What is the treatment for hemolysis, specifically autoimmune hemolytic anemia?

Treatment of Autoimmune Hemolytic Anemia

For autoimmune hemolytic anemia, initiate corticosteroids immediately as first-line therapy: prednisone 1-2 mg/kg/day orally for moderate cases (Grade 2) or intravenous methylprednisolone 1-2 mg/kg/day for severe cases (Grade 3-4), with addition of IVIG 0.4-1 g/kg/day for 3-5 days if no response within 1-2 weeks. 1, 2

Severity-Based Treatment Algorithm

Grade 1 (Mild): Hemoglobin < LLN to 10.0 g/dL

• Continue close monitoring with weekly hemoglobin checks and hemolysis markers (LDH, haptoglobin, bilirubin, reticulocyte count). 1, 2
• Add folic acid 1 mg daily supplementation to support erythropoiesis. 1, 2
• No immunosuppression required at this stage. 1

Grade 2 (Moderate): Hemoglobin < 10.0 to 8.0 g/dL

• Start oral prednisone 0.5-1 mg/kg/day immediately. 1, 2
• Add folic acid 1 mg daily. 1, 2
• Monitor hemoglobin weekly and track hemolysis markers to assess response. 2, 3
• Expected response rate is 70-80% for warm autoimmune hemolytic anemia. 2

Grade 3-4 (Severe): Hemoglobin < 8.0 g/dL or transfusion-dependent

• Admit to hospital immediately and consult hematology stat. 1, 3
• Start intravenous methylprednisolone 1-2 mg/kg/day as first-line therapy. 1, 2
• If no improvement within 1-2 weeks or clinical deterioration, add IVIG 0.4-1 g/kg/day for 3-5 days (up to total dose of 2 g/kg). 1, 2, 4
• Transfuse RBCs only if symptomatic or hemoglobin < 7-8 g/dL in stable patients—avoid over-transfusion as it suppresses endogenous erythropoiesis. 1, 2, 3
• Use extended antigen-matched red cells (C/c, E/e, K, Jka/Jkb, Fya/Fyb, S/s) if transfusion is necessary to minimize alloimmunization risk. 1, 4

Diagnostic Workup Before Treatment

Complete the following tests to confirm diagnosis and exclude secondary causes:

• Direct antiglobulin test (DAT/Coombs test) with monospecific antisera to differentiate immune from non-immune hemolysis. 2, 3, 5
• Hemolysis markers: LDH, haptoglobin, indirect bilirubin, reticulocyte count, free hemoglobin. 1, 2, 3
• Peripheral blood smear for spherocytes, schistocytes, or other morphologic abnormalities. 2, 3
• Glucose-6-phosphate dehydrogenase level to exclude enzymatic deficiency. 1, 3
• Autoimmune serology and paroxysmal nocturnal hemoglobinuria screening. 1, 2, 3
• Comprehensive drug exposure history (ribavirin, rifampin, dapsone, cephalosporins, penicillins, NSAIDs, quinolones). 1
• Protein electrophoresis and cryoglobulin analysis to exclude lymphoproliferative disorders. 1

Refractory Cases and Second-Line Options

If no response to corticosteroids plus IVIG after 2-4 weeks:

• Rituximab 375 mg/m² weekly for 4 weeks is the preferred second-line agent, particularly for prevention of additional alloantibody formation in patients requiring future transfusions. 1, 4
• Consider other immunosuppressive agents: cyclosporine, mycophenolate mofetil, or azathioprine for steroid-refractory cases. 2
• For delayed hemolytic transfusion reactions with hyperhemolysis (particularly in sickle cell disease), escalate to eculizumab 900-1200 mg weekly if clinical deterioration continues despite steroids and IVIG. 1
• When using eculizumab, administer meningococcal vaccination (MenACWY and MenB) immediately and start ciprofloxacin prophylaxis to prevent meningococcal infection. 1

Critical Monitoring During Treatment

• Monitor hemoglobin weekly until steroid tapering is complete. 2, 3
• Track reticulocyte count to confirm bone marrow response—relative reticulocytopenia suggests hyperhemolysis. 4, 3
• Assess hemolysis markers (LDH, haptoglobin, bilirubin) to gauge treatment response. 2, 3
• Monitor for steroid-related complications: hyperglycemia, hypertension, mood changes, insomnia, fluid retention. 2
• In transfusion-dependent patients, monitor ferritin levels regularly and consider liver MRI to assess iron deposition; initiate iron chelation if systemic iron loading develops. 3

Critical Pitfalls to Avoid

Never delay treatment in severe cases (Grade 3-4)—this directly increases mortality. 2, 3 Start intravenous methylprednisolone immediately upon diagnosis of severe hemolysis. 1

Never use IV anti-D in autoimmune hemolytic anemia—it can exacerbate hemolysis and worsen outcomes. 2, 3

Avoid transfusing additional blood in hyperhemolysis without concurrent immunosuppressive therapy, as this can worsen hemolysis and potentially cause multiorgan failure and death. 4 This is particularly critical in delayed hemolytic transfusion reactions in sickle cell disease patients. 1

Do not over-transfuse—transfuse only to hemoglobin 7-8 g/dL in stable patients to avoid suppressing endogenous erythropoiesis and increasing alloimmunization risk. 2, 3

Recognize that DAT-negative autoimmune hemolytic anemia exists (2-4% false negative rate)—diagnosis is supported by exclusion of other causes of hemolysis and response to steroids. 6, 7

Special Considerations

Serological Subtypes with Higher Severity

Certain subtypes are associated with lower hemoglobin, higher transfusion needs, and increased mortality: warm AIHA with complement-positive DAT, mixed AIHA, and atypical AIHA. 8 These patients require more aggressive monitoring and earlier escalation to second-line therapies.

Secondary AIHA

Always investigate for underlying causes through careful history and targeted testing: lymphoproliferative disorders (ultrasound/CT, bone marrow evaluation), immunodeficiencies (immunoglobulin levels), systemic autoimmune diseases (autoantibody screening), infections, and malignancies. 7 Treatment of the underlying condition is essential alongside immunosuppression.

Pregnancy

AIHA in pregnancy is usually manageable with corticosteroids and IVIG, though refractory cases have been described requiring close maternal-fetal monitoring. 7