Autoimmune haemolytic anaemia – diagnosis and treatment

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Abstract

Autoimmune haemolytic anaemia (AIHA) occurs as a result of antibodies directed against self-red blood cell (RBC) antigens, leading to the premature destruction of RBC. RBC destruction may occur within the vasculature, often mediated by the membrane-lysing complex, which is generated upon complement activation or occur extravascularly, within the reticulo-endothelial system that expresses FcγR and C3 receptors that bind antibody and complement coated RBC. The laboratory hallmark of AIHA is a positive direct antiglobulin test (DAT) although it has to be recognized that occasional cases of DAT-negative AIHA may occur. Secondary causes for AIHA such as an underlying autoimmune disorder, infections or malignancies should be considered as part of the investigation process for AIHA.

Immunohaematology investigations for AIHA should always include a DAT using monospecific anti-IgG and anti-C3d. On occasions, further testing with anti-IgA or -IgG subtypes may be necessary. While the DAT provides information on bound RBC antibodies, the indirect antiglobulin test (IAT) using screening and antibody identification cells will provide information on the specificity of circulating antibody. Often this will give a pan-reactive pattern although it is not unusual to identify coincident autoantibodies with defined red cell specificity. Negative IAT with screening and identification cells in the presence of a positive DAT should raise suspicion of drug-induced AIHA. In patients who may have been potentially alloimmunized, further procedures should be performed to exclude the coincident presence of alloantibodies as failure to recognize alloantibodies may result in an immediate or delayed haemolytic transfusion reaction if red cell transfusions are initiated. Elution and auto- or allo-adsorbtion techniques are useful to separate allo- and autoantibodies. Complete red cell phenotyping should be concurrently performed to aid in identifying antibody specificities. Heavily antibody-coated red cells may be difficult to phenotype with some anti-sera, in which case, molecular based red cell genotyping should be initiated. Molecular based red cell typing is also particularly useful where the patient has recently been transfused and the initial red cell phenotype of the patient is not known.

The primary management of the patient with AIHA is amelioration of the underlying condition and suppression of immune mediated haemolysis. This is usually achieved with administration of steroids or immunosuppressive agents. Splenectomy may be an effective second line treatment. Rituximab is increasingly becoming an effective treatment option in patients who are steroid-refractory and not suitable for splenectomy.

Red cell transfusions in patients with AIHA should be undertaken carefully although they should never be denied blood transfusions because of inability to find compatible units. As far as possible, phenotype matched red cells, cross-match compatible with the patient's autoadsorbed serum should be transfused. If coincident alloantibodies are identified, antigen-negative red cells will need to be selected.

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