_____________________________

64 IM! 2005, eI. 55, 8e. 1

IN1RODUC1ION
1HL MANAGLMLN1 OI OS1LOAR1ICULAR
COMPLICA1IONS IN HALMOPHILIA
REVlEW ARTlCLES
loan L. Branea
1
, Dan V. Poenaru
1
, Marglt Serban
2
, Florln Blrsasteanu
S
, Jenel
M. Patrasou
1
RLZUMA1
ABS1RAC1
l| |+|u| u|||up+J| p|u||| || |+|up||||+ | ||||++|||u|+| ||J|| W||| u|(u|| ||+||||up+||]. l|| | ||+||] +u|+|J W||| |u| +||up|] +|J
+ ||J|] |u |u||| u|||+|u|. l| |u| u||u||] ||1u|1J |u||| +| ||, +||| +|J ||uW. u|u|||u|+|| ||J|| |+ +|W+] || || Wu|| |+| u|
|| u|||up+J|| W|u |+J |u ||+|, u|||| u||+||], || u|p||+||u| u| ||| J|+. l|| |+| +| | /p|+||J |] +| ||u|||||| |||| |u| ||u|+|||
|||||||u| +||| |+|u| Vlll +||||uJ|), ||+| +| ||J| || |+|+| |+|u| Vlll u||||u||u| u|p|||] ||||||||.
u |u p|u||| +u|+|J W||| u|u+|||u|+| u|p||+||u| || ||| J|+, |u||| W||| || ||| |||+||+| u|, |+|up||||+ ||+|| u| u| || |u|
J|+1uu||J p+|||| +|u||, u||| |+|JJ + J||||u|| u| ||pu||| |u ||+|. |uW1|, || || p|| u| + u|p|| J|+|u| +|J u| +J(u+| u||||u||u|,
|| 1u|u||u| |uW+|J ||u|| +||||up+||] +| | |+J|+||] |uWJ JuW| u| 1| +|||J. A|u, || || u|J|||u|, || u||+| ||+|||| +| | +pp||J
W||| ||||+| ||| |u || |u||+|up|||| pupu|+||u|. S]|u1|u|] u||+|, |||+| u| |+J|u+||1) +|J u||| p|uJu| |u||| J|||J|||, u|u|u||,
+||||up|+|] u| +||||uJ|) |+| |+||| |u||| W||| || +1+||+|||||] u| |+|u| Vlll, lX +|J Vll+ u||||+|.
A |u|||J||p|||+|] +pp|u+| u|p|||| || u|||up+J| u|u|, || |+|+|u|u||, p|]|u|||+p|| +|J uu+||] || p+J|+||||+|, || + p|+||J |+|up||||+
+| ||| | || |] |u u || ||+||| u|u+|||u|+| u|p||+||u| || |+|up||||+.
key werds: |+|up||||+, +||||up+||], u||+| ||+||||, |+|+||||u|.
!
0|||upJ| +|J l|+u|+|u|u] C|||| Z,
Z
PJ|+||| C|||| 3,
3
p+|||||
u| R+J|u|u] +|J |J|+| l|+||, V||u| B+| u||1|||] u| |J||| +|J
P|+||+], l|||u+|+
Cu||pu|J| |u.
lu+| |. B|+|+, Zc+ B+|u |+|+|| S||., l|||u+|+, l|. -4J4J5Z9JZ
E|+||. |u+|_||+|+@|u||+||.u|
R|1J |u| pu|||+||u|. . , ZJJ4. R1|J. ||. Z!, ZJJ5.
P|u|||+ |+|u|+ u||upJ|+ || ||u|||| | ||+|+ ||||++|||u|+|+ u ||+|||up+|| u|1||+. A+|+ | || ||+| +u|+|+ u +||u|| |uu|+|+ |
u u ||J|||+ +|| |||+|| +|||u|+|+. C| |+| +||| +|||u|+||| u|| |u||||, ||| | u|u|. S||+|+ |u|||u|+|||+ + u||||u|| J|||u|J+u|+ p|||p+|+
||| + u||upJu|u| ||+| + ||+|, u|u|| |||u||+|, u|p||+|||| +|| |u||. A+|+ |+|+ pu+| || u|||u|+ J u| |||| ||u||||| p|||u |||||||u||
||u|+||| +|||u|p| +||||+|u| Vlll) +| pu+| |+ ||||||| ||+|+|||u| u||||u||1 |+| u |+|u| Vlll.
+|u|||+ p|u||||u| +u|+| ||+|+|||u|u| u|p||+||||u| u|u+|||u|+| || ++|+ |u+|+, p|u| | u|u|u| ||J|+|, ||u|||||| |+|| u|+ J|||| | |+|
J|+1u||+| +|u||| J p+||||, u||J|+|| +J+ J|||||| +u |||+|+||||. l| p|||+ u|u| J|+|u|| u|p|| | + u|u| ||+|+||| u||||u||1 +J1+|
pu+| u|||| |||||||+ +u ||+| up|||+ p|u||| +|||up+||||u| ||u||||. lu|uJ+|+, ||+|+|||u| |||u||+| pu+| || +p||+| || +| u|J|||| u ||u|| ||+||1
||||+| u p+||||| |||u|||||. S||u1|u||+ |||u||+|+, |+J|u+||1+ +u ||||+), p|u| | +|| p|uJu|| J|||J+|+ +|||u|+|+, +|||up|+||+, u|u|u||+,
+|||uJ+) +u J1||| |+||| uJ+|+ u J|pu|||||||+|+ u||||+||u| J |+|u| J u+u|+| Vlll, lX | Vll+.
u| +|u|J |u|||J||p|||+| |||| u||upJ, ||+|u|u, |||u||||u||+pu| |, J u|||, |J| pJ|+||u || +J|u| u|u| ||| J ||+|+||| +| ||u||||| | ||+
|u||| || ||+|+|+ |||u| u|u+|||u|+| || ||u||||.
