Current treatment options for severe autoimmune hemolytic anemia

Dear Editor,

I have read the article of Özdemir et al. (1) published in the final issue of your journal with interest. I primarily congragulate the authors for their efforts. On account of this case presentation, I would like to draw attention to current treatment of severe autoimmune hemolytic anemia (AIHA) in the accompaniment of the literature published in recent years.

In warm antibody AIHA, IgG type antibodies bind to erythrocyte surfaces at 37 °C and cause mostly splenic hemolysis and extravascular hemolysis. The first line treatment for this subtype in current guidelines is steroids. Currently, rituximab is recommended instead of splenectomy which was formerly the second line treatment (2, 3). Use of high dose steroid and intravenous immunoglobulin (IVIG) is recommended in patients with warm antibody AIHA in whom the course is severe and rapid hemolysis develops. Therapeutic plasma exchange (TPE) is recommended in unresponsive patients (2, 4).

In the case presented by the authors, IgM type autoantibodies lead to agglutination and hemolysis of erythrocytes by adhering to erythrocyte surface with complement (C3b) opsonization at low temperature (3–4 °C) in cold antibody AIHA (cold agglutinin disease) which the authors were focused on and which frequently occurs secondary to infections (1, 2, 4, 5). Unlike warm antibody type, hemolysis mostly occurs intravascularly and in the liver. In current treatment of cold agglutinin disease (CAD), primary and preventive tretment consists of enabling the patient to avoid cold environments, warming the patient and rapidly treating the underlying disease and infections. In medical treatment, steroid is not recommended as the first line treatment and splenectomy is not recommended as the second line treatment unlike warm antibody AIHA. The reason for this is the fact that a high rate of steroid unresponsiveness is observed and hemolysis occurs intravascularly and in the liver rather than in the spleen. In current treatment guidelines, rituximab is recommended alone or in association with non-steroid immunosupressive drugs (including fludarabine/cyclophosphamide/azathioprine) as the first line treatment in CAD (2, 4, 5). In severe CAD, TPE is recommended as preventive treatment until these treatments are initiated or if surgery during which hypothermia is predicted to develop, is needed. By way of therapeutic plasma exchange, autoantibodies causing intravascular hemolysis and complements activated by immune complexes can be eliminated and hemolysis can be rapidly stopped for short term (4, 5). In the guideline of the American Society for Apheresis published in 2016, it is recommended that albumin equivalent to 1–1.5 plasma volume should be used as replacement fluid during TPE (4). Again, the same guideline warns that blood may get cold inside the set or filter where plasma is separated while performing TPE in CAD and thus hemolysis may increase. For prevention of this, the room temperature should be increased or the set should be warmed (4). Based on all these aspects, I think that IVIG or TPE could be used alone as the first line treatment instead of high dose steroid in the pediatric patient presented in the article (1). In addition, the first session could be performed with albumin equivalent to 1.5 plasma volume in this pediatric patient who had a severe course, after the decision for this invasive treatment which is generally applied in pediatic intensive care unit and requires en experienced team, was made. Although transfusion was not needed after treatment, I think that at least three sessions of TPE would be appropriate, because signs of hemolysis continued (increased lactate dehydrogenase and decreased haptoglubulin). The authors reported that they discontinued steroid treatment in one week, direct coombs test was negative and the patient had no problem at the follow-up visit performed one month later (1). Considering the shipment date of the article, it is understood that at least two years have passed after the patient’s discharge. Reporting of the developments which have occured during this period and if the patient currently receives medication will be beneficial for us, clinicians.