What are the key clinical features to consider when diagnosing hereditary spherocytosis in a patient presenting with anemia?

Key clinical features to consider when diagnosing hereditary spherocytosis (HS) in a patient presenting with anemia include:

• Family history: A positive family history of hemolytic anemia or splenectomy supports the diagnosis, as HS is typically inherited in an autosomal dominant pattern ¹.
• Symptoms of hemolysis: Patients often present with symptoms such as fatigue, pallor, jaundice, and episodes of dark urine due to increased red cell destruction ¹.
• Physical examination findings: Splenomegaly is common due to sequestration and destruction of spherocytes in the spleen ¹.
• Laboratory features: Anemia with reticulocytosis indicating compensatory marrow response; peripheral blood smear showing spherocytes (small, dense, sphere-shaped red cells lacking central pallor) is a hallmark ¹; however, spherocytes can be seen in other conditions, so further testing is required.
• Laboratory confirmation: The eosin-5'-maleimide (EMA) binding test is a sensitive flow cytometric assay recommended by ICSH guidelines for detecting membrane protein defects characteristic of HS (King et al., 2015). Osmotic fragility testing and autohemolysis tests may also support diagnosis but are less specific [1, (King et al., 2015)].
• Additional features: Gallstones from chronic hemolysis and aplastic crises triggered by parvovirus B19 infection may be clinical clues ¹.

In summary, the diagnosis of hereditary spherocytosis in an anemic patient relies on a combination of clinical history, physical findings, characteristic blood smear morphology, and confirmatory laboratory tests such as the EMA binding test, integrating both clinical and laboratory data as per UK guidelines and ICSH recommendations (King et al., 2015) ¹.