Crosmatched units: Donor 1 Compatible, Donor 2 Compatible, Donor 3 Compatible, Donor 4 Incompatible. What is the most likely cause of Donor 4 incompatibility?

• A. ABO incompatibility
• B. Antibody to a high-frequency antigen
• C. Antibody to a low-frequency antigen
• D. Hemolyzed sample

Answer: (C)

In crossmatching, incompatibility patterns reflect antibodies in the recipient reacting with donor red-cell antigens. The frequency of the antigen in the donor population shapes which units will be affected. If the recipient has an antibody against a low-frequency antigen, most donor units will lack that antigen and crossmatch as compatible, while the rare unit that does have the antigen will be incompatible. That exactly fits three compatible units and one incompatible unit.

If the problem were ABO incompatibility, incompatibility would be expected with essentially all units of that ABO type, not just one. An antibody to a high-frequency antigen would cause most donor units to be incompatible, leaving only a few rare units lacking that antigen usable, which again doesn’t match three compatible units. A hemolyzed sample would tend to produce unreliable or nonspecific results rather than a clean pattern of a single incompatible donor.