The Art and Science of Infusion Nursing
Christine J. Guelcher, MS, APRN, PPCNP-BC
Evolution of the Treatments
for Hemophilia
ABSTRACT
Although hemophilia has been recognized for cen-
turies as an inherited disorder primarily affecting
males, advances in treatments have been very
recent. Initial availability of plasma-derived thera-
pies offered significant improvements in morbidi-
ty and mortality, but the transmission of viruses
quickly negated the benefit of early factor replace-
ment products. After developing successful viral
inactivation methods and subsequently develop-
ing recombinant technology, the manufacturing of
factor concentrates became much safer. Access
to safer factor products allowed for a shift from
the treatment of bleeds to prevention, called
prophylaxis. Although dosing and interval vary,
prevention of joint disease is now a realistic goal.
H
emophilia is one of the oldest recognized
genetically inherited disorders. Rabbinical
writings from the second century AD
mention exemption from circumcision for
sons who are born to a woman who had
2 or more male offspring die from prolonged bleeding
after circumcision.1 The first description of hemophilia in
Author Affiliation: Hemostasis and Thrombosis Program, Center
for Cancer and Blood Disorders, Children’s National Health
System, Washington, DC.
Christine J. Guelcher, MS, APRN, PPCNP-BC, is a program coor-
dinator in the hemostasis and thrombosis program at the Center
for Cancer and Blood Disorders of the Children’s National Health
System in Washington, DC. She currently serves as secretary on
the Board of the American Thrombosis and Hemostasis Network
(ATHN). She serves as the nurse liaison and ad hoc member on
the Board of the Thrombosis and Hemostasis Societies of North
America (THSNA).
The author has served on Nurse Advisory Boards for Baxalta, Novo
Nordisk, Biogen, Grifols, and Octapharma. She is on the Speaker’s
Bureau for Solution Sight, Baxalta, and Novo Nordisk.
Corresponding Author: Christine J. Guelcher, MS, APRN,
PPCNP-BC, Center for Cancer and Blood Disorders, Children’s
National Health System, 111 Michigan Ave, NW, Washington, DC
20010 (cguelche@childrensnational.org).
DOI: 10.1097/NAN.0000000000000175
218 Copyright © 2016 Infusion Nurses Society
Copyright © 2016 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited.
Unfortunately, despite advances in the safety of
therapy, some patients are unable to use factor
replacement products because they develop anti-
bodies, known as inhibitors. Eradication of inhibi-
tors is possible in the majority of patients, but it is
expensive and takes time. Management of acute
bleeding may require significantly higher doses of
factor replacement or the use of a bypassing
agent. As a result, patients with inhibitors are at
increased risk for sequelae, including joint dis-
ease, life-threatening bleeding, infectious compli-
cations with central vascular access devices, and
thrombotic complications.
Key words: gene therapy, hemophilia, inhibitor,
prophylaxis
the medical literature was in the early 19th century, when
the premature death of a son was attributed to the pre-
sumed sex-linked inheritance of the disorder from a
female carrier. However, the best known historical char-
acterization of hemophilia is attributed to extended royal
families starting with Queen Victoria. Her son Leopold
died of bleeding complications. Her daughters, both car-
riers, went on to have sons who had hemophilia in the
royal families of Russia and Spain.2 It was not until the
20th century that researchers recognized there were 2
types of hemophilia: factor VIII deficiency and factor IX
deficiency.3 More recently, it was discovered that members
of the royal family had factor IX deficiency, the less com-
mon of the 2 hemophilia diagnoses.
INHERITANCE OF HEMOPHILIA
As these historical accounts recognized, hemophilia is
an X-linked disorder. Women who carry a mutation on
1 of their X chromosomes do not have full expression
of the disease because they have a second X chromo-
some, although some carriers can have low factor levels.
However, they have a 50% chance of having a son with
Journal of Infusion Nursing
hemophilia and a 50% chance of passing on the muta-
tion to a daughter, making her a carrier. Males with
hemophilia will not pass on the disease to their sons
because they transmit their Y chromosome. However,
daughters born to males with hemophilia will be obli-
gate carriers.
Hemophilia is a deficiency of either factor VIII,
which is known as hemophilia A or “classic hemophilia,”
or factor IX, known as hemophilia B or “Christmas
disease,” which is named after the first patient described
in the literature. The incidence of hemophilia is 1 in
5000 male births. Hemophilia A is 4 times more com-
mon than hemophilia B. It is estimated that there are
approximately 20 000 individuals in the United States
with hemophilia.4 In both types of hemophilia, there is
a known family history approximately 70% of the time.
