Why might a patient's crossmatch be incompatible while the antibody screen is negative?

A patient's crossmatch may be incompatible while the antibody screen is negative if the incompatible donor unit has a positive direct antiglobulin test. This situation can arise when the patient has received a transfusion of red blood cells or has been sensitized in a way that leads to the production of antibodies against the donor cells, even if the pre-transfusion antibody screen is negative.

Typically, the antibody screen is designed to detect clinically significant antibodies that may cause hemolytic transfusion reactions. However, if the donor unit carries red blood cells coated with antibodies (as indicated by a positive direct antiglobulin test), the crossmatch may show that the patient’s serum reacts with the donor cells despite the absence of detectable antibodies in the patient’s serum during the screening. Thus, the presence of antibodies on the donor red blood cell surface (making that blood unit incompatible) could lead to this discordance between the crossmatch and the antibody screen results.

Understanding this concept highlights the importance of performing thorough compatibility testing, including reviewing the direct antiglobulin test results from both the donor and recipient to ensure safe and effective transfusions.