00vIate cheIe: ||u||||, +|||up+||, |||u|| u||upJ|+, u|p||+||| u|u+|||u|+|, ||+|||u+
Haemophilia is a hereditary sex-linked disease due
to a defective gene of the X chromosome, resulting in
an insufcient production of the VIIIth coagulation
factor in type A haemophilia (85% of cases) or the
IXth factor in type B haemophilia.
1-3
There are 3
forms of this disease to be distinguished: the severe
form, which accounts for more than half of the cases,
having decient factor blood levels < 1%, a moderate
form with factor levels between 1 and 5%, and a
mild form with a factor level >5%. The hemorrhagic
episodes in joints and muscles occur spontaneously in
the severe form, following minor trauma in moderate,
and only after major trauma or surgery in mild forms
of haemophilia.
Patients with severe haemophilia suffer from
repeated hemarthrosis with the early occurrence of
haemophilic arthropathy. The knee is most commonly
affected (30%) followed by elbow (25%), ankle (15%),
hip (5%) and other joints (<2.5%).
4,5
Joint lesions
usually evolve from hemarthrosis to chronic synovitis
_____________________________
Ieaa l. 8raaea et aI 65
and extensive joint surface erosions and, nally, to
the end stage of articular impairment haemophilic
chronic arthropathy.
6
Other non-haemophilic diseases are characterized
by a coagulation factor decit that can lead to chronic
synovitis and arthropathy. Von Willebrand disease,
together with coagulation factor V, VII, X, XI can affect
both sexes and evolve towards chronic arthropathy.
1,2,7,8

On rare occasions, a female carrying the haemophilic
gene may have sufciently low factor levels in order
to have osteoarticular complications.
2,4
Because of
the long list of hemorrhagic diathesis, careful patient
history and detection of possible coagulation problems
is critical.
4
Pathology and clinical features
The restitution of the joint function will always
be complete after the rst hemarthrosis; unfortunately,
the hemarthrosis is sure to recur and will progress in
adolescence or in early adulthood towards chronic
arthropathy.
6
Recurrence of joint effusions will produce
an alteration of joint structures. The synovium, irritated
by haematic dross, is inamed and hypertrophies, the
articular cartilage is attacked by proteolytic enzymes
from blood and, at its periphery, by the secondary
synovial hyperplasia.
2
After every hemarthrosis of the
same joint, the level of recovery will be lower, slowly,
favorized by subchondral additional bleeding, joint
lesions will become chronic arthropathy.
6-8
At this
stage, between painful episodes, both spontaneous
or provoked by repeated movements or effort, the
joint remains deformed and swollen, the adjacent
muscles suffers atrophy and soon the epiphysis start
to hypertrophy and widen.
8-10
Finally, the evolution is
toward brous, disabling ankylosis, causing numerous
social problems.
2,4,11
The haemophiliac can present numerous
deformities, vicious positions, joint stiffness, muscle
or capsular retractions that can induce a exum or
a valgus deviation of the knee associated with an
external rotation of the calf. At the ankle level equinus
is common. The hip is not commonly affected, but
can adopt a exion-abduction-external rotation
position.
6,7,10,12
The joint troubles of the upper limb are
less spectacular as in the lower limb. At the shoulder
level chronic arthropathy usually results in a substantial
joint mobility limitation. Hemarthrosis accelerate the
maturation of ossication nucleae, without generating
important limb discrepancy.
7
Radiological changes
One of the earliest signs will be the narrowing
of the joint space followed by moderate osteophytic
reaction. At the pressure points level subcondral
osteosclerosis can appear. Joint surface will become
irregular, eroded, with indentations. The epiphyses are
increased in volume and show a blowed aspect.
10

Knees can present a widening of the intercondylar
notch and decreased patellar height. A atten talar
dome is commonly found in ankles. In the shoulder, the
osteolytic lesions are commonly found at the humeral
neck level, similarly to the elbow, where widening of
the bony surfaces, the attening of the radial head,
joint narrowing and osteophyte formation can be
associated.
10,13
In latter stages one can mark out partial
or total dislocations. Muscular haematoma sometimes
determine soft tissue calcications and even osteoma-
like images.
14
Two classication of imagistic changes in
hemophilic arthropathy are widely used: the Pettersson
and Arnold-Hilgartner scores.
6,7,10,14
The average
Pettersson score for 12 consecutive young patients
operated in our service for knee and elbow chronic
arthropathy was 8 (13 is maximum, 0 is normal).
16,17
MRI will give an excellent assessment of both bone
and soft tissues lesions.
14
Echography is useful in
detecting haematomas, and is currently nding a role
in the evaluation of the haemophilic knee joint.
18
FI0re 1. u|||+||+| || ||u|| +||||up+||] || + !Z ]+| u|J |]p A
1| ||up||||+
_____________________________
66 IM! 2005, eI. 55, 8e. 1
Generally, the treatment has 2 distinct goals:
to obtain the haemorrhage cessation and maintain
haemostasis until cicatrisation. Apart from substitution
treatment, one should improve on the haemostatic
environment using local measures. These can be
direct, like prolonged compression at the bleeding
point, strict immobilisation of the affected region,
blood and clot evacuation, or indirect measures: the
battle against secondary inammatory changes using
NSAIDS or corticotherapy, antibiotics in the presence
Other findings
Barnes, Monagle et al. reported osteopenia in all
of 19 children suffering from severe haemophilia.
15

Thus they recommend screening and early detection
of these problems in young haemophiliacs.
The decrease in bone density translated into
osteopenia or patent osteoporosis was found in 11
out of 12 patients with moderate or severe chronic
haemophilic arthropathy treated in 2
nd
Orthopaedic
Clinic of Timisoara.
16
DXA osteotomodensitometry
targeted lumbar spine and hip joint.
An early diagnosis of haemophilia has its main
premise in a thorough knowledge from all the
physicians of epidemiology and capital symptoms
of this disease.
4,12
In our country, 15.38% of the
haemophiliacs are diagnosed following major
complications after surgery, and 16.13% have severe
postoperative anaemia or haemorrhagic shock at
diagnosis.
4
Also, it has been considered that in half of
cases an early active diagnosis could be reached before
the onset of clinical signs, but is hindered by inadequate
attention given to family history during anamnesis.
