Pediatric Clinics of North America - CIPERJ

ADVANCES IN HEMOPHILIA
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prophylaxis can prevent this subclinical bleeding from producing even minimal
arthropathy years later.
Timing of prophylaxis
The question of when to start primary prophylaxis has been a subject of
controversy among hemophilia caregivers worldwide. To date, there is no
consensus. Several studies show that children who have hemophilia and
few or no joint bleeds [5–8] who are started on prophylaxis early (mean
age of 3 years) exhibit a better musculoskeletal outcome. Progression of
joint arthropathy, even after starting prophylaxis, is described in patients
who have at least five joint bleeds occurring at the same or different joints
[5–8].
In a study published by Astermark and colleagues [5], the only significant
predictor for development of hemophilic arthropathy was the age of patients
when prophylaxis was started. Using the Pettersson score, a scoring system
that allows radiologic evaluation of the joints in patients who have hemophilia,
Fischer and colleagues [9] described the Pettersson scores increasing
by 8% each year that prophylaxis was postponed after the first occurrence
of hemarthrosis. These studies show that irreversible joint damage may
follow after a few joint bleeds and that even early prophylaxis may not abrogate
that process completely. Therefore, worldwide recommendations to
start prophylaxis before joint damage are favored to promote joint integrity,
ideally before 3 years of age.
Secondary prophylaxis
Patients who have preexisting joint disease and who experience frequent
acute hemarthroses may be treated with periodic use of factor concentrates
for a short or long period of time to curtail bleeding recurrence. This
approach is known as secondary prophylaxis and is used commonly to minimize
bleeding frequency and lessen the progression of joint disease. Even
though secondary prophylaxis cannot reverse the changes of chronic arthropathy,
it may be beneficial by reducing frequency of bleeding, hospital
admissions, and lost days from school or work and by decreasing damage
progression.
The use of secondary prophylaxis versus on-demand therapy has been the
subject of various studies done in children and adults who have severe hemophilia
[10–12]. In summary, the results indicate that patients treated
with secondary prophylaxis have decreased number of joint bleeds at the expense
of higher clotting factor consumption. A recent study, however, does
not confirm the higher cost of this approach.
A long-term outcome study (follow-up of 22 years) published by Fischer
and colleagues [13] compared the costs of prophylaxis (primary and secondary)
versus secondary prophylaxis alone versus on-demand therapy in
patients who had severe hemophilia. In this study, short-term prophylaxis