MFA presented to the daycare of the Paediatric department with left ankle swelling for one day after hitting his ankle on a stone while playing in the evening one day prior to admission. There was pain and bruising seen at the ankle joint after the trauma. The swelling increased in size and became more painful throughout the night. His parents then brought him to the daycare early the next morning.
Physical examination revealed swelling and tenderness at the left ankle joint as well as reduced range of movement on both passive and active movement due to pain. There were also multiple ecchymosis in different stages seen at the upper and lower limbs.
A diagnosis of haemarthroses of the left ankle joint was made. MFA was transfused with 200IU of Factor VIII. The pain and swelling were reduced in severity but persisted throughout the day. MFA returned to the daycare the next day for more Factor VIII. He was given Factor VIII transfusion 200 IU twice daily for the next two days. The pain and swelling subsided after 3 days.
MFA was diagnosed with severe Haemophilia A when he was eight months of age. The diagnosis was made at the national blood bank. Genetic testing also done at the national blood bank revealed that his mother was a haemophilia gene carrier.
MFA receives transfusion of Factor VIII when he develops haemarthroses or bleeding due to trauma. He requires factor transfusion on an average of once every three months. He has had repeated hospital admissions with an average duration of stay for three to four days.
MFA has good family support and is a member of the haemophilia society. He and his family have adapted well to his illness.
STUDENT NAME: Tan Hai Liang ID NO : M0409146
NAME OF SUPERVISOR : Dr Kyin ROTATION: Paediatrics
PATIENT'S DETAILS
I/C NUMBER : (B) 630902-01-6092 AGE : 9 years old
SEX : Male DATE OF ADMISSION : 23/04/09
R/N NUMBER : N/A
2) CLINICAL HISTORY
Chief complaint:
MFA is a nine year old boy who was diagnosed with haemophilia A since eight months old. He presented with swelling in the left ankle for one day.
History of present illness:
MFA was running in the field at school when he knocked his ankle against a large stone in the ground on the evening of the day prior to presenting at the daycare. There was pain after he hit his ankle but he was able to bear weight and walk. There was some bruising but no bleeding at the site of injury.
The joint became more painful towards the night and there was some swelling, warmth and redness which progressively increased. The pain increased in severity so much so that MFA was unable to bear weight and used a wheelchair belonging to his brother to move about the house. The pain caused him some discomfort but he was able to sleep. He did not take any analgesia for the pain.
The next day, MFA's parents brought him to the daycare of the paediatric department for a factor transfusion.
Systemic review was unremarkable.
MFA was first diagnosed with haemophilia A when he was 8 months of age. His parents noticed that he developed bruises at his hands and knees. This occurred when he was leaning to crawl. A blood test was done in the national blood bank, and his parents were told that MFA had severe haemophilia A. His immediate family underwent testing and his mother was found to be a carrier of the haemophilia gene.
MFA receives factor VIII transfusion on an average of once every three months. The transfusions are required when he develops haemarthroses or gum bleeding due to tooth decay. The joint most commonly affected is his right knee joint. He has not developed any contractures. He does not usually seek medical treatment for bruises which are a common occurrence. He has not had mucosal bleeding as epistaxis or haematuria.
MFA would sometimes require hospital admission for factor VIII transfusion. This is usually when he has bleeding or severe pain due to a haemarthroses or a haematoma. At other times he would receive the transfusion at the daycare and return home. His parents would bring him again to the hospital for the next dose till the pain and swelling in the joint resolves. If a transfusion were required at night when the daycare is not open, MFA would go to the paediatric ward where the medical officer would be able to administer the factor VIII. His symptoms would improve with the factor VIII transfusion.
MFA is an active boy who likes playing and running around. However his teachers in school restrict his physical activity to non-contact sports such as badminton and running. He is also discouraged from rough play with his schoolmates. He wears elastic guards around his elbows and knees to protect them from injury. However the elastic guards do not help much as he still develops haemarthroses at those joints. MFA is currently shedding his decidual teeth. As such he requires factor VIII transfusion cover prior to tooth extraction.
