10-Year Risk of Gallstones in Congenital Red Blood Cell Disorder Patients: A Nationwide Cohort Study

Am J Hematol. 2025 Feb;100(2):229-235. doi: 10.1002/ajh.27558. Epub 2024 Dec 9.

Abstract

Chronic hemolysis potentially elevates the risk of gallstones in several types of congenital red blood cell (RBC) disorders. However, the magnitude of the risk is unknown. We investigate the risk of gallstone disease in congenital RBC disorder patients, compared with general population comparators. Patients were identified from the Danish National Patient Registry covering all Danish hospitals and the National Reference Laboratory for RBC disorders during 1980-2016. Patients were matched by sex, age, and region of origin with up to 50 general population comparators. Gallstone events were identified using hospital-registered diagnoses and surgery codes. Our study included 9354 congenital RBC disorder patients, grouped according to type of congenital RBC disorder, and 416 994 general population comparators. The cumulative 10-year incidence of gallstone disease was 4.2% in patients with congenital RBC disorders and 1.7% among comparators. Adjusted csHR's [95% confidence interval] were 8.1 [6.8, 9.7] for hereditary spherocytosis; 3.3 [1.6, 6.8] for glucose-6-phosphate dehydrogenase deficiency; 21.6 [10.6, 44.1] for pyruvate kinase deficiency; 3.7 [1.9, 7.0] for sickle cell disease; 0.8 [0.4, 1.6] for sickle cell trait; 1.5 [1.1, 2.2] for α-thalassemia trait; 1.8 [1.4, 2.3] for β-thalassemia minor; and 2.1 [1.8, 2.6] for other congenital hemolysis. We found a markedly higher risk of hospital-registered gallstone diseases in nearly all groups of patients with congenital RBC disorders compared with the general population.

Keywords: Congenital red blood cell disorders; chronic hemolysis; gallstones.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia, Hemolytic, Congenital Nonspherocytic / complications
  • Anemia, Hemolytic, Congenital Nonspherocytic / epidemiology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Gallstones* / complications
  • Gallstones* / epidemiology
  • Glucosephosphate Dehydrogenase Deficiency / complications
  • Glucosephosphate Dehydrogenase Deficiency / epidemiology
  • Humans
  • Incidence
  • Infant
  • Male
  • Middle Aged
  • Pyruvate Kinase / deficiency
  • Pyruvate Metabolism, Inborn Errors / epidemiology
  • Registries
  • Risk Factors
  • Spherocytosis, Hereditary / complications
  • Spherocytosis, Hereditary / epidemiology
  • Young Adult
  • alpha-Thalassemia / complications
  • alpha-Thalassemia / epidemiology
  • beta-Thalassemia / complications
  • beta-Thalassemia / epidemiology

Substances

  • Pyruvate Kinase

Supplementary concepts

  • Pyruvate Kinase Deficiency of Red Cells