Hemophilia: a cautionary status report

In this issue of Blood, Mazepa and colleagues analyzed a nationwide US Centers for Disease Control and Prevention registry covering adult patients with severe hemophilia from 1998 to 2011 and identified two major issues: untreated chronic hepatitis C and inadequate control of joint hemorrhages.¹ 

In reaction to the hideous AIDS epidemic of the 1980s and 1990s, which killed some 80%²  of infected hemophilia patients, effective anti-HIV drugs were developed and widely employed, and virus-inactivated or recombinant concentrates were introduced, thus gaining control over HIV infection. Fortunately, the virus inactivation methods employed in the 1990s to destroy HIV also killed hepatitis C virus (HCV), which was identified at the end of the 1980s.³  But how are the survivors of that era getting along? Mazepa et al found that patients who had received earlier clotting factor concentrates were at very high risk of HCV infection: 3490 (71%) of this study’s patients with severe hemophilia, plus 1109 (41.5%) of those with mild hemophilia (whom they also followed.) Only a rough third of infected patients had received any anti-HCV therapy, and liver failure was now the leading cause of death. Today, effective anti-HCV therapy exists but its price makes it inaccessible to most patients. This impasse is an outrage.

The major targets of hemorrhage in persons with hemophilia are, mysteriously, the large joints of the limbs. Repeated bleeding leads to inflammation, erosion, arthritis, and high rates of disability. Ideally, prevention with clotting factor concentrate prophylaxis starts in toddlers, as was pioneered in Sweden⁴  and confirmed in a sentinel US study reported in 2007.⁵  Prophylaxis has become the standard of care in children, but it is not easy. Concentrates must be frequently administered by IV infusions. Children supervised by concerned parents maintain their schedules reasonably well, but teenagers and young adults are less reliable. Among this study’s youngest subjects (aged 19-28 at end of study), 45% were on prophylaxis, but 35% (not on prophylaxis) had frequent joint hemorrhages. The preservation of joint health in these youths should be a major concern.

Can hemophilic bleeding be controlled by anything easier than frequent IV infusions? Newer clotting factor concentrates with longer half-lives have extended infusion intervals from 2 to 3 days for hemophilia A, and reduced their frequency from twice weekly to once weekly for hemophilia B. An experimental, subcutaneously administered factor VIII mimetic shows promise as a more easily administered, longer-acting prophylactic agent for hemophilia A.⁶  We look forward to the possibility of gene therapy, despite ongoing obstacles.⁷ 

Roughly 70% of American patients with severe hemophilia now are under the care of the dedicated centers established by Congress some 40 years ago. These leadership centers now need to persuade patients, especially young adults, to continue prophylaxis. They should also encourage patients to build strength in the muscles that support the at-risk joints, an effective but underused preventive effort. All concerned entities, hemophilia centers, and hemophilia organizations need to be committed to the treatment of hepatitis C as universally as we now treat HIV infection.