Decreased antioxidant capacity with serum native thiol and total thiol levels in children with hemophilia A: a prospective case-control study

Abstract

Background. Experimental studies have addressed the role of oxidant stress in the pathogenesis of Hemophilia A. This study aimed to determine whether dynamic thiol-disulfide exchange, a recently recognized cellular defense system against oxidative stress, is disturbed in children with hemophilia A. Methods. This prospective case control study included male children with hemophilia A (n=62) and randomly selected healthy age and sex-matched controls (n=62). Serum native thiol, total thiol and disulfide levels were analyzed with a novel spectrophotometric method. Ratios of disulfide/total thiol, disulfide/native thiol, and native/total thiol were calculated. Statistical comparisons were made using the independent samples t-test or the Mann-Whitney U test, according to whether the data were normally distributed or not. Results. Serum native thiol (385.0 ± 35.9 versus 418.0 ± 44.3, respectively; p<0.001) and total thiol (424.2 ± 38.7 versus 458.0 ± 46.3, respectively; p>0.001) levels were significantly lower in children with Hemophilia A compared to controls. Children with hemophilia A had significantly lower serum native thiol to total thiol ratio than controls (p=0.024). Serum disulfide levels of children with hemophilia A were close to controls (19.2 [17.6-22.1] versus 19.8 [17.8-21.2]), respectively; p=0.879) whereas disulfide to native thiol ratio (p=0.024) and disulfide to total thiol ratio (p=0.024) were significantly higher. Conclusions. Decreased antioxidant capacity with levels of serum native thiol and total thiol in children with hemophilia A might be regarded as evidence for the disturbance of thiol/disulfide balance. Antioxidant treatment can be a future target of therapy in children with hemophilia A.