What condition is most likely indicated by an antibody screen that is negative at AHG and a direct antiglobulin test that is positive with anti-C3d?

A negative antibody screen at the AHG phase alongside a positive direct antiglobulin test (DAT) with anti-C3d is indicative of cold agglutinin syndrome. In this condition, cold-reactive antibodies (typically IgM type) bind to red blood cells at lower temperatures, leading to agglutination and complement activation. When the sample is warmed, these antibodies may dissociate, which can result in a negative antibody screen during routine testing.

The positive DAT with anti-C3d suggests that complement components are binding to the erythrocytes, which is typical for cold agglutinin syndrome, as the antibodies fix complement at cold temperatures. This scenario is further supported by the fact that the DAT may show a positive result for complement without showing the presence of IgG, which is often associated with warm autoimmune hemolytic anemia or drug-induced hemolytic anemia.

Conditions like warm autoimmune hemolytic anemia generally involve positive findings for IgG, and drug-induced hemolytic anemia often presents with specific drug antibodies, which would not correspond with the negative antibody screen. Paroxysmal cold hemoglobinuria is characterized by a positive DAT with anti-IgG rather than anti-C3d, indicating that the other conditions do