In 30% of cases, the diagnosis is thought to be the result
of a spontaneous mutation.5 Potential carriers can be
evaluated to determine their carrier status by testing the
affected male in the family to identify the specific muta-
tion. This information then can be used to perform
directed testing in potential carriers. Women who are
carriers also can have prenatal testing. Chorionic villi
sampling can be done between 10 and 12 weeks of ges-
tation. Amniocentesis also can determine whether the
fetus has hemophilia, but usually this cannot be done
until after 14 weeks’ gestation. Prenatal diagnosis can
allow for education of the family and medical providers
before delivery. Despite the availability of testing, only
35% of carriers agree to prenatal testing.6
When a pregnant mother is an obligate or suspected
carrier and the status of the fetal diagnosis is unknown,
every effort should be made to minimize the risk of
bleeding with delivery. There is no consensus about the
mode of delivery at this time. Current recommendations
focus on ensuring that delivery is as atraumatic as pos-
sible. If a vaginal delivery is planned, avoidance of fetal
scalp monitoring or vacuum- or forceps-assisted delivery
are common recommendations.7 One drawback with
vaginal delivery is the reality that there is no way to
ensure that a delivery will go as planned, and transition-
ing to a cesarean section often is done emergently. One
review reports that planned cesarean section is estimated
to reduce the risk of intracranial hemorrhage by 85%.8
BLEEDING IN HEMOPHILIA
Regardless of the mode of delivery and whether carrier
status is known, bleeding complications can and do
occur in the newborn period. Intracranial hemorrhage is
still a major cause of morbidity and mortality in new-
borns with hemophilia.6 In 1 review, the most common
bleeding symptoms during the newborn period were
bleeding from circumcision (27.4%), intracranial hem-
orrhage (19%), and oral mucosal bleeding (9.6%). Less
VOLUME 39 | NUMBER 4 | JULY/AUGUST 2016
Copyright © 2016 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited.
common bleeding occurred from the heel stick (5.9%)
and intramuscular injection sites (4%). After the imme-
diate newborn period, there is often an interval during
which there are fewer bleeding complications because
most infants are not experiencing challenges. However,
as infants become more active, the likelihood that they
will experience bleeding symptoms increases. The most
common bleeding in younger toddlers is mucosal mem-
brane bleeding, usually related to trauma.9 Ultimately,
joint bleed is widely recognized as the most common
type of bleeding, although the onset and frequency of
bleeding varies among patients. In patients with severe
factor deficiencies (factor level < 1%), more than 90%
of patients experience joint bleeding, 80% of which
occurs in the ankles, knees, and elbows.10
EVOLUTION OF FACTOR
REPLACEMENT IN HEMOPHILIA
Although the inheritance pattern of hemophilia has been
understood for some time, treatment of the bleeding
symptoms was not available until the latter half of the
20th century. Early treatments were limited to whole
blood transfusions. In the 1960s, the use of plasma and
then cryoprecipitate made targeted factor replacement a
possibility for the first time.2 Soon after, manufacturers
developed methods to pool plasma donations and pro-
duce lypholized concentrates. In the 1970s, having tar-
geted treatment allowed bleeding episodes to be treated
at home for the first time. As a result of the availability
of home treatment, more bleeds were treated, which
initially had a positive effect on mortality rates.11
Unfortunately, some donor centers were located in
areas where paid donors were more likely to be in high-
risk groups, and plasma was contaminated by hepatitis
B, C, and human immunodeficiency virus (HIV).12
Hemophilia patients who received plasma-derived con-
centrates between 1979 and 1985 were exposed to
hepatitis and HIV.13 Ninety percent of patients treated
with these products were infected with hepatitis; half
were also positive for HIV, 90% of patients with severe
disease.11 After the introduction of viral inactivation
methods to kill these viruses in plasma-derived products
in 1985—ie, heat treatment, solvent detergent, pasteuri-
zation, vapor treated—there have been no further expo-
sures to these viruses in factor concentrates. However,
the impact on the hemophilia community was profound.
