Demography, annual incidence, and risk factors of inhibitors for pediatric hemophilia A in Basra Center for Hereditary Blood Diseases

Abstract

Background: Hemophilia A is a rare X-linked congenital bleeding disorder characterized by a tendency to bleed. This is the primary tendency of the disorder, with most of the bleeding occurring internally into the joints. A significant complication of hemophilia treatment is the development of neutralizing antibodies against factor VIII replacement therapy, known as inhibitors. Aim: This study aimed to investigate the demography of pediatric hemophilia A patients at the Basra Center for Hereditary Blood Diseases and assess the annual incidence of positive inhibitors and their associated risk factors. Methods: A descriptive, retrospective, registry-based study was conducted for hemophilia A patients registered at the Basra Center for Hereditary Blood Diseases from October 2018 to October 2023. A total of 110 males aged < 1 year to £ 15 years, with a median age of 8.7 ± 3.8 years, were included in this study. Patient Information collected included the date of birth, age at diagnosis, severity of disease, symptoms at diagnosis, quantitative inhibitor levels, and risk factors for inhibitor development. Results: In this study, 46 patients (42%) were ≥10 years old, and 53 patients (48.1%) were diagnosed between 1–5 years. Among the hemophilia A patients, between one year and five years, 48 (43.7%) had moderate severity. The primary symptom at diagnosis was postoperative bleeding in 29 patients (26.3%), followed by mucocutaneous bleeding in 26 patients (23.7%). A total of 22 out of 110 (20%) patients developed inhibitors, with 21 of these (95.5%) classified as high-titer, predominantly in severe hemophilia A patients with factor VIII levels < 1 (12/22 patients, 54.5%). The annual incidence of inhibitors decreased over the last five years from 46 to 13 (registered patients/year) and from 18 to 2.7 (examined patients/year). Severity of disease, family history of positive inhibitors, age at first exposure to factor VIII therapy, history of intensive factor VIII treatment, and type of factor VIII replacement were statistically significant correlates of inhibitor development. Conclusions: The annual incidence of inhibitor development has decreased over the last five years. Severity of disease, family history of positive inhibitors, age at first exposure to factor VIII therapy, history of intensive factor VIII treatment, and type of factor VIII replacement are significant risk factors for inhibitor development.