Haemophilia is a genetic condition where the clotting factor in the blood is either partly or completely missing, leading to a life-long tendency to excessive bleeding with very slow clotting of the blood. It affects females as carriers and males who inherit the condition.Blood clotting involves a complicated process occurring in stages. The sequence is called a cascade and it involves a series of chemical factors described as factor I to factor XIII. There is no factor VI. These factors are proteins, and there is a gene that sets out the chemical structure of each one. The genes for two of the factors, VIII and IX, are on the X (sex) chromosome.

The blood-clotting cascade ends in the formation of a substance that converts a blood protein called prothrombin into the protein thrombin, which actually forms the substance of the blood clot. Thrombin tangles up a lot of small cell fragments in the blood, called platelets, to form a mass that can effectively seal off small bleeding blood vessels.

A gene mutation is a change in the gene code. This change is likely to change the structure of the protein that the gene causes to be made. There are different kinds of mutations, some having a more serious effect on the structure of the protein than do others. If a male person has a significant mutation in the gene for factor VIII or factor IX, he will have haemophilia.

Haemophilia A occurs in about 1 baby in 5,000 live births. Haemophilia B is much less common, occurring in about 1 in 30,000. Haemophilia can be mild, moderate or severe, depending on the amount of functioning factor VIII or IX the mutated gene is able to produce. About 6,000 people are affected with haemophilia in the UK.

Causes

Haemophilia A is due to the absence of Factor VIII. Haemophilia B is due to absence of Factor IX. These clotting factors are two of the many elements necessary for normal blood coagulation. The disease is passed from mother to son on the X chromosome. (The father passes a Y chromosome to their son). Thus women can be carriers having one affected chromosome and transmitting the disease to 50 per cent of their male offspring.

In about 30 per cent of cases, however, there is no family history of haemophilia, these cases arise as a result of new mutations occurring in the cells that produce eggs or sperms in the parents.

The severity of haemophilia varies with the level of Factor VIII activity in the individual and in severe cases this may be less than two per cent of normal.

Treatment

Factor VIII is a protein substance, a globulin. The substance can be isolated from donated blood and given to haemophiliacs to control their bleeding tendency. Unfortunately, factor VIII is active only for a short period – it loses half its activity after only 12 hours – so repeated injections are necessary. The severity of haemophilia varies with the level of natural factor VIII activity in the individual. In severe cases the levels are less than five per cent of normal, and they may be less than two per cent of normal. The level of clotting-factor activity determines the need for replacement therapy, and the dosage. The replacement factors are given by slow injection into a vein.

Injections may be given on a regular basis, this helps prevent bleeding and minimise joint damage, or only when the bleeding occurs.A fairly recent development involves treatment is with genetically engineered factor VIII, ‘recombinant’ clotting factor, rather than donated human factor VIII.