Tuesday 17th April, 2012, was observed globally as the World Haemophilia Day with the theme: “CLOSE THE GAP”. On that day, the Haemophilia Foundation of Nigeria (HFN) joined the international bleeding disorders community to observe the important occasion.
The theme was necessitated by the fact that the World Federation of Hemophilia (WFH), found out that, to date, out of 100 persons with bleeding disorders, only 25 per cent get access to right treatment. The remaining 75 per cent have limited or no access to treatment at all.
Nigeria falls among this category. Thus, the HFN calls on everyone to help spread the message.
“Join us as we spread the news by sticking one ‘CLOSE THE GAP’ sticker on your car, house, books, refrigerators etc., for a token donation of just N10,” the body stated in a statement.
“Each sticker reminds you of a child in the village, who is bleeding either from circumcision, fall, or tooth extraction. It also reminds you of a mother who is bleeding non-stop from child birth. Help us STOP THE BLEED today,” it concluded.
What, therefore, is haemophilia? According to the online resource, Wikipedia, haemophilia is a group of hereditary genetic disorders that impair the body’s ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken.
The HFN describes haemophilia as an inherited bleeding disorder. “People with haemophilia do not bleed any faster than normal, but longer. This is because their blood does not have enough clotting factors. Clotting factors are proteins in blood that help control bleeding.”
Haemophilia lowers blood plasma clotting factor levels of the coagulation factors needed for a normal clotting process. Thus when a blood vessel is injured, a temporary scab does form, but the missing coagulation factors prevent fibrin formation, which is necessary to maintain the blood clot. A haemophiliac does not bleed more intensely than a person without it, but can bleed for a much longer time. In severe haemophiliacs even a minor injury can result in blood loss lasting days or weeks, or even never healing completely. In areas such as the brain or inside joints, this can be fatal or permanently debilitating.
Characteristic symptoms vary with severity. In general symptoms are internal or external bleeding episodes, which are called “bleeds”. Patients with more severe haemophilia suffer more severe and more frequent bleeds, while patients with mild haemophilia typically suffer more minor symptoms except after surgery or serious trauma. Moderate haemophiliacs have variable symptoms which manifest along a spectrum between severe and mild forms.
Prolonged bleeding and re-bleeding are the diagnostic symptoms of haemophilia. Internal bleeding is common in people with severe haemophilia and some individuals with moderate haemophilia. The most characteristic type of internal bleed is a joint bleed where blood enters into the joint spaces. This is most common with severe haemophiliacs and can occur spontaneously (without evident trauma). If not treated promptly, joint bleeds can lead to permanent joint damage and disfigurement. Bleeding into soft tissues such as muscles and subcutaneous tissues is less severe but can lead to damage and requires treatment.
Children with mild to moderate haemophilia may not have any signs or symptoms at birth especially if they do not undergo circumcision. Their first symptoms are often frequent and large bruises and haematomas from frequent bumps and falls as they learn to walk. Swelling and bruising from bleeding in the joints, soft tissue, and muscles may also occur. Children with mild haemophilia may not have noticeable symptoms for many years. Often, the first sign in very mild haemophiliacs is heavy bleeding from a dental procedure, an accident, or surgery. Females who are carriers usually have enough clotting factors from their one normal gene to prevent serious bleeding problems, though some may present as mild haemophiliacs.
Severe complications are much more common in severe and moderate haemophiliacs. Complications may be both directly from the disease or from its treatment:
Deep internal bleeding, e.g. deep-muscle bleeding, leading to swelling, numbness or pain of a limb.
Joint damage from haemarthrosis (haemophilic arthropathy), potentially with severe pain, disfigurement, and even destruction of the joint and development of debilitating arthritis.
Transfusion transmitted infection from blood transfusions that are given as treatment.
Adverse reactions to clotting factor treatment, including the development of an immune inhibitor which renders factor replacement less effective.
Intracranial haemorrhage is a serious medical emergency caused by the buildup of pressure inside the skull. It can cause disorientation, nausea, loss of consciousness, brain damage, and death.
The Nigerian Challenge
According to the HFN, about 70 per cent of boys born with haemophilia die before they are even diagnosed. This is because in a country where circumcision is both a religious and cultural belief many of these boys die at circumcision. The 30 per cent which do survive face a life of crippling pain and disability. It is almost impossible for a boy with a bleeding disorder in Nigeria to attain adolescent without a limb disability.
