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Paediatric care of the child with haemophilia.
Ljung, Rolf
Published in:
Haemophilia
DOI:
10.1046/j.1365-2516.2002.00631.x
2002
Link to publication
Citation for published version (APA):
Ljung, R. (2002). Paediatric care of the child with haemophilia.
Haemophilia
,
8
(3), 178-182.
https://doi.org/10.1046/j.1365-2516.2002.00631.x
Total number of authors:
1
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Paediatric care of the child with haemophilia
R. LJUNG
Departments of Paediatrics and Coagulation Disorders, Lund University, University Hospital, Sweden
Introduction
The future for a boy with newly diagnosed haemo-
philia is totally different in a developed compared
with a developing country. As I work with children
in Sweden, my perspective in this presentation is the
perspective of a paediatrician in a developed country.
What is today’s reality in some countries is the vision
for tomorrow for other countries. The aim of my
presentation is to focus on a few aspects of the care
of the child with haemophilia which I think are
important today, but also to take the opportunity to
speculate or have visions for the future. The aim is
not to give a comprehensive overview of all aspects
of haemophilia care in children.
To focus on the healthy part of a child
In countries with limited resources for health care, it
is natural that focus has to be on the disease itself,
and literally how to survive from day to day. In most
countries with well-developed health care, the ability
to treat haemophilia has dramatically improved
during the past decades due to the availability of
factor VIII and factor IX concentrates. The focus in
these countries should be switched towards the
healthy child and not the disorder itself. The word
haemophilia and the description of the disorder have
a great impact on how it is perceived by parents. It is
a disease with a dramatic history; older persons with
haemophilia and healthcare personnel remember
how it once was in developed countries.
I think that the first information given to a family
with a child who has been diagnosed as having
haemophilia is of crucial importance and influences
how this family and later the child will cope with
haemophilia in their daily lives. For the family, the
life with a child with haemophilia starts with this
information and it is often given by a paediatrician.
The experienced paediatrician knows how to inform
parents that their child has a chronic disorder. The
information should ideally be given to both parents
and, if possible, together with older siblings. As we
all know, parents are in a state of shock during this
first talk and may only remember fragments of the
information given. Our goal with this first talk
should be that they understand that ‘it is possible to
live a practically normal life with a normal life
expectancy although you have haemophilia’. Usually
the boy with haemophilia is too young to understand
the information, but if he is a little older, one has to
understand that the boy in this situation is in need of
different information from parents. It is important
that the boy does not feel guilt, having caused
problems and sorrow to his parents for not being
healthy. He has to understand that the sadness and
sorrow the parents may show are signs of love for
him. The small boy lives here and now and the future
is only what will happen during the next hours or
Summary. The paediatric care of children with
haemophilia in developed countries should focus on
the health of the child, not on the disorder. Gene
therapy offers the hope of an ultimate ‘cure’ for the
disorder, but until this is a viable proposition,
patients should be given more control over their
treatment, and the focus should be on ‘self-mon-
itored and self-adjusted’ prophylaxis. New instru-
ments for measuring joint function and radiographic
changes, and quality of life are valuable tools in
improving the treatment of paediatric care for
children with haemophilia.
Keywords: haemophilia A, haemophilia B, factor
VIII, factor IX.
Correspondence: R. Ljung, Departments of Paediatrics and
Coagulation Disorders, Lund University, University Hospital,
SE-205 02 Malmo
¨
, Sweden.
Tel.: + 46 40331639, fax: + 46 40336226,
E-mail: rolf.ljung@paediatrik.mas.lu.se
Accepted after revision 26 February 2002
Haemophilia (2002), 8, 178–182
178 2002 Blackwell Science Ltd
days – will the nurse take another blood sample?
Does he have to stay in the hospital? These questions
must be answered. The parents, however, have a
totally different perspective of time in this situation,
influenced by existential thoughts, for example, will
he survive into adulthood? Will he be able to play as
normal children? Will he be able to attend school and
get an education? Parents usually feel guilt for the
child being ill. It is easier to cope with something if
there is an explanation to it. The mother who might
be a genetic carrier is obviously at risk for feeling
guilt for the child’s disease but sometimes it may be
totally irrelevant events in the past that are brought
up as potential causes of the disorder. For an optimal
outcome of the crisis reaction, it is important to try
to find out if the parents have anything that they
consider they have done wrong in the past as an
explanation of the disorder.
