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, Yta, 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 patients taking this drug (and another anti-CD38 drug approved more recently) will appear to be incompatible with pretty much all screening red cells; we call the pattern of reacting against every test red cell “panagglutination.” DTT can be used in this setting to treat the screening red cells and remove CD38 from their surface. Then when you run the screening tests with the DTT-treated cells, the reactions due to anti-CD38 go away (yay!). This allows us to screen accurately for alloantibodies. There is one caution, though: Since DTT eliminates Kell system antigens as noted above, the patient should receive K- blood unless the patient is K+, since the DTT treatment of our screening RBCs makes us unable to detect antibodies against Kell system antigens. For more info on DARA and DTT, see episode 010 of the BBGuy Essentials Podcast.

Updated January 2024 by Joe Chaffin, MD.

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