Prior to 2005 in Nigeria, the only available means of treatment had been whole blood, fresh frozen plasma and cryoprecipitate, all of which has the risk of blood borne diseases. From as early as a 15 day old, a boy started experiencing blood transfusion; and by the time he was 8 years old, he has had as many as 7 blood transfusions.
“The search for alternative treatment yielded results in 2004, when I met the WFH. I found out that there were genetically prepared anti-hemophilic concentrates which are safer. However, this too came with its own challenge; they are very expensive,” said Megan Adediran, HFN founder.
“A boy who weighs 30kg requires 450 IU (international unit), while and adult of 60kg requires 900 IU to treat a moderate bleed. With 300 IU costing around N91,000, it means the child needs about N140,000 while the adult N273,000 respectively per dose.
For a family with two sons weighing 45 kg and 23kg respectively; both with the severe form, it means such a family needs about N364,000 weekly to keep the boys alive. This is because a person with severe haemophilia bleeds at least once a week. How much must a parent earn to be able to cope? No parent in Nigeria can afford this.
In 2005, Nigeria’s factor concentrate consumption stood at 0 i.u per capita; whereas the WFH and WHO’s approved consumption rate is a minimum of 1 i.u per capita. HFN with the support of the WFH has in six years distributed for free factor concentrates worth over half a billion naira to persons across the nation. These donations moved our consumption rate to 0.002 i.u by 2010; a data we hope to improve upon this year.
Between 2008 and 2009, a number of persons with bleeding disorders died due to bleeds that could be averted if we had enough treatment products. Presently, many of these boys and men are confined to wheel chairs and crutches requiring surgeries to correct their affected limbs. A number cannot go to school, while those working face threats of losing their jobs, because of constant absenteeism from work. Some have even had their legs amputated.”
Life Expectancy
Like most aspects of the disorder, life expectancy varies with severity and adequate treatment. People with severe haemophilia who don’t receive adequate, modern treatment have greatly shortened lifespans and often do not reach maturity. Prior to the 1960s when effective treatment became available, average life expectancy was only 11 years. By the 1980s the life span of the average haemophiliac receiving appropriate treatment was 50–60 years. Today with appropriate treatment, males with haemophilia typically have a near normal quality of life with an average lifespan approximately 10 years shorter than an unaffected male.
Since the 1980s the primary leading cause of death of people with severe haemophilia has shifted from haemorrhage to HIV/AIDS acquired through treatment with contaminated blood products. The second leading cause of death related to severe haemophilia complications is intracranial haemorrhage which today accounts for one third of all deaths of patients with haemophilia. Two other major causes of death include: hepatitis infections causing cirrhosis and, obstruction of air or blood flow due to soft tissue haemorrhage.
Causes
Haemophilia A is a recessive X-linked genetic disorder involving a lack of functional clotting Factor VIII and represents 80% of haemophilia cases.
Haemophilia B is a recessive X-linked genetic disorder involving a lack of functional clotting Factor IX. It comprises approximately 20% of haemophilia cases.
Haemophilia C is an autosomal genetic disorder (i.e. not X-linked) involving a lack of functional clotting Factor XI. Haemophilia C is not completely recessive, as heterozygous individuals also show increased bleeding.
Severity
There are numerous different mutations which cause each type of haemophilia. Due to differences in changes to the genes involved, patients with haemophilia often have some level of active clotting factor. Individuals with less than 1% active factor are classified as having severe haemophilia, those with 1-5% active factor have moderate haemophilia, and those with mild haemophilia have between 5-40% of normal levels of active clotting factor.
Management
Commercially produced factor concentrates such as “Advate”, a recombinant Factor VIII, come as a white powder in a vial which must be mixed with sterile water prior to intravenous injection.
Though there is no cure for haemophilia, it can be controlled with regular infusions of the deficient clotting factor, i.e. factor VIII in haemophilia A or factor IX in haemophilia B. Factor replacement can be either isolated from human blood serum, recombinant, or a combination of the two. Some haemophiliacs develop antibodies (inhibitors) against the replacement factors given to them, so the amount of the factor has to be increased or non-human replacement products must be given, such as porcine factor VIII.
If a patient becomes refractory to replacement coagulation factor as a result of circulating inhibitors, this may be partially overcome with recombinant human factor VII (NovoSeven), which is registered for this indication in many countries.
