Treatment for Hemophilia / Haemophilia
Up to a few decades ago a considerable proportion of patients with haemophilia died prematurely because of haemophilia. Tragically, many deaths were the result of childhood injury or surgery. Over the last forty years treatment has advanced so much that the vast majority of patients today are expected to live long and active lives.
The main breakthrough in treatment occurred when coagulation factor deficiencies linked to haemophilia could be identified and then replaced, using products derived from human blood.
In the past patients used to receive whole blood or plasma infusions to control episodes of bleeding. Even though this helped, levels of clotting factors, especially factors VIII and IX, never reached the levels required for really effective blood coagulation, nor could these levels be sustained - in other words, serious bleeding was only partly treated.
Cryoprecipitate, made through the cold precipitation of frozen plasma from1965 onwards, was the first really effective treatment for haemophilia A. Freeze-dried concentrates made from human plasma containing the right levels of Factors VIII and IX became available in the late 1960s and early 1970s. Being able to keep the treatment at home and use it as required meant that patients could travel, leave the home, go to work, and enjoy a level of independence. However, a large number of patients subsequently became infected with blood-borne pathogens, such as hepatitis B, hepatitis C and HIV.
From the mid 1980s rigorous donor selection and viral inactivation procedures reduced the risk of blood-borne viral transmission to nearly zero. During the 1990s it became possible to prepare recombinant factors, using specially prepared mammalian cells and these recombinant concentrates are now widely used.
Haemophilia treatment will mainly depend on its severity and for patients with Haemophilia A or B involves clotting factor replacement therapy. There are two approaches:
On demand - giving treatment to stop prolonged bleeding when it occurs. This is more common in the management of patients with mild haemophilia.
Preventative treatment (prophylaxis) - medication to prevent bleeding episodes, and subsequent complications, such as joint and/or muscle damage. More commonly used for patients with moderate or severe haemophilia.
Clotting factor concentrates
Clotting factor concentrates can be made in two different ways:
Plasma-derived clotting factors - prepared from the plasma of donated human blood.
Recombinant clotting factors - the first generation of recombinant products use animal products in the culture medium and had human albumin (a human blood product) added as a stabiliser. Second generation products use animal-derived materials in the culture medium but do not have added albumin and instead use sucrose or other non-human derived material as a stabiliser. Third generation clotting factors have no albumin present at any stage of their preparation. Mouse monoclonal antibodies have been routinely used in the purification of coagulation factors for many years but one recombinant factor VIII employs a synthetic ligand for this step. This has resulted in the production of the first factor VIII concentrate to be free of all exogenous human and animal protein, a goal which was reached for haemophilia B when the first recombinant factor IX was licensed in 1997.
Desmopressin (DDAVP)(for mild haemophilia A)
This medication is a synthetic hormone which encourages the body to produce more of its own Factor VIII. It is unsuitable for patients with haemophilia B and those with severe haemophilia A. In patients with milder forms of haemophilia A, factor VIII replacement therapy may be necessary, especially for severe bleeds, or after serious injury or major surgery.
RICE (Rest, Ice, Compression, Elevation)
RICE is a treatment many health care professionals recommend for joint bleeds. It also reduces swelling and tissue damage when used together with clotting factor concentrates.
Administering clotting factor concentrates
The medication is injected into a vein - generally in the back of the hand or at the crook of the elbow. Initial treatments are usually administered by a doctor or nurse at a hospital or clinic. Most adults can learn how to do this themselves, which means they can stop bleeding rapidly and effectively wherever they are.
If the patient is a child the parents or caregivers (UK/Ireland/Australia: carers) can learn how to administer treatment. The majority of very young patients can receive most of their treatment at home.
If a patient is finding it hard to access a suitable vein, or if intensive treatment is required, a port-a-cath, or an external catheter called a Broviac or Hickman line can be placed surgically into a vein, allowing factor replacement therapies to be given, and blood to be drawn easily for routine emergency tests. The use of such catheters can be complicated by infection and blockage and they have to be used with great care.
Bleeding episodes (bleeds) are an inevitable complication for patients with haemophilia A and B, even for patients with mild forms. As the underlying problem is one of prolonged bleeding, rather than rapid bleeding, they often appear not to be medical emergencies.
If a person with haemophilia experiences any of the following he should seek immediate skilled medical help:
There is an injury to the neck, mouth, tongue, face or eye.
There is a severe blow to the head.
Bleeding is heavy or persistent.
There is severe pain or swelling in any part of the body.
An open wound requires stitching.
Most other bleeds, such as joint/muscle bleeds, small injuries and cuts that do not require stitches, and nosebleeds are generally treated at home, but patients should always seek the advice of a healthcare professional when in doubt. Any treatment will be more effective if it is started early.
Some factor concentrates have to be stored in a refrigerator while some are stable at room temperature for quite long periods. They should not be frozen as this may damage the vials or syringes. Some may be taken out for travel but should ideally be kept in a cool bag. Read instructions on product storage. If you are unsure, check with a health care professional or qualified pharmacist.
Approximately 30% of people with severe haemophilia A develop antibodies to transfused factor VIII, usually shortly after their first few treatments. These antibodies (also called inhibitors) prevent the factor VIIII treatment working properly. It is often the case that, after a while, the inhibitors disappear and only about 10% or less of people with severe haemophilia A will suffer from long term inhibitors. In recent years it has become possible to prevent inhibitors becoming persistent through immune tolerance induction therapy. Where inhibitors do not respond to this approach alternative treatments are available.
Inhibitors rarely develop in mild haemophilia A or in haemophilia B of any severity.