MFA is under follow-up at the paediatric clinic of Batu Pahat. He has defaulted the follow-up as his parents feel that nothing much was done during the visits. He only presents to the daycare when requiring factor VIII transfusion. MFA has also been referred for physiotherapy after episodes of haemarthroses which limit movement in the joints. He has attended a few sessions of physiotherapy in order to prevent contracture at joints which have haemarthroses. He does not have regular appointments.
MFA is a member of the haemophilia society. His parents regularly attend meetings where talks are given to educate parents on caring for haemophiliac children. The members also relate their experiences and encourage one another. MFA has a medic alert necklace which says that he has haemophilia A. However, he seldom wears the medic alert.
Past medical history
MFA has not had any other hospital admissions other than those due to haemophilia.
Family history
MFA is the youngest of three siblings. His elder sister is twenty years old and is well. His elder brother is fifteen years old and has a bone cyst. He has undergone eight surgeries to repair the bone cyst as well as due to complications such as refractures. The wheelchair which MFA used at home was bought for his brother's use. MFA's parents are well. There is no family history of haemophilia on his maternal side even though she is a carrier. MFA's mother has 3 brothers but all of them are well and do not have haemophilia. There is no history of bleeding disorders in the family.
Social history
MFA's parents are both teachers. However they have to miss going to work often due to MFA's condition which necessitates frequent visits to the hospital. As such, MFA's mother has a special arrangement with her headmaster which allows her to teach from 11 to 4 pm. As such, she is free in the morning to bring MFA to the hospital when he needs it. His parents also provide good support for MFA in that they often attend haemophilia meetings to update themselves on means to best care for their child.
Birth history
MFA was born at term in Hospital Batu Pahat. He was delivered through an elective caesarean section due to a breech presentation. There were no antenatal abnormalities detected during routine antenatal checkups. There were no perinatal or post natal complications. He was nursed with his mother after birth and discharged uneventfully.
Developmental history
MFA is currently in primary three of a religious school. He is an above average student who finishes in the top ten of his class. His teachers have no complaints about his schoolwork. Developmental milestones prior to this were all achieved at the appropriate times.
Dietary history
MFA is on an adult diet now. He eats balanced meals which are usually prepared by his mother. He was breastfed till the age of seven months. Weaning was with porridge at the age of five months.
Immunization history
MFA has been immunized according to the immunization schedule. After he was diagnosed with haemophilia A, his immunizations were done at the paediatric clinic under factor VIII cover. His last immunization was at seven years of age.
STUDENT NAME: Tan Hai Liang ID NO : M0409146
NAME OF SUPERVISOR : Dr Kyin ROTATION: Paediatrics
3) FINDINGS ON CLINICAL EXAMINATION
On general examination, MFA was friendly and communicative. He was sitting in a wheelchair with a bandage around his left ankle. There were some ecchymosis seen at his arms and thighs. He looked well nourished. He was not in severe pain.
Anthropometric measurements:
Weight: 24kg (10th to 25th centile)
Height:130cm (25th to 50th centile)
His vital signs were normal:
Pulse: 82 beats per minute
Respiratory rate: 18 breaths per minute
Blood pressure: 108/72
Temperature: 37 degrees Celsius
Examination of the lower limbs:
There were ecchymosis seen on both lower limbs at the thigh as well as at the shin and calf. The left ankle was swollen and there was a bruise seen on it. It was tender on palpation but there was no increase in temperature. There was reduced movement of the left ankle joint due to pain.
The right ankle joint as well as both the left and right knee joints were normal. There were no contractures seen.
Examination of the upper limbs:
There was also some bruises seen on both the upper limbs. The elbow and wrist joints were normal on both hands. The range of movement for all the joints on both upper limbs were normal.
Examination of the cardiovascular and respiratory systems as well as examination of the abdomen was normal.
