The Change Regulation of Joint Structure and Function in Children with Severe Hemophilia a Receiving Low and Intermediate-Dose for Prophylaxis

Objective: A comprehensive evaluation of the newly developed joint structure and functional status was used to explore change of the condition of children with severe hemophilia A.

Method: 20 cases in the intermediate-dose prophylaxis group,18 cases in the low-dose prophylaxis group and 15 cases in the on-demand treatment group. The changes of clinical hemorrhage phenotype, joint structure, joint function, activity and quality of life were observed.

Results:

1. Low and intermediate-dose prophylaxis groups can improve the clinical bleeding phenotype obviously(P=0.000-0.003).The intermediate-dose prophylaxis group was better than the low-dose prophylaxis group (P=0.005-0.016).

2. The variation of the low and intermediate-dose prophylaxis groups were less than the on-demand treatment group (P=0.000-0.012), but there was no significant difference between the intermediate-dose prophylaxis and the low-dose prophylaxis group (P>0.05).The variation of FISH total score of three groups of children with hemophilia A was negative, and the variation of low and intermediate-dose prophylaxis groups were less than that of the on-demand treatment group (P=0.000-0.020).

3. The ultrasound imaging structure changes of the most serious single target joint: the variation of ultrasound score of the most serious single target joint in the three groups were positive, The three groups of children with the most serious single target joint ultrasound score changes were positive.The variation of ultrasound of the most serious single target joint in low and intermediate-dose prophylaxis groups were less than those in the on-demand treatment group(P = 0.000-0.044)。The variation of HJHS score of the most serious single target in the three groups were positive, and which of the low and intermediate-dose prophylaxis groups were less than which in the on-demand treatment group, followed up for 6 months, 9 months and 12 months (P = 0.000-0.030); the variation of HJHS score of the most serious single target joint in the intermediate-dose prophylaxis group were less than low-dose prophylaxis group(P=0.023).

4. Quality of life: the CHO-KLAT scores in the three groups were all decreased. The variation of the CHO-KLAT score of the low and intermediate-dose prophylaxis groups were lower than which of the on-demand treatment group (P=0.000-0.023). The variation of the CHO-KLAT score in the intermediate-dose prophylaxis group was less than which in the low-dose prophylaxis group, and there was a significant difference (P=0.031, 0.039).

5. There was no significant correlation between the annual bleeding rate and the the variation of ultrasonic score of the most serious single target in the three groups (P>0.05). There was no significant correlation between the annual bleeding rate and the the variation of HJHS score of the most serious single target after 12 months in the three groups (P>0.05). There was no significant correlation between AJBR and the variation of FISH total score after 12 months in the on-demand treatment group and the low-dose prophylaxis group (P>0.05).

6. There was positive correlation between the variation of ultrasound and HJHS score after 12 months of the most serious single target joint in the low and intermediate-dose prophylaxis groups (r=0.818, P=0.000, r= 0.809, P=0.000). There was no significant correlation between the the variation of HJHS total score and FISH total score after 12 months in the three groups (P>0.05).

7. In the follow-up of sixth month, there was positive correlation between ultrasound and MRI score in the three groups (r=0.944, 0.980, 0.953, P=0.000).

Conclusion: Low and intermediate-dose prophylaxis could significantly improve the clinical bleeding phenotype. At the same time, ultrasound score, and HJHS score of the joint and FISH score in the low and intermediate-dose prophylaxis groups were also not reversed, but the damage progress were delayed with the increase of time, and CHO-KLAT score was obviously improved.The clinical hemorrhagic phenotype was not sufficient to assess the changes of the joint condition.