The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia

Abstract

To prevent hemophilic arthropathy, prophylactic treatment of children with severe hemophilia should be started before joint damage has occurred. However, treatment is expensive, and the burden of regular venipunctures in young children is high. With the aim of providing information on starting prophylaxis on the basis of individual patient characteristics, the effect of postponing prophylaxis on longterm arthropathy was studied in a cohort of 76 patients with severe hemophilia born between 1965 and 1985. The median age at first joint bleed was 2.2 years (range, 0.2-5.8). Prophylaxis was started at a median age of 6 years (interquartile range [IQR], 4-9), and the median annual clotting factor use on prophylaxis was 1750 IU/kg/y (31 IU/kg/wk). Hemophilic arthropathy was measured by the Pettersson score (maximum, 78 points). At a median age of 19 years, the median Pettersson score was 7 points (IQR, 0-17). After 2 decades of follow-up, the Pettersson score was 8% higher (95% confidence interval, 1%-16%) for every year prophylaxis was postponed after the first joint bleed. This effect was independent of age at Pettersson score, age at first joint bleed, and prophylactic dose used. In conclusion, most patients have their first joint bleed after the age of 2 years. Patients who start prophylaxis soon after the first joint bleed show little arthropathy in adulthood. The longer the start of prophylaxis is postponed after the first joint bleed, the higher the risk of developing arthropathy.

Initiation of degenerative joint damage by experimental bleeding combined with loading of the joint: A possible mechanism of hemophilic arthropathy

“…In addition, long-term studies in which animals were injected with blood have shown that cartilage matrix is adversely affected (18,19). Moreover, these data corroborate clinical findings that a limited number of joint hemorrhages in childhood, before the initiation of prophylactic treatment, may result in joint damage more than a decade later (10). Whether the changes observed in the present study will indeed lead over a period of years to fullblown joint damage remains to be investigated.…”

“…In the clinical setting it has been shown that early treatment of joint bleedings in patients with hemophilia may protect against arthropathy in later years; starting treatment with clotting factors after the third joint hemorrhage during early childhood results in better clinical outcome after 22 years of followup (10). However, this early prophylaxis cannot completely prevent arthropathy.…”

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

“…These data in a large prospective cohort confirm earlier results of smaller retrospective analyses. [13][14][15] Therefore, primary prophylaxis, or the prevention of joint damage by prevention of any joint hemorrhage is the only therapy effective to preserve joint structure and function. In addition, in over 12 years of observation, there was no observed benefit of prophylaxis to regain previously lost joint motion.…”

Bleeding before prophylaxis in severe hemophilia: paradigm shift over two decades

“…3,4 These strategies are reflected in the two most frequently used definitions of primary prophylaxis. The European Pediatric Network for Hemophilia Management (PedNet) first specified primary prophylaxis as starting before two years of age OR before the second joint bleed, 5 and The World Federation of Hemophilia (WFH) as starting before the age of three years AND before the second joint bleed, in the documented absence of osteochondral joint disease.…”