What are haemophilia A & B?

• Haemophilia A is more common than haemophilia B, affecting one in 5,000 males compared to one in 40,000 males.
• Both haemophilia A and B are disorders caused by mutations on genes on the X chromosome (X-linked disorders).
• Queen Victoria was a carrier of haemophilia A.

Genetics

• Haemophilia A and B are both recessive conditions, which means that someone has to have two mutated copies of the gene to display symptoms (with just one mutated copy they are a carrier).
• However, because the mutated gene is on the X chromosome, it is much more common for males to be affected than females because males only have one X chromosome.
• The disease genes are called F8 and F9 and are found close together on the X chromosome.
• A mutation in the F8 gene results in haemophilia A and a mutation in the F9 gene results in haemophilia B.

Biology

• The F8 and F9 genes code for the proteins Factor VIII and Factor IX respectively.
• Factor VIII and Factor IX are coagulation factors that each have an important role in the blood clotting process.
• A mutation in either the F8 gene or F9 gene can result in abnormal or reduced amounts of Factor VIII and Factor IX.
• In cases of severe haemophilia the activity of these factors can be lost altogether.
• Without these factors, the blood clotting process does not work as efficiently and blood clots cannot form properly in response to injury.
• The result is continuous bleeding that can be difficult to control, leading to extensive blood loss.

Symptoms

• The symptoms of haemophilia are easily recognisable as bleeding, haemorrhaging and bruising.
• Haemophilia A and B have very similar symptoms that can range from mild to very severe depending on how much the levels of Factor VIII and IX are affected.
• Healing after trauma or surgery often takes a lot longer in patients with haemophilia.
• Delays in clotting can cause internal bleeding that result in swelling and pain in the joints.

Diagnosis

• Physicians can determine whether a patient has haemophilia A or B by seeing whether symptoms are reduced by prescribing Factor VIII or IX.
• If Factor VIII relieves the symptoms of the disease the patient has haemophilia A, if Factor IX does it is haemophilia B.
• Genetic testing can also be used to identify whether the F8 or F9 gene is mutated, and therefore whether the person has haemophilia A or B.

A blood sample.
Image credit: Shutterstock

Treatment

• Regular injections of Factor VIII or Factor IX into the blood are used to manage haemophilia A or B respectively.
• Additional injection of clotting factors may be required in situations where bleeding may occur, for example, during surgery.
• Gene therapy is being investigated as a potential treatment option.
  • One study at University College London has looked at injecting haemophilia B patients with a virus containing a section of DNA carrying the instructions for making normal Factor IX.
  • Levels of Factor IX in the blood of those injected with the virus rose for the 16 months of the study. As a result some of the patients no longer needed to continue their routine Factor IX injections.
  • Although a promising result, this technique will need to be tested on a much larger number of patients before the benefits and risks can be properly assessed.