Daratumumab interferes with blood compatibility testing. (A) The plasma of daratumumab-treated patients is panreactive in routine serologic tests as a result of binding of daratumumab to endogenous CD38 on reagent red blood cells. This causes positive antibody screen tests and panreactive plasma in erythrocyte panel testing (indirect antiglobulin test). (B) Therefore, daratumumab interferes with the detection of irregular antibodies, which complicates the selection of suitable blood products for the transfusion of daratumumab-treated patients. (C and D) Interference of daratumumab in blood compatibility testing can be abrogated by neutralizing daratumumab in plasma samples from daratumumab-treated patients with (1) an anti-idiotype antibody (mouse-anti-daratumumab antibody) or (2) by denaturation of surface CD38 from reagent red blood cells by using the reducing agent dithiothreitol (DTT). (D) With both methods, underlying allo-antibodies against red blood cells can be identified in the presence of daratumumab.