The cause of haemophilia is a defective gene on the X sex chromosome. Males have one X and one Y chromosome, and if the X has the defective gene, they will have haemophilia. Females have two X chromosomes, only one of which needs to be normal; the chances of having two abnormal ones are vanishingly small. So women do not develop haemophilia, but may pass on the defect to their male children. In Britain one in 10,000 boys is born with the defective gene, but in about one-third of cases there is no family background of the disorder, and the defect seems to be due to a new mutation.
The blood circulation has evolved a twin-track system of damage limitation. A cut finger bleeds from the small blood vessels that have been severed. Within seconds the bleeding first slows and then stops, as the muscles in the walls of the damaged blood vessels go into spasm. This reflex action is powerful enough to be life-saving when someone loses a limb in an accident. Once the bleeding has stopped or slowed to a trickle, the second defence completes the job: the blood clots into semi-solid jelly, which seals the ends of the cut blood vessels. In haemophilia, the failure of the blood to clot allows bleeding to start again when the reflex muscular contraction of the blood vessels wears off.
The formation of a blood clot starts with small blood cells called platelets, which clump together in the injured blood vessels. Platelets release the first of a series of chemicals which act on others in the blood, in a biological mechanism known as a cascade. The first plasma factor triggers a second, which triggers a third, until after a dozen or so steps the initial one or two molecules have activated many thousands of the final factor, fibrinogen, which is converted into the main material of the blood clot, fibrin. The individual chemicals in the cascade were given Roman numerals as they were discovered, and in haemophilia there is a deficiency of Factor VIII.
Once the chemical and genetic defects underlying haemophilia had been worked out, treatment became possible, and in the 1970s boys and men with haemophilia began to be given regular treatment with Factor VIII obtained from blood donors. The process required the Factor VIII to be extracted from large volumes of blood obtained from thousands of donors, and this exposed the patients given the treatment to the risk of infection from viruses in the donated blood. Before these risks were fully understood thousands of these patients had become infected with hepatitis or with HIV, and many have now died from Aids. Others have chronic liver disease. The grim lessons have been learnt, however, and the Factor VIII from donors in current use is treated to make it safe, while advances in genetic engineering have made it possible to produce a totally safe man-made product.Reuse content