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

Treatment of Microangiopathic Hemolytic Anemia (MAHA)

The treatment of Microangiopathic Hemolytic Anemia (MAHA) should be directed at the underlying cause, with plasma exchange and immunosuppression as first-line therapy for thrombotic thrombocytopenic purpura (TTP), which is the most common and life-threatening form of MAHA. 1, 2

Diagnostic Approach

Before initiating treatment, proper diagnosis is essential:

• Obtain blood smear to identify schistocytes, which are characteristic of MAHA 1, 2
• Check laboratory values including complete blood count, LDH, haptoglobin, reticulocyte count, and bilirubin 1
• Test ADAMTS13 activity and inhibitor levels to distinguish TTP from other forms of thrombotic microangiopathy (TMA) 1, 2
• Evaluate renal function, as this helps differentiate between various forms of TMA 1
• Rule out other causes of hemolysis through direct antiglobulin test (Coombs test) 1

Treatment Algorithm Based on Etiology

Thrombotic Thrombocytopenic Purpura (TTP)

For suspected TTP (ADAMTS13 activity <10%):

• Initiate plasma exchange immediately - this is life-saving and should not be delayed while awaiting ADAMTS13 results 1, 2, 3
• Administer high-dose corticosteroids (methylprednisolone 1 g IV daily for 3 days) 1
• Add rituximab early in the treatment course to reduce relapse risk 1, 3, 4
• Consider caplacizumab (anti-vWF nanobody) which reduces time to platelet normalization and decreases early recurrence risk 3
• For refractory cases, consider:
  • Increased frequency of plasma exchange 5
  • Cyclophosphamide, vincristine, or cyclosporine 5
  • Bortezomib or daratumumab for plasma cell-directed therapy 4

Hemolytic Uremic Syndrome (HUS)

• For complement-mediated atypical HUS:
  • Consider eculizumab therapy (900 mg weekly for four doses, then 1,200 mg week 5, followed by 1,200 mg every 2 weeks) 1
  • Supportive care including blood pressure control and renal support 1

Drug-Induced MAHA

• Discontinue the suspected causative agent immediately 1, 6
• Provide supportive care with RBC transfusions as needed 1
• Monitor for recovery, which typically occurs after drug discontinuation 6

Cancer-Associated MAHA

• Treatment should focus on the underlying malignancy 6
• Plasma exchange has no proven benefit in cancer-induced MAHA 6
• Chemotherapy or other cancer-directed therapies are the mainstay of treatment 6

Lupus-Associated MAHA/TMA

• Follow the underlying etiology of TMA as shown in treatment algorithms 1
• Test for ADAMTS13 activity and antiphospholipid antibodies 1
• For lupus nephritis with TMA, consider:
  • Plasma exchange for TTP-like presentations 1
  • Anticoagulation for antiphospholipid antibody syndrome 1
  • Eculizumab for complement-mediated TMA 1

Supportive Care

• RBC transfusions according to existing guidelines; transfuse only the minimum necessary to relieve symptoms or return to safe Hb range (7-8 g/dL) 1
• Folic acid supplementation (1 mg daily) 1
• Monitor hemoglobin levels weekly until treatment is complete 1
• Avoid platelet transfusions in TTP unless life-threatening bleeding occurs, as they may worsen microvascular thrombosis 3

Special Considerations

• Pregnancy: Continue hydroxychloroquine if applicable and start low-dose aspirin before 16 weeks gestation in patients with history of TMA 1
• Pediatric patients: Treatment approach is similar to adults but requires dose adjustments and consideration of growth, fertility, and psychosocial factors 1
• Elderly patients: Consider comorbidities when selecting therapy, particularly with immunosuppressive agents 1

Monitoring and Follow-up

• Regular blood counts to detect worsening cytopenias 1
• For TTP in remission, monitor ADAMTS13 activity regularly and administer rituximab when ADAMTS13 activity falls below 20% to reduce relapse risk 3
• For patients receiving transfusions, monitor for iron overload 1

Common Pitfalls and Caveats

• Delay in diagnosis and treatment of TTP significantly increases mortality; maintain high index of suspicion 1, 2
• Do not wait for ADAMTS13 results before initiating plasma exchange in suspected TTP 2, 3
• Avoid inappropriate use of plasma exchange in cancer-induced or drug-induced MAHA 6
• Be aware that normal serum ferritin does not exclude liver iron loading in patients receiving multiple transfusions 1
• Consider that MAHA may be the presenting feature of undiagnosed cancer 6