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

Treatment of Autoimmune Hemolytic Anemia

For autoimmune hemolytic anemia, first-line treatment is corticosteroids (prednisone 1-2 mg/kg/day for warm antibody AIHA), with escalation to IVIG, rituximab, and/or eculizumab for refractory cases or severe ongoing hemolysis. 1, 2

Diagnostic Workup

• Complete blood count showing anemia, peripheral smear examination for abnormalities, and hemolysis markers (LDH, haptoglobin, bilirubin, reticulocyte count, free hemoglobin) 3, 1
• Direct and indirect antiglobulin test (Coombs test) to confirm autoimmune etiology 1, 2
• Evaluation for potential causes including drug exposure history, glucose-6-phosphate dehydrogenase levels, autoimmune serology, and paroxysmal nocturnal hemoglobinuria screening 3, 1
• Blood chemistry, disseminated intravascular coagulation panel, protein electrophoresis, and cryoglobulin analysis 3
• Assessment for secondary causes including infections, drugs, lymphoproliferative disorders, and immunodeficiencies 4

Treatment Algorithm Based on Severity

Moderate Hemolytic Anemia (Grade 2)

• Oral prednisone 0.5-1 mg/kg/day 3, 2
• Folic acid supplementation 1 mg daily to support increased erythropoiesis 1, 2
• Monitor hemoglobin levels weekly until steroid tapering is complete 1
• Hold any immune checkpoint inhibitor therapy if applicable and consider permanent discontinuation 3

Severe Hemolytic Anemia (Grade 3-4)

• Intravenous methylprednisolone 1-2 mg/kg/day as first-line treatment 3, 1
• Consider hospital admission for close monitoring 3
• Hematology consultation is recommended 3
• RBC transfusion only if symptomatic or hemoglobin <7-8 g/dL in stable patients 3, 1
• If no improvement or worsening while on corticosteroids, permanently discontinue any immune checkpoint inhibitor therapy if applicable 3

Management of Refractory Cases

• If no response to corticosteroids within 1-2 weeks, add intravenous immunoglobulin (IVIG) 0.4-1 g/kg/day for 3-5 days (up to total dose of 2 g/kg) 3, 1
• For ongoing hyperhemolysis, consider eculizumab as a second-line agent 3
• Rituximab (375 mg/m² repeated after 2 weeks) is primarily indicated for prevention of additional alloantibody formation or as treatment for refractory cases 3, 5
• For hemolytic anemia not responding to first-line therapy, consider other immunosuppressive agents such as cyclosporine, mycophenolate mofetil, or azathioprine 1, 2

Special Considerations for Delayed Hemolytic Transfusion Reactions

• For delayed hemolytic transfusion reactions with hyperhemolysis, first-line treatment includes high-dose steroids and IVIG 3
• Avoid further transfusion unless experiencing life-threatening anemia 3
• If transfusion is necessary, extended matched red cells should be considered 3
• Supportive care should include erythropoietin with or without IV iron 3

Monitoring and Follow-up

• Monitor hemoglobin levels weekly until steroid tapering is complete 1
• Patients on long-term steroids should be monitored for complications including hyperglycemia, hypertension, mood changes, insomnia, and fluid retention 1, 2
• Serial monitoring of hemoglobin, hematocrit, reticulocyte count, bilirubin, LDH, and urinalysis for hemoglobinuria is advised 3

Important Pitfalls to Avoid

• Delaying treatment in severe cases can increase morbidity and mortality 1, 6
• IV anti-D should be used with caution as it can exacerbate hemolysis 1, 2
• Incomplete removal of platelets and leukocytes can lead to false-normal enzyme activity levels in diagnostic testing 2
• Failure to recognize and treat underlying causes may lead to treatment resistance 4
• Overlooking complications such as thrombotic events, renal disorders, and infections that can occur during the course of AIHA 7