Through the ensuing years, treatment of HIV and hepa-
titis has improved so that patients today who are living
with these comorbidities can live longer. Recent advanc-
es in hepatitis treatment offer a sustained virological
response for many patients with hepatitis C.14
As home treatment became available in the 1970s, spe-
cialized hemophilia treatment centers (HTCs) were estab-
lished using federal funding to provide a multidisciplinary
Copyright © 2016 Infusion Nurses Society 219
approach to manage the unique challenges associated with
such a rare, expensive, and debilitating disease. Patients
cared for at HTCs were noted to have a 40% reduction in
mortality.11 The patients also had lower associated health
care costs and increased employment. These benefits were
attributed to the expertise of the HTC staff, the multidisci-
plinary approach, development of programs to support
instruction for home infusion, and access to other disease-
specific resources.13 Access to these expert caregivers and
advances in therapy have helped increase life expectancy
from an average of just 20 years in 1960 to close to today’s
national average of 76 years.15
In 1984, the factor VIII gene was cloned, and this led
to the development of recombinant technology.2 The first
recombinant products were licensed in the 1990s. With
the advent of safer factor concentrates, patients not only
could treat bleeding symptoms at home but also could
infuse factor regularly to prevent bleeding—prophylaxis.
The rationale for prophylaxis came from the understand-
ing that patients with moderate (factor levels 1%-5%)
and mild (factor level > 5%) hemophilia had less bleeding
than patients with severe disease (< 1%).16 The first study
that demonstrated the benefit of maintaining factor
troughs over 1% by using prophylactic infusions was
published by Nilsson et al17 in 1992. In 1994, the Medical
and Scientific Advisory Council of the National
Hemophilia Foundation recognized prophylaxis as opti-
mal therapy for patients with severe hemophilia.18
Over the past few decades, improvements have been
made in recombinant products to increase safety and con-
venience, but the pharmacokinetics of the products were
very similar. First-generation products use recombinant
technology but are stabilized with human albumin.
Second-generation recombinant products still have some
human plasma in the culture medium. Third-generation
products do not have human or animal plasma in the
formulation. The US Food and Drug Administration
recently approved the first extended-half-life products,
and there are others in the development pipeline. These
products were designed with the intent to decrease the
frequency of infusions with the continued goal of main-
taining trough levels of factor that are sufficient to pre-
vent spontaneous bleeding.19
GENE THERAPY
The early cloning of factor genes brought optimism that
a cure for hemophilia was on the horizon. Unfortunately,
because of the size of the factor VIII gene, finding a viral
vector that could successfully deliver the gene without
stimulating an immune response has proved to be a sig-
nificant challenge. As a result, there have been more
advances and progress with factor IX to date. Patients on
clinical trials have been able to sustain factor IX levels
above 1% for extended periods of time. In some cases,
220 Copyright © 2016 Infusion Nurses Society
Copyright © 2016 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited.
participants have been able to discontinue factor replace-
ment; in other participants, the number of factor infu-
sions has been significantly reduced. More research is
necessary before gene therapy will be available as front-
line therapy.20
PROPHYLAXIS
In 2007, the results of the first prospective randomized
trial of prophylaxis in the United States were published.
The investigators randomized boys with severe hemo-
philia who were younger than 30 months to receive
prophylactic infusions or enhanced episodic infusions.
The patients were followed until the age of 6 and evalu-
ated with magnetic resonance imaging studies of the 6
index joints. Ninety-three percent of the boys in the
prophylaxis group had normal joints versus 55% of the
patients in the episodic arm.21 Although there is agree-
ment that prophylaxis therapy is optimal, there contin-
ues to be little consensus on the best dose and interval
for prophylactic infusions. Understanding the pharma-
cokinetics of available products is necessary to achieve
the desired goal of maintaining an adequate trough to
prevent spontaneous bleeding. Review of the hemophilia
literature reveals numerous small studies examining a
variety of regimens, ranging from daily low dose, higher
dosing every other day, convenience dosing 3 times a
week, and pharmacokinetic dosing.15 Regardless of the
regimen, the goal remains the same: to prevent life-
threatening bleeding and the development of chronic
joint disease, known as hemophilic arthropathy.
