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.
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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
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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
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.
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 AND PRIORITISE THE PROBLEMS
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
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.
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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
– Referral to the physiotherapist for joint rehabilitation
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.
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,
Hospital Batu Pahat
Haematology department, 14th October 2009
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.
Hospital Batu Pahat
11) LEARNING ISSUES IN THE 8 IMU OUTCOMES
1) Professionalism, ethics and personal development
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.
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
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, pr
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