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Mild and Moderate Hemophilia a in Iran: A Clinical Spectrum and Molecular Insights From a Cohort of 110 Patients Including Novel F8 Variants Publisher



Moghadam AA ; Manafzadeh AR ; Nikoonia MR ; Ramezan F ; Abdolkarimi B ; Hamidpour M ; Tabibian S
Authors

Source: Indian Journal of Hematology and Blood Transfusion Published:2025


Abstract

There is limited observational data on mild and moderate hemophilia A (HA). This study aimed to comprehensively characterize the clinical, laboratory, and molecular features of patients with mild and moderate hemophilia A (MHA) using a large Iranian cohort.This single-center study included patients diagnosed with MHA between March 20, 2000, and June 31, 2023. Polymerase chain reaction (PCR) was used to amplify major regions of the F8 gene, including the promoter, all exons, adjacent intronic sequences, and untranslated regions. PCR products were analyzed using Sanger sequencing.A total of 110 patients (63 mild, 47 moderate) were enrolled. The median age at diagnosis was 5 years (interquartile range: 1.25–18.0 years). A positive family history was present in 68 patients (61.8%). The most common bleeding symptoms were hemarthrosis, bruising, and oral mucosal bleeding. FVIII inhibitors were detected in three patients. The most frequent variant was p.Arg2326Gln (c.6977G>A) in 17 patients (15.5%), followed by p.Arg612Cys (c.1834 C>T) and p.Gly439Ser (c.1315G>A), each found in 5 patients (4.5%). Two novel F8 variants were identified: c.3111 A>G and c.5404T>A.To our knowledge, this is the first comprehensive study to evaluate the genotype–phenotype correlations in Iranian patients with MHA. Our findings enhance the understanding of the clinical and molecular landscape of MHA and highlight the potential association between certain genotypes and the development of FVIII inhibitors. © Indian Society of Hematology and Blood Transfusion 2025.
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