Despite the recommendations for prophylaxis and
the flexibility of various regimens reported in the litera-
ture, rates of prophylaxis in the United States are just
over 50%. The adoption of the recommendation for
prophylaxis may be affected by a lack of understanding
of the benefit by patients and families. It’s likely that
psychosocial barriers also have an impact. Mothers may
experience feelings of guilt. Patients with hemophilia
may experience denial or fail to recognize bleeding
symptoms. All of these well-recognized phenomena may
result in delays in adoption of prophylaxis.22
Additionally, the cost of factor replacement accounts
for the majority of expense in hemophilia care, so
patients and families may be hesitant to use factor on a
regular basis.23 Finally, adherence is likely to be affected
by the challenges associated with infusing factor intra-
venously, particularly in young children.
TREATMENT DELIVERY
CHALLENGES
Despite the advances in hemophilia care, factor products
must be administered intravenously. The ideal mode of
Journal of Infusion Nursing
administration remains peripheral infusion because this
does not require surgery and infection rates are very low.
However, this is understandably difficult for parents who
must learn to infuse at home. Peripheral infusion requires
practice and is not always a realistic option in young
children.
When peripheral infusion is not an option, central vas-
cular access devices (CVADs) can help facilitate home
infusion. There are 3 types of CVADs: nontunneled
(peripherally inserted central catheters, or PICCs), tun-
neled catheters (such as Broviac and Hickman catheters),
and tunneled fully implantable CVADs, or ports. Of the 2
tunneled catheter options, ports are usually the device of
choice for patients with hemophilia. Although PICCs are
easier to place than Broviac catheters or ports, they are
not intended for long-term use in hemophilia patients.
Both PICCs and nontunneled catheters require daily care
and can be dislodged.24 Placement of an implanted port
carries the risk of bleeding and should be done in consul-
tation with experts in the management and monitoring of
bleeding and factor replacement.25
Using an implanted port requires additional training and
support. Parents who infuse factor using a port still have to
“poke” their child using a special noncoring percutaneous
needle. The procedure requires sterile technique, so return
demonstration of competence is key for parents to safely
infuse in the home. The infection rates of CVADs are as
high as 0.66 per 1000 catheter days among hemophilia
patients, and in 1 review, 70% of CVADs were removed
because of infection.24 As a result of frequent use, it is pos-
sible to have erosion of the skin over the port, resulting in
exposure of the port. In addition, swelling around the port
site from excessive bruising can lead to dehiscence.25
Long-term use of CVADs in hemophilia patients also
has been associated with thrombosis. In a recent review,
25% of ports were associated with thrombosis.26 Finally,
there are also potential mechanical complications. Although
rare, catheters can fracture and embolize or migrate.25
COMPLICATIONS OF TREATMENT
Although advances in the treatment of hemophilia con-
tinue to improve on safety and convenience, 1 compli-
cation of hemophilia has been consistent: the develop-
ment of antibodies to factor replacement, known as
inhibitors. It stands to reason that patients who do not
make their own factor may recognize infused factor as
“nonself” and, as such, mount an antibody response.
Approximately 25% of patients with factor VIII defi-
ciency and less than 5% of patients with factor IX defi-
ciency develop inhibitors. These inhibitors usually occur
early in treatment, typically within the first 50 exposure
days to factor.27 Although inhibitors in hemophilia B
are less common, they can be more clinically significant,
because patients can develop hypersensitivity reactions
VOLUME 39 | NUMBER 4 | JULY/AUGUST 2016
Copyright © 2016 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited.
to factor replacement products, often as the first sign of
inhibitor development. Some patients can develop
nephrotic syndrome with continued exposure to factor
IX replacement after inhibitor development.28 Some
hemophilia clinicians recommend administration of the
first 10 to 20 factor IX infusions in the clinical setting,
with some period of observation afterward. Because
inhibitors are increased in association with some types
of mutations, early identification of the specific muta-
tion that resulted in the factor deficiency (hemophilia)
can help inform about potential risk for inhibitor devel-
opment. However, in both hemophilia A and B, there is
no current method to reliably identify patients who will
develop inhibitors.29
Patients with a positive family history of inhibitors are
at high risk for inhibitor development, as it is recognized
that certain mutations are associated with higher inhibi-
tor rates. However, there is growing evidence to suggest
that there are other genetic factors that contribute to the
risk.30 Although hemophilia has no racial or ethnic
prevalence, inhibitors are more common in African
Americans and Hispanics, which is not well understood.
