What is the diagnosis and treatment approach for Microangiopathic Hemolytic Anemia (MAHA)?

Diagnosis and Management of Microangiopathic Hemolytic Anemia (MAHA)

Microangiopathic hemolytic anemia (MAHA) requires immediate diagnosis and treatment with plasma exchange for TTP cases and complement inhibition for atypical HUS to prevent mortality and irreversible organ damage. 1

Diagnostic Approach

Initial Laboratory Evaluation

• Complete blood count with peripheral smear (looking for schistocytes 1-5%)
• Reticulocyte count
• Lactate dehydrogenase (LDH)
• Haptoglobin (typically low or undetectable)
• Direct antiglobulin test (Coombs test) - negative in MAHA
• Renal function tests (BUN, creatinine)
• Coagulation studies (PT, PTT, fibrinogen)
• ADAMTS13 activity level (critical for TTP diagnosis)

Key Differential Diagnoses

1. Thrombotic Thrombocytopenic Purpura (TTP)

   • Severe ADAMTS13 deficiency (<10%)
   • Pentad: thrombocytopenia, MAHA, neurological symptoms, renal dysfunction, fever
   • Medical emergency requiring immediate intervention 1

2. Hemolytic Uremic Syndrome (HUS)

   • Normal or mildly reduced ADAMTS13 activity
   • Typical HUS: associated with Shiga toxin-producing E. coli (STEC)
   • Atypical HUS (aHUS): associated with complement dysregulation
   • Presents with renal failure, MAHA, and thrombocytopenia 1

3. Cancer-Associated MAHA

   • Common in gastric, breast, prostate, lung cancers, and lymphomas
   • May be the presenting feature of undiagnosed malignancy 2

4. Drug-Induced MAHA

   • Common culprits: chemotherapeutic agents, immunosuppressants (tacrolimus, cyclosporine), quinine/quinidine 1

5. Other Causes

   • Disseminated intravascular coagulation (DIC)
   • Malignant hypertension
   • Pregnancy complications (HELLP syndrome, preeclampsia)
   • Hematopoietic stem cell transplantation

Treatment Approach

Thrombotic Thrombocytopenic Purpura (TTP)

1. Plasma Exchange (PEX)

   • First-line therapy for TTP
   • Begin immediately upon suspicion, don't wait for ADAMTS13 results
   • Continue daily until platelet count normalizes and LDH decreases 1

2. Corticosteroids

   • Methylprednisolone 1g IV daily for 3 days
   • Then transition to oral prednisone with slow taper 1

3. Rituximab

   • Consider for refractory cases
   • Particularly effective for immune-mediated TTP 1

Atypical Hemolytic Uremic Syndrome (aHUS)

1. Complement Inhibition

   • Eculizumab (anti-C5 monoclonal antibody) or Ravulizumab (longer-acting C5 inhibitor)
   • Initiate within 4-8 hours of diagnosis 1, 3
   • Important safety measures:
     • Meningococcal vaccination prior to or concurrent with therapy
     • Antimicrobial prophylaxis with penicillin (or macrolides if allergic) 1

2. Supportive Care

   • Fluid and electrolyte management
   • Blood pressure control
   • Renal replacement therapy if indicated 1

STEC-HUS (Typical HUS)

• Supportive care is the mainstay of treatment
• Avoid antibiotics in suspected STEC infection as they may increase toxin release
• Monitor for complications and provide supportive measures

Cancer-Associated MAHA

• Treatment directed at the underlying malignancy
• Note: Plasma exchange has no proven benefit for cancer-induced TMA 2

Drug-Induced MAHA

• Discontinue the offending agent
• Supportive care
• Note: Plasma exchange has no proven benefit for drug-induced TMA 2

Monitoring and Follow-up

• Regular assessment of platelet count, hemoglobin, LDH levels
• Monitor renal function and neurological status
• For aHUS patients on complement inhibitors:
  • Continue therapy long-term in most cases
  • Monitor for breakthrough hemolysis 1, 3

Important Considerations

• MAHA with thrombocytopenia is a medical emergency requiring rapid diagnosis and treatment
• Distinguish between TTP (ADAMTS13 <10%) and other forms of TMA to guide appropriate therapy
• Avoid inappropriate use of plasma exchange in cancer-induced or drug-induced TMA 2
• Consider genetic testing in aHUS cases, as 60% have detectable mutations in complement proteins 1
• For patients with unexplained MAHA, consider occult malignancy in the differential diagnosis 4

Common Pitfalls

• Delaying treatment while awaiting ADAMTS13 results in suspected TTP
• Misdiagnosing cancer-associated MAHA as TTP, leading to inappropriate plasma exchange
• Failing to recognize drug-induced causes of MAHA
• Not providing meningococcal vaccination and prophylactic antibiotics with complement inhibitor therapy
• Overlooking the possibility of occult malignancy in patients with unexplained MAHA

By following this structured approach to diagnosis and management, clinicians can improve outcomes for patients with this potentially life-threatening condition.