Case 2: Panreactive Screen in a Patient on Anti-CD38 Therapy
Ms. L is a 66-year-old woman with multiple myeloma receiving weekly daratumumab (last dose 9 days ago) plus lenalidomide. Hemoglobin is 6.9 g/dL and platelets are 34 × 10^9/L. The antibody screen is 3+ panreactive in gel and 3+ panreactive by PEG-IAT tube technique; the autocontrol is 2+; the DAT is 2+ IgG and negative for C3; the eluate is panreactive. Records from 2019 document an anti-E that was never retested. Her red cell phenotype is documented as C-negative, E-negative, K-negative, Jk(a+b+), Fy(a+b-). She has no history of a transfusion reaction. The oncology team wants 2 units today because she is scheduled for a stem cell harvest tomorrow, and the technologist has never worked up a patient on daratumumab.
1. Explain the panreactive antibody screen and describe how you would demonstrate whether a clinically significant alloantibody is hiding underneath it.
Read the worked answer
Daratumumab is a human IgG1κ monoclonal anti-CD38. CD38 is expressed on reagent red cells, so drug in the patient's plasma binds every screen and panel cell and produces panreactivity at the AHG phase. It also coats the patient's own cells - which is why the autocontrol is positive, the DAT is IgG-positive, and the eluate is panreactive. None of this represents an alloantibody.
To unmask a real alloantibody, treat reagent panel cells with 0.2 M DTT (dithiothreitol), which cleaves CD38 from the membrane, then repeat the panel with the patient's plasma. Any reactivity remaining against DTT-treated cells is a genuine alloantibody.
Critical caveat: DTT also denatures Kell, LW, and Yt antigens, so a Kell-system antibody would be missed. This patient is documented K-negative and will receive K-negative units, which closes that gap; RBC genotyping (or KEL-null cells) can close it further if needed.
Her 2019 anti-E must be presumed still present - anti-E is notorious for falling below the limit of detection. She is E-negative by phenotype, so provide E-negative units regardless of what the DTT panel shows.
2. Which units will you select, and how will you perform compatibility testing?
Read the worked answer
Select E-negative, K-negative units, and phenotype-match further (C, c, Jk, Fy) if inventory allows. She is already Jk(a+b+) and Fy(a+b-), so no additional exclusions are mandatory from her phenotype.
Electronic (computer) crossmatch is not permitted: the antibody screen is positive and she has a historical antibody.
A standard AHG crossmatch will look incompatible because of the drug. Two acceptable approaches:
- Crossmatch against DTT-treated donor red cells - removes the CD38 target and lets true incompatibility show.
- Release phenotype-matched units with a documented, medical-director-approved note stating that the AHG crossmatch is uninterpretable owing to daratumumab.
Never report a unit as 'incompatible' without explaining the interference, and never let a positive crossmatch alone push you into giving group O blood when the ABO type is known.
3. She starts oozing from a central line and the team wants blood in the next 15 minutes. What do you do, and what must be documented for the next several months of her care?
Read the worked answer
Do not delay. Give ABO/Rh-specific, E-negative, K-negative units through a blood warmer while the workup continues. Insufficient time is not a reason to switch to group O once ABO is established, and it is never a reason to withhold blood.
Document in the LIS and the chart, and attach an alert to her record:
- 'Antibody screen panreactive due to anti-CD38 (daratumumab); crossmatch interference expected.'
- 'Historical anti-E (2019). Phenotype C-, E-, K-, Jk(a+b+), Fy(a+b-). Transfuse E-negative, K-negative.'
This protects her at every future admission, because the interference will look identical for months after the last dose and someone will eventually mistake it for a new panagglutinin.
Also notify oncology that the drug limits your ability to detect new alloantibodies, and ask them to flag start and stop dates of therapy in the chart. If a new antibody is suspected later, DTT-treated panels and RBC genotyping are your tools.