Daratumumab Causes a Positive Indirect Antiglobulin Test Strategies for Transfusion Medicine

A new human IgG monoclonal antibody against CD38 (daratumumab) for treatment of multiple myeloma was recently approved by FDA and is currently in evaluation process by EMA for granting a marketing authorization in Europe. During clinical studies daratumumab caused a positive indirect antiglobulin test but a negative direct antiglobulin test of the autologous red cells. This reaction pattern indicates the presence of an alloantibody against a high frequent antigen and typically prompts sophisticated laboratory work up and a delay in issuing of red cell concentrates. Therefore the following measures are required: i) establishing awareness of this phenomenon and mandatory information of the laboratory about daratumumab treatment, ii) creating appropriate laboratory maneuvers to overcome this problem. Three laboratory methods are available to solve daratumumab interference with red blood cell serology tests, of which pretreatment of red cells with dithiothreitol (DTT) is currently the most practicable.