الفهرس | Only 14 pages are availabe for public view |
Abstract Background : The development of alloantibodies (inhibitors) against the transfused factor VIII in Hemophilia A patients is the most serious therapy complication. The pathophysiology of their formation is still unknown. Many cytokines, including tumor necrosis factor-Ü (TNF-Ü), may play a role in the perpetuation of such complication. Aim of the Work: The aim of this study is to evaluate the influence of TNF-Ü gene polymorphism (308G/A) on the development of FVIII inhibitors. Also, the effects of some treatment related risk factors of the formation of FVIII inhibitors in multi-transfused hemophilia A patients.Patients and methods: Fifty patients with moderate to severe hemophilia A were examined for existence of FVIII inhibitors by Bethesda method, and classified into 25 patients positive inhibitor group and 25 patients negative inhibitor group. In addition, all the patients, were genotyped for TNF-Ü gene polymorphisms (308G/A) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi square test and Fisher{u2019}s exact test were used for statistical analysis. Results: The 25 patients developed FVIII inhibitors, 19 patients (76%) had low titer (< 5 BU/ml) and 6 patients (24%) had high titer (> 5BU/ml). The studied treatment related risk factors has no relation with FVIII inhibitor development. No statistically significant correlation was found between the positivity of anti FVIII antibodies and the TNF-Ü gene polymorphism (308A/G) (P =0.426). The difference between positive inhibitor group and negative inhibitor group regarding the genotype frequency of TNF-Ü (308A/G) is not statistically significant (P = 0.083). We did not find a significant correlation between the existence of such polymorphism and any of the studied treatment related risk factors |