommendation). Lower doses are also effective, and fewer side effects are seen, in younger children; but usually it is used for emergencies where a higher dose eg 1g/kg may be more appropriate.

Anti-D immunoglobulin is less expensive than IVIg and can be given to Rh (D) positive individuals as a short infusion, and is therefore amenable to outpatient therapy. It is as effective as IVIg in children when given at sufficient dosage (45–50 lg /kg). The mechanism of action is not fully understood. Like IVIg, anti-D is a pooled blood product; some degree of haemolysis is commonly seen, occasionally severe and is associated with renal failure. Lower dose treatment is less effective at raising the platelet count than IVIg.

Tranexamic acid (oral) – not if macroscopic haematuria (risk of obstruction).

Use of platelet transfusions

Life-threatening haemorrhage is the only indication for platelet transfusion in ITP, a destructive platelet disorder where transfusions of normal doses are unlikely to be effective. In a life-threatening situation (such as the rare ICH) larger than normal doses are required with monitoring of the increment as a guide, and other modalities such as high dose IV steroids and IVIg should be given at the same time to maximise the chances of raising the count and stopping the haemorrhage.

Chronic ITP in childhood

The management of children with continuing thrombocytopenia (6 months) is essentially the same as for acute ITP. Many children settle with an adequate platelet count (i.e. more than 20 /fl) and have no symptoms unless injured. In children under 10 years of age at diagnosis spontaneous remission is likely to occur eventually eg within 15 years; expectant management can continue.

Children more than 10 years of age at diagnosis, esp girls, are more likely to sustain a chronic course but tends to attenuate over time.

Most children need no specific therapy to raise the count unless injured or requiring surgery or dental extraction. Particular problems may arise for girls at the onset of menstruation. It is advisable for the family to carry a card, letter or medical bracelet with details of the disorder in case of emergency eg trauma.

Children with counts persistently below 10 /fl are likely to have some symptoms, e.g. easy bruising or odd petechiae. Very rare, and are difficult to manage – refer such chronic severe ITP (CSITP) cases to paediatric haematologists with a special interest.

A significant group of children with ITP have counts of 10–30 /fl, and although they have no serious bleeding, are nevertheless troubled by purpura esp physical appearance, secondary school. Lifestyle issues and restrictions on sporting activities become more important and should be taken into account in considering therapy. Intermittent treatment with IVIg can be given to cover activity holidays after appropriate discussion of the risks.

Splenectomy is often considered, but it is ineffective in around 25% of cases, and most chronic cases remit spontaneously. It does bump the platelet count up with fewer symptoms but it is clear that the relapse rate with longer follow-up is high. Given that the risk of dying from ITP in childhood is extremely low (less than 1 in 500), that the mortality associated with splenectomy is 1.4 to 2.7% and that the risk of over-whelming sepsis probably persists for life, splenectomy is only justified in exceptional circumstances eg life-threatening bleeding.

The ITP Support Association