Immune thrombocytopenia

Immune thrombocytopenia (ITP), historically known as idiopathic thrombocytopenic purpura, is an autoimmune disorder characterized by a decrease in platelet numbers to <100 x 10⁹/L. In most cases it is a primary condition, i.e. no underlying cause is found.

Terminology

Historically, immune thrombocytopenia was known as immune thrombocytopenia purpura or idiopathic thrombocytopenic purpura. However it was formally renamed 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"

    • cases with a known cause would be known as "secondary ITP"

• the abbreviation "ITP" was kept the same to facilitate consistency between the historic and new medical literature and to avoid confusion; historically, ITP stood for "idiopathic thrombocytopenic purpura", and now stands for immune thrombocytopenia

• the definition of thrombocytopenia has been fixed at a platelet count of <100 x 10⁹/L

  • previously the criteria was <150 x 10⁹/L, however 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 2.2-5.3/10,000/year, whilst in adults the incidence was ~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.

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

  • systemic lupus erythematosus (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

  • 80% of patients exhibit a rapid response, many within 7 days

  • ~65% cases are still in remission a decade post splenectomy 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

• for reasons which remain unclear, patients with primary immune thrombocytopenia seem to have a higher risk of arterial and venous thromboembolism than controls ³

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

History and etymology

The term immune thrombocytopenia was coined by the American hematologist Robert Evans (1912-1974) who was the eponymous discoverer of Evans syndrome ¹¹.