2026 CAMLPR Hematology Practice Test – Comprehensive Exam Prep

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A CBC shows anemia with spherocytes; DAT is 4+ at 37°C; LDH elevated; uBIL elevated. Which diagnosis is most likely?

Cold agglutinin disease

Paroxysmal nocturnal hemoglobinuria

Hereditary spherocytosis

Warm autoimmune hemolytic anemia

Spherocytes with a direct antiglobulin test positive at body temperature points to IgG-coated red cells undergoing extravascular destruction, which is characteristic of warm autoimmune hemolytic anemia. In this disorder, autoantibodies (usually IgG) bind red cells and are removed by splenic macrophages, leading to spherocytes and hemolysis, as reflected by elevated LDH and unconjugated bilirubin. The key distinction is the temperature at which the DAT reacts: a strong 37°C positive result indicates warm-reactive antibodies; cold agglutinin disease involves IgM that binds at lower temperatures and is often detected by DAT with C3d and may not show the same IgG pattern at 37°C. Hereditary spherocytosis can also produce spherocytes, but the DAT is typically negative because there is no autoimmune antibody coating the cells. Paroxysmal nocturnal hemoglobinuria causes hemolysis without a positive DAT, due to complement-mediated destruction of PNH clones.

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