Joint Disease Management and Therapies Among Obese Hemophiliac with Alloantibody Inhibitors

1
Joint Disease Management and Therapies Among
Obese Hemophiliac with Alloantibody Inhibitors
Hong Nguyen, DO Craig Kessler, MD2 Sherry
Herman-Hilker, PT3
1Department of Medicine, Georgetown University
Hospital, Washington, DC 2Georgetown University
Medical Center, Washington, DC
Georgetown University
Concept Project in Progress
Introduction
STUDY AIMS Aim 1 To examine among various BMI
ranges, whether hemophiliacs with alloantibody
inhibitors receive different or similar
approaches to joint-specific therapies, e.g.
chemical or surgical synovectomies vs.
arthroplasty vs. total joint replacements, for
their joint disease compared to hemophiliacs
without alloantibody inhibitors over a 10 year
time period (1995-2005). It is hypothesized
that hemophiliacs with alloantibody inhibitors
and high BMI levels are less likely to be offered
or undergo invasive and definitive surgical
interventions, such as total joint replacements.
This trend may also be apparent when obese
non-inhibitor patients are compared to optimal
BMI patients without alloantibody
inhibitors. PRELIMINARY DATA
Individuals with hemophilia (who never received
primary prophylaxis) and hemorrhage-induced
arthropathy continue to require focused medical
and/or surgical approaches for their pain and
reduced mobility issues. As they age, these
needs will continue to increase. Obesity will be
expected to exacerbate these complications and
will also affect the success of any
interventions. There is a well-recognized
increased risk of bleeding with any surgery in
alloantibody inhibitor patients compared to
non-inhibitor patients and the ability to predict
whether adequate hemostasis will be achieved in
inhibitor patients with whatever by-passing
factor concentrate is administered in the
surgical scenario is difficult. This is
despite the fact that orthopedic surgery
(including synoviotheses and total joint
arthroplasties) among hemophiliacs with high
titers of alloantibody inhibitors titers is
considerably safer now with the availability of
recombinant factor VIIa (rFVIIa) and/or factor
eight inhibitor bypassing activity (FEIBA).
Nevertheless, because of these uncertainties in
hemostasis control, there is reluctance among
physician experts to recommend orthopedic surgery
in inhibitor patients until the level of pain and
limitation of joint function are great enough to
justify the risks of life and limb threatening
bleeding versus the ability to achieve an
improved quality of life. Little is known about
the relationship between obesity and its effects
on progression of joint disease among
hemophiliacs with inhibitors.
Aim 2 To compare rates of deterioration in
range-of-motion (ROM) parameters in selected
weight-bearing joints among multiple age and BMI
cohorts of HIV seronegative and seropositive
adult hemophiliacs (aged 19 years and older) with
alloantibody inhibitors over a 5 and 10 year time
period. The data will be stratified according
to A. High-titer alloantibody inhibitors and
use of only on demand infusion of Factor
replacements B. Low-titer alloantibody inhibitors
and use of only on demand infusion of Factor
replacements C. Low-titer alloantibody inhibitors
and use of immune tolerance induction D. High
titer alloantibody inhibitors and use of immune
tolerance induction It is hypothesized that
hemophiliacs across all BMI cohorts with high
titer alloantibody inhibitors (Groups A and D)
experience a greater rate of joint ROM
deterioration in their weight bearing joints
independent of the approaches to (ITI versus on
demand) and products utilized for their
replacement therapy.
Preliminary Data Discussion
The preliminary data on Aim 1 suggests that
hemophiliacs with alloantibody inhibitors and
high BMI levels are less likely to be offered or
undergo invasive and definitive surgical
interventions, across all age groups. This trend
seems to also be apparent when obese
non-inhibitor patients are compared to optimal
BMI patients without alloantibody inhibitors.
However, statistical analyses is limited due to
the low number of obese hemophiliacs with
alloantibody inhibiters who undergo joint
surgeries in the UDC database. For example, the
sample size for groups of obese hemophiliacs with
alloantibody inhibitors is at most 26 for each
age group.
Obesity and Hemophilia
Obesity rates have increased markedly, beginning
earlier in life, afflicting youth and adults,
including those with congenital hemophilia.
Obesity is known as a significant but potentially
modifiable risk factor involved in the
development and progression of musculoskeletal
complications, including increased risk of
fractures and advancement of osteoarthritis of
hips, knees, ankles, feet, and shoulders. In
young hemophiliacs with moderate to severe
disease, increased BMI is associated with greater
limitations in joint range of motion. The
presence of an alloantibody inhibitor confounds
joint health and concurrent obesity may
complicate adherence to and success of immune
tolerance induction regimens.
Next Steps
Both Aim 1 and 2 need to be revised to include
valid measures of joint range of motion and
deterioration. These measures will help define
the relationship between obesity, alloantibody
inhibitors and joint management among a
vulnerable population of hemophiliacs.

CDCs Universal Data Collection Project
Centers for disease Controls (CDC) Division of
Hereditary Blood Disorders, working with the
Nations 136 federally supported hemophilia
treatment centers, developed a system of routine
viral testing and standardized clinical data
collection known as the Universal Data (UDC)
Collection Project Since its inception in May
1998, testing has been performed and data have
been collected on over 18,000 people with
bleeding disorders Inclusion criteria (1) aged
2 yrs or older with a bleeding disorder due to
congenital deficiency or acquired inhibitors and
with a functional level of less than 50, or (2)
aged 2 years or older with a diagnosis by a
physician of von Willibrand disease 2
standardized collection forms 1. Initial
Registration form, includes demographics,
diagnosis information And 2. Annual visit form,
includes list of treatment information,
infectious disease, risk reduction, orthopedic
surgeries on one or more joints, log of all
bleeds and location of bleeds, height, weight,
ROM measurements In 2006, a Quality of Life
Questionnaire was added.
References
1. Scalone, L., et. al., Quality of Life
Associated to the Orthopaedic Status in
Hemophilic Patients with Inhibitors.
Hemophilia. 2006 Mar12(2)154-62. 2. Morfini,
M., et. al., European study on orthopaedic status
of haemophilia patients with inhibitors.
Hemophilia. 2007 Sep13(5)606-12. 3. Harms, S.,
et al., Obesity Increases the Liklihood of Total
Joint Replacement Surgery Among Younger Adults.
Int Orthop. 2007 Feb31(1)23-6. 4.
Rodriguez-Merchan, EC., Some Recent Developments
Regarding Arthropathy and Inhibitors in
Haemophilia. Haemophilia. 2008 Mar14(2)242-7. 5.
Rodriguez-Merchan, EC., et. al., Orthopaedic
Surgery for Inhibitor Patients a Series of 27
Procedures. Haemophilia. 2007 Sep13(5)613-9.
Acknowledgments
Thank you, Dr. Craig Kessler for your continuing
support and mentorship.