RESUMO
OBJECTIVE: To investigate the relationship between the type of Fâ §gene mutation and the development of Fâ § inhibitors in patients with severe haemophilia A (HA). METHODS: The medical records of 172 patients with severe hemophilia A from January 2009 to September 2020 were reviewed. The types of Fâ §gene mutations and the production of factor â § inhibitors were collected and divided into high-risk mutation group ( intron 1 inversions, large deletions, nonsense mutations), low-risk mutation group (missense mutations, small deletions and insertions, splice site mutations) and intron 22 inversions group. The correlation of Fâ §genotype and the production of Fâ § inhibitors in patients with HA were analyzed. RESULTS: Among 172 patients with severe HA, 21 cases(12.21%) developed Fâ § inhibitors. The cumulative incidence of Fâ § inhibitor development was 32%(10/31) in high risk group (75% patients with large deletions, 43% patients with intron 1 inversions, 20% patients with nonsense mutations) and 5%(2/43) in low risk group(6% patients with missense mutations, 5% patients with small deletions or insertions and 0% patient with a splice site mutation) and 9%(9/98) in intron 22 inversions group. Compared with the risk of Fâ § inhibitor development in intron 22 inversions group, the risk of Fâ § inhibitor development in high risk group was higher (ORï¼4.7, 95% CIï¼ 1.7-13.0), the risk of Fâ § inhibitor development in low risk group was equal (ORï¼0.5, 95% CIï¼ 0.1-2.3). Compared with the risk of inhibitor development in low risk group, the risk of Fâ § inhibitor development in high risk group was higher (ORï¼9.8, 95% CIï¼ 2.0-48.7). CONCLUSION: Gene mutations of patients with severe HA in high-risk group which include intron 1 inversions, large deletions, nonsense mutations are a risk factor for Fâ § inhibitor production.