Case Study

Haemophilia

Of

Boy

With

Published: 23, March 2015

MM is a five years old boy who was diagnosed with Haemophilia A since six months
of age. He presented to the daycare of the Paediatric department with left elbow
swelling for one day after hitting it against the wall while playing. The swelling
increased in size and became more painful. The left elbow had decreased in range
of motion as the day progressed. He was unable to fully extend his arm. His father
then brought him to the daycare the next morning. There was no other swelling or
bruises noticed by the father. On systemic review, there was no fever, no
haematuria, no bleeding noticed, bowel movement was normal. He was still active.
There was no lethargy and no loss of appetite.
On physical examination, he looks well and his vitals were stable. There was no
pallor or jaundice. On examination of his upper and lower limbs, there were no
bruises noted on the skin. There was a joint deformity with valgus deformity noted
on his right elbow however range of motion of the right elbow was normal. On the
examination of the left elbow, there was a swelling. There was loss of bony
prominences. On palpation, the joint was warm and tender to touch. There is
presence of moderate effusion in the left elbow joint. There was restricted joint
movement. Flexion was 0°-140° however on extension movement there
was a 90° fixed flexion. Examination of other systems was normal.
He was diagnosed with haemarthrosis of the left elbow joint. MM was transfused
with 250 IU of Factor VIII. MM returned to the daycare the next day for another dose
of Factor VIII. He was given Factor VIII transfusion 250 IU once daily for the next
four days. The dose was then increased to 300 IU twice daily for two days. The pain
and swelling subsided and improved after the first dose of Factor VIII transfusion
and his range of motion improved. He was discharge after 7 days of Factor VIII
transfusion when the left elbow haemarthrosis resolved.

2) CLINICAL HISTORY
Chief complaint
MM is a five years old boy who was diagnosed with Haemophilia A since six months
of age. He presented to the daycare of the Paediatric department with left elbow
swelling for one day.
History of present illness
MM presented with left elbow swelling for one day after hitting it against the wall
while playing with his brother in the afternoon prior to admission. There was no
bruising or bleeding at the site of injury. The swelling had increased in size and
became more painful and had decreased in range of motion as the day progressed.
He was unable to fully extend his arm. He did not use any medications to relieve the
pain and movement of the joint will aggravate the pain. MM's father noticed that MM
had not been moving his left hand. His father then brought him to the daycare the
next morning. There was no other swelling or bruises noticed by the father. On
systemic review, there was no fever, no haematuria, no mucosal bleeding such as
gum bleeding or epistaxis noticed, bowel movement was normal. He was still active
despite the pain in his left elbow. His sleep was not affected. There was no lethargy
and no loss of appetite.
MM was first diagnosed with Haemophilia A when he was six months of age. His
parents noticed that he bruised easily when he learned how to turn over from supine
to prone position. There would be bruises seen on the flexors' surface of his
forearms and on the extensors' surface of the legs. He was referred to the national
blood bank and had investigations done. He was diagnosed with moderate
Haemophilia A. His parents and his two sisters and younger brother went for testing,
however, they were all tested negative for the Haemophilia.
MM has had four hospital admissions due to haemarthroses. Each admission, he
requires Factor VIII transfusion. There are occasions when MM's parents prefers to
bring him to the daycare daily for factor VIII transfusion instead of admission to the
ward when MM develop haemarthroses. Therefore, MM will receive Factor VIII
transfusion at the daycare and returns home. His father would bring him back to the
hospital again the next day for the next dose till the pain and swelling in the joint
resolves. His symptoms always would improve with Factor VIII transfusion. MM
receives Factor VIII transfusion about twice a year on average. The joint most

