Delays in maturation among adolescents with hemophilia and a history of inhibitors

Abstract

Inhibitory antibodies to factors VIII or IX have the potential to affect a broad range of outcomes among people with hemophilia; however, their possible effect on growth and maturation has not been explored. We evaluated skeletal maturation (bone age), pubertal progression, serum testosterone levels, height velocity, and stature in the multicenter Hemophilia Growth and Development Study. A total of 333 children and adolescents (mean age, 12.4 years) were enrolled from 1989 to 1990 and followed for 7 years. Of these, 18% (n = 60) had a history of inhibitors. Bone age among HIV(-) adolescents with a history of inhibitors lagged 9 or more months behind those without inhibitors at every age from 12 to 15 years. Those with a history of inhibitors were older at every Tanner stage transition, attained a lower maximum growth velocity, and their serum testosterone levels were significantly lower compared with those without inhibitors. Delays were greater among HIV(+) patients with a history of inhibitors compared with those without inhibitors; however, the differences were generally small and not statistically significant. The results of this investigation underscore the importance of monitoring the growth and maturation of children and adolescents with hemophilia, particularly those with inhibitors.

Figure 1

Cubic spline interpolation of baseline bone age among HIV⁻ participants with hemophilia (with and without a history of inhibitors) and a group of siblings without hemophilia. A total of 158 baseline films were used in the analysis: 19 participants had hemophilia and an inhibitor, 101 participants had hemophilia without an inhibitor, and 38 were sibling control participants. Altogether, 6 participants with hemophilia and 6 siblings were excluded from the analysis because they were skeletally mature at baseline, and 3 siblings lacked bone age measurements.

Figure 2

Predicted bone age by inhibitor status for HIV⁻ study participants. A total of 319 films from 120 HIV⁻ participants were used in the analysis. A total of 10 films from 6 participants were excluded from the analysis because they were skeletally mature at baseline.

Figure 3

Predicted height velocity curves by inhibitor status among HIV⁻ study participants. A total of 1188 height measurements for 126 HIV⁻ participants were used in the analysis. Horizontal line indicates maximum growth velocity; and vertical line, age at maximum growth velocity.