4
Beginning the prophylaxis treatment together with
early synovectomy of the hemarthrosis targeted joints
can prevent the onset of chronic arthropathy.
19-21
FI0re 2. B||+||+| ||uW ||u|| +||||up+||] || + 3Z ]+| u|J 1| |]p B)
of infectious risk, and the offset of physiological
brinolytic process with brinolytic inhibitors.
22
Substitution treatment. Haemophilia treatment
became efcient starting 1940, when whole blood
transfusion were rst used.
2
Substitution treatment
rapidly evolved with the use of fresh frozen plasma
and cryoprecipitate (the precipitating proteins from
fresh frozen plasma heated at 4C, rich in factor VIII
and brinogen) and in 1970 with the use of specic
factor concentrate.
2
Still, each of these methods
needs the use of human blood, with devastating
consequences due to the possible viral transmission of
HIV and B and C hepatitis. To eliminate this problem,
monoclonal puried factor concentrate using afnity
cromatography or recombinant factor VIII and
factor IX (a synthetic product prepared in Chinese
hamster egg cells or in baby hamster renal cells), are
today the substitution treatment of choice.
2,3,23
The
substitution treatment in B type haemophilia includes
the administration of factor IX factor concentrate or
fresh frozen plasma. Cryoprecipitate and factor VIII
have no effect.
Treatment of acute events in mild to moderate
forms of haemophilia associates local measures with
desmopresine administration, which increases factor
VIII and von Willebrand factor levels.
24
On demand treatment. This means substitution
treatment prior to the constitution of joint swelling.
Hemarthrosis is usually preceded by a strange sensation
called haemophilic aura.
2-4
This treatment can imply
home administration of FVIII, avoiding hospital
environment. The method is based on the ability of
the patient and parent to detect the rst symptoms of
the illness and on the comunication between family
and physician.
25
Prophilactic treatment. Firstly used by Nilsson in
Sweden in 1958, this approach seeks to maintain factor
VIII levels inside 1-5% on almost permanent basis.
26

Factor VIII concentrate is administrated 3 times/week
and factor IX twice a week.
20,26
It is astronomically
expensive (440.000 $/year according to Rodriguez-
Merchan),
27
and with complicated maintenance of a
non-infected venous access. It is reserved to severe
forms of haemophilia. Its main justication is the low
rate of chronic poliarthropathy in moderate forms of
haemophilia (factor levels=1-5%). In some countries,
prophylaxis started at the age of 2, before the rst
hemarthrosis, proved to avoid the onset of chronic
arthropathy in adulthood.
20,26
Analgesia. The optimal choice is patient controlled
analgesia. A high tolerance to opiates usually exists in
haemophiliacs, so one should watch out for possible
CONSLRVA1IVL 1RLA1MLN1
_____________________________
Ieaa l. 8raaea et aI 67
which permits a concurrent workup in ideal conditions
for different muscle groups of the lower limb and
pelvic girdle.
1reatment of haemophilic neurapraxy. This
problem is caused by bleeding adjacent to nerves
like the sciatic, femoral or peroneal. The treatment is
usually conservative with substitution, bed rest and
physiotherapy. If an improvement is not achieved,
surgical treatment might be considered. Neurolysis
of the ulnar nerve may be necessary if ulnar paralysis
occurs in elbow hemarthrosis.
32
Non-surgical synovectomy (synoviorthesis).
Can be chemical or radioactive. This term describes an
intraarticular injection of a substance that will produce
synovial sclerosis of an inamed, hypertrophied
synovial membrane. There are two groups of drugs,
chemical and radioisotopical, both used with great
success.
Radioactive synovectomy. The indications are
low activity synovitis (joint pressure can cause leakage
of isotopes outside the joint with irritation and joint
stula) with minimal radiographic changes.
33,34,35
Used
isotopes are Au
198
or Itrium
90
. Slow energy release
produces the destruction of synovial membrane and
subsynovial connective tissue resulting in an avascular
tissue. Radiation penetrates for 1-4 mm in depth.
36

Chemical synovectomy. The indications are
stage I and II synovitis with 3 haemorrhagic episodes
in 6 months and reccurent hemarthrosis with chronic
synovitis and decreased joint mobility.
36,37
It is not
indicated during acute hemarthrosis. Synoviorthesis
with Rifampicine has a proteolitic effect producing
brosis in subsynovial venous plexus similarly to
Adriamicine in pleurodesis.
37
Until recently, some concerns on the risk of
radioactive synoviorthesis on an immature skeleton
due to possible lesions of growth cartilage and
cromosomial aberrations.
33
Recent studies do not
endorse this hypothesis.
34-35,37
An average efcacy
of 76-80% of cases using radioactive synovectomy
without any complication due to radioactivity has
been reported.
35
In a review of the literature, Heim
states that synoviorthesis is the procedure of choice
in the treatment of haemophilic synovectomy, if
conservative treatment fails to control joint bleeding
and the synovium starts to hypertrophy.
37
Rehabilitation in haemophiliacs.
J. Haemarthrosis. It is necessary to break the
vicious circle of amyotrophy and joint instability which
rapidly follows a hemarthrosis.
22
Once the pain is
controlled, rehab is started during the immobilisation
period and will be exclusively manual, on bedside.
addiction.
28
Higher doses of analgesics are to be
administered and long term treatment is necessary.
The optimal administration modality is intravenous
or subcutaneous, not intramuscular. Aspirin should
be avoided due to its antiaggregant properties, but
specic COX2 inhibitors can be administered.
29
1reatment of acute haemarthrosis. The key
to prevent chronic arthropathy is to treat the rst
hemarthrosis before the onset of chronic synovitis
and joint erosions. Joint aspiration is controversial
due to its infectious risk.
6
Joint aspiration can thus be
performed only if factor levels have reached 20% and
not later than 12 hours after the bleeding onset. Luck,
Silva and Rodriguez-Merchan (2004) recommend
aggressive hemarthrosis treatment in a previously
healthy joint using joint aspiration puncture under
substitution treatment.
30
In joints already suffering
from moderate and severe chronic arthropathy, the
same authors indicate joint aspiration for pain control.