commonly affected is his right knee joint. His last hospital admission was in May
2009 which is 5 months ago he was admitted due to his right knee haemarthrosis
and was transfused with Factor VIII for 2 days. He has not developed any
contractures.
MM also bruised easily and on average once every two weeks. He does not usually
seek medical treatment for bruises because they are a common occurrence and
these bruises resolve spontaneously. However if the bruising is large in size, then
the parents will bring him to the daycare. If the daycare is closed, they will bring MM
straight to the paediatric ward if he develops any haemarthroses. His parents always
need to restrict and supervise his activity because MM is an active boy who likes
playing and running around. His parents also need to warn his siblings to be careful
while playing with him. There have been episodes where there was delay in seeking
medical consultation sometimes because MM's parents had been busy, or MM's
father was outstation. However, there had never been any major complications
occurred before.
He never had mucosal bleeding such as epistaxis. He never had haemetemesis,
maleana or haematuria before. He never had much bleeding when he was shedding
his decidua teeth and does not require Factor VIII. His parents are aware that he
requires Factor VIII cover if MM undergoes tooth extraction or any surgeries.
Past medical history
MM has not had any other hospital admissions other than those due to Haemophilia.
He never had any blood transfusion before. He never had any surgeries done. He
does not have any known drug allergies.
Family history
MM is the second child of four siblings. His eldest sister is 7 years old and he has a
younger brother who is 4 years old and his youngest sister is 2 years old, they are
all well. MM's parents are also well. There is no family history of haemophilia on both
his maternal and paternal side. MM's mother has two older brothers but they do not
have haemophilia. There was no history of bleeding disorders in the family.
Birth history

MM was born at term in Hospital Batu Pahat via spontaneous vaginal delivery. There
were no antenatal abnormalities detected during routine antenatal checkups. There
were no perinatal or post natal complications. He developed neonatal jaundice at
day 4 of life and was admitted to the hospital for phototherapy for two days.
Developmental history
MM is currently not attending pre-school. He will attend kindergarten next year. His
developmental milestones are appropriate to age. He did not develop any
contractures or joint deformity. Therefore, he does not have problems with his gross
motor and fine motor development.
Dietary history
MM is on an adult diet now. He eats balanced meals which are usually prepared by
his mother. He was breastfed till he was 18 months old and weaned with porridge at
the age of five months.
Immunization history
MM has been immunized according to the immunization schedule. Each time he had
his vaccination, he only develop a mild haematoma which resolves spontaneously.
He usually develops a mild haematoma with the intramuscular injections during
immunization. He did not require Factor VIII cover for his immunizations. His last
immunization was at 18 months.
Social history
MM's father is a teacher and his mother is a housewife. MM's father had to miss
work occasionally or he sometimes is late to school due to MM's condition which
requires frequent visits to the hospital. The school's headmistress understands MM's
father's situation and arranged for substitute teacher when he needs to come in late
to school. MM's mother stays home to take care of the other children. His parents
finds it hard to make arrangement with the school and taking care of the other
children, which is why occasionally they prefer sending MM to the daycare daily for
his factor VIII transfusion rather than hospital admissions when MM develop
haemarthroses. His parents have a car and lives about thirty minutes away from the
hospital. They find it much more convenient even though they had to travel several
times for a few days to the hospital until MM's haemarthroses resolve.

In MM's home, there is minimal furniture to prevent MM from injuring himself. They
only have a small coffee table, and otherwise they all sit on the mats on the floor.
They all sleep together in the same room because all the children are still young.
They also do not have beds for they all sleep on mattresses only. He lives in a single
storey house with no stairs to prevent MM from falling off the stairs.
MM's father has heard of the Haemophilia society and he is interested in joining the
society. However, he had been busy and has not joined the society yet. He knows
about the importance of Medic alert for MM and plans to make a medic alert chain
for MM.

3) FINDINGS ON CLINICAL EXAMINATION

On general examination, MM was alert and comfortable. He was sitting comfortably
with a sling bandage of his left elbow. He looked well nourished. He was not in
severe pain. There was no jaundice or pallor.
Anthropometric measurements:
Weight: 18kg (on the 50th percentile)
Height: 105cm (on the 25th percentile)
His vital signs were normal:
Pulse: 92 beats per minute
Respiratory rate: 18 breaths per minute
Blood pressure: 100/70
Temperature: 37°Celsius
Examination of the upper limbs:
There were no bruises noted on the skin. On the examination of the left elbow, there
was a swelling. There was loss of bony prominences. On palpation, the joint was
slightly warm and mildly tender to touch. There is presence of moderate effusion in
the left elbow joint. There was restricted joint movement. Flexion was 0°140° however on extension movement there was a 90° fixed flexion. On

