If a major crossmatch and screening cells show 2+ at IS, 1+ at 37°C, and negative at the IAT phase, what is the most likely problem?

The scenario presented suggests that the serological testing is yielding different results at various temperatures, specifically a 2+ reaction at immediate spin (IS), a 1+ at 37°C, and a negative result at the indirect antiglobulin test (IAT) phase. This pattern is indicative of the presence of a cold alloantibody.

Cold alloantibodies are those that react at colder temperatures, usually at IS, and may lose reactivity or decrease in reactivity as the temperature rises, thus showing a weaker reaction at 37°C or being completely negative at IAT where RBCs are typically agitated and warmed. The fact that the IS phase shows a stronger reaction (2+) suggests there is an antibody present that is reacting at cold temperatures, which is consistent with the behavior of cold alloantibodies.

Other options do not accurately explain the observed reactions. A combination of antibodies could lead to varying results, but it would not specifically account for the strong IS reaction and diminishing strength at higher temperatures. Rouleaux, which is the stacking of red blood cells due to plasma protein abnormalities, would typically cause false positives that would not correlate with the temperature-dependent reactivity seen here. Lastly, while test error is always a potential consideration