The remarkable progress made in medicine over the past 50 years means many patients with a variety of conditions and congenital diseases are reaping the benefits of improved care. No exception are men living with hemophilia, the genetic bleeding disorder, who have experienced new and transformative treatments, some of which resulted from tragic transfusion-transmitted infections during the HIV/AIDS crisis. Beyond the historical record, though, how would an actual hemophilia patient describe his journey through the American medical system?

To create a snapshot of the ways improvements in care have had real-world impact, the Centers for Disease Control and Prevention (CDC) collaborated with 130 hemophilia treatment centers. Although there was some positive progress identified, the research team also discovered some surprising deficits in care among the men. In particular, they say frequent bleeding persists in up to half of all men studied. Worse, a disability gap exists between severe and mild hemophilia cases for the years reported (prior to Obamacare).

“The two youngest cohorts had the largest proportion of uninsured men,” wrote Dr. Paul E. Monahan, a professor of hematology and oncology at UNC-Chapel Hill, and his co-authors. “This finding is due to both a larger proportion of minorities compromising the younger [cohorts] and an increase in Whites who were uninsured.”

Progress

Hemophilia is a disorder that prevents blood from clotting normally, which can lead to spontaneous bleeding internally or externally. It also places patients at a high risk of complications in the joints, muscles, and organs. The disease is inherited through a defect in the X chromosome. Because males inherit just one X chromosome from their parents, while females inherit two, hemophilia, though rare, is dramatically more common in men. Roughly 1 in 5,000 males are born with this disorder each year, according to the CDC. The national health agency does not record the number of females born with the disorder.

Severity of illness is based on the amount of clotting factors in the blood. Most patients are considered severe by this standard. The National Hemophilia Foundation reports 60 percent of men living with hemophilia constitute severe cases, 25 percent mild, and 15 percent moderate. Generally, treatment consists of infusing clotting factor into a patient’s blood.

“The oldest generation of men with hemophilia in the U.S. experienced childhood with no or little availability of clotting factor replacement,” wrote Monahan and his co-authors.

In the 1970s, home infusion therapy became possible when pharmacologists learned how to lyophilize (essentially, freeze-dry) drugs. While some clotting factor products are made from donated blood plasma, others are genetically engineered in a laboratory. Recombinant factor products do not contain blood and so cannot transmit viruses. Pioneered in the 1990s, these products are a direct result of previous crises that caused people to become infected with Hepatitis B (discovered in 1976), HIV (1983), and Hepatitis C (1989) from contaminated donated blood.

For the study, Monahan and his colleagues asked a simple question: How has this dramatic medical progress impacted access to care and consequences for actual patients?

Analysis

Concentrating on the years 1998 through 2011, the team analyzed data, collected by 130 federally supported hemophilia treatment centers, for 7,486 men living with hemophilia: 4,899 men diagnosed with a severe condition and 2,587 mild. Hemophilia A was the diagnosis for 81.4 percent.

The researchers grouped the men into four birth cohorts based on critical changes in hemophilia therapy: Era A included men born prior to 1958, average age of 58; Era B born between 1958 and 1975, average age of 40; Era C born between 1976 and 1982, average age of 28; and Era D born between 1982 and 1993, average age of 21. The men born within any given era shared broadly similar treatment experiences.

Crunching the numbers, the research team found men with severe hemophilia, regardless of their era, were three times as likely to report disability or limitations compared to men with mild cases.

Among men with severe hemophilia, one in three reported having more than five bleeding episodes in six months, and one in four has a joint affected by recurrent bleeding, the team discovered. Frequent bleeding was common even among men with severe hemophilia in the youngest birth cohort — despite having access to effective, safe clotting therapies throughout their lifetimes. A surprised team had expected health differences between severe and mild cases would have narrowed over time due to widespread availability of therapies for home use, Monahan explains.

Researchers also observed men in the two youngest eras were most likely to be uninsured: 6.7 percent of severe and 13.8 percent of mild cases in Era C; 7.3 percent of severe and 9.1 percent of mild cases in Era D. Finally, liver failure has surpassed bleeding issues and HIV as the leading cause of death among hemophiliacs.

Monahan and his colleagues say diagnosing and quickly treating hepatitis C infections needs to become a priority. “National surveillance in the US hemophilia population remains vital to inform improvements in hemophilia treatment center access, therapeutics, and outcomes,” they concluded.

Source: Mazepa MA, Monahan PE, Baker JR, et al. Men with severe hemophilia in the United States: Birth cohort analysis of a large national database. Blood. 2016.