Joint rest for hemarthrosis of the lower limb should
include bed rest (one day) followed by walking with
crutches without weightbearing, together with limb
elevation with the patient in sitting position (3-4 days).
Elastic bandage is useful at knees although painful
joints should be immobilized in a posterior splint.
Weight lifting is prohibited until the remission of the
bleeding (4-5 days). Ice application for 24-48 hours
can facilitate pain and bleeding volume control. Ice
application efciency resides not only in its physical
effects but also in its simplicity and ease of use.
22
Subacute hemarthrosis should be treated with
substitution treatment and 2-3 weeks to 6-8 weeksof
joint immobilization on a semi exible device.
28
The
decient factor should be administered 3 times weekly,
to obtain 20-30% of normal blood levels. After each
administration the patient should follow an exercise
program concentrated on active mobilisation under
the supervision of an experienced physiotherapist.
29
Haematoma treatment. In iliopsoas haematomas,
a sharp inguinal pain and psoitis is present. A crural
paralysis can coexist and can be afrmed through
quadricipital decit, patellar reex abolition and
anterior thigh anaesthesia.
6,22,30
Differential diagnosis
with hip hemarthrosis
30
is difcult. Echography, CT or
MRI conrms the diagnostic. The treatment consists
of aggressive substitution (100%), and immobilisation.
Femoral nerve paralysis will be treated with electro
stimulation (exponential currents) and through active
assisted extension attempts.
22
In the psoitis stage,
traction and reduction manoeuvres are vane and
dangerous.
31
As in the treatment of hemarthrosis, the
swimming pool represents a very effective treatment
_____________________________
68 IM! 2005, eI. 55, 8e. 1
Any force manoeuvre is prohibited. Immediately
after the pain disappears, one can start mobilisation,
aiming to recover joint movement through gentle
postures and active mobilisation. Walking will be
authorised starting with the 10th day
29
, depending
on evolution, with or without the help of a plastic or
plaster of Paris splint, to avoid exum recurrence and
prevents any muscular insufciency, a factor of knee
instability. When exion contracture occur, it should
be treated early and aggressively to prevent irreversible
changes.
30
A 2-3 days old exion contracture can be
corrected using continuous skin traction followed
by recuperation treatment and orthesis.
28
This is the
moment in which haemophiliacs can beneciate
from swimming pool re-education. During water
immersion, due to Archimedess law, a reduction of
body weight is obtained and joint loading is decreased.
Associated muscular contractions are dimmed by water
temperature (34-35 C, so called neutral temperature),
and their additional compression is diminished; the
algogenic substance production is stopped by these
measures.
22
This last consideration explains the relief
of residual pain during balneophysiotherapy and its
fortunate effects on rehabilitation. It is important to
know that massage has no effect in haemophiliacs and
is contraindicated.
28
2. Chronic arthropathy. At this stage of the
disease rehab is limited to the correction of mobility
loss with regards to the joint status. Postures and
mobilisation are of outmost importance and must be
performed following biomechanical axes. Additionally,
different types of orthosis with regards to joint levels
and deformity can be used. Passive orthosis which
reduce exum but do not authorize function can be
rapidly replaced with splints or orthosis which maintain
extension or permit a low degree exum and permit
loading and walking.
29
Through therapeutical movement repetitions we
can obtain an increased joint mobility and stability.
In severe cases where patient independency is at
risk, ergo therapy will help re-educate the patient
regarding daily activities. Thus he will learn again self
hygiene, dressing-undressing, transfer (from bed to
pram), in short terms to resume an independent life.
6
Mecanotherapy is prohibited in haemophiliac, except
ergometric bicycle with variable pedal length.
23
In the
particular case of surgical intervention, which are by
no means exceptional in haemophiliacs, rehab will be
crucial in postoperative period and will aim to recover
normal tonicity and trophicity to the muscles and,
subsequently, to obtain normal mobility.
Admittance in a specialized centre and schooling
during this period is indicated (as is the case with
Cristian Serban Center in Buzias).
4,23
Circulating inhibitors. Substitution treatment
often leads (especially after repeated use 15%
from severe haemophilia cases according to
some authors) to the development of antibodies
directed against factor VIII or IXcirculating
inhibitors.
38
Their presence demands the use of
much higher substitution factor amounts with
often poor results and can contraindicate elective
surgery.
2,25,27,30
A modern approach to this problem
consists in the administration of coagulation
factors which can bypass factor VIII and factor
IX respectively inside the coagulation cascade.
In type A haemophilia this agent is factorVIIa.
25

Unfortunately the half-time of this factor is only 2
hours and its cost is several times higher than that
of recombinant FVIII.
30
It is essential to detect the
presence of circulating inhibitors before starting
any substitution regimen.
25,30,34,38
This disease should be precisely diagnosed
before even considering surgical treatment.
4
Correct substitution cannot be achieved without the
identication and dosage of the missing factor. It is
also crucial to determine a few days before surgery if
the patient has developed factor circulating inhibitors,
because this will impair haematological treatment and
can hinder an elective procedure.
2,25,27,30
Additionally,
factor dosage should be obtained just prior to surgery.
The hematocrite should be determined daily for a few
days postop, especially in A, B and AB groups, where
a positive haemolytic Coombs anaemia is possible.
2
Also the HIV and viral hepatitis status must be known
before surgery.
After a carefull screening for possible circulating
inhibitors, a substitution regimen for orthopaedic
surgery aim to obtain 100% of factor activity
immediately prior to surgery (1 IU/kg will classically
raise factor concentration by 2%), and then
progressively decrease dosage in order to maintain
levels above 5% for periods depending on the
amplitude of the surgical intervention. Factor levels
should be rechecked immediately after surgery, then
every 1 or 2 days in major procedures.
16,30
If vigorous
physical therapy is needed, some 30% of normal factor
level must be obtained prior to therapy.
29
General principles for surgery. The general
principles, indications and contraindications for
elective surgery are summarized in Table 1.
In the knee arthropaties operated upon arthro-
SURGICAL 1RLA1MLN1
_____________________________
Ieaa l. 8raaea et aI 69
scopically we have used postoperative transfusion
using a CBS II Stryker device.