Theoretical postulations about haplotype have not been
borne out in the evidence.31,32 A number of investigators
have suggested that there are treatment-related factors
that contribute to the development. Initially, age at first
exposure was considered a risk factor, but a retrospective
review determined that the reason for treatment (bleed/
surgery), dosing (>50 IU/kg), and duration of therapy
(>5 consecutive days) increased the risk of inhibitors,
while prophylactic infusion reduced the risk of inhibitor
development by 60%.29 Subsequently, investigators pro-
spectively treated a cohort of patients newly diagnosed
with hemophilia A with low-dose prophylactic factor
VIII (25 IU/kg) weekly in the absence of “danger sig-
nals,” such as surgery, bleeds, or immunizations. Patients
treated with low-dose prophylaxis weekly via peripheral
infusion in the absence of danger signals (immunizations,
bleeds, surgery) had a significant reduction in inhibitor
development when compared to a historical cohort that
was treated with standard prophylaxis (40-50 IU/kg 3
times a week).33 A multicenter, prospective clinical trial,
the Early Prophylaxis Immunologic Challenge (EPIC),
was designed to test whether early prophylaxis in the
absence of danger signals reduced the inhibitor rate, but
the study was closed early as too many patients devel-
oped inhibitors and the investigators did not feel that
they could achieve their primary aim.34 Another exami-
nation of the intensity of treatment looked at inhibitor
development in consecutive previously untreated patients
with severe hemophilia for the first 75 exposure days.
Interestingly, although they noted an overall decrease in
inhibitor development in patients on prophylaxis, this
was only true after the first 20 exposure days.35
Since the advent of recombinant factor replacement,
there have been questions about whether the incidence
Copyright © 2016 Infusion Nurses Society 221
of inhibitors has increased. However, a review of 575
patients with severe hemophilia A did not show evi-
dence of any difference in the inhibitor rates between
patients on recombinant and plasma-derived factor
replacement products.36 Recently, the results of the
Survey of Inhibitors in Plasma-Product Exposed
Toddlers (SIPPET) were published. This prospective
randomized trial attempted to determine whether there
was a difference in the incidence of inhibitor develop-
ment rates between patients who use recombinant or
plasma-derived factor VIII concentrates. The results
suggest that plasma-derived factor VIII is associated
with a lower incidence of inhibitor development.37
Once patients develop an inhibitor, management of
their hemophilia becomes more complicated and expen-
sive. Inhibitors are measured in Bethesda units (BUs).
One BU is defined as the amount of antibody that neu-
tralizes 50% of the factor after 2 hours at 37°C. If the
inhibitor titer is < 5 BU, patients may still respond to
factor replacement with the missing factor protein, but
a higher dose will be required. In this case, response to
factor can be measured with routine factor assays, and
patients continue to receive the same factor replacement
product. Low-titer inhibitors are often transient.
Unfortunately, 60% of inhibitors are high titer (>5 BU),
and in this case, replacement of the missing factor is not
effective and alternative treatment is indicated.
Currently, there are 2 alternative treatment options
(bypassing agents) when patients have high-titer inhibi-
tors and no longer respond to replacement of the miss-
ing factor. The first is a plasma-derived, activated pro-
thrombin complex concentrate (aPCC), which combines
factors II, VII, IX, and X, with small amounts of factor
VIII. The second is a recombinant activated factor VII
(rFVIIa). Although bypassing agents do not replace the
factor protein that is deficient in hemophilia, both have
been proven to be effective in the management of
bleeding.38 Given the focus on prevention of joint dis-
ease and advances in the safety of factor products, there
has been increased interest in providing prophylactic
therapy to patients with inhibitors using bypassing
agents. Both bypassing agents have been shown to
reduce bleeding episodes in prospective clinical trials.39,40
The choice of which bypassing agent to use is left to the
hemophilia clinician and the patient/family, but there
are some considerations.
The aPCC is derived from plasma, which may give
pediatric clinicians pause because most of their patients
have received exclusively recombinant products.
