Written in
Featured research from recent issues of Blood
PAPER SPOTLIGHT
How Has Living With Severe
Hemophilia Changed in the
Last 50 Years? An Analysis
of a Large National Database
In an analysis of data
from nearly 5,000 men
with severe hemophilia
collected over the last half
century, researchers have
illustrated the experience
of living with this disease
– and how the advances
and setbacks in the treatment of hemophilia have
affected patients’ clinical
outcomes.
Marshall A. Mazepa,
MD, from the Department of Pathology and
Laboratory Medicine at
the University of North
Carolina at Chapel Hill,
and colleagues, used data
from a national health
surveillance program
launched by the Centers
for Disease Control and
Prevention and the U.S.
Hemophilia Treatment
Center Network (HTCN), a
federally funded national
network of hemophilia
diagnostic and treatment
centers.
“Over approximately
the last five decades, the
experience of men and
boys with hemophilia
has been characterized
by remarkable progress
in drug therapies and the
delivery of multidisciplinary care, interrupted
by tragic setbacks from
transfusion-transmitted
infections,” Dr. Mazepa
and co-authors wrote. “Incremental improvements
in the standards and
access to care as well as
setbacks related to treatment complications have
30
ASH Clinical News
naturally created ‘eras’ of
care affecting successive
birth cohorts of men with
severe hemophilia.”
The researchers examined demographics, complications of hemophilia
and its treatment, and
mortality among patients
in each of these eras,
to provide a descriptive
analysis of how outcomes
have changed over time.
A total of 7,486 men
were included in the
study: 4,899 men (65.4%)
had severe factor VIII and
IX deficiency and 2,587
men (34.6%) had mild
hemophilia. Hemophilia
severity was classified
based on the plasma level
of baseline factor activity: Patients with severe
hemophilia had levels <1
percent of normal and
patients with mild hemophilia had levels of >5-50
percent of normal.
Patients were categorized into four birth cohorts:
• Era A: born before 1958
• Era B: born between
1958-1975
• Era C: born between
1976-1982
• Era D: born between
1983-1992
A majority of these
patients had hemophilia
A (6,094 or 81.4%); 1,392
patients (18.6%) had
hemophilia B.
Severely affected men
in each birth cohort were
compared with the corresponding “mild” hemophilia birth cohorts (2,587
men total) to control for
outcomes that might be
attributable to aging and
environmental factors
independent of severely
defective hemostasis.
Compared with men
in era A, those in era D
reported starting treatment in the home earlier
in their lives: 45 percent
started before the age of
six, versus just 2 percent in era A. Similarly,
the number of patients
visiting a hemophilia
treatment center before
the age of two increased
nearly 10-fold (7.3% in era
A vs. 69.1% in era D).
Patients with severe
hemophilia were twice as
likely to have Medicaid
and/or Medicare, compared with patients with
mild hemophilia. “Despite
this, individuals in the two
youngest cohorts [eras
C and D] were also more
likely to be uninsured,
“[Hemophilia has seen]
remarkable progress in
drug therapies... interrupted by tragic setbacks from transfusiontransmitted infections.”
—MARSHALL A. MAZEPA, MD
While the first three
eras (A-C) contained
“roughly similar” numbers
of men with severe hemophilia, Dr. Mazepa and colleagues wrote, the number of men with severe
hemophilia compared with
mild hemophilia increased
within each birth cohort in
the later eras, to the tune
of 2.0 to 2.9 times more
severe hemophilia cases in
eras B-D. Only in era A did
men surviving with mild
hemophilia outnumber
men with severe hemophilia.
a pattern that was true
regardless of severity of
hemophilia,” noted Dr.
Mazepa and colleagues.
The authors observed
several encouraging
trends through the eras,
due to the advances in
treatment, including the
proportion of participants
reporting frequent bleeds
decreasing with each
successive era. However,
frequent bleeds were still
common even in era D,
when contemporary therapies were available; more
than one in three partici-
pants with severe hemophilia in this era reported
experiencing more than
five bleeds in six months,
and 25 percent reported a
target joint with recurrent
hemorrhage.
Physical functioning
capacity was lowest in era
A, though those with severe hemophilia across all
eras were approximately
three times more likely
to report activity limitations and twice as likely
to report intermittent use
of assistive devices for
mobility and ambulation
than those in the comparative mild hemophilia
cohorts.
“As expected, we
observed infrequent
bleeding in men with
mild hemophilia consistently across all eras,”
the authors reported,
and, though “men with
mild hemophilia reported
low levels of disability or
limitations of activity in
the youngest era, these
limitations were incrementally more prevalent
in each subsequently
older birth cohort.” These
observations su ggest that
the recorded limitations in
overall activity represent
the effect of aging in combination with the infrequent bleeding events.
Despite the advances
in treatments over the
decades, infections
continued to remain
a concern among this
patient population, as
95 percent of men with
severe disease in eras A
and B, 90 percent in era
C, and 35 percent in era D
had been diagnosed with
HBV (hepatitis B), HCV
(hepatitis C), HIV (human immunodeficiency
virus), or a combination
of these. However, there
were no new infections of
HBV, HCV, or HIV attributable to plasma-derived or
April 2016