16
About 85% of patients
with severe or moderate haemophilia operated in our
clinic were infected with either B, C or both hepatitis
viruses.
17
Additional personnel precautions are
therefore welcomed.
Surgical synovectomy
The removal of the synovium from a haemophilic
joint is a major procedure of joint discharge which
removes a thick, hypertrophic, hypervascular tissue
mass which releases intraarticularly toxic enzimes like
D catepsine, and constitutes a source of reccurent
haemorrhage due to the its high friability and low
absorption capabilities.
8
Open synovectomy
First reports came from Storti and Ascari.
44
It is actually scarcely used because it offers only a
reduction of pain and hemarthrosis frequence but do
not improve joint mobility and do not prevent further
joint deterioration.
7,31,44,45
Arthroscopic synovectomy
First experiences were reported by Kim and
Wiedel in 1983.
46
The indications are chronic
haemophilic synovitis persistent for more than
six months and without response to conservative
treatment, and also as a adjuvant procedure after
non-surgical synovectomy.
43
It offers the reduction of
hemarthrosis and pain with no or little improvement
on mobility.
16,31,43,44
It is a relatively safe method and
with satisfying results. The only relative disadvantage
is the weak postoperative bleeding control and the risk
for additional hemarthrosis.
16,31
It should be performed
early in evolution.
45
It is the procedure with the highest
proven efcacy and the only one who passed the test
of time. Its main indication is synovectomy of the knee
joint. Many authors
16,31,32, 41,43-46,48
have described the
comparative results on open knee synovectomy and
arthroscopy on patients with classic haemophilia.
They concluded that in both groups hemarthrosis
frequency was signicantly reduced. Arthropathy had
progressed in both groups in the majority of cases.
The arthroscopic group had a longer surgery but
shorter hospitalisation and lower factor consumption.
Arthroscopy produced a lower morbidity rate.
Our experience on 12 patients conrms this
data, with a clear decrease in pain and hemarthrosis
frequency together with a modest increase in joint
mobility.
16,17
The elbow is a likely localisation (the most common
after the knee) of reccurent haemorrhage followed by
widening of the radial head and degenerative arthritis
of the radio-ulnar and ulno-trochlear joints. Results
reported by Le Balch et al. were satisfactory with
pain relief following open synovectomy on a single
external incision and radial head excision in patients
with a mature skeleton.
49
The improvement of
exion-extension movements of the elbow cannot be
expected, but pronosupinaton is usually increased.
Three elbows in 2 patients operated in our clinic
beneted from this procedure with good results
and social and professional integration. Due to the
friable synovium with vilonodular hypertrophy,
the arthroscopic shaver proved to be very useful
for synovial abrasion. The pronosupination was
signicantly improved at 6 months and no recurrent
bleeding occurred in the operated elbows.
16
Synovectomy has been proven useful for the
ankle joint. Greene described the results after ankle
synovectomy on 5 patients who failed conservative
treatment and had recurrent hemarthrosis and
palpable synovial hypertrophy.
47
Follow up has
shown a signicant subsidence of hemarthrosis and
increased range of motion in all patients. Greene
recommended open synovectomy in detriment of
IahIe 1. G||+| p||||p| |u| |||1 u||]

_____________________________
70 IM! 2005, eI. 55, 8e. 1
arthroscopy, because of the difcult shaving of the
posterior synovial tissue from the maleolar crypts and
risk of cartilage deterioration, even when a postero-
lateral approach and external xator joint distraction
was used. Moreover, ankle rehab proved easier than in
knee or elbow.
29,47
Knee arthroplasty
Joint surfaces erosions, together with subcondral
cysts and marked osteopenia can cause a decient bone
stock and a higher risk for perioperative fracture.
7,31,32

The disadvantages of the technique are a much
higher infection rate (7 times higher)
31
than routine
arthroplasty, the risk of early implant loosening,
arthroplasty failure, together with the fact that the vast
majority of patients are young and active. The partially
dislocated patella, usually externally, is eroded taking
a shell appearance, inadequate for the reception
of a prosthetic component. Because of synovial
hypertrophy and arthrobrosis, the approach is slower
and more difcult. The main indication for surgery is
disabling knee pain and deformity.
31,32,50
In preoperative planning and during intervention
the following aspects should be taken into
consideration:
1. The necessity of a large bony resection to correct
deformity, which might need an additionally stabilized
implant, the use of relatively small components and a
relative muscular atrophy with altered functionality.
2. A ligamentary disequilibrium after asymmetric
resection to correct deformity.
3. Numerous technical difculties which often
require complementary gestures (capsulo-ligamentary
release, subperiosteal disinsertion of the popliteal
tendon and of the lateral collateral ligament in a marked
valgus deformity, almost systematic semimembranous
disinsertion for genu varum,
50,51
tibial corrective
osteotomies and distal femoral osteotomies.
54,55
Most authors
31,32,50,51,52
recommend the use of
cemented tricompartimental prosthetic designs. The
cement can be used to cover the free osteotomy planes
to prevent bleeding.
Range of motion is not substantially improved
after arthroplasty.
50
Manipulations can be performed
between the 7th and 10th postoperative day, before
the formation of adherences.
29
Physiokynetotherapy
is essential for a good result and is postoperatively
continued for 6-9 weeks. 28 It needs factor protection
in the rst 3 weeks (30% from normal concentration
before each session)
29
and an excellent patient
compliance.
Hip arthroplasty
A unic aspect in these patients is the remarkable
limp with a stiff lower limb due to knee and ankle
arthrobrosis.
31
This produces increased tensions on
the hip because of the length of the lever arm and loss
of the shock absorbent function of knee and ankle.
In patients with important hip destruction, total hip
arthroplasty was extremely efcient. Joint mobility is
largely improved after this procedure.
54
Arthrodesis of the hip is contraindicated even
in young patients due to the presence of knee
arthropathy.