examination of the right elbow, there was a joint deformity with valgus deformity
noted on his right elbow however range of motion of the right elbow was normal.
Examination of the lower limbs:
There were no bruises seen on both lower limbs. The left knee was slightly swollen.
It was non-tender on palpation and it was not warm. The range of movement of both
knee joints was normal. Both ankle joints were normal. There were no contractures
seen.
Cardiovascular examination
There were no chest wall deformities and no scars. Apex beat was palpable in the
fifth intercostals space in the mid-clavicular line, there was no parasternal heave or
thrills palpable. First and second heart sounds were heard, there were no extra heart
sounds or murmurs.
Respiratory examination
The trachea was not deviated. The chest expansion was normal. Tactile fremitus
was equal on both sides. Percussion of the lungs was resonant and equal. There
were equal, vesicular breath sounds on both lungs. There were no adventitious
sounds.
Abdominal examination
The whole abdomen moves with respiration and normal in shape. It was not
distended. There are no surgical scars. The abdomen was soft. It was non-tender.
There were no masses palpable. There were no hepatosplenomegaly. Bowel sounds
were present.

4) PROVISIONAL AND DIFFERENTIAL

DIAGNOSES WITH REASONING
Provisional diagnosis:
Haemarthrosis of the left elbow joint
Evidence for: MM has been diagnosed with haemophilia since six months of age. In
patients with haemophilia, common sites of bleeding are the elbow joints, knee joints

and ankle joints. MM had the left elbow swelling after minimal trauma to the left
elbow. MM had developed previous haemarthroses of the joints after minimal trauma
in the past which was similar to this episode.

Differential diagnosis:
1) Septic arthritis
Patients with damaged joints are more susceptible to septic arthritis. In the case of
haemophilia patients, they have repeated haemarthroses which may cause joint
damage are more likely to be susceptible to infection.
Evidence against: Fever is a prominent feature in patients with septic arthritis. MM
was afebrile.
2) Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis presents with symmetrical arthralgia or may only affect
one joint in the oligoarthritis type of juvenile rheumatoid arthritis. MM presents with
pain and swelling in the large joints such as knees, ankles and wrists.
Evidence against: Juvenile idiopathic arthritis usually presents during childhood. It is
a chronic disease where the joint pains persist for 6 weeks or more. MM has been
having episodes of joint pain and swelling which present acutely and resolves
spontaneously after a few days since he was six months of age which makes this
diagnosis unlikely. MM also has a history of easy bruising. This is not a clinical
feature of juvenile idiopathic arthritis. In juvenile idiopathic arthritis, there is
characteristic arthritis such as polyarthritis or oligoarthritis, with fever and there is
also morning stiffness of the joints which is a symptom that MM does not have.

5) IDENTIFY
PROBLEMS

AND

PRIORITISE

THE

1. Swelling at the left elbow

MM complained of pain and swelling of the left elbow joint. The appropriate
management to relieve the pain and swelling is Factor VIII infusion. It would be the
definitive treatment because the use of analgesics such as aspirin and NSAIDS are
not recommended for him as it can cause bleeding in patients with haemophilia.

2. Risk of joint destruction and development of contractures

MM is an active boy who likes to play and running around. He is prone to injury on
minimal trauma. He has developed haemarthroses at least twice a year. Recurrent
haemarthroses at the same joint will likely to cause joint destruction which will lead
to osteoarthritis, restriction in joint movement and develop contractures. He should
also be referred for physiotherapy when the pain has subsided. Physiotherapy is an
important element to prevent the development of joint contractures.
3. Risk of bleeding
MM is also at risk of severe bleeding if he injures himself. He was admitted in the
hospital for 3 days when he was three years old in November 2007 where MM had a
fall and his face hit the floor. He developed retrobulbar haemorrhage and was under
ophthalmology follow up for three months. He did not develop intracranial bleed. The
swelling subsided with Factor VIII transfusion and had no complications with his
vision. With this past history, MM is at risk of bleeding at minimal trauma. The most
dangerous risk is that he develops intracranial haemorrhage if he had a fall and has
a head trauma. His parents will need to supervise his activity.
4. Risk of developing infection from factor or factor-related transfusions
MM requires frequent factor transfusion. As the factor VIII is derived from human
plasma, MM is at risk of contracting Hepatitis B, Hepatitis C or HIV infections. MM
has not been screened for any of these infections. It would be ideal for MM to be
screened as recommended by the Malaysian protocol for the management of
haemophilia.
5. Difficulty faced by caregivers
MM's father is working as a teacher and often forced to miss work or be late to work
in order to take care of MM when he requires factor VIII transfusion. The
headmistress of the school understands his father's difficulty and tries to arrange for
substitute teacher when he misses work or had to come in late when he needs to
take MM to the hospital. MM's mother has to take care of other younger children.
Haemophilia is a chronic condition and there will be continuous stress in taking care
of MM's needs by the parents. MM's parents may find support groups such as the
haemophillia society useful. The society enables the parents to find support and find
methods to cope with MM's condition as the society organized talks and seminars to
educate about haemophilia and also meetings with other parents whose children

