Daratumumab Anti-CD38 Interference with Compatibility Testing


Daratumumab is a monoclonal antibody that binds to CD38 antigen, which is expressed weakly on the surface of all RBCs.  It may thus cause a positive direct antiglobulin test DAT and so interfere with compatibility testing if an antiglobulin phase is required.

This effect may persist up to 6 months after discontinuing the drug.  The monoclonal antibody does not interfere with routine ABO/D typing.

Special techniques (neutralization of CD38 antibodies by CD38 anti-idiotypic antibodies, or soluble CD38 antigen) may remove the panreactivity but are not generally available.  DTT, a sulfhydryl reagent may denature the native CD38 antigen on RBCs but it should be used under a biologic hood.

Kell antigens will be denatured so Kell antibodies cannot be detected after treatment so Kell-negative RBCs should be used.  In the Gulf Area, this is about 72% of RBCs. In the Medinfo software a rule to require K-negative RBCs has been built.


  1. The clinical services must inform Transfusion Medicine of patients who will be receiving daratumumab therapy BEFORE treatment is started.
  2. Transfusion Medicine staff will enter a general comment (i.e. not associated with a particular result) in the patients Medinfo HIIG record:  PATIENT ON DARATUMUMAB.
  3. If not already done, Transfusion Medicine staff will perform an extended antigen typing:  at least C, c, E, e, K, k, Kpa, Jka, Jkb, Fya, Fyb ,M, N, S, s, Lea, Leb, P1—even if no antibodies are currently identified.
  4. Transfusion Medicine staff will send each such patient’s record to a Transfusion Medicine Physician to determine the blood type including extended antigens to match for future transfusions.
  5. When compatibility testing is requested, perform it as per our SOPs.
  6. If available, prepare DTT-treated cells for testing but realize that this will denature Kell antigens.  Use K-nell RBCs.
    1. Medinfo has a rule to automatically require K-negative RBCs if this medication is used.
  7. Release least “incompatible” RBCs must be approved by the Transfusion Medicine Physician.
  8. When the DAT becomes negative (i.e. up to SIX months after cessation of Daratumumab therapy), routine compatibility testing and RBC selection will apply.


Trick or Treatment, Anti-CD38 Reactivity and How to Treat It, AABB Satellite Symposium transcript, U. Cincinnati and RedMedEd, October, 2015 (attachment)