The information given in the first conversation
should be repeated in subsequent meetings with the
parents to ensure that they have received all relevant
information. Positive information such as treatment
strategies with prophylaxis and the possibility to cure
the disease in the near future by gene therapy should
be given together with straightforward information
about complications such as the development of
inhibitors. All information during this sensitive
period has to be communicated by the same doctor
and nurse to avoid uncertainty and frustration,
which could result from the slight interpersonal
differences that exist between care-providers giving
the same medical information. One may wonder why
I put such effort into discussing these trivial things. It
is my belief that the psychological events and
processes at the time of diagnosis are the most
important factors in deciding if later we have to deal
with a ‘haemophilic child in a haemophilia family’ or
‘a healthy family with a child who feels healthy,
despite having a disorder called haemophilia’.
Gene therapy vs. prophylactic treatment
For the child with haemophilia, gene therapy is of
course the ultimate goal. Today, primary prophylac-
tic therapy may be considered as the gold standard of
therapy. However, this therapy is only offered to a
small proportion of children with haemophilia and,
due to its cost, it is widely debated. We do not know
when gene therapy will be a treatment option for all
children with haemophilia and we do not know if it
will offer a permanent or a periodic cure of the
disease. Furthermore, the problem with inhibitor
development will not be solved by gene therapy.
Thus, for the foreseeable future, there is a need to
refine the prophylactic treatment of children with
haemophilia. Today’s prophylactic treatment, in my
vision, should be developed to ‘self-monitored and
self-adjusted prophylaxis’. Measurement of factor (F)
VIII and FIX concentrations should be possible with
easy-to-use methods in the home setting in the same
way as blood glucose in a child with diabetes mellitus.
Depending on the planned activity, the factor con-
centration could be adjusted accordingly. A crucial
prerequisite for such an approach is uncomplicated
venous access allowing frequent injections.
It has been clearly shown that if FVIII or FIX is
given at shorter intervals, the total consumption of
concentrate may be reduced without resulting in a
less protective prophylaxis [1]. Even in early studies,
it was noted that scheduling short intervals between
infusions was more important than achieving high
peaks of plasma factor concentrations [2,3]. Thus,
we need to improve venous access devices to allow
frequent administration of concentrates to small
children. The first option should always be to use a
peripheral vein. If this is not feasible, another option
is a central venous line, preferably an implantable
venous access device such as the Port-A-Cath
[4–9].
As shown in Table 1, there seem to be two major
experiences concerning infections, the most serious
complication with central venous lines, in non-
inhibitor patients. One is » 0.2 infections per
1000 days [8,9] and the other » 1.0 (range 0.7–1.6)
per 1000 days [5,6,10]. Whether this is an acceptable
frequency of infections for this group of patients
depends on the situation and the treatment regimen
for the individual patient. The child prone to spon-
taneous bleeds, who should start primary prophylac-
tic treatment from the age of 1 year, is a greater
challenge for venous access than the child receiving
on-demand treatment with infrequent bleeds. The
indication for a central line should be discussed with
the parents, and the social situation and the need for
home treatment should be to be taken into account
when making a decision. The use of venous catheters
in children were studied in the centres belonging to
the European Paediatric Network for Haemophilia
Management and it was found that in three out of 19
centres, > 50% of the boys under the age of six had a
port while none had the device in seven out of 19
centres. A few children at some centres used ports
after the age of 6 years [11].
Some groups report the use of peripheral intra-
venous access devices in children [P.A.S. Ports, SIMS,
Deltec Inc., Slim-Ports (Bard)] [6]. These seem to be
well accepted by the children and parents. In young
children, it is less threatening to insert a needle in the
periphery of the body and they can avoid the visible
PAEDIATRIC CARE OF HAEMOPHILIA 179
2002 Blackwell Science Ltd Haemophilia (2002), 8, 178–182
profile of the port on the chest. However, peripheral
ports have been associated with a higher frequency of
thrombophlebitis and thrombosis, and the average
time the patient may benefit from the device is
probably shorter [6]. Another approach to venous
access could be a modified version of the Percuseal
(device under development; Percuseal Medical, Hus-
qvarna, Sweden) [12]. This device is implanted into
the subcutaneous tissue, with the top portion pro-
truding from the surface of the skin and enables
administration without skin puncture in an attempt
to combine the benefits from both an external and an
implanted device. Continuous infusion of factor
concentrates using portable pumps has been prac-
tised only on a short-term basis in haemophilic
patients, and not for the purpose of prophylaxis, but
may perhaps be a vision for the future.
