Description

• Thrombotic thrombocytopenic purpura (TTP) is a severe disorder of abnormal clotting affecting 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; 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 plasma von Willebrand factor–cleaving protease (ADAMTS13)
• Acquired TTP – primary thrombotic microangiopathy with severe ADAMTS13 deficiency
• Hereditary TTP – inherited thrombotic microangiopathy with inherited ADAMTS13 mutations

• 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:
  • Hereditary or acquired
  • Familial, chronic, or relapsing
  • Drug induced:
    • Allergic or immune mediated (quinine, ticlopidine, clopidogrel)
    • Dose-related toxicity (mitomycin C, cyclosporine)
  • Pregnancy, postpartum associated:
    • 10–25% of cases
  • Bone marrow transplantation associated
  • Infection
• Acquired TTP incidence is approximately three cases per one 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; possibly systemic endothelial cell damage results inactivation of coagulation pathway
• May also be due to other autoimmune disorders such as lupus
• 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, and adrenal glands
• Deficiency of vWFcp causes failure of control of coagulation pathway

Risk Factors

• Some cases are genetic/familial
• VWFcp was recently identified as new member of ADAMTS family and designated ADAMTS13
• Mutations in ADAMTS13 gene cause autosomal recessive form of chronic relapsing TTP