What condition does a 17-year-old female with spherocytes and a negative Coomb’s test most likely have?

The presence of spherocytes along with a negative Coombs test strongly indicates hereditary spherocytosis. This condition is characterized by the formation of spherocytes—red blood cells that are sphere-shaped rather than the normal disc shape—which leads to increased destruction in the spleen. The negative Coombs test is particularly relevant here because it rules out autoimmune hemolytic anemia, in which the immune system incorrectly targets and destroys red blood cells, leading to a different hemolytic pattern marked by positive Coombs results.

In hereditary spherocytosis, the underlying defect is usually in the proteins that maintain the red blood cell membrane's structure, leading to these abnormally shaped cells. As a result, patients commonly present with symptoms of hemolytic anemia, such as fatigue, pallor, and possibly jaundice, but the negative Coombs test distinguishes it from other hemolytic processes.

In summary, the combination of spherocytes and a negative Coombs test points clearly to hereditary spherocytosis as the most likely diagnosis.