What other features on history and physical exam are suggestive of Hemolytic Uremic Syndrome (HUS) or Thrombotic Thrombocytopenic Purpura (TTP)?

Key Features on History and Physical Exam Suggestive of HUS or TTP

The most important historical and physical examination features suggestive of Hemolytic Uremic Syndrome (HUS) or Thrombotic Thrombocytopenic Purpura (TTP) include prodromal gastrointestinal symptoms, neurological manifestations, and evidence of microangiopathic hemolytic anemia with thrombocytopenia.

Historical Features

Prodromal Symptoms

• Gastrointestinal symptoms:

  • Bloody diarrhea (particularly suggestive of STEC-associated HUS) 1
  • Abdominal pain
  • Vomiting

• Recent infections:

  • History of diarrheal illness within previous 2 weeks (especially in HUS) 1
  • Upper respiratory infections (seen in 20% of HUS cases) 2

• Medication exposure:

  • Recent use of high-risk drugs associated with drug-induced TTP-HUS:
    • Quinine, ticlopidine, clopidogrel (immune-mediated mechanism)
    • Mitomycin C, cyclosporine (dose-related toxicity) 3
    • Chemotherapeutic agents, immunosuppressants
    • Tacrolimus, sirolimus 1

• Neurological symptoms:

  • Headache (more common in TTP)
  • Visual disturbances
  • Altered mental status
  • Seizures (seen in 50% of HUS cases) 4
  • Focal neurological deficits (more specific for TTP, seen in 19% of cases) 4

• Exposure history:

  • Consumption of undercooked ground beef
  • Unpasteurized juice or milk
  • Raw produce (lettuce, spinach, alfalfa sprouts)
  • Contact with animals or their environment 1

Physical Examination Findings

General Appearance

• Pallor (due to anemia)
• Petechiae or purpura (due to thrombocytopenia)
• Jaundice (from hemolysis)

Vital Signs

• Hypertension (common in both HUS and TTP, present in 67% of cases) 2
• Tachycardia (due to anemia)
• Fever (may be present in both conditions)

Neurological Examination

• Encephalopathy (present in 69% of TTP and 68% of HUS episodes) 4
• Focal neurological deficits (more common in TTP)
• Seizures (more common in HUS)

Ophthalmologic Examination

• Advanced retinopathy (particularly in malignant hypertension-associated TMA) 1
• Visual field defects

Renal Manifestations

• Oliguria or anuria
• Hematuria (microscopic or gross)
• Edema (due to renal failure)

Cardiovascular Examination

• Hypertension
• Signs of fluid overload (if renal failure is present)

Distinguishing Features Between HUS and TTP

Features More Suggestive of HUS

• Prodromal bloody diarrhea (especially in children)
• More prominent renal involvement
• History of E. coli O157:H7 or Shigella exposure 2
• Seizures as the predominant neurological manifestation 4

Features More Suggestive of TTP

• More severe neurological manifestations
• Focal neurological deficits 4
• Less severe renal involvement
• Absence of diarrheal prodrome

Important Diagnostic Considerations

1. ADAMTS13 activity:

   • Very low activity levels (<5%) suggest TTP
   • Normal or slightly reduced activity levels suggest HUS or other causes of TMA 1

2. Presence of schistocytes on peripheral blood smear is critical for diagnosis of both conditions 5

3. Severity of thrombocytopenia:

   • TMA associated with malignant hypertension usually has only moderate thrombocytopenia compared to TTP and HUS 1

4. Rate of blood pressure increase appears more important than absolute BP value in development of hypertensive emergencies associated with TMA 1

Clinical Pitfalls to Avoid

1. Failing to consider drug-induced TMA - Always take a thorough medication history 3

2. Delayed diagnosis - High index of suspicion is crucial as delay in identification is associated with increased mortality/morbidity 1

3. Misdiagnosis of hypertension-induced TMA as primary TTP or HUS - The coexistence of severe BP elevation with advanced retinopathy usually helps distinguish this condition 1

4. Missing atypical HUS - Consider complement testing (C3, C4, CH50) in suspected cases without clear diarrheal prodrome 1

5. Overlooking neurological manifestations - Posterior Reversible Encephalopathy Syndrome (PRES) is the most common neuroimaging finding in these syndromes 4