Despite advancements, men with severe hemophilia still experience frequent bleeding, disability

Although significant advancements in hemophilia treatment and access to integrated treatment centers have occurred in the last 50 years, men with severe hemophilia continue to experience substantial physical limitations and disability, according to results of a birth cohort analysis.

The incidence of joint bleeding in this population also remains higher than expected, according to the researchers.

“Clear disparities remain in terms of frequent bleeding and disability between men with severe hemophilia and mild hemophilia across every decade of adult life,” Paul E. Monahan, MD, who served as an attending physician at the Gene Therapy Center at University of North Carolina during the conduct of the study, said in a press release. “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 was not the case.”

Most patients with hemophilia receive treatment at one of 130 federally supported centers in the Hemophilia Diagnostic and Treatment Centers network. In 1998, this network launched the Universal Data Collection surveillance initiative with the CDC.

To assess how access to care, physical and social functioning, complications and mortality have changed in the past 50 years, Monahan and colleagues evaluated data from 1998 to 2011 on 7,486 men with hemophilia from this database. Overall, 4,899 of the men (65.4%) had severe hemophilia and 2,587 men (34.6%) had mild hemophilia. The cohort included 6,094 men (81.4%) with hemophilia A and 1,392 (18.6%) with hemophilia B.

Researchers divided the men into four birth cohorts: Era A (born prior to 1958), Era B (born between 1958 and 1975), Era C (born between 1976 and 1982) and Era D (born between 1983 and 1992).

To describe the impact of changes in hemophilia care on the outcomes of men with severe hemophilia, researchers divided the study into two analyses. In the first analysis, researchers evaluated men within the separate birth cohorts.

In the second analysis, the researchers sought to control for the effect of aging on outcomes in men with severe hemophilia in each birth cohort by comparing them to men in the identical cohorts with mild clotting factor deficiency.

Eras B through D had a comparable number of men with severe hemophilia, with nearly threefold more men with severe hemophilia than mild hemophilia within each cohort. However, only in the era of men born before 1958 did those surviving with mild hemophilia outnumber those with severe hemophilia.

A significantly greater proportion of men in Era D vs. Era A reported starting home infusion before age 6 years (more than 45% vs. less than 2%). Further, the proportion of those who visited a hemophilia treatment center before age 10 years increased nearly tenfold.

Use of a continuous prophylactic factor regimen was threefold greater in the youngest vs. oldest adults.

Researchers also found that men born between 1976 and 1993 were most likely to not have health insurance.

The proportion of men who experienced frequent bleeds decreased with each era. However, even in Era D, one in three men with severe hemophilia reported frequent hemorrhages, or more than five bleeds in 6 months. One in four of these men reported a target join for recurrent hemorrhage.

Men with severe hemophilia were threefold more likely to report limitations in their activities or be disabled and twofold more likely to report intermittent use of assistive devices for mobility/ambulation than men with mild hemophilia, regardless of birth era. These men also were two- to three-times more likely to report missing 10 days of work or school during the previous year.

“What needs examination is why — despite widespread availability of preventive and on-demand therapies for home use — we still see disparities,” Monahan said. “It speaks to the need for continued disease surveillance to monitor and inform hemophilia interventions and outcomes.”

Five hundred fifty-one deaths were reported during the study period, with the Era A and B cohorts accounting for 82% of deaths among men with severe hemophilia and 96% of deaths among men with mild hemophilia.

Researchers found liver failure surpassed bleeding events and HIV as the leading cause of death among the overall cohort. Although no one in the youngest cohort experienced liver-related deaths, liver failure was the leading cause of death among men with severe (33% of deaths) and mild (26% of deaths) hemophilia. Hemophilia-related deaths accounted for 14.6% of deaths among men with severe hemophilia and 10.7% of deaths among men with mild hemophilia.

“Our analysis provides a snapshot of how improvements in care have translated into outcomes across different generations of men with hemophilia,” Monahan said in the release. “While there is reason to be pleased with the progress we have 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.” – by Jennifer Southall

Disclosure: The study was funded by the CDC and supported through a cooperative agreement with the U.S. Hemophilia Treatment Center Network. The researchers report no relevant financial disclosures.