Secondary Prophylaxis Versus On-Demand Treatment in Adult Hemophilia Patients – Increased Factor Use without Increased Benefit?

Primary prophylaxis treatment for hemophilia (hem) patients (pts) during childhood has become the standard of care, however there is little consensus on the guidelines for adult management. Currently depending on the physician preference and experience, an adult hem pt can either be treated in response to bleeding (on-demand(OD)), or with regular infusion of clotting factor to prevent bleeding and further joint damage (secondary prophylaxis(P)). This study was undertaken to assess the differences in annual bleeds rates and utilization of clotting factor concentrates between P and OD treatment strategies in adults.

A retrospective study of the 46 patients with moderate or severe hem at the Newark Beth Israel Comprehensive Hemophilia Center was undertaken. Data on treatment and outcomes were evaluated for pts treated with P and those treated with OD. A chart review was done to evaluate the extent of joint arthropathy, incidence of bleeds per calendar year, type of treatment P or OD, and quantity of factor utilized annually. Data was also collected on the utilization of analgesics medications, employment history, and psychiatric history.

The data was evaluable for 5 Hemophilia B pts, 4 severe, and 1 moderate; and 41 Hemophilia A pts, 25 severe, and 16 moderate. Forty-six percent (21/46) of the hem pts were receiving P as adults. Fifteen percent (7/46) hem pts had received P as a child or adolescent, and continued into adulthood. The pts ages ranged from 18 to 66 years of age. The mean age of pts receiving P was 32 years, while it was 34 years in the OD group. There was no difference in the average number of target joints between the two groups, with a mean of 2 target joints per patient. Fifty-two percent of hem on P (11/21) had 0–1 bleed per month, while only 40% of OD pts (12/25) had 0–1 bleed per month. In the P group 48% (10/21) had more than 1 bleed per month, while 60% in the OD group had more than 1 bleed per month. Overall there was no statically significant difference between the incidence of annual bleeds between the two groups, p=0.51. Forty-six percent of patients (21/46) were taking analgesic managements, and of these 48% (10/21) were on P, p=.806. Thirty-three percent (15/46) of the pts were unemployed or not enrolled as a student, and more than half (8/15) of those pts were on P treatment. Twenty-four percent (11/46) of hem pts were found to have a psychiatric history with either depression, or anxiety, of which 82% were on P. In 43 of the 46 hem pts the amount of factor utilized over a 5-year period (2006–2010) was available for analysis. Patients receiving P utilized more factor than pts on OD, 385,124 units versus 115,367 units, p =.0013.

The initiation of primary prophylaxis in childhood has decreased much of the morbidity associated with hemophilia, however the benefit of secondary prophylaxis has not been clearly established. The treatment of hemophilia is costly, and there are both medical and economical advantages and disadvantages. Prophylaxis in this older population of moderate and severe hem pts did not have an impact on the reduction of annual bleeds, or the number of target joints, though pts on P utilized more units of clotting factor concentrate. Additionally, our pts did not have improvement in quality of life factors such as pain alleviation, increased employment, or mental well-being. Lack of benefit may be obscured as these pts who had not received primary prophylaxis, already had significant joint damage. Studies on continuation of P or OD in pts who have received primary prophylaxis will be necessary to determine long term prophylaxis in these pts.

No relevant conflicts of interest to declare.