Thrombotic Thrombocytopenic Purpura (TTP)

Snapshot

  • A 21-year-old woman with past medical history of SLE presents with fever, fatigue, and altered mental status. On physical exam, a petechial rash is seen on her upper extremities.  Her temperature is 103°F (39.4°C). Her labs are notable for Hgb 7.3 g/dL, platelets 17,000/mm3, and creatinine of 3.4 mg/dL.

Introduction

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  • Thrombotic microangiopathy characterized by a pentad
    • microangiopathic hemolytic anemia
    • acute renal failure
    • thrombocytopenia
    • fever
    • neurologic abnormalities
  • Similar to HUS but with fever and neurologic symptoms
  • Epidemiology
    • female > male
    • most commonly in young adults
  • Pathogenesis
    • deficiency or inhibition of metalloproteinase ADAMTS13  
      • most commonly disabled by an autoantibody 
      • ADAMTS13 degrades vWF multimers 
      • deficiency → large vWF multimers → increased platelet adhesion → platelet thrombosis 
      • important underlying risk factor, but requires a secondary trigger
    • triggers
      • drugs (ticlopidine, clopidogrel, and cyclosporine)
  • SLE

Presentation

  • Symptoms (recall pentad)
    • thrombocytopenia
      • easy bleeding
      • epistaxis
    • neurological symptoms
      • confusion
      • seizures
    • thrombosis
    • renal dysfunction (less so than HUS)
  • Physical exam
    • fever
    • pallor (from anemia)
    • purpura/petechiae
    • jaundice (from hemolysis)
  • splenomegaly

Evaluation

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  • Complete blood count
    • anemia
    • thrombocytopenia
  • Peripheral blood smear
    • schistocytes (helmet cells) 
  • Serum
    • ↑ LDH
    • ↑ creatinine
    • negative Coomb’s
  • ↑ bleeding time
  • normal PT/PTT

Differential Diagnosis

  • DIC 
  • HUS 
  • Sepsis

Treatment

  • Plasma exchange transfusion with fresh frozen plasma
  • Steroids
  • Splenectomy
  • Platelet transfusion contraindicated
  • platelet transfusion will worsen disease by feeding the platelet consumption

Prognosis, Prevention, and Complications

  • Prognosis
    • remission with plasma exchange in majority of patients
    • mortality rate 13-15%
  • Complications
    • permanent neurologic sequelae