Abstract
BACKGROUND: Hemophilia A is an X-linked bleeding disorder caused by mutations in the F8 gene, with intron 22 inversion being the most common genetic alteration in severe cases. This study aimed to determine the prevalence of intron 22 inversion in hemophilia A patients in Assam, Northeast India, and evaluate its correlation with disease severity. METHODS: This hospital-based observational study included 80 hemophilia A patients at Assam Medical College from March 2023 to February 2024. Clinical history, coagulation tests (activated partial thromboplastin time (APTT), prothrombin time (PT), and factor VIII assay), and nested long-distance polymerase chain reaction (NLD-PCR) for intron 22 inversion detection were performed. Statistical analysis was conducted using SPSS v25 (IBM Corp., Armonk, New York, USA). RESULTS: Among the 80 patients, 41 (51.25%) had severe hemophilia A, 22 (27.5%) moderate, and 17 (21.25%) mild. Intron 22 inversion was detected in 24 patients (30%), with a significantly higher prevalence in severe cases 22/41 (53.65%) compared to moderate 2/22 (9.09%) and mild cases (0%) (p < 0.001). APTT was significantly prolonged in severe cases (109.35 ± 15.62 sec) compared to moderate (86.92 ± 9.87 sec) and mild cases (61.71 ± 8.94 sec) (p < 0.001), reinforcing the genetic basis of disease severity. CONCLUSION: This study confirms a strong correlation between intron 22 inversion and severe hemophilia A, consistent with global and Indian studies. It emphasizes the need for routine genetic screening for early diagnosis and personalized treatment strategies, including genetic counseling. Future research should explore other F8 mutations, gene therapy, and the role of intron 22 inversion in inhibitor development.