Daratumumab + Isoagglutinin Titers

Daratumumab

Daratumumab (Darzalex, Anti-CD38) is a known troublemaker for Blood Bankers everywhere. It typically causes panagglutination in antibody screens and panels but thankfully does not interfere with Blood Typing (I'm looking at you Anti-CD47/Magrolimab). Daratumumab typically mimics the appearance of a high-titer low-avidity (HTLA) antibody and as a result does not always disappear when moving to less sensitive methods, such as a "non-additive" or "non-enhanced" antibody screen/panel. 

DTT (Dithiothreitol) Testing

The most common method of removing Daratumumab interference is to use DTT (Dithiothreitol). DTT denatures CD38 by disrupting integral disulfide bonds within the CD38 glycoprotein ensuring that Daratumumab (Aka. Anti-CD38) cannot attach to your testing cells (screen and panel) and cause interference. 

ABO Titers

As mentioned before...this does not interfere with ABO/Rh blood typing. But that doesn't mean Dara is completely off the hook just yet. Blood Typing is done at immediate spin with no extra help but cells and antisera. But what if an Anti-A1 or Anti-B titer needs to be performed? Many titer procedures follow the same course whether for an alloantibody or an isoagglutinin. As such, a titer would be prepared using non-enhanced saline only medium. It would then be washed x4, have anti-IgG added, and read as you would anything else. This presents a problem though...if the patient is on Daratumumab, it would be attaching to the A1 reagent red cell you are using for your titer. Upon adding anti-IgG it would bind the Daratumumab bound to the CD38 on the cell and you will visualize the positive reaction. How do you know if it's the Daratumumab reacting or the Anti-A1 reacting? Without modifying your titer procedures, this would present the possibility of over-reporting titer results if you aren't careful. Daratumumab can potentially titer out to the thousands. 

In this specific circumstance, a DTT treated titer would likely be warranted. A study showed the difference between Anti-A1 titers in a patient actively on Daratumumab. The untreated titer went out to >2048 at AHG with the study patient. The DTT treated titer showed a more modest titer of 32 at AHG phase.

Daratumumab makes us have to look at a lot of our procedures differently.