DTT (Dithiothreitol) is a “thiol reagent” that dissolves disulfide bonds between cysteine amino acids, potentially affecting both red cell antigens and antibodies. Other, less commonly used examples of thiol reagents are 2-mercaptoethanol (2-ME) and 2-aminoethylisothiouronium bromide (AET). DTT was historically used in reference lab settings as a way to distinguish IgM from IgG antibodies. DTT dissolves IgM antibody disulfide bonds and eliminates activity of the antibody. IgG antibodies are generally unaffected. DTT is also used to treat red blood cells to eliminate Kell system antigen activity (the Kell antigens are held together by, you guessed it, disulfide bonds; see the “Kell Kills” video for more details). Some other blood group antigens are also altered by DTT (LW, Lutheran, Yt^a, and Dombrock, to name a few).

In 2015, the U.S. FDA approved the multiple myeloma drug daratumumab, a monoclonal antibody that targets the CD38 antigen on plasma cells. Unfortunately, mature RBCs also carry CD38, so those on this drug will have what appears to be a panagglutinin, easily confused with a warm autoantibody. DTT removes CD38 from the RBC surface, and eliminates the panagglutinin effect, allowing accurate alloantibody screening to occur (though, because DTT eliminates Kell system antigens, the patient should receive K- blood unless the patient is K+). For more info on DARA and DTT, see the BBGuy Essentials Podcast.