STUDENT NAME: Tan Hai Liang ID NO: M0409146
NAME OF SUPERVISOR: Dr Kyin ROTATION: Paediatrics
4) PROVISIONAL AND DIFFERENTIAL DIAGNOSES WITH REASONING
Provisional diagnosis: Haemarthroses of the left ankle joint ----
Evidence for: MFA has been diagnosed with haemophilia since the age of eight months. The joints are a common site of bleeding for haemophiliacs. In addition, MFA has had prior episodes of pain and swelling in the joint similar to this episode. The pain reduced when he was given factor VIII transfusion which further supports this diagnosis. He also has multiple bruises on his arms and legs which indicate that he has a bleeding disorder.
Differential diagnosis:
1) Juvenile Rheumatoid Arthritis
The pauciarticular type of juvenile rheumatoid arthritis presents with pain and swelling in the large joints such as knees, ankles and wrists. It may present as symmetrical arthralgia or may only affect one joint.
Evidence against: Juvenile rheumatoid arthritis usually presents during childhood while MFA has been having episodes of joint pain and swelling since he was an infant at eight months of age. Juvenile rheumatoid arthritis is also associated with morning stiffness which MFA does not have. MFA also has easy bruising which is not a feature of juvenile rheumatoid arthritis
2) Septic arthritis
Patients with damaged joints are predisposed to septic arthritis. As such, a haemophiliac patient who has repeated haemarthroses may have damaged joints which are susceptible to infection.
Evidence against: Patients with septic arthritis usually have fever while MFA did not. They are also more common in patients who are immunocompromised. On physical examination, there was no increased warmth in the joint which would be more indicative of septic arthritis.
3) Ankle ligament injury
A sudden twist of the ankle may cause a wrenching of the soft tissue and ligaments around the ankle causing pain and swelling.
Evidence against: MFA did not twist his ankle while playing. He merely knocked it against a rock. As such the mechanism of injury does not suggest that the ligaments were strained. He was also able to bear weight after hitting his ankle and the swelling and pain gradually developed. This is contrary to what is expected in a sprained ankle where there would be immediate swelling and pain around the ankle.
STUDENT NAME: Tan Hai Liang ID NO: M0409146
NAME OF SUPERVISOR: Dr Kyin ROTATION: Paediatrics
5) IDENTIFY AND PRIORITISE THE PROBLEMS
1. Swelling at the left ankle
MFA has pain and swelling at the left ankle joint. He was in moderate pain which he rates as 6 out of 10 on the pain score. Analgesics such as aspirin and NSAIDS are not recommended for him as they cause bleeding in haemophiliacs. As such the best means for rapid relief of the pain and the swelling would be Factor VIII transfusion.
2. Risk of joint destruction
MFA is currently eight years old and is an active boy who enjoys playing with his friends. As such he is prone to injury from even mild trauma. He has developed haemarthroses on an average of every 3 months. Recurrent haemarthroses at the same joint could cause destruction of his joints leading to osteoarthritis, limitation in movement and development of contractures. A delay in treatment could also cause damage to the joint. As such, prompt and adequate factor VIII transfusion is essential for MFA. He should also be referred to the physiotherapy department when the pain has subsided. Physiotherapy would help in preventing the development of joint contractures
3. Risk of bleeding
Due to his active nature, MFA is also at risk of severe bleeding if he injures himself. He was last admitted to the hospital for one week due to bleeding when he fell while playing. There was severe bleeding from his mouth and gums when he hit his face on a table. MFA is also currently shedding his decidual teeth. As such, he is at risk of gum bleeding from the site of tooth extraction. The most dangerous risk is that of an intracranial haemorrhage
4. Risk of recurrent factor transfusions
MFA requires frequent factor transfusion. As the factor VIII used in Batu Pahat is derived from human plasma, there is a risk that MFA may get Hepatitis B, Hepatitis C or HIV infections. In addition, MFA has not been screened for any of these infections. As such it is necessary for MFA to be screened as recommended by the Malaysian protocol for the management of haemophilia.
5. Effect of illness on schoolwork and daily activity
MFA misses school for about a week on an average of once every three months. This may affect his performance in school. In addition there is an increase need for him to get good academic results as he would need to think about a future with a career that does not require heavy physical activity due to his condition.
