Thrombotic Thrombocytopenic Purpura

Basics

Description

  • Thrombotic thrombocytopenic purpura (TTP) is a severe disorder of widespread microvascular thrombosis resulting in microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and ischemia
  • Affects multiple organ systems
  • Classically characterized by pentad of:
    • Thrombocytopenia
    • Hemolytic anemia
    • Mild renal dysfunction
    • Neurologic signs
    • Fever
  • Uncommon to see all 5 features in a single patient (<10%); if present, severe end-organ damage or ischemia has likely taken place
  • Thrombocytopenia and hemolytic anemia are the most common features
  • Associated with acquired or congenital deficiency of von Willebrand factor–cleaving protease ADAMTS13:
    • Immune (iTTP) primary thrombotic microangiopathy with anti-ADAMTS13 autoantibodies
    • Congenital (cTTP) inherited thrombotic microangiopathy with inherited ADAMTS13 mutations

Classic Course

  • Acute onset
  • Fulminant course lasting days to a few months
  • Nearly always fatal without treatment:
    • >90% mortality without treatment
    • Reverses to >90% survival with modern treatment
  • Clinical presentations include:
    • Congenital or acquired
    • Familial, chronic, or relapsing
    • Drug induced:
      • Allergic or immune mediated (acyclovir, clopidogrel, quinine, quetiapine, ticlopidine)
      • Dose-related toxicity (cyclosporin, mitomycin C, tacrolimus)
    • Pregnancy, postpartum associated:
      • 10–25% of cases
    • Bone marrow transplantation associated
    • Infection (HIV, sepsis)
  • Acquired TTP incidence is approximately 3–4 cases per 1 million adults per year
  • Median age is 41. Range is 9–78
  • Acquired TTP is uncommon in pediatric or geriatric populations
  • Women affected about twice as frequently as men
  • More common in African Americans

Etiology

  • Unknown primary stimulant
  • Idiopathic or due to autoimmune disease, pregnancy, drugs, infection (HIV)
  • May also be due to specific autoimmune disorders such as lupus, RA
  • Platelet aggregation and fibrin deposition occurring in arterioles and capillaries leading to microthrombi and obstruction to blood flow
  • Platelet aggregation leads to:
    • Consumption of platelets
    • Widespread microvascular hyaline thrombotic lesions
  • Microvasculature obstruction with platelet aggregates leads to:
    • Red cell hemolysis
    • Accumulation of heme breakdown products
    • Anemia
  • End-organ ischemia results from diffuse thrombosis in small vessels:
    • Most common in heart, brain, kidney, pancreas, mesentery, and adrenal glands

Risk Factors

Genetics

  • Some cases are genetic/familial
  • Biallelic recessive variants in ADAMTS13 gene cause autosomal recessive form of chronic relapsing TTP

There's more to see -- the rest of this topic is available only to subscribers.