Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project

Abstract

This analysis of the US Hemophilia Treatment Center Network and the Centers for Disease Control and Prevention surveillance registry assessed trends in prophylaxis use and its impact on key indicators of arthropathy across the life-span among participants with severe hemophilia A. Data on demographics, clinical characteristics, and outcomes were collected prospectively between 1999 and 2010 at annual clinical visits to 134 hemophilia treatment centers. Trends in treatment and outcomes were evaluated using cross-sectional and longitudinal analyses. Data analyzed included 26 614 visits for 6196 males; mean age at first registry visit was 17.7 years; and median was 14 (range, 2 to 69). During this time, prophylaxis use increased from 31% to 59% overall, and by 2010, 75% of children and youths <20 years were on prophylaxis. On cross-sectional analysis, bleeding rates decreased dramatically for the entire population (P < .001) in parallel with increased prophylaxis usage, possibly because frequent bleeders adopted prophylaxis. Joint bleeding decreased proportionately with prophylaxis (22%) and nonprophylaxis (23%), and target joints decreased more with prophylaxis (80% vs 61%). Joint, total, and target joint bleeding on prophylaxis were 33%, 41%, and 27%, respectively, compared with nonprophylaxis. On longitudinal analysis of individuals over time, prophylaxis predicted decreased bleeding at any age (P < .001), but only prophylaxis initiation prior to age 4 years and nonobesity predicted preservation of joint motion (P < .001 for each). Using a national registry, care providers in a specialized health care network for a rare disorder were able to detect and track trends in outcomes over time.

Figure 1.

Trends in prophylaxis use for children and adults with severe hemophilia A from 1999 to 2010. The proportion of each participant age cohort (in decades) using continuous prophylaxis is displayed for each year of the study from 1999 to 2010.

Figure 2.

Trends in mean number of joint hemorrhages in the preceding 6 months by prophylaxis status, 1999 to 2010. (A-C) The vertical axis on the right displays the mean number of joint hemorrhages per 6 months during each study year for participants using (▲) or not using (▪) continuous prophylaxis. The vertical axis on the left displays the proportion of the entire age cohort using prophylaxis for each study year (□). (A-C) Displays results for children ages 2 to 9 years (A), adolescents 10 to 19 years (B), and adults 20 to 29 years (C), respectively. Prophy, prophylaxis; Prophy +, data from patients on prophylaxis; Prophy −, data from patients not on prophylaxis.

Figure 3.

Cross-sectional analyses: mean changes in bleeding rates and joint range of motion from 1999 to 2010. (A-D) Shows changes in outcome rates from 1999 to 2010 stratified by age cohort and prophylaxis usage. (A) Rates of joint hemorrhages; (B) rates of target joints; (C) total bleeding rates; and (D) percentage of normal joint ROM in participants. Patients on prophylaxis in 1999 (red); patients on prophylaxis in 2010 (blue); patients not on prophylaxis in 1999 (green); and patients not on prophylaxis in 2010 (purple).