Warm autoimmune hemolytic anemia and the best treatment strategies

Abstract

Warm autoimmune hemolytic anemia (wAIHA) is characterized by evidence of red blood cell (RBC) hemolysis and a direct antiglobulin test positive for IgG and sometimes complement. While varying with the extent of the compensatory increase in RBC production, symptoms of anemia predominate, as does jaundice, the latter often exacerbated by concurrent Gilbert's syndrome. Initial treatment with corticosteroids is highly effective, with over 85% of patients responding but with less than one-third maintaining that response upon weaning. Subsequent rituximab administration in those failing corticosteroids provides complete remission in over 75% of patients and may be long-lasting. Over 50% of patients failing rituximab respond to erythropoiesis-stimulating agents or immunosuppressive agents. Splenectomy is best deferred if possible but does offer long-term remission in over two-thirds of patients. A number of new treatments for wAIHA (fostamatinib, rilzabrutinib, and FcRn inhibitors) show promise. A treatment algorithm for wAIHA is proposed to avoid the excessive use of corticosteroids.

Graphical abstract

Figure 1.

RBC production and catabolism in states of normal (A) or accelerated (B) RBC turnover. The RBC half-life of 5 to 10 days is simply illustrative. The changes denoted in RBC production and markers of catabolism vary with the extent of RBC turnover.

Figure 2.

RBC surface antigen targets in wAIHA.

Figure 3.

Peripheral blood smear in patient with wAIHA failing splenectomy. Increased numbers of spherocytes (red arrows) and polychromatophilic reticulocytes (black arrows), as well as one RBC with a Howell-Jolly body (green arrow), are indicated.

Figure 4.

Proposed treatment algorithm for wAIHA.