Association between hereditary spherocytosis and gallstone disease: Pathophysiology, diagnosis, and management

Abstract

Hereditary spherocytosis (HS), a common inherited hemolytic anemia, is characterized by red blood cell membrane protein defects leading to chronic hemolysis. This condition significantly predisposes patients to gallstone disease, including both gallbladder and bile duct stones, due to excessive bilirubin production from hemolysis. Gallstones in HS patients, primarily composed of bilirubin, can lead to complications such as cholecystitis, cholangitis, and obstructive jaundice. This review provides a comprehensive landscape of the pathophysiological mechanisms linking HS to gallstone formation, emphasizing the roles of hemolysis, bile composition, and genetic factors. It also discusses the clinical manifestations of gallstone disease in HS, including recurrent jaundice and biliary obstruction, and highlights the diagnostic value of imaging modalities such as ultrasonography and magnetic resonance cholangiopancreatography. Furthermore, current management strategies, including splenectomy, cholecystectomy, and endoscopic approaches for bile duct stones, are examined in the context of HS. By synthesizing existing knowledge, this review aims to provide insights into improving the diagnosis, prevention, and treatment of gallstone disease in patients with HS, while identifying gaps for future research.

Keywords: Bilirubin metabolism; Gallstone disease; Hemolysis; Hereditary spherocytosis; Multidisciplinary management.

Figure 1

Mechanistic diagram of pigment gallstone formation in hereditary spherocytosis.