Is Thrombotic Thrombocytopenic Purpura (TTP) the same as Hemolytic Uremic Syndrome (HUS)?

TTP and HUS Are Different Disorders Within the Thrombotic Microangiopathy Spectrum

No, Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS) are not the same condition, but rather distinct disorders within the thrombotic microangiopathy (TMA) spectrum with different pathophysiological mechanisms, clinical presentations, and treatment approaches. 1, 2

Key Differences Between TTP and HUS

Pathophysiological Mechanisms

• TTP: Characterized by severe deficiency of ADAMTS13 enzyme (<5-10% activity), which leads to accumulation of ultra-large von Willebrand factor multimers and subsequent microvascular thrombosis 2
• HUS: Multiple subtypes with different mechanisms:
  • Typical HUS: Associated with Shiga toxin-producing E. coli (STEC) infection
  • Atypical HUS (aHUS): Results from dysregulation of the alternative complement pathway due to genetic mutations or autoantibodies 1
  • Secondary HUS: Triggered by medications, pregnancy, malignancy, or infections 1

Clinical Presentation

• TTP:

  • Neurological manifestations predominate (occurs in majority of cases)
  • Pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological abnormalities, renal dysfunction, and fever
  • Less severe renal involvement compared to HUS 2

• HUS:

  • Renal manifestations predominate
  • In typical HUS: Prodromal bloody diarrhea (usually 4-5 days before HUS onset) 1
  • In atypical HUS: May present without diarrhea; can have neurological involvement (10-20% of cases) 1
  • Triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury 1

Laboratory Findings

• TTP: ADAMTS13 activity severely reduced (<5-10%)
• HUS: Normal or mildly reduced ADAMTS13 activity 2
• Both: Share findings of microangiopathic hemolytic anemia (schistocytes, elevated LDH, reduced haptoglobin) and thrombocytopenia 1, 2

Diagnostic Approach

When presented with a patient showing signs of TMA (microangiopathic hemolytic anemia and thrombocytopenia):

1. Test ADAMTS13 activity urgently 1

   • If <10% → TTP diagnosis
   • If normal or mildly reduced → Consider HUS or other TMA causes

2. For HUS diagnosis:

   • Test for STEC/verocytotoxin in stool (typical HUS) 1
   • Evaluate complement pathway components (atypical HUS)
   • Consider triggers like medications, pregnancy, malignancy (secondary forms)

Treatment Approaches

• TTP: Plasma exchange with fresh frozen plasma is the cornerstone of treatment 3
• Typical HUS: Primarily supportive care; antibiotics generally not recommended 4
• Atypical HUS: Complement inhibition with eculizumab/ravulizumab 1

Clinical Pearls and Pitfalls

• Diagnostic pitfall: Not all HUS cases present with the complete triad of hemolytic anemia, thrombocytopenia, and renal involvement at onset 1
• Age considerations: Typical HUS is more common in children, while acquired TTP is more common in adults 5
• Schistocytes: While presence of >1% schistocytes supports TMA diagnosis, their absence should not exclude early TMA diagnosis due to low test sensitivity 1
• Neurological involvement: While more common in TTP, it can occur in 10-20% of aHUS cases 1

Emerging Concepts

Recent research suggests complement hyperactivation may be a common pathogenic pathway in both TTP and various forms of HUS, which may explain some clinical overlap and potential therapeutic targets 6