A CBC shows RBC agglutination and a positive direct antiglobulin test at room temperature with an anti-I specificity on the antibody screen. Which diagnosis fits best?

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Multiple Choice

A CBC shows RBC agglutination and a positive direct antiglobulin test at room temperature with an anti-I specificity on the antibody screen. Which diagnosis fits best?

Cold agglutinin disease is suggested by RBC clumping together and a direct antiglobulin test that remains positive at room temperature, along with an antibody screen showing anti-I specificity. Here, an IgM cold autoantibody targeting the I antigen binds red cells at cooler temperatures. That binding activates complement, coating the red cells with C3 and causing hemolysis and clumping that you can observe in routine testing. The anti-I specificity is a classic finding in cold agglutinin syndrome, making this the best fit. In contrast, warm autoimmune hemolytic anemia involves IgG antibodies that react at body temperature and typically show an IgG (and sometimes C3) pattern on the DAT, not the anti-I specificity described here. Other antibodies listed would not align with the anti-I cold-reactive pattern, so the anti-I cold agglutinin diagnosis best explains the observed data.

Cold agglutinin disease is suggested by RBC clumping together and a direct antiglobulin test that remains positive at room temperature, along with an antibody screen showing anti-I specificity. Here, an IgM cold autoantibody targeting the I antigen binds red cells at cooler temperatures. That binding activates complement, coating the red cells with C3 and causing hemolysis and clumping that you can observe in routine testing. The anti-I specificity is a classic finding in cold agglutinin syndrome, making this the best fit.

In contrast, warm autoimmune hemolytic anemia involves IgG antibodies that react at body temperature and typically show an IgG (and sometimes C3) pattern on the DAT, not the anti-I specificity described here. Other antibodies listed would not align with the anti-I cold-reactive pattern, so the anti-I cold agglutinin diagnosis best explains the observed data.

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