Snapshot A 12-year-old Swedish boy presents to the emergency room for jaundice. He is recovering from a recent upper respiratory infection. He has a history of jaundice as a neonate but no other significant past medical history. On physical exam, he is noted to have splenomegaly and to be mildly jaundiced. Right upper quadrant ultrasound shows gallstones present. Suspicious for a familial hemolytic disorder, the physician orders an osmotic fragility test, which comes back as abnormal. Introduction Overview hereditary spherocytosis is a hereditary disorder characterized by small, round red blood cells (RBCs) without central pallor, resulting in premature removal by the spleen and hemolytic anemia treatment is usually splenectomy Epidemiology Incidence most common cause of hereditary hemolytic anemia in patients of northern European descent Genetics inheritance pattern autosomal dominant mutations multiple mutations implicated, leading to variety of clinical manifestations, ranging from asymptomatic to fulminant hemolytic anemia most commonly caused by spectrin deficiency ETIOLOGY Pathogenesis mechanism intrinsic defect in RBC membrane proteins leading to decreased RBC membrane surface area and increased fragility abnormal RBCs are lysed by the spleen, resulting in extravascular hemolysis Presentation History may have family history of relatives who have undergone splenectomy may have a history of intermittent scleral icterus, jaundice, and dark urine color, often associated with viral infections Symptoms clinical severity varies onset may occur in neonatal period, or in adulthood in the context of environmental stress cholelithiasis may be the presenting sign gallstones are pigmented common symptoms colicky abdominal pain Physical exam inspection splenomegaly jaundice may be triggered by stress, fatigue, pregnancy, or infection pallor dark urine Studies Osmotic fragility test or acidified glycerol lysis test increased fragility Serum labs normocytic anemia ↑ reticulocyte count ↑ bilirubin ↑ mean corpuscular hemoglobin concentration (MCHC) Peripheral blood smear round RBCs (spherocytes) without central pallor Differential Autoimmune hemolysis key distinguishing factor may also present with spherocytes but is Coombs positive Gilbert syndrome key distinguishing factors may also present with jaundice intermittently, but patients often also have abdominal cramps, fatigue, and malaise laboratory studies show normal reticulocyte count and peripheral blood smear Treatment Medical folic acid supplementation indications folic acid is required for continued erythropoiesis folic acid deficiency can result in megaloblastic crisis RBC transfusion indication aplastic crisis Surgical splenectomy indications definitive treatment can be deferred in patients with mild HS (hemoglobin > 11 g/dL) patients must undergo vaccination against pneumococcus and H influenzae prior to splenectomy Complications Parvovirus B19-induced aplastic crisis Cholecystitis Megaloblastic crisis secondary to folate deficiency