Etiology

ADAMTS13 deficiency

Pathophysiology

Mnemonic

ADAMTS13 deficiency → excess vWF → microthrombus formation → blockage of small vessels → RBC fragmentation (hemolysis) and end-organ damage

TTP is a thrombotic microangiopathy, a condition in which microthrombi form and occlude the microvasculature.

1. Autoantibodies or gene mutations → deficiency of ADAMTS13 (a metalloprotease that cleaves von Willebrand factor)
2. ↓ Breakdown of vWF multimers → vWF multimers accumulate on endothelial cell surfaces
3. Platelet adhesion and microthrombosis
4. Microthrombi → fragmentation of RBCs with schistocyte formation → hemolytic anemia
5. Arteriolar and capillary microthrombosis → end-organ ischemia and damage, especially in the brain and kidneys (potentially resulting in acute kidney injury or stroke)

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Clinical features

• Fever
• Neurological signs and symptoms
  • Altered mental status, delirium
  • Seizure, focal defects, stroke
  • Headache, dizziness
• Low platelet count (i.e. thrombocytopenia)
  • Petechiae, purpura
  • Mucosal bleeding
  • Prolonged bleeding after minor cuts
• Microangiopathic hemolytic anemia
  • Fatigue, dyspnea, and pallor
  • Jaundice
• Impaired renal function
  • Hematuria, proteinuria

Mnemonic

The typical patient is a previously healthy adult presenting with mental status changes, fever, petechiae, fatigue, and pallor. Laboratory tests will then indicate hemolytic anemia and possibly acute kidney injury (AKI). Impaired kidney function may not be present, and only a minority of patients will present with all five clinical findings.