What is immune thrombocytopenic purpura (ITP)?

What is Immune Thrombocytopenic Purpura (ITP)?

ITP is an autoimmune disorder in which the immune system produces antibodies and cytotoxic T cells against platelet surface proteins, causing both accelerated platelet destruction and impaired platelet production, resulting in isolated thrombocytopenia (platelet count <100 × 10⁹/L) in the absence of other identifiable causes. 1, 2

Pathophysiology

The disease involves a dual mechanism that represents a paradigm shift from historical understanding:

• Increased platelet destruction occurs when autoantibodies (primarily against glycoproteins IIb-IIIa and/or Ib-IX) bind to circulating platelets, leading to their removal by the reticuloendothelial system through phagocytosis or complement-mediated lysis 1, 2, 3

• Impaired platelet production has been demonstrated in many patients through morphologic megakaryocyte damage, antibody-induced inhibition of megakaryocyte maturation, and normal or decreased platelet turnover—contradicting the older belief that ITP was solely a destructive process 1, 2, 3

• Cytotoxic T-cell involvement adds a cell-mediated component, as these lymphocytes can directly lyse autologous platelets independent of antibody mechanisms 2, 3

Classification

ITP is categorized by both etiology and duration:

• Primary (idiopathic) ITP occurs in isolation without an identifiable trigger, representing the majority of cases 1, 2

• Secondary ITP is associated with other conditions including:

  • Viral infections (HIV, hepatitis C, Epstein-Barr virus) 1, 2
  • Autoimmune disorders (antiphospholipid syndrome, systemic lupus erythematosus) 2, 4
  • Common variable immune deficiency 2
  • Helicobacter pylori infection 2
  • Medications (heparin, quinine, sulfonamides) 2, 4

• Temporal classification divides ITP into newly diagnosed, persistent (3–12 months), and chronic (≥12 months duration) 1

Epidemiology

• The incidence is 2–5 cases per 100,000 population annually 1

• Age-related spontaneous remission rates differ dramatically:

  • Children <1 year: 74% remission 1
  • Children 1–6 years: 67% remission 1
  • Children 10–20 years: 62% remission 1
  • Adults: significantly lower remission rates with chronic disease more common 1

• Adult mortality is 1.3–2.2-fold higher than the general population due to cardiovascular disease, infection, and bleeding complications 1, 2

Clinical Presentation

The bleeding manifestations vary by severity:

• Mild disease presents with skin findings only—petechiae, purpura, and ecchymoses 1

• Moderate disease involves mucosal bleeding including epistaxis, gingival bleeding, gastrointestinal hemorrhage, and hematuria 1

• Severe bleeding occurs in 9.5% of adults and 20.2% of children 1

• Intracranial hemorrhage is the most feared complication but remains rare: 1.4% in adults and 0.1–0.4% in children 1

Diagnosis

ITP is a diagnosis of exclusion requiring three elements: isolated thrombocytopenia, normal peripheral blood smear except for reduced platelets, and absence of other obvious causes of thrombocytopenia. 1, 4

Essential diagnostic steps:

• Complete blood count must show isolated thrombocytopenia without unexplained anemia or leukopenia 1, 4

• Peripheral blood smear review by a hematopathologist is mandatory to exclude pseudothrombocytopenia and identify normal-sized or mildly enlarged platelets 1, 4

• Mandatory infectious testing in all adults includes HIV and hepatitis C serology regardless of risk factors, because these infections can be clinically indistinguishable from primary ITP 2, 4

• Bone marrow examination is generally unnecessary in patients with typical ITP features but is required for:

  • Age ≥60 years (to exclude myelodysplastic syndrome or leukemia) 1, 4
  • Systemic symptoms (fever, weight loss, bone pain) 1, 4
  • Additional cytopenias beyond isolated thrombocytopenia 1, 4
  • Organomegaly or lymphadenopathy on exam 1, 4
  • Prior to splenectomy 1, 4

Treatment Principles

Treatment decisions must be based on bleeding risk rather than platelet count alone. 1

• Observation only is recommended for children with no bleeding or mild bleeding regardless of platelet count, given the high spontaneous remission rate and low risk of serious hemorrhage 1, 4

• First-line treatments when therapy is indicated include:

  • Intravenous immunoglobulin (IVIg) 0.8–1 g/kg as a single dose 1, 4
  • Short-course corticosteroids 1, 4
  • IV anti-D immunoglobulin 50–75 µg/kg for Rh(D)-positive patients 1, 4

Prognosis

• Children have a generally favorable prognosis with high spontaneous remission rates, particularly in younger age groups 1

• Adults are more likely to develop chronic ITP with lower remission rates and require long-term monitoring 1

• Regular monitoring of platelet counts and bleeding symptoms is essential for all patients 1