What most likely accounts for pretransfusion testing results showing an autocontrol with a positive reaction?

A positive autocontrol in pretransfusion testing indicates that the patient's serum has antibodies that are reacting with their own red blood cells. This scenario often suggests the presence of a warm autoantibody, which typically reacts at body temperature (37°C). Warm autoantibodies usually result from conditions such as autoimmune hemolytic anemia and can bind to the red blood cells, leading to agglutination in the autocontrol.

In contrast, rouleaux formation can mimic positive reactions, but it is primarily due to increased plasma protein levels, causing red blood cells to stack together—this does not represent an immune-mediated reaction. Cold autoantibodies react at lower temperatures and are less likely to produce a positive autocontrol at 37°C. Multiple alloantibodies would generally show a reaction to specific tested antigens rather than an autocontrol reaction to the individual’s own cells.

Therefore, the presence of a warm autoantibody is the most likely explanation for a positive autocontrol in pretransfusion testing.