Autoimmune hemolytic anemia: current knowledge and perspectives

Abstract

Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.

A 71-Year-Old Man Presenting with Anemia and a Solitary Skin Lesion Associated with Primary Cutaneous Marginal Zone Lymphoma

“…It is currently estimated that the incidence of AIHA is 1.77 cases per 100,000 per year [2,4]. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of multimorbidity, bone marrow compensatory abilities, and the presence of fibrosis and dyserythropoiesis [6,7]. This clinical case brings forth the possibility of therapy resistant AIHA on the basis of different burdened risk factors such as the presence of lymphoproliferative neoplasm, R-CHOP protocol treatment, 5-year medical history, multimorbidity, age, and absence of medical monitoring and management during last two years.…”

“…This clinical case brings forth the possibility of therapy resistant AIHA on the basis of different burdened risk factors such as the presence of lymphoproliferative neoplasm, R-CHOP protocol treatment, 5-year medical history, multimorbidity, age, and absence of medical monitoring and management during last two years. The aging processes, as well as multimorbidity, increases the probability and severity of oxidative stress and eryptosis, (i.e., erythrocyte cell membrane changes) leading to RBC senescence and premature death [2,6].…”

Epidemiology and Risk Factors of Warm and Cold Autoimmune Hemolytic Anemia

“…AIHA is a relatively rare disease with a currently estimated incidence of 1.77 cases per 100,000 populations per year and 0.2 cases/1,000,000 in individuals under 20 years of age [2]. Old nations which has its age structure changing, having more number of older population like in the U.S., has an estimated incidence of about 2 per 100,000 per year [3].…”

“…Genetic background, immunodeficiency, autoimmune disease, infections, medication -especially novel anti-cancer drugs, neoplasia -especially CLL (5-10% cases) or NHL (13-19%) and transplants are common risk factors suggested based on different studies [2,15,16]. One of the main single risk factor for developing AIHA is ageing.…”

Autoimmune hemolytic anemia in COVID-19 patients, the « transmissible » direct Coombs test

“…These last causes need to be excluded in case of AIHA suspicion. AIHA can be of unknown etiology or secondary to infection (several bacteria and viruses, notably CMV or EBV), neoplasia or immune dysregulation, like autoimmune disorders or immune de iciencies [4,5].…”