Difficulty faced by caretakers
MFA's father and mother are both working and often are forced to miss work in order to take care of MFA when he develops episodes of bleeding. Both the parents are teachers who have understanding headmasters who sympathize with them and give them much leeway in order to care for their child. However the continuous stress of taking care of a chronically ill child needs to be addressed. Support groups such as the haemophillia society would be able to help the parents by giving them access to other parents who face similar difficulties. These parents would be able to encourage one another and share tips on caring for haemophilliac children
STUDENT NAME: Tan Hai Liang ID NO: M0409146
NAME OF SUPERVISOR: Dr Kyin ROTATION: Paediatrics
6) PLAN OF INVESTIGATION, JUSTIFICATIONS FOR THE SELECTION OF TESTS OR PROCEDURES, AND INTERPRETATION OF RESULTS
Investigations done at 8 months of age by the national blood bank:
1. Coagulation profile
Justification: MFA presented with purpura at his limbs which indicates that might have a bleeding disorder. As such a coagulation profile would be useful to see if the coagulation pathways are affected.
Results: APTT prolonged. More than 90 seconds
Interpretation: The prolonged APTT indicates that the intrinsic pathway is affected and that one of the factors in the intrinsic pathway may be deficient.
2. Serum factor VIII level
Justification: To ascertain which specific factor that is deficient causing the bleeding disorder.
Results: Factor VIII level: 0.6%
(No inhibitors detected)
Interpretation: MFA has severe haemophilia A due to his Factor VIII level being less than 1 %. He will respond to factor VIII transfusion as there are no inhibitors to factor VIII detected.
No investigations were done for this presentation at the daycare.
I would suggest the following investigations:
1) A plain radiograph of the ankle joint AP and lateral view
Justification: In order to rule out other causes of the joint pain such as septic arthritis or fracture at the joint.
Possible reasons why it was not done: The clinical presentation of the patient did not suggest that he has septic arthritis as he did not have a fever and the joint was not red. As the clinical picture was typically suggestive of a haemarthroses given that he is a haemophiliac, it would be unfair to the patient to subject him to an x ray as this would mean he would be exposed to radiation every three months.
2) Full blood count
Justification: A full blood count would be useful to see if there is an increased white cell count which may indicate an infection.
Possible reasons why it was not done: MFA is clinically well with no symptoms of infection such as fever. As such a full blood count may not be necessary as it would probably be normal. There is also a risk of bleeding or haematoma from venepuncture.
STUDENT NAME: Tan Hai Liang ID NO: M0409146
NAME OF SUPERVISOR: Dr Kyin ROTATION: Paediatrics
7) WORKING DIAGNOSIS AND PLAN OF MANAGEMENT ON ADMISSION
Working diagnosis: Haemarthroses of the left ankle due to Haemophilia A
My proposed plan of management:
i) Factor VIII transfusion with a target serum factor level of 30% eight hourly till the swelling and pain resolves
ii) Elastic bandage and ice pack around the left ankle
iii) To rest the ankle joint by non-weight bearing till swelling and pain reduces
iv) To examine patient for joint deformity or contractures prior to discharge from daycare
v) Refer the patient to physiotherapy for joint rehabilitation of the affected joint.
vi) To educate the parents on care for their child and protective measures to prevent injury.
STUDENT NAME: Tan Hai Liang ID NO: M0409146
NAME OF SUPERVISOR: Dr Kyin ROTATION: Paediatrics
8) SUMMARY OF INPATIENT PROGRESS (INCLUDING MAJOR EVENTS, CHANGE OF DIAGNOSIS OR MANAGEMENT AND OUTCOMES)
MFA was given 200 IU of Factor VIII transfusion. He was then asked to return the next day to be reviewed by the medical officer in charge. Only one transfusion was insufficient for the swelling and MFA had to endure much discomfort and pain throughout the night. This is despite the Malaysian Paediatrics protocol recommendation that factor VIII is given every 8 to 12 hours. The reason for this could be the prohibitive cost of the factor.