has haemophilia and are faced with similar difficulties. These parents would be able
to encourage one another and share tips on caring for haemophilliac children.

6)
PLAN
OF
INVESTIGATION,
JUSTIFICATIONS FOR THE SELECTION OF
TESTS
OR
PROCEDURES,
AND
INTERPRETATION OF RESULTS
Investigations done at 6 months of age by the national blood bank:
1. Coagulation profile
Justification: MM presented with easy bruising at his limbs which indicates that may
be due to a bleeding disorder. As such a coagulation profile would be useful to see if
the coagulation pathways are affected.
Results: Prothrombin time (PT): 9.9 sec (normal) [Normal range: 9.8 - 13.5 seconds]
APTT: 72.5 sec (prolonged) [Normal range: 23-33 seconds]
Interpretation: Prolonged APTT indicates that the intrinsic pathway is affected and
that one of the factors in the intrinsic pathway may be deficient. In Haemophilia, the
APTT is usually prolonged.
2. Factor VIII assay
Justification:
To ascertain the specific factor that is deficient that is causing the bleeding disorder.
Results: Factor VIII level: 2.4%
Interpretation: MM has moderate haemophilia A due to his Factor VIII level is in
between 1-5%.
For this current presentation, there were no investigations were done at the daycare.

7) WORKING DIAGNOSIS AND PLAN OF

MANAGEMENT ON ADMISSION
Working diagnosis: Haemarthroses of the left elbow joint due to Haemophilia A

My proposed plan of management:

1) Factor VIII transfusion with a target serum factor level of 40% twice daily till the
swelling and pain resolves
2) Sling bandage of the left elbow
3) Ice pack to the left elbow
4) To rest the elbow joint by restricting movement until swelling and pain reduces
5) Refer the patient to physiotherapy for joint rehabilitation of the affected joint.
6) To educate the parents to care for the IV access at home and understand how to
manage in case of bleeding at that site occurs.
7) To educate the parents on care for their child and protective measures to prevent
injury
8) To advised and encourage the parents that MM will benefit if he starts cycling with
a tricycle for safety and wears a hard helmet such as motorcycle face helmet. When
he is old enough to learn to ride the bicycle, he should always wear protective gear
such as the helmet with protective elbow and knee guards.

8) SUMMARY OF INPATIENT PROGRESS

(INCLUDING MAJOR EVENTS, CHANGE OF
DIAGNOSIS
OR
MANAGEMENT AND
OUTCOMES)
08/10/2009 - 12/10/2009: MM presented to the daycare and was transfused with 250
IU Factor VIII once a day for five days. On reassessment, the left elbow joint
haemarthrosis improved after the first dose of Factor VIII. There were reduced in
swelling and it was non-tender. On the third dose, the left knee swelling that was
noted on physical examination had resolved. The range of movement of the left
elbow was markedly improved by the fourth dose. On admission, the range of
motion for extension was at fixed flexion 90°. After four days of factor VIII
transfusion, the range of motion for extension was at fixed flexion 45°.
13/10/2009 - 14/10/2009: On reassessment of the range of movement had
improved, however the range of movement was still restricted. The range of motion

