Diagnosis Peripheral blood smear, red blood cell (RBC) fragility assay, RBC autohemolysis assay, and direct antiglobulin (Coombs) test Hereditary spherocytosis or hereditary elliptocytosis is suspected in patients with unexplained hemolysis (as suggested by the presence of anemia and reticulocytosis), particularly if splenomegaly, a family history of similar manifestations, or suggestive RBC indices are present.