The next day MFA was given another 200 IU of Factor VIII transfusion in the morning and again in the evening, twelve hours apart. He was given two more transfusions on the third day. The transfusions were given at the daycare in the mornings and at the paediatric ward at night by the medical officer who was on call.
The pain and swelling resolved on the fourth day post injury. He was examined by the medical officer and was told to only return to the daycare if he had another episode of joint swelling or overt bleeding.
STUDENT NAME: Tan Hai Liang ID NO: M0409146
NAME OF SUPERVISOR: Dr Kyin ROTATION: Paediatrics
9) DISCHARGE PLAN, COUNSELLING AND MOCK PRESCRIPTION
Discharge plan:
i) MFA was asked to rest him left ankle and to partially bear weight till it was completely pain free.
ii) Referral to the physiotherapist for joint rehabilitation to be done
Counseling:
i) MFA was advised to avoid sports which involve physical contact as the even minimal trauma may cause a bleed.
ii) MFA's parents were told to bring him back to the daycare if there were anymore episodes of bleeding into the joints or 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.
iii) MFA and his parents were also educated on complications that they need to look out for such as intracranial haemorrhage. They were taught about the signs and symptoms that they should be wary of.
iv) MFA was encouraged to go for physiotherapy which he had previously defaulted. He was told about the dangers of joint destruction due to recurrent haemarthroses and how physiotherapy may assist in preventing contractures.
STUDENT NAME: Tan Hai Liang ID NO: M0409146
NAME OF SUPERVISOR: Dr Kyin ROTATION: Paediatrics
10) REFERRAL LETTER (MANDATORY)
Dr Tan Hai Liang,
Paediatric Department,
Hospital Batu Pahat
Physiotherapist,
Physiotherapy department,
Hospital Batu Pahat 27 May 2009
Dear sir,
Patient's name: Mohammad Faiz Affizuddin
Patient's I/c number: (B) 630902-01-6092
Problem: Haemarthroses of the left ankle joint
Thank you for seeing this nine year old boy who was diagnosed with Haemophilia A for the past eight years. He has had recurrent episodes of bleeding into the joints. The joints most usually affected are the knee joints and elbow joints. His current presentation is for a haemarthroses of the left ankle joint.
Physical examination: Redness and swelling of the left ankle joint. Tenderness on palpation. Reduced range of movement both active and passive.
He has been given Factor VIII transfusion which has reduced the swelling and pain.
Kindly review the patient and perform joint rehabilitation for him. He has good family support and his family could also be taught exercises to prevent joint contractures that can be done at home in view of his recurrent bleeding into the joints.
Thank you.
Yours truly,
______________
(Dr Tan Hai Liang)
STUDENT NAME: Tan Hai Liang ID NO: M0409146
NAME OF SUPERVISOR: Dr Kyin ROTATION: Paediatrics
11) LEARNING ISSUES IN THE 8 IMU OUTCOMES
1) Family and community issues in healthcare
How are parents affected by having a haemophiliac child?
I had the opportunity to talk to MFA's parents and ask them about the challenges faced when caring for him. They related many of their experiences and confided that many changes to the lifestyle of the family were done in order to adapt to living with and caring for a haemophiliac. Both parents have had to miss work regularly due to MFA's frequent hospital admissions. Family activities also are limited to light physical activity with minimal risk of injury. Furthermore MFA's mother admitted to initially feeling guilty as she was the carrier of the gene that leads to his condition.
As such, I wondered if haemophilia had an impact on parent's quality of life in light of the many adjustments that they had to make to their lifestyle.
A study by Beeton et al [1] involved 12 parents of children with haemophilia whose age ranged from 18 months to 16 years of age. The parents were interviewed and qualitatively assessed on their experiences in caring for a child with haemophilia.
