Background and Introduction:

Prophylaxis treatment is considered optimal care for patients with severe hemophilia during childhood to prevent bleeding and reduce the incidence of joint disability. However, tertiary prophylaxis may also benefit Adults with Severe Hemophilia, but the optimal dose tailoring of FVIII is still unknown. We initiated a study to compare the low-dose and intermediate-dose regimen for tertiary prophylaxis in adults with severe hemophilia A.


Patients with severe hemophilia A (F VIII < 1%) born between January, 1978, and January, 1988, who were treated at the hemophilia treatment centre at Nanfang hospital and treatment data available were eligible for enrollment in the study. The main exclusion criteria were a history of FVIII inhibitor (titer ≥ 0.6BU [Bethesda unit]), detectable FVIII inhibitors at screening (titer ≥ 0.4 BU), chronic liver disease, immunodficiency, another hemostatic defect and the need for major surgery. A total of 40 adults with severe hemophilia were enrolled, including 25 patients with low-dose prophylaxis (5-10 IU/kg twice a week) and 15 patients with intermediate-dose prophylaxis ( FⅧ 15-20 IU/kg twice a week). Breakthrough acute bleedings were treated according to the regular practice and guidelines.


The study was conducted over a 2-year period (January 2014 to December 2015).Compared to low-dose prophylaxis group, Intermediate-dose tertiary prophylaxis group reduced the annual number of total and joint bleeds (median 13 vs 5.5 and median 10 vs 4; P= 0.001, respectively), and annual target joint bleeding rate were also significantly lower (median 8 vs. 3.5, P =0.002). The breakthrough bleeding events were largely lower in intermediate-dose group than in low-dose group (P=0.03). After prophylaxis, the FISH score in Intermediate-dose group increased from median 21 (range 15-28) to median 24 (range 17-28) (P=0.02) and in low-dose group from median 22 (range 14-28) to median 24 (range 14-28) (P=0.02) respectively. The improvement of FISH score were different between two groups (P=0.04). Meanwhile, The Health-related Qualityof life (HRQoL) in patients with severe hemophilia were measured by the SF-36. The SF-36 score showed better results in terms of overall perceived health status between patients with Intermediate-dose and with low-dose prophylaxis (P < 0.01).


Compared to low-dose prophylaxis, Intermediate-dose tertiary prophylaxis may show a better joint protection in Adults with Severe Hemophilia, for Intermediate-dose regimen not only means less joint bleeding, but also helps joint function restore and Quality of life improvement. Our study established that Intermediate-dose tertiary prophylaxis may be a better choice for adults in a number of hemophilia treatment centers in China.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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