The child with moderate or mild haemophilia
In a survey of 20 centres in Europe treating children
with haemophilia, it was found that most children
had severe haemophilia (52%) and only 29% mild
haemophilia [11]. The proportion of mild haemo-
philia has been found in epidemiological studies to be
50–55% of the total haemophilia population [13].
The results can be interpreted either as mild haemo-
philia being underdiagnosed in some countries or
more probablly, many boys with mild haemophilia
not being treated at haemophilia centres. For the
future, a goal should be that boys with mild
haemophilia should be registered and regularly seen
by paediatricians at haemophilia centres. In this way,
we can ensure that this group of boys receives the
same quality of information, general treatment and
optimal choice of concentrate as the boys with
clinically severe haemophilia.
Another interesting group to discuss for the future
are the children with moderate haemophilia (FVIII/
IX ¼ 1–5 U dL
–1
). Some of these children have the
same clinical manifestations as the boys with severe
haemophilia (<1 U dL
–1
), while some rarely bleed.
On the other hand, approximately 10–15% of the
boys with, by definition, severe haemophilia, have a
low bleeding tendency [14]. What effect does having
‘a low bleeding tendency’ as a child has on joint
function later in life? In the series studied by
Petterson and coworkers [15], some patients already
showed joint changes at the start of prophylaxis,
although they had had no clinically recognized joint
bleeds. This suggests that subclinical bleeds may
trigger the development of arthropathy in children
with only isolated clinical bleeds. In a country with a
well-developed prophylactic treatment of children
with severe haemophilia, the group at highest risk for
bleeding complications, excluding the patients with
inhibitors, are the ones with moderate haemophilia.
Do we know if they slowly develop arthropathy that
will be clinically manifested in adulthood? To be able
to answer this question we need better instruments to
monitor different aspects of joint status early in life.
New functional joint scoring systems
for children
Today, most countries use the WFH approved
orthopaedic scoring system and some also use a
radiological scoring system (Pettersson or Arnold–
Hilgartner scales) [15,16]. However, these scoring
systems were originally devised for the monitoring of
mainly adult patients 20–25 years ago and they are
not sensitive enough for the follow-up of the child
with haemophilia today who is being treated more
intensively. New joint evaluation systems have been
Study
Number of
patients
(n)
Rate of infection
per 1000 patient
days Comment
Blanchette et al. 1996 19 0.7 3 patients with
inhibitors, 3 HIV+
Perkins et al. 1997 35 1.2 (central)
0.7 (peripheral device) 7/32 inhibitor,
2/32 vWD
Ljung et al. 1998 53 0.19 11 patients with
inhibitors
Miller et al. 1998 41 0.14 Includes external
McMahon et al. 2000 58 1.6 (without inhibitor) 77/86 devices
Port-A-Cath
;
4.3 (with inhibitor) 37/58 patients
haemophilia
Table 1. The rate of infection in recent
series with haemophilia patients using
central venous lines [5,6,8–10].
180 R. LJUNG
Haemophilia (2002), 8, 178–182 2002 Blackwell Science Ltd
proposed by Manco-Johnson and coworkers, who
expanded the WFH joint examination instrument to
detect more subtle abnormalities of joint structure
and function, and also suggested a new scale tailored
to the dynamic growth and gait development of
children [17]. The Child instrument in that study
(n ¼ 43) was significantly correlated to the WFH pain
scale and was more sensitive to the performance
capabilities of young children. A similar attempt has
been made by the European Paediatric Network for
Hemophilia Management (PedNet), which has two
working groups charged with the tasks of developing
new paediatric orthopaedic and MRI scoring systems
[11]. Petrini and coworkers at the Karolinska Hospi-
tal, Stockholm, have in a small pilot study introduced
a new orthopaedic scoring based on the practical
experience as well as scores from the WFH scoring
system (personal communication). Parameters such
as swelling, muscle atrophy, crepitus on motion, and
flexion contracture were diversified into three instead
of two grades. Range of motion was subdivided by
degree instead of percentage. Axial deformity and
instability were replaced by gait and strength against
gravity. Two more parameters were added describing
a target joint and a joint with chronic synovitis.