It found that medical management frequently focused on helping the haemophiliac adjust to his or her condition with little emphasis on the wider family network. The early years of the child's life after diagnosis were characterized by the parents lacking experience and feeling uncertain. This is coupled with the frequent need of factor transfusion and the associated difficulty in venous access in infants and young children. Quality of life at the early years post diagnosis was found to be poor due to parents feeling 'out of control'.
Parents caring for a haemophiliac child also reported that the way in which they engaged with the people around them had changed. There was a necessity in being more assertive in order to protect their child. This was confirmed by MFA's mother who relates that she had arguments with the hospital director and headmaster of MFA's school in order to insist on special measures to be put into place to improve MFA's quality of life.
The study also found that mothers usually took up a greater responsibility in caring for the child. Fathers who were at work during the day did not have the same level of experience and this could be a source of conflict between parents. Parents were also found to have higher levels of stress and anxiety. However the level of the stress and anxiety was dependant upon on the stage that parents had achieved in managing the condition as well as successful adaptation.
Another study by Bullinger et al [2] showed that the quality of life for patients and families with haemophilia was higher when compared to patients with other chronic illnesses such as asthma. This shows that families with haemophiliacs are able to live a relatively normal life with good quality of life if certain steps were taken to achieve successful adaptation. The study found that improvement in quality of life can be attained by providing an environment in which patients and parents feel understood and well informed.
In conclusion, I learned that haemophilia has a profound effect, not only on the child who has the disease but also on his primary caretakers which are his parents. As such I need to also enquire about how parents are coping and offer professional help such as counselling if necessary.
2) Critical thinking and research
Is clotting factor concentrate prophylaxis effective in the management of patients with haemophilia?
A paper by Ljung [3] proposed that management of a patient with haemophilia should move away from focusing on the disorder itself and instead look towards maintaining a healthy child. This means that patient's should not be repeatedly managed with factor transfusions when they present with bleeding but instead be kept healthy by preventing the bleeding from happening in the first place. As such the author proposed that primary prophylactic therapy should be the gold standard in the management of patients with haemophilia.
However is clotting factor concentrate prophylaxis effective in managing patients with haemophilia, and what are the associated factors which prevent this management from being a practical option?
I looked at a Cochranre review by Stobart et al [4] which analysed four separate studies involving 37 patients. The results of the review showed that there was a statistically significant difference in the reduction of bleeding episodes 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.
An independent retrospective study by Khoriaty [5] showed that primary prophylaxis has some promise. The study recruited 133 patients with Haemophilia A and B with a mean age of 27.93. It compared the 91 patients who were on primary prophylaxis and the remaining 42 patients receiving on-demand treatment when they developed bleeding. The study found that there was a statistically significant reduction in the number of spontaneous bleeding per year. Patients on primary prophylaxis were found to have 3.2 bleeds per year while those who received on-demand therapy bled 5.7 times per year. It found no statistical difference between the two groups in terms of bleeding after trauma.
However the results for this study needs to be read with care due to the large age range. Further studies need to be done for the paediatric age group due to differences such as a higher propensity for trauma and injury in active children compared to adults who are better at caring for themselves.
One reason why primary prophylaxis is not used in the treatment of haemophiliacs despite its promise is the high cost of the factor VIII. One vial of 200 IU costs in the region of RM 800. As such it may not be cost effective for primary prophylaxis to be carried out especially in the context of the Malaysian healthcare system with its limited budget. A cost effectiveness analysis by Miners et al [6] in England showed that it would cost £547 to prevent one episode of bleeding from happening. This cost is largely prohibitive in the Malaysian context.
In conclusion I found that there is evidence that primary prophylaxis has much promise in the prevention of bleeding among haemophilia patients but additional studies need to be carried out especially in the local environment in order to ascertain the cost-effectiveness of primary prophylaxis.
3) Self directed life long learning
What is the future in terms of management of haemophilia?