32
FI0re 3. A||||uup| ]|u1|u|]. |u| || ]|u1|+| ||u|J||||
||p||+||u|
FI0re 4. E||uW ]|u1|u|] +|J |+J|+| |+J /||u| || + 3Z ].u. W|||
1| B |]p ||up||||+
_____________________________
Ieaa l. 8raaea et aI 71
Unlike in the knee, cemented prosthesis have not
performed as well as non-cemented designs. A reason
for the early loosening of hip prosthesis in haemophilia
can be the additional stress of the limp. Another
consideration refers to the possibility of bone-cement
interface bleeding.
40,54
Elbow arthroplasty in haemophiliacs is rarely
performed due to limited reconstructive options in
case of an infection.
31,32
It can become an option in
the future. There are few studies on small series on
shoulder arthroplasty in haemophiliacs, especially
because of the good results of arthrodesis.
6,7,31,40
One
of the problems seems to be the insufcient bone
stock at the glenoid cavity level. 31 The increase in
range of motion after arthroplasty is also modest.
31
Knee arthrodesis is to be considered in extremely
damaged joints with exum and axial deformity,
especially in young patients, where endoprosthethic
arthroplasty is impossible. It has the advantages of good
functional results and correction of joint deformity. It
is crucial however to preserve the contralateral joint in
a good condition.
6,7,40
Ankle and shoulder arthrodesis prove
satisfactory on small series of patients with
haemophilia.
6,7,31,33,40
The use of internal xation in
detriment of the external xation is recommended to
eliminate bleeding and infection around the xation
rods.
33
Flexion contractures can be corrected by
removing bony ridges during arthrodesis.
33
Luck et
al. recommend tibiotalar compression arthrodesis to
relieve pain, reduce hemarthrosis and equina in adult
patients with haemophilia.
31
Shoulder arthrodesis
presents the privilege of a lower infection rate, longer
life span and force in the upper limb, compared to
arthroplasty.
31,32
The optimal arthrodesis position
is 20-30 abduction, 30 exion and 30-40 internal
rotation.
31
Corrective osteotomy
For hemophiliacs with axial deformities osteotomies
can be necessary.
52,53,55,56
In patients with symptomatic
genu varum, proximal tibial valgus osteotomy can be
performed.
52,53,55
Rodriguez-Merchan et al. described
14 haemophiliacs suffering from symptomatic genu
varum treated with osteotomy. They preferred the
excision of tibioperoneal syndesmosis to peroneal
osteotomy. Their conclusion was proximal tibial
osteotomy is efcient and feasible.
32
Iracture treatment
Some authors think these are rare in haemophiliacs
who presumably lead a very cautious life.
6,22,40
Others
suggest that haemophiliacs are predisposed to fractures
due to osteopenia, cysts resulted after intraosseous
haemorrhage, prolonged imobilisation and oral
steroids treatment.
4,31
Joint instability, axial deformities,
muscular retraction and atrophy predispose to falling
injuries.
Fractures are frequently produced after minor
trauma, being sometimes masked by muscular
haematoma and associated hemarthrosis. Femoral
fractures are most frequent representing 50% of all
fractures.
32
After obtaining haemostasis, the fracture
can be treated following the general principles of
fracture treatment in non-haemophilic patients.
Circular casts are prohibited in fracture treatment, in
haemophilia, due to a considerable risk of extensive
haematoma and secondary ischaemia.
32
Due to its considerable risk, osteosinthesis should
be, whenever possible, avoided.
30
Osteotaxis
16,33
is
controversial. In a patient suffering of a moderate
haemophilia and with a highly comminutive fracture
in the distal femur we performed closed reduction
and osteotaxis with external xation. The evolution
was slow, with recurrent bleeding around the
transcutaneous xation rods and haematoma needing
repeated surgical drainage. The resulted callus was
hypertrophic.
16
Conservative treatment can be followed if closed,
stable reduction is obtained. Hospital admission is
recommended. An unstable fracture has a risk of
haematoma and later haemophilic pseudotumor
formation.
16,30,31,32
Pseudotumors
They are specic to haemophilia. Pathogenesis of
this lesion includes progressive haemorrhage resulting in
a encapsulated haematoma whose growth can produce
adjacent tissue destruction. Bone erosion can produce a
pathological fracture and soft tissue and skin erosions,
local and general infection, bleeding and anaemia. These
complications can be lethal. 57 About 1-2% of the
haemophiliacs have pseudotumors and death rate is 30%.
7,40. It has been shown that the main favourising factor
in pseudotumor formation is inadequate substitution
treatment and the presence of inhibitors.
25,31,57
FI0re 5. lW|1 ]+| u|J p+|||| W||| 1| || +||||up+||], ||/u|
+|J 1+|u J|u||||] +|J p+||+| u||u/+||u|. Cu||||1 u|u|u|] +|J
+||||uJ| W+ |+|]
_____________________________
72 IM! 2005, eI. 55, 8e. 1
Bone cysts can be considered early stage
pseudotumors, with uncertain evolution. They can be
mistaken for an osteoid osteoma.
14
Diagnosis includes
echography and MRI.
Giant pseudotumors are expansive and locally
destructive and can be multiple. The nal growth
result is the rigid structures destruction (bones) and the
displacement (e.g. kidneys) or compression of mobile
structures (e.g. nerves). The content of a pseudotumor
is usually vascularized so that arterial embolisation can
be benecial. CT, MRI and arteriography
14,57
are usually
necessary preoperatively. Treatment options include:
1. Radiotherapy, not indicated before but after
surgery.
2. Aspiration and instilation, used only for small
tumors, present an infectious risk.
3. Percutaneous evacuation, which can be difcult
and with a high infectious risk.
57

4. Surgery with complete resection whenever
possible, cavity lling with brin, muscle, internal
xation and bone grafting.
31
Haemophilic patients remain one of the most
defavourized patient category, often regarded as
difcult or impossible to treat. They are obviously
underdiagnosed in our country, with a national
prevalence of 4/100000, while in whole of Europe
is around 10/100000 (data from the National
Haemophilia Register remarkably in Timis county the
prevalence is 9.2/100000).
4
The surgical interventions
on these patients without substitutive coverage will
have serious consequences. Access to substitution
treatment, quality and quantity remains decient.
