How I treat autoimmune hemolytic anemias in adults

Abstract

Autoimmune hemolytic anemia is a heterogeneous disease with respect to the type of the antibody involved and the absence or presence of an underlying condition. Treatment decisions should be based on careful diagnostic evaluation. Primary warm antibody autoimmune hemolytic anemias respond well to steroids, but most patients remain steroid-dependent, and many require second-line treatment. Currently, splenectomy can be regarded as the most effective and best-evaluated second-line therapy, but there are still only limited data on longterm efficacy and adverse effects. The monoclonal anti-CD20 antibody rituximab is another second-line therapy with documented short-term efficacy, but there is limited information on long-term efficacy and side effects. The efficacy of immunosuppressants is poorly evaluated. Primary cold antibody autoimmune hemolytic anemias respond well to rituximab but are resistant to steroids and splenectomy. The most common causes of secondary autoimmune hemolytic anemias are malignancies, immune diseases, or drugs. They may be treated in a way similar to primary autoimmune hemolytic anemias, by immunosuppressants or by treatment of the underlying disease. IntroductionAutoimmune hemolytic anemia (AIHA) is a rare disease. In a recent population-based study 1 the incidence was 0.8/100 000/year, but the prevalence is 17/100 000. 2 Primary (idiopathic) AIHA is less frequent than secondary AIHA. Secondary cases are often challenging because not only AIHA but also the underlying disease(s) must be diagnosed and treated. AIHA is essentially diagnosed in the laboratory, and considerable improvement has been made in this field. However, progress in treatment has been much slower. [3][4][5][6][7][8] Therapy has been reviewed by several investigators, [8][9][10][11][12][13][14][15] but no treatment guidelines have yet been published. DiagnosisThe diagnosis of AIHA is usually straightforward and made on the basis of the following laboratory findings: normocytic or macrocytic anemia, reticulocytosis, low serum haptoglobin levels, elevated lactate dehydrogenase (LDH) level, increased indirect bilirubin level, and a positive direct antiglobulin test with a broad-spectrum antibody against immunoglobulin and complement ( Figure 1). However, there are pitfalls, particularly in secondary cases, because not always are all of the typical laboratory findings of AIHA present. 15 Two pieces of information are of utmost importance for the clinician to make an appropriate treatment decision: (1) What type of the antibody is involved? (2) Is the AIHA primary or secondary? The type of antibody can be identified with the use of monospecific antibodies to immunoglobulin G (IgG) and C3d. When the red cells are coated with IgG or IgG plus C3d, the antibody is usually a warm antibody (warm antibody AIHA [WAIHA]). When the red cells are coated with C3d only, the antibody is often but not always a cold antibody. For definite diagnosis of a cold antibody AIHA (CAIHA), the cold agglutinin titer should be markedly elevated (Ͼ 1:512)...

Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single‐center experience with 60 patients

“…Consequently, the sole presence of high ANA titers without clinical features of SLE and/or positive anti-DNA antibodies does not discount searching for an underlying lymphoma [19]. Corticosteroids remain the cornerstone of first-line treatment [6,7], but two patients with primary wAIHA were watched only and remained without treatment because they had partially compensated wAIHA with stable and moderate anemia. Beyond corticosteroids, the use of rituximab off-label in the past decade has emerged as the preferred second-line and corticosteroid-sparing option, most often before splenectomy in corticosteroid-dependent wAIHA.…”

“…The management of wAIHA is still mainly empirical and based on expert opinion and corticosteroids remain the cornerstone of therapy [6,7]. However, since 2000, rituximab has been increasingly used as second-or third-line treatment first in children and then in adults [8][9][10][11].…”

Fatal Hematologic Alphabet Soup: A Complicated Case with Overlapping Features of TTP, AIHA, and HLH

“…The initial diagnosis of warm autoimmune hemolytic anemia was supported by a positive direct coombs, laboratory evidence of hemolysis, and by the splenic histology. 80% of patients will have a response to prednisone therapy and of those refractory to steroids, 38-82% responds to splenectomy, suggesting our patient, who was refractory to both, had additional coexisting pathology [1]. Concomitant parvovirus infection and AIHA have been described and most likely parvovirus precipitated the autoimmune phenomena or suppressed the appropriate response in a previously compensated hemolysis [2].…”

Resolution of Serologic Problems Due to Cold Agglutinins in Chronic Lymphocytic Leukemia

“…The autoantibodies may be idiopathic (primary) or secondary to conditions such as infection, malignancy, or immune disease [2]. Cold-antibody mediated hemolytic anemias are further categorized into cold agglutinin disease and paroxysmal cold hemoglobinuria [3].…”