The management of haemophilia is currently with factor transfusions which aim to stop bleeding when it has already happened. The other alternative is primary prophylaxis with regular factor infusions to prevent bleeding. However this approach is costly and does not deal with the problem of patients developing inhibitors which make transfusions ineffective. As such, researchers are looking into a means for a cure of haemophilia. This cure is by using 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. Haemophilia is seen as the ideal candidate for gene transfer therapy as firstly 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 prior to initiation of human trials. [7]
Phase 1 clinical trials are currently being done using mostly viral vectors to insert the gene. Retroviruses have shown promise in this therapy. The genes are inserted via developing hepatocytes or haemopoietic stem cells. Currently safe long term expression of clotting factors has been successfully achieved in large animal models of haemophilia using multiple gene transfers. [8]
Gene transfer therapy however still faces many obstacles before it can be seen as a viable therapy for haemophilia. There is risk of experimentation in humans in order to validate this therapy. Many questions also remain unanswered such as inhibitor development after the insertion of the gene and also the transmission of the additional gene to the children of the patient who receives the gene therapy. One paper suggested a generous timeline of at least 20 to 30 years before the potential of gene therapy can even be considered. These issues are 'merely medical' issues. Religious and ethical issues also have to be taken into consideration before pursuing this management.
In conclusion, I learned that though there is much potential in this field of gene therapy, much research still has to be undertaken to ascertain its safety as well as efficacy. However it has been a valuable experience in learning about new modalities of treatment and to catch a glimpse of what the future holds. This has taught me to continue learning as there are always new opinions and therapies available in the management of any illness.
4) Professionalism, ethics and personal development
What are the ethical implications of genetic testing for hemophilia?
After MFA was diagnosed with hemophilia, his immediate family underwent genetic testing. The testing revealed that his mother was a carrier and that his elder brother and elder sister were normal. The genetic testing was done voluntarily. There is no recommendation in the Malaysian Paediatric protocol for genetic testing to be done.
Genetic testing is usually done in patients with no clear family history in order to ascertain which parent is a carrier 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. However genetic testing also raises many ethical questions.
Firstly there is guilt, grief and self blame when a mother with no known family history of haemophilia finds that she was the gene carrier that passed it on to her child. A paper by Thomas et al [9] on attitudes towards genetic testing in an Australian community found that mothers who were 'sporadic' carriers (no known family history of haemophilia) were had feelings of guilt. Performing genetic testing to ascertain that a mother of a haemophiliac child is a carrier would only be of value if additional steps were taken such as offering genetic testing to the mother's siblings. This in itself would raise questions of confidentiality and disclosure since offering the testing would require the doctor to disclose to the other family members that the mother is a carrier. This disclosure could then lead to stigmatization.
In this specific case, MFA's mother was found to be a carrier. She related that she felt anguished at 'causing' her son to suffer much pain. The knowledge that the mother was the carrier who had passed on the gene to her son did not alter the management of MFA. As such there was little merit in performing the genetic testing in this case.
A second consideration of genetic testing is the implications that it has on a person's decision of whether or not to have children. This is again more relevant for female carriers. Carriers should be counseled that there is a fifty percent chance that their child would have haemophilia if he were a boy. However the ethical issue arises when there is no means of correlating between the genotype and phenotype. [10] Just because the child may have haemophilia does not predict the degree of severity of the haemophilia. The only means to know for sure about the status of a fetus in terms of whether he would have haemophilia and the degree of severity is by doing prenatal genetic testing such as chorionic villi sampling.
Prenatal genetic testing itself is associated with many ethical issues such as the implications of carrying out such a test. Would the fetus be terminated? There is legal leeway for termination if it can be proven that the child's illness would bring about mental distress to the mother. Where do we draw the line to decide that such a fetus has too severe a hemophilia so as to warrant termination? Who makes the decision?
In the case of MFA, the parents decided not to have any more children due to the risk of having another haemophiliac child. It ca be seen that the genetic testing had a profound impact on their decision. However proper and thorough genetic counseling was not given to the parents.
In conclusion I learned that genetic testing for haemophilia is fraught with many ethical considerations. It should only be offered when proper follow-up such as counseling, support and options can be offered to those undergoing the test. In the absence of proper framework of support, it may be better to withhold genetic testing.
