Immune thrombocytopenia

Immune thrombocytopenia (ITP) was historically known as idiopathic thrombocytopenic purpura (see Terminology section). It is characterized by an immune-mediated decrease in platelet numbers to <100x10⁹/L and in most cases is primary, i.e. no underlying cause is found.

Terminology

Historically, immune thrombocytopenia was known as immune thrombocytopenia purpura or idiopathic thrombocytopenic purpura. However it was decided to formally rename it in 2007 at the Vicenza Consensus Conference ^1,2.

• "purpura" was removed as bleeding-related symptoms are often lacking
• "idiopathic" was dropped
  • to stress the immune-mediated nature of the condition
    • idiopathic cases would now be known as "primary ITP"
    • if a known cause, would be "secondary ITP"
• "ITP", its abbreviation was kept the same to facilitate consistency between the historic and new medical literature and not to confuse people. Historically, ITP stood for "idiopathic thrombocytopenic purpura", and now stands for immune thrombocytopenia
• the definition of thrombocytopenia has been fixed at <100x10⁹/L
  • previously <150x10⁹/L but this included a large number of 'normal' individuals

Epidemiology

The epidemiological data on immune thrombocytopenia in adults is fairly limited and most studies are of European cohorts. Rates of incidence in children have been estimated as 2.2 to 5.3/10,000/year, whilst in adults ~3.3/10,000/year. Females are more likely than males to develop immune thrombocytopenia and it seems to be more common in older age-groups ^4,5.

Clinical presentation

An increased tendency to bleed is the commonest way to present:

• petechiae: pinprick microhemorrhages with no blanching on exam
  • usually dependent body parts, especially hands and feet
  • platelet count usually <15 × 10⁹/L
• ecchymoses: large areas of bruising ("dry purpura")
• mucosal bleeds: oral mucosa ("wet purpura")
  • associated with systemic hemorrhage, e.g. GI bleeds
• less commonly, other types of bleeding
  • menorrhagia
  • epistaxis
  • bleeding from the gums

In most cases, the bleeding risk is inversely proportional to the platelet count ².

Curiously though, a significant minority of patients remain asymptomatic for years despite very low platelet counts. Greater than 50% cases with platelets of 30-50 × 10⁹/L remain symptom-free ². 

Complications

For reasons which remain unclear, patients with primary immune thrombocytopenia seem to have a higher chance of arterial and venous thromboembolism than controls ³.

Pathology

Etiology

Primary

• most cases are primary, i.e. no known cause ²

Secondary

• infection
  • viruses
    • hepatitis C virus
    • HIV
    • varicella zoster virus (VZV)
    • cytomegalovirus (CMV)
    • COVID-19 ⁷
  • Helicobacter pylori
• autoimmune
  • SLE
  • Wiskott-Aldrich syndrome
  • antiphospholipid syndrome
  • common variable immunodeficiency
• hematological ^2,6
  • chronic lymphocytic leukemia
  • myelodysplastic syndromes
• solid organ malignancy: rare in non-hematological cancers ^8,9
  • common: breast, lung
  • uncommon: renal, ovarian, prostate
• medications 
  • quinine
  • co-trimoxazole
  • vaccinations: diphtheria-tetanus-poliomyelitis, influenza, measles, mumps, and rubella (MMR) ¹⁰
  • NSAIDs
  • acetaminophen

Treatment and prognosis

Initial therapy strategy relies on first-line medication:

• corticosteroids
• intravenous immunoglobulin (IVIG)
• intravenous Anti-Rho(D)

Further management consists of splenectomy and/or second-line drugs

• splenectomy is the most effective treatment for immune thrombocytopenia
  • four out of five exhibit a rapid response, many within 7 days
  • a decade postsplenectomy, ~65% cases are still in remission ²
• second-line agents
  • cyclosporine A, danazol, dapsone, mycophenolate mofetil, rituximab, thrombopoietin receptor agonists
• cytotoxics are now less favored than they were historically, e.g. cyclophosphamide, vinca alkaloids, and azathioprine

Complications

• splenectomy is associated with an elevated risk of infections by encapsulated micro-organisms, so vaccinations for the pneumococcus, Haemophilus influenzae type B and meningococcus advised