Thrombotic Microangiopathies - TMA

Thrombotic Microangiopathies - TMA

 

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are thrombotic microangiopathies associated with hemolysis and renal and neurologic dysfunction in adults and children.

Epidemiology

  • Incidence – 4-10/1,000,000
  • Age
    • TTP – almost exclusively in adults except for inherited forms
    • HUS – bimodal distribution in children and older adults
  • Gender – equal distribution

Risk Factors

  • TTP
    • Autoimmune disorders
    • Black race
    • Certain drugs (e.g., quinine)
    • Malignancy (e.g., lymphoma)
    • Obesity
    • Pregnancy
  • HUS
    • Gastroenteritis – specifically highest risk with E. coli 0157:H7, although S. dysenteriae and other toxin-producing species are also a risk factor
    • Use of antimotility drugs or antibiotics during the course of above diarrheas

Pathophysiology

  • Characterized by systemic or intrarenal aggregation of platelets leading to the hallmark thrombocytopenia
  • Microvascular aggregation leads to organ ischemia
  • TTP associated with severe deficiency of ADAMTS13 (von Willebrand factor cleaving protease)

Clinical Presentation

  • TTP
    • Nonspecific symptoms – nausea, vomiting, diarrhea, abdominal pain, weakness, fever
    • Hallmark of the presentation is hemolytic anemia and thrombocytopenia
    • Neurologic – confusion, fluctuating neurologic deficits, seizures, coma
    • Renal – renal insufficiency, hematuria
  • HUS
    • Oliguria
    • Thrombocytopenia
    • Microangiopathic hemolysis
    • Acute renal failure

Diagnosis

  • Laboratory testing
    • Complete blood count demonstrating thrombocytopenia and anemia
    • Peripheral smear – evidence of hemolysis, including schistocytes, helmet cells and reticulocytes
    • BUN/creatinine – elevated
    • Indirect evidence – elevated indirect bilirubin, negative Coombs testing, elevated lactate dehydrogenase (LDH)

Differential Diagnosis

  • Acute renal failure
  • Adverse drug reaction
  • Disseminated malignancy
  • Disseminated intervascular coagulation (DIC)
  • Heparin-associated antibody syndrome
  • Malignant hypertension
  • Pregnancy-related TMA
  • Sepsis
  • Stroke

Treatment

  • TTP
    • Mainstay is plasma exchange, begun early in the disease course
      • Mortality approaches 90% in untreated patients
  • HUS
    • Supportive

See Also