for extension of the left elbow joint was at fixed flexion 30°. There was still
presence of mild haemarthrosis of the left elbow. The target percentage of factor
was then aimed to be 40%, therefore, the dose of Factor VIII was increased to 300
IU twice a day which is 12-hourly.
15/10/2009: After 7 days of infusion of factor VIII, the swelling completely resolved
and the range of motion of the left elbow joint was full.
MM's duration of treatment required seven days. He had Factor VIII transfusion of
250 IU once daily for five days, which was the target serum factor VIII was aimed at
30%. According to the Paediatric Protocols for Malaysian Hospital, the
recommended dose was aimed at 30%-40% in haemarthroses. Factor VIII should
ideally be given every 8-12 hours and the duration for haemarthroses is usually 2-3
days.

9) DISCHARGE PLAN, COUNSELLING AND

MOCK PRESCRIPTION
Discharge plan:
- Referral to the physiotherapist for joint rehabilitation

Counseling:
1) MM's father was advised to supervise and restrict certain activities that may
increase risk of trauma or bleeding such as jumping or contact sports games.
2) MM's father was told to bring him back to the daycare if there were episodes of
bleeding into the joints or any joint swelling or any spontaneous bleeding. They were
given a contingency plan to go directly to the paediatric ward and see the medical
officer on call if any bleeding were to happen when the daycare is closed.
3) MM was encouraged to go for physiotherapy. MM's father was educated
regarding recurrent haemarthroses will cause of joint destruction. Physiotherapy is a
useful exercise to prevent contractures.

Mock prescription

Name: MM 1. Syrup paracetamol 270 mg prn for pain

Age: 5 years old
I/C no: 040611-01-0387
Diagnosis: Haemarthrosis of left
elbow Signature and stamp

10) REFERRAL LETTER (MANDATORY)

Dr Karen Lai,
Paediatric Department,
Hospital Batu Pahat
Haematologist,
Haematology department, 14th October 2009
Dear Sir,
Re: Patient: MM, I/C number: 040611-01-0387 : Haemarthrosis of the left elbow joint
Thank you for seeing MM who is a five years old boy who was diagnosed with
Haemophilia A since he was six months of age. He has had recurrent episodes of
bleeding into the joints and it usually affect the knee and elbow joints. He currently
presents with haemarthrosis of the left elbow joint. On physical examination, there
was warmth and tenderness of the left elbow joint on palpation. There was reduced
range of movement on both active and passive movement. On the right elbow, there
was a joint deformity noted with valgus deformity however it was non-tender and
range of movement was full. He has been given Factor VIII transfusion for one week
and the swelling and pain had resolved. The range of movement of the left elbow
joint was also improved.
We would like to refer him for physiotherapy for joint rehabilitation. We hope that his
family could also be taught rehabilitation exercises that can be done at home to
prevent joint contractures in view of his recurrent bleeding into the joints. Kindly
review the patient and assess if he needs factor VIII transfusion prior to
physiotherapy session. Thank you.

Yours truly,

___________
Karen Lai,
Paediatric Department,
Hospital Batu Pahat

11) LEARNING ISSUES IN THE 8 IMU

OUTCOMES
1) Professionalism,
development

ethics

and

personal

Does every family members of patients diagnosed with haemophilia needs to

undergo genetic testing?
In approximately 30% of patients who have hemophilia, occurs as a result of
spontaneous mutations as there is no family history of the disease.1 To be able to
identify the mutations in 95% to 98% of patients with haemophilia, the more accurate
method is genetic testing.1 In those patients with haemophilia with unclear family
history should have genetic testing as it is relevant to determine which parent or
family is a carrier or affected with the haemophilia gene so that further steps of
management can be carried out. These further steps may include offering genetic
testing to the siblings of the carrier parent and also counseling about risk of having
additional children. Candidates for genetic testing also include patients who have a
diagnosis of hemophilia, at-risk women who are related to an affected man who has
a known mutation, and female carriers of hemophilia A or B seeking prenatal
diagnosis.
In prenatal diagnosis, it can be done via chorionic villus sampling or amniocentesis.
The family's mutant gene can be identified by either gene sequencing or restriction
fragment length polymorphisms (RFLPs).
In conclusion, genetic testing is not mandatory in patients with haemophilia.
However, it is recommended for family members of the affected patients who were

