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Autoimmune hemolytic anemia (AIHA) is caused by autoantibodies with and without complement activation. The risk of thromboembolic complications is often increased. In heat-type AIHA, corticosteroids are considered first-line therapy; in cold-type AIHA, they are not effective, but rituximab is. If there is an association with an underlying disease, its treatment must be clarified.
In cases of AIHA with severe anemia, a blood transfusion may be required initially, although certain safety precautions are advisable.

Haemolytic anaemias are caused by an increased or premature breakdown of erythrocytes and are classified as hyperregenerative anaemias, i.e. they are characterized by a compensatory increase in erythropoiesis with peripheral reticulocytosis [1]. They are divided into the two large groups of corpuscular and extracorpuscular hemolytic anemias. The condition of patients can vary considerably depending on the rate of hemoglobin loss. In addition to the severity of the hemolysis, the course and prognosis depend on the specific causes and their treatment. Autoimmune hemolytic anemia (AIHA) is one of the extracorpuscular, acquired forms of hemolytic anemia. The erythrocytes covered by autoantibodies are destroyed by macrophages. The gold standard for diagnosis is the Coombs test (direct antiglobulin test, DAT) as the basis for classification according to the isotype and thermal characteristics of the autoantibodies [2]. However, a negative Coombs test does not definitively rule out AIHA [2]. Traditionally, antibodies are classified according to their optimal reaction temperature into heat antibodies (optimal temperature 37°C, predominantly IgG) or cold antibodies (optimal temperature 4-30°C, predominantly IgM) [3].

A distinction is made between the following three groups of AIHA [4]:

Autoimmune hemolytic anemia with heat antibodies (especially IgG),
Autoimmune hemolytic anemia with cold antibodies (especially IgM),
Autoimmune hemolytic anemia with mixed or bithermic autoantibodies (Donath-Landsteiner antibodies)

Autoimmune hemolytic anemia with heat antibodies (WAIHA) accounts for around 70% of all cases of AIHA, autoimmune hemolytic anemia with cold antibodies (CAIHA) for 20% and the remainder have mixed or bithermic autoantibodies.

Case 1: WAIHA with indication for blood transfusion

Dr. Gregor Stehle, MD, Senior Physician in the Hematology Department, University Hospital Basel, described the case of a 67-year-old woman with no previous illnesses who showed classic signs of hyperregenerative, hemolytic anemia [5]. A Coombs test and an antibody screening test were carried out to clarify the reason for the hemolysis. Both were positive and the final diagnosis was autoimmune hemolytic anemia of the heat type (WAIHA). If the anemia worsens to a life-threatening degree, blood transfusions may be necessary. However, these are complicated by the presence of autoantibodies. In the present case, a decision was made to transfuse due to the severe anemia. The speaker advised to determine the blood group and rhesus antigens in such cases and to administer the transfusion slowly and under supervision [5].

In terms of treatment options, the administration of corticosteroids is considered standard for WAIHA, e.g. prednisone at a dose of 1.5 mg/kg daily for 2 weeks, followed by tapering over a period of 8-12 weeks [6]. Suppression of autoantibody production, reduction of autoantibody affinity and reduced destruction of erythrocytes by splenic macrophages are cited as mechanisms of action [7,8]. If corticosteroids prove ineffective, the monoclonal anti-CD20 antibody rituximab can be used. Dr. Stehle pointed out that haemolysis is a thrombogenic condition. This is a possible explanation for the acute worsening of a previously slowly progressive dyspnea in the present case [5].

Case 2: CAIHA in the context of lymphoma

In another case example, Dr. Stehle reported on a 67-year-old man who complained of a drop in performance, weakness, night sweats and exertional dyspnoea [5]. He had also lost weight and had jaundice. It turned out that hemolysis was also present here: the hemoglobin was 57 g/l; the reticulocytes were above twice the norm; bilirubin and LDH were elevated. The Coombs test was positive. In comparison to the previous case example, cold antibodies (IgM) were predominantly present. The measurement of the cold agglutinin titer confirmed the suspected diagnosis of autoimmune hemolytic anemia of the cold type (CAIHA). There are two subtypes of cold agglutinin disease:

No primary disease present: CAD = “cold agglutinin disease”
Symptom of a primary disease: CAS = “cold agglutinin syndrome”

Further clarification showed that a lymphoma-associated CAIHA was present. Immunophenotyping by flow cytometry revealed a mature cell clonal B-cell population (82% of all lymphocytes; 58.5% of all nucleated cells; absolute lymphocytes about 15.5 g/l), consistent with B-cell non-Hodgkin’s lymphoma. This patient was recommended treatment with the biologic Rituximab.

Congress: medArt Basel

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