Although emergency and general measures for warm antibody autoimmune hemolytic anemia (AIHA) and AIHA due to cold agglutinin disease (CAD) are similar, specific therapies available for warm AIHA are not effective for CAD. Therefore, the preliminary identification of the type of antibody involved in each case is particularly relevant, according to a recently published article in Clinical and Experimental Medicine.

The authors aimed to conduct a general review and analysis of the treatments for warm AIHA and CAD, separating them into emergency measures, general measures, and specific therapies.

Blood cell transfusions and prophylaxis against thromboembolism with low-molecular-weight heparin may be required in a hemolytic crisis in both warm AIHA and CAD. Other emergency measures, such as intravenous immunoglobulin transfusion and plasma exchange, also have proven efficacy in both types of AIHA.

Continue Reading

However, measures such as high-dose steroid therapy and emergency splenectomy are not recommended in CAD; instead, complement inhibitors are preferred. 

Read more about CAD complications

General measures, such as folic acid supplementation to prevent folate deficiency due to hemolysis-induced erythropoiesis and the use of proton pump inhibitors to prevent bleeding due to peptic ulcer disease, are considered necessary in both cases, as are anticoagulant and antiplatelet therapies for patients over the age of 60 years.

Specific therapy varies greatly depending on the type of AIHA. Most drugs used in warm AIHA are useless in CAD, including steroids, azathioprine, or cyclophosphamide. However, the drug rituximab, used in warm AIHA treatment, constitutes first-line therapy for CAD. The combination of rituximab and bendamustine has been proven to be more effective and have fewer adverse effects than alternative therapies.

“Preliminary identification of the type of antibody involved in the genesis of the disease and careful exclusion of a secondary form are particularly important. Rituximab plays a central role in the treatment of primary warm AIHA and AIHA from CAD,” the authors concluded.


Fatone MC, Cirasino L. Practical therapy for primary autoimmune hemolytic anemia in adults. Clin Exp Med. Published online August 18, 2022. doi:10.1007/s10238-022-00869-2