Identifying haemochromatosis patients with C282Y homozygosity from inpatient electronic patient records in England using a novel algorithm: a retrospective observational study.

Abstract

Hereditary haemochromatosis (HH) is the most common genetic condition among populations of northern European ancestry, but it does not have a specific International Classification of Diseases 10th revision (ICD-10) diagnosis code. HH is commonly assigned the ICD-10 code E83.1 defined as 'disorders of iron metabolism'. However, the E83.1 diagnosis code is also applied to patients with transfusion-related iron overload and hyperferritinaemia from non-iron loading conditions. Venesection is the main treatment option for patients with HH and is assigned the Office of Population, Census and Surveys Classification of Interventions and Procedures, 4th revision (OPCS-4) code X36.2. We aimed to develop a novel algorithm to identify haemochromatosis patients with C282Y homozygosity from electronic patient records (EPR) using ICD-10 and OPCS-4 codes. The Hospital Episode Statistics Admitted Patient Care (APC) database was used to identify all patients with the ICD-10 code E83.1 from 1 April 2018 to 31 March 2023 in our NHS Trust. Case notes were reviewed to evaluate the presence of HH, genotype, medical history and associated procedures. Algorithms were generated using Stata MP V.18 by applying a combination of ICD-10 and OPCS-4 codes to all patients with the diagnosis code E83.1 including those without HH gene mutations. A total of 9264 patient episodes were identified from the HES APC database corresponding to 787 unique patients: 479 (60.9%) C282Y homozygous, 107 (13.6%) C282Y/H63D compound heterozygotes, 42 (5.3%) other HH genetic mutations and 159 (20.2%) without any HH gene mutations. Six algorithms were developed to identify patients with HH within inpatient EPR, all of which showed improved positive predictive value (PPV) compared with the baseline cohort. The application of the OPCS-4 code for venesection (X36.2) in five of the algorithms resulted in large improvements in specificity and increased all their PPVs to >70%. Algorithms 4 and 6 had the best PPV at 74.3% and 74.4%, respectively, and included the removal of patients with ICD-10 codes associated with transfusion-related iron overload and other conditions treated with venesection. These novel algorithms represent a more reliable method to detect haemochromatosis patients with C282Y homozygosity from EPR than the single ICD-10 code E83.1. It may be applied to large administrative datasets for investigation of HH in population studies.