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    About 5-10% of patients with autoimmune hemolytic anemia (AIHA) and a negative result on the direct antiglobulin test (DAT) are difficult to diagnose. Most of these patients with AIHA have red blood cell-associated IgG levels below the cut-off value of DAT. Comprehensive diagnosis and classification of DAT-negative AIHA can be made with additional tests of low-affinity IgG and IgA/IgM autoantibodies. However, 17% of patients with DAT-negative AIHA show negative results on all these tests and are diagnosed with "clinically diagnosed DAT-negative AIHA," after excluding other hemolytic anemias and responsiveness to steroids. This percentage can be reduced to 4% if tests are conducted during pretreatment stage. Patients with "clinically diagnosed DAT-negative AIHA" show relatively worse prognosis than patients with low-affinity IgG, and tend to receive treatment in the later stages of the disease. When treating a patient with DAT-negative hemolysis, DAT-negative AIHA should be considered and tested in reference laboratories, especially at pretreatment stage.


    Toyomi Kamesaki. Diagnosis and classification of direct antiglobulin test-negative autoimmune hemolytic anemia]. [Rinsho ketsueki] The Japanese journal of clinical hematology. 2021;62(5):456-462

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    PMID: 34108329

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