Although the aPCC has a longer half-life than rVIIa, it
also takes longer to infuse (typically, 30-45 minutes) than
all other factors, which can be given by intravenous push
in less than 5 minutes, which may pose challenges for
patients on home infusion. Additionally, the aPCC has
factor IX and small amounts of factor VIII, so this may
be a contraindication for patients with hypersensitivity
222 Copyright © 2016 Infusion Nurses Society
Copyright © 2016 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited.
reactions to factor IX or an anamnestic response of their
inhibitor titer to factor exposure. Alternatively, rVIIa is a
recombinant product, which does not have an impact on
inhibitor titer. The volume is much smaller, so adminis-
tration is faster. However, rVIIa has a very short half-life
of approximately 2 hours, so frequent repeat dosing may
be necessary to manage bleeding episodes. Use of either
bypassing agent is complicated by the fact that there is
no standardized laboratory testing to measure treatment
response, so clinicians rely on subjective reports from
patients with minimal objective data. Lastly, patients
receiving either of these bypassing agents are at risk for
thrombosis because they are not deficient in the factor
proteins being administered. Caution should be used
with dosing, and close monitoring is important.41
Although the frequency of bleeding is not increased
in patients with inhibitors, management of bleeding
certainly becomes more complicated, expensive, and
less effective, so eradication of the inhibitor is para-
mount.42 Eradication has been achieved using immune
tolerance induction (ITI), although there are a number
of treatment regimens reported in the literature. Most
retrospective reviews indicate success rates of over 50%
in most treatment regimens.43 Because hemophilia B is
less common and the rate of inhibitors is much lower,
there is far less evidence in the literature about eradica-
tion. The limited cases in the registries include an over-
representation of patients with hypersensitivity reac-
tions who do not tend to respond to ITI, so there is little
consensus on ITI regimens for hemophilia B.44 There
are obvious downsides to using registry data to deter-
mine recommendations for therapy because there is
likely to be selection bias, which will skew the findings.
Most of the prospective investigations about ITI have
been done in hemophilia A patients with inhibitors.
The determination about when to initiate ITI is up to
the clinician and family. Data from several registries are
in agreement that patients are more likely to be success-
fully tolerized if their historical inhibitor titer is <200
BU. Comparison of findings in these registries also
seems to suggest a benefit to delaying the initiation of
ITI until the inhibitor titer was below 10 BU.43 However,
a recent retrospective review calls into question whether
the inhibitor titer at the time of ITI initiation is a predic-
tor of the outcome.45 Ultimately, initiation of ITI is
dependent on the willingness and ability of the patient
and family to be adherent to a difficult treatment regi-
men. Although some independent factors may have an
impact on success, it is imperative that patients on ITI
receive regular factor replacement because recurrence of
inhibitors is often associated with refractoriness to ITI.43
Most patients considering ITI will require frequent
factor replacement for an extended period of time, so
this often necessitates the placement of a CVAD. As
previously stated, the most commonly used CVAD in
patients with hemophilia is an implanted port, because
Journal of Infusion Nursing
it is associated with lower infection rates. However, the
infection rate is higher in younger patients. Not surpris-
ingly, the rate of infection is increased in younger chil-
dren and those who infuse daily.46
Once the determination is made to start ITI, a dosing
regimen must be selected. Like prophylactic regimens,
there have been a number of variations on ITI regimens
with varying dosing and administration of concomitant
medications. A prospective study of inhibitor patients in
the United States with hemophilia A looked at 2 dosing
regimens for ITI (200 IU/kg/d vs 50 IU/kg, 3 times week-
ly). Successful tolerization was defined as eradication of
the detectable inhibitor, recovery of at least 66% of factor
activity, and a half-life of at least 6 hours. Patients who
were tolerized usually had success within 33 months.
Whereas 70% of patients were tolerized on both treat-
ment arms, tolerization took longer on the low-dose arm
(15.5 months vs 10.6 months), and the incidence of bleed-
ing was higher. As a result, the study was closed early.44,47
DISCUSSION
Although it has been recognized that hemophilia has
been around for a very long time, huge strides have been
made in diagnosis, treatment, and management of com-
plications in just the past 60 years. Efforts are ongoing
to identify and educate potential carriers about the
benefits of early diagnosis and preparation for delivery
of a child with hemophilia. Development of safer prod-
ucts that can be infused to prevent bleeding and maxi-
mize adherence continues to be a focus in the hemo-
philia community. With the advent of prophylaxis,
patients have less joint disease. As a result, these
patients are living longer and more productive lives,
with less missed school and work. Adult patients with
comorbidities, such as hepatitis and HIV, are living
longer lives as a result of successful treatment strategies
of these chronic illnesses. As a result, hemophilia clini-
cians are now working to gain a better understanding of
the impact of aging on patients with hemophilia. The
future is bright for patients with hemophilia.
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