tested positive for Haemophilia. If the mother was tested to be a carrier, it will be
beneficial and important to know if she desires to have more children in the future. If
prenatal diagnosis establishes the fetus to have carried the haemophilia gene, or an
affected fetus, she has to be counseled that in Malaysia it is illegal to have abortion.
Termination of pregnancy however, may occur if the fetus endangers the physical or
mental health of the mother. If she does have a daughter who is a carrier, her
daughter is recommended to have screening before marriage. If she has an affected
son, he should be counseled that all his future daughters will be carriers. Family
members that are affected that plan to marry should be counseled regarding the risk
of transmission of the affected gene from one generation to another. Genetic testing
and counseling should only be offered when proper follow-up such as counseling,
support and options can be offered to those undergoing the test.

References:
1. Rodriguez NI, Hoots WK. Advances in Haemophilia: Experimental Aspects and
Therapy. Pediatr Clin N Am 55 (2008) 357-376

2) Clinical Skill
What is the laboratory approach to diagnose haemophilia?
Hematological investigation is important laboratory test in diagnosis of haemophilia.
A coagulation screen typically consists of a Prothrombin Time (PT), activated Partial
Thromboplastin Time (aPTT), Thrombin Clotting Time (TT), fibrinogen level, a
platelet count, and a full blood count.1 The PT measures the factors of the extrinsic
and common pathways. Deficiencies of these factors especially Factor VII will
prolong the PT. Vitamin K is required for the synthesis of the factors of these
pathways. Therefore, patients with vitamin K deficient conditions may also have a
prolonged PT. On the other hand, aPTT measures the factors of the intrinsic and
common pathways. Deficiencies of these factors, including factor VIII and factor IX
will have a prolonged aPTT.1 Therefore, in the case of my patient, MM, he has a
normal PT and a prolonged aPTT. In very mild cases of hemophilia, the aPTT may
remain within the normal range. In such cases it will be necessary to perform a
direct measurement of specific factor levels to make the diagnosis.

A mixing study may be useful as it determines if the patient has a clotting factor
deficiency or an inhibitor to a factor. A mixing study is a test performed on blood
plasma and is describe as when one part of the patient's blood is mixed with one
part of normal blood that contains 100% of normal factor levels. When the blood
from a patient with a factor VIII deficiency is mixed with normal blood, the PTT
should normalize or correct. However, if there is inhibitor to a factor in the patient's
blood, it disables the factor in the normal blood which results in factor level being low
and the aPTT will be prolonged or fails to correct. Therefore, in summary, correction
with mixing indicates factor deficiency; failure to correct indicates an inhibitor.
Inhibitor assays are then performed to identify which inhibitor is present and factor
assays are performed to identify which factor is deficient.2

Reference:
1. Soliman DE, Broadman LM. Coagulation defects. Anesthesiology Clin 2006;
24:549-578
2. Ballas M, Kraut EH.Bleeding and bruising: A Diagnostic Work-up. Am Fam
Physician. 2008; 77(8):1117-1124.

3) Critical thinking and research

Is prophylactic factor concentrate therapy in haemophilia beneficial and effective?
In prophylaxis factor concentrate therapy, hemophiliacs receive factor concentrates
one or more times a week to prevent bleeding. The goal is to keep the levels of
factor VIII or IX in the blood high enough that bleeding does not happen. There is
primary prophylaxis, secondary prophylaxis and individualized tailored prophylaxis.
Primary prophylaxis therapy is when giving the factor concentrates before bleeding
occurs. Secondary prophylaxis therapy is the periodic use of factor concentrates for
a short or long period of time to reduce bleeding recurrence in those patients with
preexisting joint disease and those who have frequent acute hemarthroses.
Individualized tailored prophylaxis therapy is given based on the severity of
haemophilia, the bleeding patterns and joint involvement and individual needs.1
The Medical and Scientific Advisory Council (MASAC) had recommended that
primary prophylaxis be considered optimal therapy for individuals with severe
hemophilia A or B (factor VIII or factor IX <1%).2 This recommendation had been

