A large study suggests that, despite treatment advances, men with severe hemophilia have not seen great reductions in bleeding events.
Data on more than 7000 men with hemophilia revealed substantial differences in the care received by men born before 1958 and those born between 1983
and 1992.
However, the data also showed that frequent bleeding was common in patients with severe hemophilia, regardless of when they were born.
These data were published in Blood.
“Our analysis provides a snapshot of how improvements in care have translated into outcomes across different generations of men with hemophilia,” said study author Paul E. Monahan, MD, of The University of North Carolina-Chapel Hill.
“While there is reason to be pleased with the progress we’ve made, our data show some surprising deficits and suggest that efforts are needed to more consistently apply the integration of standard-of-care multidisciplinary services and preventive blood clotting factor treatments to further normalize the lives of men living with hemophilia.”
Dr Monahan and his colleagues analyzed data on 7486 men—4899 with severe hemophilia (65.4%), 2587 with mild hemophilia (34.6%), 6094 with hemophilia A (81.4%), and 1392 with hemophilia B (18.6%).
The data were collected prospectively by the US Centers for Disease Control and Prevention and 130 federally supported Hemophilia Treatment Centers (HTCs) between 1998 and 2011. This represents the largest database of men living with hemophilia.
The researchers grouped the men into 4 eras (birth cohorts) to evaluate how outcomes—access to care, physical and social functioning, complications, and mortality—have changed over the last 50 years.
The cohorts were as follows:
- Era A: born before 1958 (median age 58)
- Era B: born between 1958 and 1975 (median age 40)
- Era C: born between 1976 and 1982 (median age 28)
- Era D: born between 1983 and 1992 (median age 21).
Access to care
The researchers found that the proportion of men who started home infusions before age 6 was far greater in Era D than Era A—50.4% and 2%, respectively. And the proportion of patients reporting a first HTC visit before age 2 rose nearly 10-fold from Era A to Era D—8.8% and 100%, respectively.
In addition, the use of a continuous prophylactic regimen was nearly 3-fold greater in Era D than Era A—46.7% and 16%, respectively.
However, patients in the youngest 2 birth cohorts were more likely than their older counterparts to be uninsured. The proportion of uninsured patients was 16.4% in Era D, 20.5% in Era C, 11.1% in Era B, and 5.7% in Era A.
Bleeding events
The proportion of patients reporting frequent bleeds decreased from Era A to Era D. However, frequent bleeding was common in men with severe hemophilia regardless of when they were born.
Even men from Era D—who had access to effective, safe clotting therapies and multidisciplinary care throughout their lifetimes—reported frequent bleeds.
The proportion of patients with severe hemophilia reporting 5 or more joint bleeds in the last 6 months was 42.6% in Era A and 35.5% in Era D. The proportion of patients with a joint affected by recurrent bleeding was 32.6% and 24.9%, respectively.
Functioning
The researchers also discovered that patients with severe hemophilia were 3 times as likely to report limitations in their activities or to be disabled, when compared to patients with mild hemophilia, regardless of when they were born.
Still, men from Era A were more likely to report limitations in their overall activity level—68.8% of severe hemophilia patients and 21.1% of mild hemophilia patients—than men from Era D—14.9% of severe hemophilia patients and 4.3% of mild hemophilia patients.
Men with severe hemophilia were more likely than men with mild hemophilia to report missing more than 10 days of work or school during the previous year. In Era A, the proportions were 6.9% and 2.6%, respectively. In Era D, the proportions were 5.6% and 3%, respectively.
“Clear disparities remain in terms of frequent bleeding and disability between men with severe hemophilia and mild hemophilia across every decade of adult life,” Dr Monahan said.
“We thought the difference in functional outcomes would have narrowed over the years. That is, men with severe hemophilia should look more like those with
mild disorder, given improved therapeutics and access to care, but this wasn’t the case.”
“What needs examination is why, despite widespread availability of preventive and on-demand therapies for home use, we still see disparities. It speaks to the need for continued disease surveillance to monitor and inform hemophilia interventions and outcomes.”
Mortality
There were 551 deaths during the study period. The Era A and B cohorts accounted for 82% of the deaths in the severe hemophilia population and 96% of the deaths in the mild hemophilia population.
The researchers noted that liver failure has surpassed bleeding issues and HIV as the leading cause of death among US men with hemophilia.
Although there were no liver-related deaths in the 2 youngest cohorts, liver failure was the most commonly reported cause of death across all the cohorts, for both severe hemophilia (33% of deaths) and mild hemophilia (26% of deaths).
The researchers said this finding underscores the need to swiftly evaluate and treat HCV infections.
“Liver disease worsens bleeding, so eradicating hepatitis C infections needs to be a priority, especially as we now have remarkably effective therapies,” Dr Monahan said.
Across all the birth cohorts, hemophilia-related deaths accounted for 14.6% of deaths in patients with severe hemophilia and 10.7% of deaths in those with mild hemophilia.
