Comparison of Short-Term Tertiary Prophylaxis at Low-Dose and Intermediate-Dose for Adults with Severe Hemophilia a in China

Background: Low-dose prophylaxis and intermediate-dose prophylaxis in hemophilia A both had been proved in reducing bleedings in some developing country, but there was rare attention in terms of the Health-related Quality of life (HRQoL) and patients' adherence. So we initiated a retrospective study to compare the differecen between low-dose and intermediate-dose regimen of tertiary prophylaxis for adults with severe hemophilia A.

Methods: Data collected from the hemophilia treatment centre at Nanfang hospital from July 2010 to February 2015(median 2 years of follow-up), a total of 40 adult patients with severe hemophilia A (FVIII < 1%) who are receiving prophylaxis treatment≥1 year and treatment data available were eligible for enrollment in the study, including 25 patients in low-dose regimen(F‡[8-15 IU/kg 1-2times weekly or weekly<30IU/kg), and 15 patients in intermediate-dose regimen( F‡[ 15-20 IU/kg 2-3 times weekly or weekly≥40IU/kg and <75 IU/kg). Collect the data with patients' characteristics, previous condition and treatment, annual total bleeding rate(ABR). Use SF36 to evaluate patients' quality of life, use the difference between the beginning of this study and one year ago of SF36 score to represent the improvement of quality of life. Use "hemophilia bleeding and factor injection record handbook" to collect information about patients' bleeding and injection record, use HO's measuring method to evaluate adherence.

Results: 1. There were no statistical differences between two groups in age, weight, age at first bleeding, age at first treatment, family history of hemophilia and history of hepatitis.(the range of P-value was 0.221-1.000). 2.The Health-related Quality of life (HRQoL) in patients with severe hemophilia A were measured by the SF-36. Only on bodily pain(P=0.965) and vitality(P=0.101)the differences did not exist between two groups ,beyond that intermediate-dose group were better in other aspects(included total SF36, physical functioning, role-physical, general health, social functioning, role-emotional and mental health) than low-dose group(the range of P-value was 0.000-0.045, P<0.05),which inferred that the improvement of quality of life was better in patients in intermediate-dose group. 3. Used HO's measuring method for adherence to evaluate the 40 patients in two groups. The dosage and dosing intervals adherence of low-dose group were 78.6A88.5 respectively, while the intermediate-dose group were 90.3A95.2 respectively, the differences in dosage and dosing intervals adherence between two groups were statistically significant(P=0.003). Intermediate-dose prophylaxis treatment reduced the annual total bleeding rate(ABR) than the low-dose group(median 13 vs. 5.5,P=0.000), while poor dosage adherence correlates with more ABR(B=-0.555,P=0.000), which meant worse adherence was association with much bleeding, but there was no correlation between dosing intervals adherence and ABR(B=0.171,P=0.507).

Conclusion: 1. Compared to low-dose regimen, intermediate-dose regimen for short-term tertiary prophylaxis in adults with severe hemophilia A would improve quality of life. 2.Patients in intermediate-dose prophylaxis regimen had better adherence than low-dose regimen. There are negative correlation between dosage adherence and ABR, which means poor adherence lead to more bleeding events, while there's no correlation between dosing intervals adherence and ABR.