In the presence of a complete diagnosis and of
an adequate substitution treatment the slowing or
even the arrest of the progression towards chronic
arthropathy can be achieved. Also, surgical treatment
can be applied in these conditions with risks similar to
the non-haemophilic patients. Prophylaxis treatment
CONCLUSIONS
remains actually prohibitive in our country due to
its astronomical costs.
27
Patients with pseudotumors
should always be directed towards a orthopaedic
center specialized in treating haemophilia, having an
experienced surgeon, nurse and anesthesiologist, in close
cooperation with a haematology department. We also
recommend that all the elective surgical interventions
(artroplasty, synovectomy etc.), be done in such
centres. In the case of severe chronic arthropathy with
important deformity and depleted bone stock we must
be prepared for nonstandard situations and implants.
Hemophilic patients with manifestations similar to
non-haemophiliacs, especially those with trauma and
acute hemarthrosis, should be immediately treated
in any hospital with a haematology department and
sent to a specialized centre only after the management
of the acute event. We must keep in mind that the
rst step in the management of any osteoarticular
complication of haemophilia is the administration
of the decient factor as soon as possible and that
any surgical manoeuvre is allowed only after total
substitution coverage by a haematologist.
Haemophilia is a singular disease. Without
treatment the severe haemophiliacs will die during
adolescence or early adulthood. However with an ideal
substitution these patients can be considered healthy
and suffer no bleeding episodes or disability. That
depends on many factors, especially on the economical
status of the health system and that of the patient. In
a wealthy system, the substitution depends only on the
haematologist and the patients discipline.
The severity of the manifestations depends
on the severity of the disease and of the quality of
the substitution treatment. The management of
haemophilia needs a multidisciplinary approach and is
extremely expensive.
FI0re 6. G|+|| puJu|u|u| u| J||+| ||u|+| p|p|]|. |Rl ||+ u| +
!3 ]+| u|J.
1. Manhalter C. Molekularbiologische Grundlagen der Haemophilie A und
B und des von Willebrand-Syndroms. Haemophilie. Die Antworten
2000:12-18.
2. erban M, Schramm W. Hemostazeologie clinic. Brumar Ed, Timioara,
2001.
3. Aronstam A, Rainsfad SG, Painter MJ. Patterns of bleeding in adolescents
with severe hemophilia A. BMJ 1979;1:469-79.
4. Petrescu C. Hemolia - complicaii i sechele. PhD Thesis, Timioara.
5. Klein I, Andricovics H, Bors A, et al. A haemophilia A and B molecular
genetic diagnosis programme in Hungary: a highly informative and
costeffective strategy. Haemophilia 2001;7(3):306-12.
6. Aledort LM, Haschmeyer RH, Pettersson H. A longitudinal study of
orthopaedic outcomes for severe factor VIII-decient haemophiliacs.
The Orthopaedic Outcome Study Group. J Intern Med 1994;236:
391-9.
7. Arnold WD, Hilgartner MW. Hemophilic arthropathy: current concept of
pathogenesis and management. J Bone Surg Am 1977;59:287-305.
RLILRLNCLS
_____________________________
Ieaa l. 8raaea et aI 73
8. Mohr W. Pathogenese der Arthropathie. In: Scharrer I, Schramm W.
(eds)23. Hmophilie-Symposium, Hamburg. Springer Ed, 1992:83-94.
9. Morris CJ, Blake DR, Wainwright AC, et al. Relationship between iron
deposits and tissue damage in the synovium: an ultra structural study.
Ann Rheum Dis 1986;45:21-6.
10. Pettersson H, Ahlberg A, Nilsson IM. A radiologic classication of
haemophilic arthropathy. Clinical Orthopaedic. 1980;149:153-9.
11. Schramm W, Royal S, Kroner B et al. Clinical outcomes and resource
utilization associated with haemophilia care in Europe. Haemophilia
2002;8:3343.
12. Branea I, Poenaru D, Serban M, et al. Hemolia i complicaiile sale
osteoarticulare etiopatogenie i elemente de diagnostic. Revista de
Ortopedie i Traumatologie 2005;1(5),53-7.
13. Pettersson H, Gilbert MS. Classication of the hemophilic arthropathy.
In: Pettersson H, Gilbert MS (eds) Diagnostic imaging in hemophilia.
Springer Ed, New York, 1985:5668.
14. Nuss R, Kilcoyne RF, Geraghty S, et al. Utility of magnetic resonance
imaging of hemophilic arthropathy in children. J Pediatr
1993;123:388-92.
15. Barnes C, Wong P, Egan B, et al. Reduced Bone Density Among
Children With Severe Hemophilia. Pediatrics 2004;114(2):177-81.
16. Poenaru D., erban M., Patrascu J., Branea I., Birsasteanu F. Chirurgia
electiv n artropatiile cronice hemolice, Revista Societii Romne
de Ortopedie i Traumatologie (SOROT), 2005;1:9-14.
17. Branea I., Poenaru D., erban M., Ptracu J., Brsteanu V. Tratamentul
chirurgical al artropatiilor hemolice, Jurnalul zilelor academice
timiene 2004:103-7.
18. Klukowska A., Czyrny Z., Laguna P., Brzewski M. Corelation between
clinical, radiological and ultrasonographical image of knee joints in
children with hemophilia, Haemophilia 2001;7(3):286-92.
19. Nilsson IM,Berntorp E, Lofqvist T, Pettersson H Twenty-ve years
experience of prophylactic treatment in severe hemophilia A and B.
J Intern Med 1992;232:2532.
20. Royal S, Schramm W, Berntorp E et al. Quality of life differences
between prophylactic and on-demand factor replacement therapy in
European haemophilia patients. Haemophilia 2002;8:4450.
21. Heim M. (The treatment of intra-articular synovitis by the use of
chemical and radioactive substances. Haemophilia. 2000;8:369-371.
22. Chantraine A., Chapard R.(1977) La reeducation et les problemes
orthopediques dans lhemophilie, Medicine et Hygiene 35, 945-950
23. Mller AA, Kurth L, Hovy A. Konservative Behandlungs massnahmen
der hmophilen Arthropathie Orthopde 1999;28:347-55.
