One of ten units crossmatched is incompatible in the antiglobulin phase of testing. Which antibody is most likely to cause this result?

• A. anti-K
• B. anti-D
• C. anti-Fya
• D. anti-Lu^a

Answer: (A)

Incompatibility detected at the antiglobulin phase means an IgG alloantibody in the patient is reacting with a donor red cell antigen that's present on that unit. The Kell system antibody anti-K is a classic, clinically significant IgG antibody that frequently shows reactivity in the antiglobulin test. Kell antigens are highly immunogenic, so anti-K antibodies readily bind to donor cells and are detected by the Coombs reagents used in AHG testing, making them a common cause of AHG-phase incompatibilities in crossmatches. While anti-D can also react at this phase, transfusion practice often avoids D-positive units for D-negative recipients, reducing the likelihood of an AHG mismatch due to anti-D in routine crossmatching. Antibodies to Fya or Lu^a can be AHG reactive as well, but Lu^a is less commonly causing incompatibilities and Fya, while common, is less typically singled out in this specific crossmatch scenario. Therefore, anti-K is the antibody most likely to drive an antiglobulin phase incompatibility.