Hereditary Spherocytosis

Hereditary spherocytosis (HS) is an inherited red-cell membrane disorder. Variants affecting ankyrin, spectrin, band 3, or protein 4.2 weaken the connection between the membrane skeleton and lipid layer. The red cell progressively loses surface area, becomes spherical, and cannot deform normally. The spleen retains and removes these cells, producing chronic extravascular hemolysis. Most affected families have autosomal dominant inheritance, but a negative family history does not exclude HS. Expression varies from an incidental laboratory pattern to clinically important anemia, jaundice, splenomegaly, or transfusion dependence. People with northern or central European ancestry are affected more often, but HS occurs in every population. The rapid-recognition pattern is spherocytes with evidence of hemolysis, an appropriate reticulocyte response, and a negative direct antiglobulin test (DAT). Normal hemoglobin does not exclude HS when marrow production compensates for shortened red-cell survival. Spherocytes are not specific to HS, and a DAT result must be interpreted with the film, hemolysis markers, history, and confirmatory testing. The dangerous change is a falling hemoglobin accompanied by an inappropriately low reticulocyte count. That pattern indicates impaired production rather than a simple...