24. Argenti D, Ireland D, Heald DL. A pharmacokinetic and pharmaco-
dynamic comparison of desmopressin administered as a whole,
chewed or crushed tablets, and as an oral solution. J Urol
2001;165(5):1446-51.
25. erban M, Petrescu C, epeneu P et al. Evaluarea ecienei clinice a
rFVIIa n pediatrie. Documenta Haematologica 2000;2:59
26. Nilsson IM, Hedner U, Ahlberg A.Haemophilia prophylaxis in Sweden.
Acta Paediatr Scand 1976;65:129-35
27. Rodriguez-Merchan EC, Lee CA. Inhibitors in patients with haemophilia.
Blackwell, Oxford, 2002.
28. Heim M, Martinowitz U, Horoszowski H. Orthotic management of the
knee in patients with hemophilia. Clin Orthop 1997;343:54-7.
29. Zimmermann R. Rehabilitationstherapie der hmophilen Arthropathie.
In: Scharrer I, Hovy L. Orthopdische Hmophiliebehandlung. Ein
Leitfaden mit Patientenratgeber. Springer, 1996, p. 73-80.
30. Luck JV, Lin JC, Kasper CK, et al. Orthopaedic management of
hemophilic arthropathy, in Chapman MW. Orthopaedic Surgery,
Lippincott William and Wilkins, 2001.
31. Luck JV, Silva M, Rodriguez-Merchan C, et al. Hemophilic arthropathy,
JAAOS, 2004;12:234-45.
32. Rodriguez-Merchan EC. Orthopaedic surgery in persons with
haemophilia. Thromb Haemost 2003;89:34-42.
33. Canale ST, Dugdale M, Howard S. Synovectomy of the knee in young
patients with hemophilia.TN South Med J 1998;81(12):1480-6.
34. Lfquist T, Petersson C, Nilson IM. Radioactive synoviorthesis in
patients with hemophilia with factor inhibitor. Clin Orthop Relat
Res 1997;343:37-41.
35. Rodriguez-Merchan EC, Magallon M, Martin-Villar J, et al. Long term
follow up of haemophilic arthropathy treated by Au-198 radiation
synovectomy. International Orthopaedics (SICOT) 1993;17:120-4.
36. Caviglia H, Galatro G, Duhalde C, et al. Haemophilic synovitis: is
rifampicin an alternative? In: Lee CA, Kessler CM (eds) Haemophilia
1998;4:514-7.
37. Heim M. The treatment of intra-articular synovitis by the use of
chemical and radioactive substances.Haemophilia 2000;8:369-71.
38. Ehrenforth S, Kreuz W, Scharrer I, et al. Incidence of development of
factor VIII and factor IX inhibitors in haemophiliacs. Haemophilia
1999;7:254-8.
39. Horoszowski H, Heim M, Schulman S, et al. Multiple joint procedure
in a single operative session on hemophilic patients. Clin Orthop
1996;328:60-4.
40. Post M, Telfer M.C. Surgery in hemophilic patients. J Bone Joint Surg
1975;57A:1136-46.
41. Phillips AM, Sabin CA, Ribbans WJ, et al. Orthopaedic surgery in
hemophilic patients with human immunodeciency virus. Clin
Orthop 1997;343:81-7.
42. Rodriguez-Merchan EC. Total knee arthroplasty in patients with
haemophilia who are HIV-positive. J Bone Joint Surg Br 2002;84:
170-2.
43. Triantafyllou SJ, Hanks GA, Handal JA, et al. Open and arthroscopic
synovectomy in hemophilic arthropathy of the knee. ClinOrthop
1992;283:196-204.
44. Storti E, Ascari E. Surgical and chemical synovectomy. Ann NY Acad
Sci 1975;240:316-27.
45. Montane I, McCollough NC, Lian EC. Synovectomy of the knee for
hemophilic arthropathy, J Bone Joint Surg Am 1986;68(2):210-6.
46. Wiedel JD. Surgical and chemical synovectomy Ann NY Acad Sci
1983;240:316-27.
47. Greene WB. Synovectomy of the ankle for hemophilic arthropathy, J
Bone Joint Surg Am 1994;76:812-9.
48. Klein KS, Aland CM, Kim HC, et al. Long term follow-up of
arthroscopic synovectomy for chronic hemophilic synovitis.
Arthroscopy 1987;3(4):231-6.
49. Le Balch T, Ebelin M, Laurian Y, et al Synovectomy of the elbow in
young hemophilic patients. J Bone Joint Surg Am. 1987;69(2):264-9.
50. Teigland JC, Tjonfjord GE, Evensen GA, et al. Knee arthroplasty in
hemophilia: a 15 year follow-up of 15 patients. Acta Orthop Scand
1993;64;153-6.
51. Cohen I, Heim M, Martinowitz V, et al. Orthopaedic outcome of total
knee replacement in haemophilia A. Haemophilia 200;6:1049.
52. Trieb K, Cetin E, Bitzan P, et al. Total knee arthroplasty after high tibial
osteotomy. J Bone Joint Surg Am 2001;83:785.
53. Meding J, Keating EM, Ritter MA, et al. Total knee arthroplasty after
high tibial osteotomy. J Bone Joint Surg Am 200;82:1252-9.
54. Lofqvist T, Sanzen L, Petersson C, et al. Total hip replacement in
patients with hemophilia. Acta Orthop Scand 1996;67:321-4.
55. Wallny T, Saker A, Hofmann P, et al. Longterm follow-up after
osteotomy for haemophilic arthropathy of the knee. Haemophilia
2003;9:69-75.
56. Caviglia HA, Perez-Bianco R, Galatro G, et al. Extensor supracondylar
femoral osteotomy as treatment for exed haemophilic knee.
Haemophilia 1999;S1:28-32.
57. Caviglia HA, Fernndez-Palazzi F, Galatro G, et al. Percutaneous
treatment of haemophilic pseudotumours. In: Rodriguez-Merchan
EC,Goddard NJ, Lee CA (eds) Musculoskeletal aspects of haemophilia.
Blackwell, Oxford,2000, p. 97-104.