Prophylactic treatment with low- and intermediate-dose factor VIII in children with severe hemophilia A: comprehensive evaluation of joint outcomes and correlation analysis / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of low- and intermediate-dose factor VIII (FVIII) for prophylactic treatment of severe hemophilia A in children by comprehensively evaluating the outcomes of the joints.</p><p><b>METHODS</b>Forty-seven children with severe hemophilia A (FVIII activity ≤2%) were enrolled in this study. Eighteen of the children received prophylactic treatment with low-dose FVIII (10 U/kg, 2-3 times a week), 20 received prophylactic treatment with intermediate-dose FVIII (15-30 U/kg, 3 times a week), and 9 received on-demand treatment with FVIII infusion when bleeding occurred according to the Chinese Expert Consensus on the Diagnosis and Treatment of Hemophilia. The children were followed up for 180 days to observe the changes in the indexes of clinical bleeding phenotype, joint structure, joint function, and joint mobility, and the correlation of these indexes were analyzed.</p><p><b>RESULTS</b>Compared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII significantly improved the clinical hemorrhage phenotype (P<0.01), and the improvement was significantly more conspicuous with intermediate-dose prophylactic treatment (P<0.05). Comprehensive evaluation of the joint structure and function changes showed that compared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII resulted in significant improvements in the total score of Hemophilia Joint Health Score (HJHS), Functional Independence Score in Hemophilia (FISH), the single most severe target joint ultrasound and HJHS score of the target joint (P<0.05) and prophylactic treatment with intermediate-dose FVIII appeared to produce better outcomes of the joint than low-dose FVIII. No correlation was found between annual target joint bleeding rate (ATJBR) and ultrasound score, between ATJBR and HJHS change, or between annual joint bleeding rate (AJBR) and the total score of FISH (P>0.05).</p><p><b>CONCLUSION</b>Compared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII can significantly improve the bleeding phenotype and delay the progression of joint injury, but the clinical hemorrhagic phenotype is not sufficient to monitor the disease progression.</p>