Turning severe into moderate haemophilia by prophylaxis: are we reaching our goal?

Abstract

Background: Since the introduction of prophylaxis, physicians have tried to convert the clinical phenotype of severe haemophilia (SH) into that of moderate haemophilia (MH), but the outcome of patients with SH has never been compared to that of patients with MH.

Material and methods: The outcome of 80 patients with SH on long-term, intermediate dose prophylaxis was compared to that of 40 patients with MH in a single-centre study. Data on treatment history, activities (assessed by the IPAQ and HAL), quality of life (assessed by the SF-36 and EQ5D), and 5-year bleeding and clotting factor consumption were collected for patients born between 1970-1995.

Results: The median age of the patients was 24 years (IQR 18-30). All patients with SH received long-term prophylaxis, which was started at a median age of 4.8 years (IQR 3.2-6.2). Among the patients with MH, ten (25%) received prophylaxis, starting at a median age of 10.8 years (IQR 3.8-13.8). The annual number of bleeds, including joint bleeds, was significantly higher in patients with SH (median 2.0 joint bleeds/year, IQR =0.8-3.7) than in patients with MH (median 0.8 joint bleeds/year, IQR =0-1.2). Due to greater use of prophylaxis, the annual clotting factor consumption of SH patients (median 2,120 IU/kg; IQR 1,514-2,768), was higher than that of MH patients (median 133 IU/kg; IQR 49-468). Patients with SH showed slightly but significantly more loss of clinical function (assessed by the Haemophilia Joint Health Score): a median of 8 points (IQR 3-15) vs a median of 2 points, IQR 0-6). Quality of life, as measured by the SF-36, EQ5D and physical activity, was similar between patients with disease of different severity, as well as compared to that of the general population.

Discussion: When comparing unselected cohorts, the bleeding pattern of patients with SH does not appear to be fully converted to that of the milder bleeding pattern of MH by long-term, intermediate-dose prophylaxis, although activities and quality of life were similar.

Figure 1

SF-36 scores of patients with severe or moderate haemophilia compared to the score in the genera, malel population. The solid black line represents the male population in The Netherlands.