15
Hemofilie
→
Author, year
(
ref.) Design Patients
Median age
at start of
prophylaxis,
years; range)
Main results
Nillson, 1992
Retrospective
cohort
35
(30
HA, 5 B)*
3
cohorts, age
at study evalu-
ation 3-6, 7-12
and 13-17 yrs
1.1 (1-1.5),
n=6
1.2 (0.5-2),
n=9
2.6 (1-4.5),
n=20
The two younger cohorts, starting prophylaxis before
the age of 2, minimized joint bleeds (median 0.1/
yr) and maintained OJS and PS 0, with higher FVIII/
IX consumption compared to patients who started
prophylaxis later, experiencing higher frequency of
joint bleeds (median 3/year) and worse joint status
(
median OJS and PS 1.2 and 4.8, respectively).
Aledort, 1994
Prospective,
observational
48
HA**
n.a.
At 6-year follow-up absence of progression of
OJS and PS was correlated to significantly lower
frequency of joint bleeds (mean, 1.8 vs. 11.2,
p=0.0001) and higher use of prophylaxis longer
than 45 weeks/year (9 vs. 0, p=0.002).
Kreuz, 1998
Retrospective
cohort
14
(11
HA, 3 HB)*
2
groups,
median age at
Study evaluation
12
and 9.
1.75 (1-2.5),
n=8
4.25 (3.1-5.5),
n=6
At study entry median OJS and PS 0 in both groups;
at 4-year follow-up similar frequency of joint bleeds
(0.14
vs. 0.22/year) but better joint outcome (median
PS 0 vs. 4) in the first group, starting prophylaxis
earlier and with history of ≤1 joint bleed.
van den Berg,
2001
Retrospective
cohort
22
HA
4.0
+/- 0.5
At mean age of 14.7 years, patients, starting prop-
hylaxis after 2-5 joint bleeds and a 2.3 years mean
from the first bleed, had mean 3.2 joint bleeds/year
and mean PS 2.3.
Panicker, 2002
Retrospective
cohort
20
(17
HA, 3 HB)
4.5
Reduction of mean frequency of major bleeds from
15.4
to 1.9/year at median age of 11.4 years, with
significant reduction of target joints and of number
of visits and hospitalisations.
Yee, 2002
Retrospective
cohort
29
(24
HA, 5 HB)
4.0 (2-12.7)
At median follow-up of 4.1 yrs (0.3-11.5),
reduction of median joint bleeds from 3.5 to
0.5/
year; 20 children (70%) maintained OJS 0,
in the orther 9 median OJS 1.5.
Manco-Johnson,
2007
Prospective,
randomised
65
HA
(57
evaluable)° 1.6 (≤2.5)
At median follow-up of 49 months, higher rate of
preserved joint structure at MRI evaluation (93% vs.
55%,
p=0.002) and lower median total and joint bleeds
(1.15
and 0.2 vs. 17.1 and 4.35, p<0.001) in children on
prophylaxis vs. intensive on-demand therapy.
Gringeri, 2008
Prospective,
randomised
40
HA
2.0 (
≤7)
At 10-years follow-up, lower median frequency of
joint bleeds (0.2 vs. 0.52 per month) and rate of
absence of radiological signs of arthropathy
(29%
vs. 74%, median PS 5 vs. 8) in children on
prophylaxis vs. on-demand therapy.
Abbreviations : n.a. : not available ; HA : haemophilia A ; HB : haemophilia B ; OJS : orthopaedic joint score ;
PS : Petterson score ; MRI : magnetic resonance imaging. *only patients considered on primary or early
secondary prophylaxis from the whole study population (60 patients, 52 HA, 8 HB, in the Swedish study,
21
patients, 18 HA, 3 HB in the German study) are mentioned. **the subgroup of children with orthopaedic
and Petterson scores 0 at study entry is considered.° for the primary end-point (preservation of joint structure
at MRI and/or radiography).
Table 1. Relevant clinical studies of primary / early
secondary prophylaxis in children with hemophilia