adopted and practiced by the National Hemophilia Foundation in the US. The
recommendation is that prophylactic therapy should be administered early which is
prior to the onset of frequent bleeding, with the target of monitoring trough factor
levels above 1% between doses.2 This can usually be accomplished by giving 25-50
FVIII units/kg three times per week or every other day, or 40-100 Factor IX units/kg
two to three times weekly. It is also recommended that individuals on prophylaxis
have regular follow-up visits to evaluate joint status, to document any complications,
and to record any bleeding episodes that occur during prophylaxis.2 It has been
recommended that prophylaxis be started before joint damage, which is ideally
before 3 years of age.1
In a Cochrane review by Stobart et al 3, included four studies where the results
showed that there was a statistically significant difference in the reduction of joint
bleeds in patients who were given standard prophylaxis when compared to a
placebo. It also found that secondary outcomes such as time loss to school and
employment due to the illness was statistically significantly reduced among those
receiving primary prophylaxis compared to a placebo. The review also quoted one
study which showed that a twice weekly infusion of higher dose of factor concentrate
had a statistically significant advantage in reducing the number of bleeds a year
when compared to a lower dose and less frequent administration of transfusion.
However the authors concluded that there was insufficient evidence from
randomized control trials to recommend the use of primary prophylactic factor
infusion in the management of patients with haemophilia.
In conclusion, to initiate prophylactic therapy remains a controversial issue among
the healthcare givers. In the case of my patient, MM, he is diagnosed with moderate
haemophilia, it is a question where prophylactic therapy is recommended for him.
Prophylactic therapy is usually recommended in those with severe haemophilia.
Studies had showed it is effective and beneficial in preventing bleeding and joint
arthropathy. However it may not be cost-effective in Malaysian hospital (one vial of
200 IU costs around RM 800) as compared to other hospitals in developing and
developed countries. Prophylactic therapy shows much promise in the treatment of
haemophilia. With more research and additional studies, prophylactic therapy may
be feasible in Malaysia.

References:

1. Rodriguez NI, Hoots WK. Advances in Haemophilia: Experimental Aspects and

Therapy. Pediatr Clin N Am 2008; 55: 357-376
2. National Hemophilia Foundation. MASAC Recommendation Concerning
Prophylaxis (Regular Administration of Clotting Factor Concentrate to Prevent
Bleeding).
[ONLINE][2007]
Available
from:
http://www.hemophilia.org/NHFWeb/Resource/StaticPages/menu0/menu5/menu57/
masac179.pdf
3. Stobart K, Iorio A, Wu JK. Clotting factor concentrates given to prevent bleeding
and bleeding-related complications in people with hemophilia A or B. Cochrane
Database of Systematic Reviews 2006, Issue 2.

4) Self directed lifelong

information management

learning

and

What is the long term management and future advances of treatment of

Haemophilia A?
The management of haemophilia is factor transfusion which is aimed to stop the
bleeding that had occurred. Other alternative is primary prophylaxis with regular
factor infusions to prevent bleeding. However this approach is costly and transfusion
is ineffective in those patients that had developed inhibitors. As such, researchers
are looking into a means for a cure of haemophilia which is gene therapy.
The objective of gene therapy is to edit a defective gene sequence to achieve
complete reversion of disease phenotype in the lifetime of the patient. There are
three reasons that haemophiliacs are the ideal candidates for gene transfer therapy.
Firstly, is because there are many cell types which are able to synthesize biologically
active clotting factor. Secondly, there is a wide therapeutic window which makes it
unnecessary to have strict gene expression. Thirdly, there are large and small
animal models that permit the study of safety and efficacy of gene therapy prior to
initiation of human trials.1
Gene therapy involves the transfer of genes that express a particular gene product
into human cells resulting in a therapeutic advantage. In haemophilia, the goal of
gene transfer is targeted at the secretion of a functional factor VIII or IX protein.
Some studies revealed that therapeutic effect has been seen with the gene transfer,

however stable production of the coagulation protein is had yet to be demonstrated

in human subjects. These trials have failed to show long-term gene expression
observed in preclinical animal models.2 There is still much research and
investigations needs to be done to have gene therapy as a modality of treatment for
haemophilia.