Immune Thrombocytopenic Purpura

Introduction

Immune thrombocytopenic purpura (ITP) is an acquired condition in which antibodies directed against platelet surface glycoproteins (commonly GPIIb/IIIa) cause accelerated platelet destruction by the reticuloendothelial system, chiefly the spleen. Impaired platelet production, from the same antibodies affecting megakaryocytes, also contributes.¹

ITP is a diagnosis of exclusion: there is no single confirmatory test, and the diagnosis rests on finding isolated thrombocytopenia with no other identifiable cause, after a careful assessment for secondary causes and mimics.

Classification and aetiology

Primary vs secondary

• Primary (idiopathic) ITP - no identifiable underlying cause; the majority of cases
• Secondary ITP - occurring in association with SLE, HIV, hepatitis C, Helicobacter pylori infection, lymphoproliferative disorders (e.g. CLL), common variable immunodeficiency, or certain drugs (e.g. heparin - though heparin-induced thrombocytopenia is a distinct, prothrombotic entity - quinine, some antibiotics)

Childhood vs adult disease

Clinical features

Patients are typically otherwise well, with bleeding manifestations proportional to how low the platelet count has fallen:

• Petechiae - pinpoint, non-blanching red-purple spots, typically on the lower legs
• Purpura and easy bruising
• Mucosal bleeding - epistaxis, gum bleeding, menorrhagia
• Gastrointestinal or urinary bleeding in more severe thrombocytopenia
• No fever, weight loss, bone pain, lymphadenopathy or organomegaly - their presence points away from ITP

Investigations

• FBC - isolated thrombocytopenia, with other cell lines normal
• Blood film - essential, to exclude pseudothrombocytopenia (EDTA-induced platelet clumping - an artefact, not true thrombocytopenia, confirmed by repeating in a citrate tube), and to look for schistocytes (suggesting TTP/HUS/DIC) or blasts (suggesting leukaemia), both of which would exclude a simple ITP diagnosis
• Clotting screen - typically normal in ITP, unlike DIC
• HIV and hepatitis C serology, and consideration of H. pylori testing and autoimmune screen (ANA) if secondary ITP is suspected
• Bone marrow biopsy is not routinely required. It is reserved for atypical presentations - additional cytopenias, systemic symptoms, an unexpected age group, or poor response to first-line treatment - to exclude leukaemia, aplastic anaemia or myelodysplasia before immunosuppressive treatment is given
• Antiplatelet antibody testing is not routinely used, given limited sensitivity and specificity

Differential diagnosis

• Pseudothrombocytopenia - an EDTA sample artefact; always confirm with a citrate sample or blood film before treating a surprising thrombocytopenia result
• Thrombotic thrombocytopenic purpura / haemolytic uraemic syndrome - thrombocytopenia with schistocytes, haemolysis and (in TTP) neurological signs/renal impairment - a medical emergency requiring urgent specialist management, quite different from ITP
• Disseminated intravascular coagulation - deranged clotting and low fibrinogen, unlike the normal coagulation profile in ITP
• Drug-induced thrombocytopenia (including heparin-induced thrombocytopenia, a prothrombotic condition requiring immediate cessation of heparin)
• Bone marrow failure or infiltration (aplastic anaemia, leukaemia, myelodysplasia) - usually with additional cytopenias or abnormal film findings
• Hypersplenism - splenomegaly present, unlike typical ITP
• Gestational thrombocytopenia in pregnancy - mild, incidental, and not ITP

Management

The decision to treat is based on bleeding symptoms and platelet count together, not the count in isolation - many patients, especially children with an asymptomatic low count, need no treatment at all beyond safety-netting advice and monitoring.²

Children

Observation alone is appropriate for most children with no or minor bleeding, even with quite low platelet counts, given the high likelihood of spontaneous resolution. Treatment is reserved for significant bleeding or very low counts with risk factors, using the same options as in adults.

First-line treatment (significant bleeding or low platelet count)

• Oral corticosteroids (e.g. prednisolone) - first line, producing a response in the majority, though relapse after tapering is common
• IV immunoglobulin (IVIG) - produces a faster rise in platelet count than steroids, useful for active bleeding or before an urgent procedure/surgery, though the effect is often temporary
• Anti-D immunoglobulin - an alternative in Rh-positive, non-splenectomised patients

Second-line/chronic disease

• Rituximab - depletes B cells, reducing autoantibody production
• TPO-receptor agonists (eltrombopag, romiplostim) - stimulate platelet production, an important option particularly for chronic/relapsing disease
• Splenectomy - removes the primary site of both antibody production and platelet destruction; effective but now used less often given the efficacy of medical alternatives, and requires the usual pre-operative vaccination and lifelong consideration of hyposplenism risk
• Treat the underlying cause in secondary ITP where identified (e.g. H. pylori eradication, antiretroviral therapy for HIV)

Emergency management of severe bleeding

IV methylprednisolone, IVIG and platelet transfusion together for life-threatening bleeding (e.g. intracranial haemorrhage) - platelet transfusion alone is usually rapidly consumed by ongoing antibody-mediated destruction and is reserved for genuine emergencies rather than used routinely.

Complications

• Intracranial haemorrhage - rare (well under 1%) but the most feared complication, and the main driver of treatment thresholds in severe thrombocytopenia
• Significant mucosal or gastrointestinal bleeding
• Chronic ITP - persistent disease beyond 12 months, more common in adults
• Treatment-related complications - steroid side effects with prolonged courses, infection risk after splenectomy or rituximab

Red flags

Prognosis

Childhood ITP has an excellent prognosis, with the majority of children achieving spontaneous remission within weeks to a few months, and only a minority progressing to chronic disease.² Adult ITP is more often chronic, with many patients requiring ongoing or intermittent treatment over years, though the overall risk of serious bleeding remains low with appropriate monitoring and treatment thresholds.

With modern management - including second-line options such as TPO-receptor agonists and rituximab for those who relapse after steroids - the large majority of patients, both children and adults, achieve good long-term control of bleeding risk, and mortality directly attributable to ITP is low.