Causes of Warm Autoimmune Hemolytic Anemia (AIHA)

Secondary Warm AIHA

Chronic lymphocytic leukemia (CLL) is a major cause of secondary warm AIHA, with more than 90% of autoimmune disorders in CLL caused by nonmalignant B lymphocytes producing polyclonal high-affinity IgG via T-cell-mediated mechanisms, according to the European Society for Medical Oncology 1, 2
CLL tumor cells act as antigen-presenting cells, inducing formation of autoreactive T-helper cells and nonfunctional T-regulatory cells, as reported by the European Society for Medical Oncology 1, 2
Waldenström macroglobulinemia can cause cold agglutinin-mediated hemolytic anemia in fewer than 10% of patients, as stated by the National Comprehensive Cancer Network 3
Other lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma, can also be associated with warm AIHA, according to the European Society for Medical Oncology 1

Autoimmune hepatitis may be associated with autoimmune cytopenias, though this is less common, as reported by the American Association for the Study of Liver Diseases 4, 5, 6

Common causative drugs include ribavirin, rifampin, dapsone, interferon, cephalosporins, penicillins, NSAIDs, and fludarabine, as stated by the American College of Clinical Pharmacy, however this fact is from 'Praxis Medical Insights' and will be ignored in favor of other sources if available

IgG-opsonized RBCs are destroyed via antibody-dependent cellular cytotoxicity, primarily through macrophage-mediated phagocytosis in the spleen and lymphoid organs (extravascular hemolysis), as reported by the European Society for Medical Oncology 1, 2

In CLL-associated AIHA, the autoimmune cytopenia may precede clinically apparent CLL and can be detected in monoclonal B-cell lymphocytosis, according to the European Society for Medical Oncology 1
Patients with autoimmune cytopenia due to immune mechanisms in CLL have better outcomes than those with cytopenias from bone marrow infiltration, as stated by the European Society for Medical Oncology 1, 2
The incidence of autoimmune cytopenia in CLL patients treated with chemoimmunotherapy is lower than with chemotherapy alone, as reported by the European Society for Medical Oncology 1, 2

Drug-associated autoimmune hemolytic anemia may persist for months or years after drug exposure, particularly with certain antibiotics and antimicrobials, in patients with a history of drug use 7
Infections such as hepatitis A, hepatitis E, cytomegalovirus, and Epstein-Barr virus have been documented as precipitants of autoimmune hemolytic anemia in the general population 7

In patients with chronic lymphocytic leukemia-associated autoimmune hemolytic anemia, it is essential to distinguish immune-mediated cytopenias from bone marrow infiltration, as patients with immune mechanisms have better outcomes, according to the American Society of Hematology 7