What are the typical presentation and lab findings of a patient with thrombotic microangiopathy (TMA)?

Clinical Presentation and Laboratory Findings in Thrombotic Microangiopathy (TMA)

Patients with thrombotic microangiopathy (TMA) typically present with a triad of microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction, particularly affecting the kidneys. 1 This condition requires prompt diagnosis and management due to its potentially life-threatening nature.

Key Clinical Manifestations

General Presentation

• Purpura (seen in 76.5% of patients) 2
• Neurological disturbances (70.5% of patients) 2 including:
  • Seizures
  • Lethargy
  • Cortical blindness
  • Encephalopathy
  • Motor symptoms
  • Generalized weakness
  • Vision changes 1
• Renal dysfunction (41.1% of patients) 2
• Fever (29.4% of patients) 2

Organ-Specific Manifestations

Renal Involvement

• Hematuria
• Proteinuria
• Elevated creatinine levels 1
• Acute renal failure requiring dialysis in severe cases

Neurological Involvement

• Hypertensive encephalopathy with cerebral edema
• Posterior reversible leukoencephalopathy syndrome (PRES)
• Bilateral and symmetrical hyperintensities of the basal ganglia on brain MRI 1

Cardiac Involvement

• Acute cardiogenic pulmonary edema
• Coronary ischemia 1

Laboratory Findings

Hematologic Parameters

• Thrombocytopenia (platelet count <150,000/mmc or a 25% reduction) 1
• Microangiopathic hemolytic anemia with:
  • Elevated lactate dehydrogenase (LDH) levels
  • Reduced haptoglobin levels
  • Elevated indirect bilirubin
  • Negative direct Coombs test 1
  • Schistocytes (fragmented red blood cells) on peripheral blood smear, though their absence does not exclude TMA 1

Renal Parameters

• Elevated serum creatinine
• Reduced eGFR
• Urinalysis showing hematuria and proteinuria 1

Specialized Testing

• ADAMTS13 activity (severely deficient <10% in thrombotic thrombocytopenic purpura) 1
• Testing for verocytotoxin-producing Escherichia coli (VTEC) in stool samples 1
• Complement studies (for complement-mediated TMA) 1
• Antiphospholipid antibodies (for APS-associated TMA) 1

Differential Diagnosis Algorithm

TMA can be categorized based on underlying etiology:

1. Thrombotic Thrombocytopenic Purpura (TTP)

   • ADAMTS13 activity <10%
   • Often presents with more severe neurological symptoms
   • Can be assessed using PLASMIC score 1

2. Complement-mediated TMA (atypical HUS)

   • Normal ADAMTS13 activity
   • Negative for STEC infection
   • Negative antiphospholipid antibodies
   • May have genetic or acquired complement abnormalities 1

3. Shiga toxin-producing E. coli HUS

   • History of bloody diarrhea
   • Positive stool culture for STEC
   • Typically appears 4-5 days after onset of diarrhea 1

4. Secondary TMA

   • Associated with:
     • Lupus nephritis 1
     • Antiphospholipid syndrome 1
     • Malignancy 3
     • Medications
     • Pregnancy (HELLP syndrome) 1
     • Severe hypertension/malignant hypertension 1

Diagnostic Pitfalls to Avoid

1. Delayed diagnosis: TMA is a medical emergency requiring prompt recognition and treatment to prevent irreversible organ damage.

2. Over-reliance on schistocytes: The absence of schistocytes should not exclude an early diagnosis of TMA due to the low sensitivity of this test 1.

3. Failure to test ADAMTS13 activity urgently: This is essential to distinguish TTP from other forms of TMA 1.

4. Missing secondary causes: Always evaluate for underlying conditions like lupus, malignancy, medications, or severe hypertension 1.

5. Confusing TMA with other causes of thrombocytopenia and hemolysis: Ensure comprehensive workup to rule out other conditions.

By recognizing these clinical and laboratory features promptly, clinicians can initiate appropriate management strategies, which may include plasma exchange, complement inhibitors, or treatment of the underlying cause, ultimately improving patient outcomes and reducing mortality.