The comparison of the original WFH scoring
system and the new scoring system adapted for
children, included a total of 116 haemophilia A and
B patients aged 4–18, 56 of whom were on primary
prophylaxis, 36 on secondary prophylaxis and 24 on
on-demand treatment. The two scoring systems were
applied to this patient population, stratified into
three age groups, 4–8, 9–13, and 14–18 years. On
primary prophylaxis, all except two children of the
oldest age group scored zero in both systems. On
secondary prophylaxis or on-demand treatment, the
age-matched mean score evaluated by the new
system was always higher (i.e. worse) than the score
generated with the old system. The new scoring
system reflected pathological alterations with a
higher sensitivity and will thus be a better instrument
to monitor the outcome of different therapeutic
regimens to prevent joint bleeding and its sequelae.
New radiographic scoring systems for children
Radiographic scoring is another way to monitor
disease progress in haemophilic arthropathy. Scoring
using conventional radiography has been useful, but
does not reveal early changes and minor progress of
the disease [15]. Magnetic resonance imaging (MRI)
has the advantage of visualizing changes in soft
tissues of the joint not detected by conventional
radiography system of haemophilia joints [18–21].
At this Congress, B. Lundin and coworkers, Lund
University Hospital, Sweden, present a new MRI
score with high resolution for progress of the disease
and which separates, in the format A(e:s:h), the
irreversible and reversible components of the arthro-
pathy. ‘A’ represents the irreversible components of
the arthropathy and the factors ‘E’, ‘S’ and ‘H’
represent effusion/haemarthrosis, synovial hypertro-
phy and haemosiderin, respectively. The ankles of
haemophilic boys, 39 ankles in 29 boys aged 4–16
years (mean 10 years), were investigated with MRI,
and classified twice by two experienced musculo-
skeletal radiologists. The results were compared for
intraobserver and interobserver agreement by calcu-
lation of kappa values. The statistical analysis
indicated a good intraobserver agreement and a
moderate or fair interobserver agreement.
This work was carried out as a collaboration in the
PedNet and the results indicate that MRI can be used
as a more sensitive tool for early signs of haemophilic
arthropathy than the conventional Pettersson radio-
logical score [15,22]. A well-documented MRI score
for haemophilic arthopathy has also been suggested
by the Denver group. This score may be designated
as ‘progressive’, i.e. progress is documented with a
higher score only if a finding belonging to a more
advanced level occur. The European score is ‘addit-
ive’, i.e. all findings influence the assessment, and the
sensitivity for progress is higher. Depending on the
aim of scoring, both systems have advantages and
disadvantages.
The quality of life of children with haemophilia
If prophylactic therapy should be improved and more
under the control of the child/parents, we would
need only to evaluate joint status in order to find the
strategy with the best cost–benefit or cost-effective-
ness. The evaluation of quality of life of the child is
the most important parameter to study. There are
very few studies that evaluate the quality of life of
children with haemophilia. An attempt has been
made by a joint study between the haemophilia
centres in Sweden, Denmark and Norway (A. Ozo-
lins, Department of Social Sciences, University of
Va
¨
xjo
¨
, Sweden; personal communication). The series
included 97 children on prophylactic treatment
(mean age 11.5), 22 on on-demand treatment (mean
age 11.6) and 992 age-matched controls (mean age
12.0). Boys on prophylactic treatment had 12.9
injections on average with factor concentrate per
month compared to 3.1 for the on-demand group.
The mean dose per injection was » 200 U higher for
the injections given on demand. These figures give a
PAEDIATRIC CARE OF HAEMOPHILIA 181
2002 Blackwell Science Ltd Haemophilia (2002), 8, 178–182
![Table 1. The rate of infection in recent series with haemophilia patients using central venous lines [5,6,8–10].](/figures/table-1-the-rate-of-infection-in-recent-series-with-2i3jcarv.webp)