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Drs Kulkarni and Wagner are correct that a small number of patients may have AHA but yet not have IgG or C3 detected on their surface by the conventional Coombs antiglobulin test. These patients are diagnosed by more sensitive assays that can detect immunoglobulin, complement components, or both on the cell surface. For example, our radiolabeled antiglobulin test can detect one tenth the number of IgG molecules on the erythrocyte surface that the conventional Coombs test can measure. However, this phenomenon, ie, Coombs'-negative immune hemolytic anemia, is quite rare. More commonly, it appears in the clinical situation of a positive Coombs test result (usually not strongly positive), without evidence for clinical hemolysis. This suggests that in most circumstances the Coombs test is sufficiently sensitive to detect an amount of IgG on the RBC surface necessary to produce hemolysis, ie, an amount of IgG on the RBC surface sufficient
Schreiber AD. The Coombs Test and Autoimmune Hemolytic Anemia-Reply. JAMA. 1983;249(12):1565. doi:10.1001/jama.1983.03330360018014