What laboratory test is most appropriate to further investigate antibody-negative hemolytic anemia?

In the context of antibody-negative hemolytic anemia, the osmotic fragility test is particularly appropriate as it assesses the presence of hereditary conditions such as hereditary spherocytosis, which can lead to hemolytic anemia. This test evaluates red blood cell membranes' stability in varying concentrations of saline, helping to determine if there is increased fragility that could explain the hemolytic anemia observed.

While a reticulocyte count would provide information on the bone marrow's response to anemia, it does not specifically clarify the etiology of hemolysis. A bilirubin level could indicate hemolysis if elevated, but it is not diagnostic for the specific type of hemolytic anemia. Coomb's test is used primarily in cases where autoimmune hemolytic anemia is suspected, particularly when antibodies are present, which is not the scenario here given the condition mentioned is antibody-negative. Thus, the osmotic fragility test stands out as the most logical next step in this diagnostic pathway.