Aetiology

Antibody binds to platelet antigens, resulting in a persistent thrombocytopenia. It is a condition which can occur in both adults and children and can be acute or chronic in nature.

Immune thrombocytopenia may occasionally also occur in patients with pre-existing autoimmune diseases, eg systemic lupus erythematosus or in some malignant conditions.

Recent studies have found a high number of ITP patients with a positive family history, indicating the likely existence of a genetic susceptibility for ITP.^[1]

Idiopathic thrombocytopenic purpura in children

ITP in children most commonly occurs following an infection, or occasionally following immunisation. It is usually a self-limiting disorder which recovers spontaneously after 6-8 weeks. It can occur at any age, but children over the age of 10 may develop chronic ITP.

Epidemiology

The incidence of childhood ITP is of the order of 2.2-5.3 per 100,000 children per year, of which 15-20% will go on to develop the chronic form.^[2] The childhood form has equal sex distribution (the adult form is 3 times more common in females).

Symptoms and signs

Many children with ITP will have no symptoms at all, although some will develop purpura and bruising over a 48-hour period, and occasionally bleeding eg nose bleeds or gastrointestinal bleeds.

Intracranial bleeds occur very rarely. In a recent study only 2.9% had severe bleeding at presentation.^[3]

Differential diagnosis

In infants, hereditary thrombocytopenia must be considered, as must ITP in the mother.

In older children the differential diagnosis includes:

• Aplastic anaemia
• Leukaemia
• Fanconi's anaemia
• Von Willebrand's disease
• Meningococcal septicaemia
• Non-accidental injury

Investigations

• FBC.
• Platelet count.
• Bone marrow examination - only required if atypical features or diagnosis in doubt.
• A positive antinuclear antibody (ANA) test may be a predictor of chronicity in childhood ITP.^[4]

Management

Treatment is considered on the basis of clinical symptoms and not on the basis of platelet count alone, as children with severe thrombocytopenia are often asymptomatic and do not have a serious risk of a bleed.

Outcomes other than platelet count are important in children with ITP, most especially the severity of haemorrhage, cost and side-effects of treatment, and overall quality of life.^[5] The estimated incidence of intracranial haemorrhage is only 0.19% to 0.78%.^[6] Identifying high-risk patients for treatment is important.

General measures

• The majority of children with acute or chronic ITP will require only advice, support and repeat FBC 10 days after diagnosis to ensure that there is no generalised marrow disorder.
• Further monitoring of the FBC is not required unless a change in the child's condition takes place to suggest that remission has occurred, or that deterioration has taken place.

Pharmacological

Any of the following may be used in a specialist setting if it is thought that the clinical condition requires that the platelet count should be raised:

• Prednisolone
• High-dose methylprednisolone
• Pulsed dexamethasone
• Intravenous immunoglobulin
• Platelet transfusion
• Anti-D immunoglobulin

It has been found that repeated doses of anti-D could maintain platelet count above the critical values, or double baseline counts in nearly two thirds of patients.^[7] This provides good control of bleeding and may serve as an alternative to splenectomy in some patients.

A recent cost-benefit analysis of these therapies found that the clinical benefit of anti-D was offset by a substantial cost increase.^[8] Although often overlooked in favour of newer agents, a brief course of high-dose prednisolone was an inexpensive and effective treatment for acute ITP.

Surgical

Splenectomy is rarely indicated in childhood ITP and is only used in the event of life-threatening bleeding, or in children with severe, chronic, unremitting ITP present for 12-24 months with severe symptoms.

Prognosis

• The vast majority of children have completely recovered within 6 months and will go on to have no further problems.
• A small number will develop a chronic thrombocytopenia, but most of these will require no treatment.
• The remainder will be treated as warranted by clinical condition.

Idiopathic thrombocytopenic purpura in adults

Unlike ITP in children, adult ITP does not normally follow an infection and usually has an insidious onset.^[4]

Epidemiology

It is predominantly a disease of women of childbearing age. The prevalence is approximately 9.5 per 100,000 persons.^[9]

Signs and symptoms

As in children, adults with ITP may demonstrate a range of symptoms from none at all through to severe haemorrhage.

Investigations

• FBC.
• Blood film.
• Autoimmune screen to exclude other autoimmune diseases.
• Platelet antibody measurements.
• Thrombocytopenia associated with HIV and hepatitis C viral infections may be clinically indistinguishable from primary ITP and can occur several years before patients develop other symptoms. Routine testing for these infections is recommended in adult patients, regardless of local background prevalence and personal risk factors.^[4]
• Bone marrow aspiration may be carried out if aged >60 years, or if there are atypical features

Differential diagnosis

• Aplastic anaemia.
• Effects of drugs or toxins on bone marrow, eg alcohol.
• Leukaemia.
• Von Willebrand's disease.
• Marrow infiltration by secondary tumour.

Management

Adults with ITP, like children, will only require active management if their symptoms are severe enough to warrant it. Any decision to treat should bear the following in mind:

• The extent of bleeding.
• Comorbidities predisposing to bleeding, eg need for major surgery.
• Complications of specific therapies.
• Activity and lifestyle.
• Tolerance of side-effects.
• Potential interventions that may cause bleeding.
• Accessibility of care.
• Patient expectations and worry or anxiety about disease burden.
• Patient need for non-ITP medications that may create a bleeding risk.

Treatment would normally only be initiated in a specialist setting and might include:

• Oral prednisolone.
• Pooled immunoglobulin (acute, not maintenance^[10]).
• Splenectomy - more likely to result in lasting response in adults. Patients post-splenectomy should be vaccinated against Pneumococcus spp., Haemophilus spp. and Meningococcus spp. and should be issued with lifelong broad-spectrum antibiotics.^[11] They should also be advised to purchase an alert bracelet.
• Danazol.
• Immunosuppressive agents, eg ciclosporin.
• Plasmapheresis.
• Numerous other agents are currently undergoing evaluation, eg rituximab and thrombopoietin-like (TPO-like) agents.^[12] Evidence currently suggests approximately 60% of patients respond to rituximab with 40% of those achieving a complete response.^[13]
• The National Institute for Health and Clinical Excellence (NICE) has decided not to recommend the novel therapy eltrombopag (TPO-like), as there appears to be insufficient benefit.^[14]

Management of patients with refractory ITP is difficult. Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody which targets T-cell regulation, is useful in the treatment of these patients, with overall response rates of about 50%.^[15][16]

Prognosis

The natural history of ITP in adults is very variable, depending on the severity of the symptoms and the response to any therapy.