Thrombotic Thrombocytopenic Purpura

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Basics

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

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:
    • 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

Genetics
  • 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

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Basics

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

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:
    • 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

Genetics
  • 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

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