Haemophilia and Thrombophilia Therapies

The appropriate treatment for haemophilia depends on the severity of the condition, and the patient’s circumstances. In mild haemophilia it is often only necessary to give treatment for surgery, or for bleeding resulting from injury. Certain drugs can stimulate the liver to produce more clotting factor; this can be enough to control bleeding in some cases. In more severe types of haemophilia, where the body produces very little or no clotting factor, the only treatment option is to replace the missing clotting factor. Haemophilia A is treated with factor VIII concentrate and haemophilia B with factor IX.

Historically, routine treatment has involved injecting clotting factor to treat a bleeding episode, or for controlling bleeding during surgery. One potential drawback is that some bleeds may be small and are not noticed, yet may still do damage. Delay in treatment can also be damaging. Typically this damage is most obvious in joints, and manifests as arthritis (haemophilic arthropathy). For many older patients, born before the development of modern methods of treatment, this has led to serious joint damage and the need for joint replacement.

Prophylaxis has been introduced in order to combat the disadvantages of on-demand treatment. In prophylaxis, infusions are given regularly in order to prevent bleeding episodes, rather than treating them. By infusing clotting factor regularly, the aim is to keep the level in the blood high enough to prevent bleeding. The other major advantage of prophylaxis is that it allows patients to take control of their condition and treat themselves at home, rather than making regular visits to hospital.

Factor IX remains in the circulation for longer than factor VIII so in haemophilia A, infusions are typically given three times a week, and in haemophilia B normally twice a week.

As the clotting factors needed for treatment are found in human blood, for many years the treatments have been made using blood as the starting material. When blood is separated during processing, a straw-coloured liquid called plasma is produced. Plasma contains proteins such as antibodies, albumin, and all the factors that are needed for normal clotting.

In the 1960s, techniques were developed to isolate individual proteins from plasma, and purify them to make therapeutic drugs - clotting factors made in this way are known as "plasma-derived." In the early years of plasma processing, donors were not selected carefully, and many donors suffered from viral diseases that can be transmitted through blood transfusion. As a result of this, many recipients of blood and plasma products developed HIV and hepatitis, which was fatal in many cases. In the haemophilia community, this led to a campaign for the development of safer products. The first outcome of this campaign was a revolution in donor selection, and improved manufacturing techniques that either remove or inactivate the viruses responsible for these diseases.

In an attempt to eliminate the risk of blood-borne infection completely, researchers have employed gene technology to manufacture the next generation of clotting factors. Having identified the human genes for the production of factor VIII and factor IX, new manufacturing techniques have been developed that are known as "recombinant". The clotting factors made in this way contain small amounts of human protein, and this significantly reduces the risk of disease transmission. As these processes have evolved over time, the exposure to human protein (as part of the manufacturing process, or as a stabiliser in the finished product) has been gradually reduced.

Thrombophilia is not a single condition, but is a "blanket" description for excess clotting. There are many causes of thrombophilia including situations where the body does not make sufficient quantities of an anticoagulant protein.

Clotting in normal circulation is a balance between those proteins that cause clotting, and those that are anticoagulants. This balance is crucial to normal circulation, and can be upset in a number of ways - disease, infection, combinations of drugs and so forth. One of the most rare inherited thrombotic conditions is a deficiency of protein C - this protein is crucial in the control of clotting, and is part of one of the "feedback" mechanisms within the body that normally prevent excess clotting.

People who are deficient in protein C are at higher risk of developing blood clots than most people: a mild deficiency may not lead to symptoms except when combined with another risk factor (disease, immobility, long-distance air travel); severe deficiency of protein C may lead to life-threatening thrombosis, both in the skin and in major blood vessels that supply the organs.

There are fewer than ten patients suffering from severe congenital protein C deficiency and, like people with haemophilia, they need to replace this missing protein regularly in order to make sure that the balance between clotting and anticoagulation remains as normal as possible.