Haemophilia A

Haemophilia A (or hemophilia A) is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. In the majority of cases it is inherited as an X-linked recessive trait, though there are cases which arise from spontaneous mutations. Haemophilia A (or hemophilia A) is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males. In the majority of cases it is inherited as an X-linked recessive trait, though there are cases which arise from spontaneous mutations. Factor VIII medication may be used to treat and prevent bleeding in people with haemophilia A. In terms of the symptoms of haemophilia A, there are internal or external bleeding episodes. Individuals with more severe haemophilia suffer more severe and more frequent bleeding, while others with mild haemophilia typically suffer more minor symptoms except after surgery or serious trauma. Moderate haemophiliacs have variable symptoms which manifest along a spectrum between severe and mild forms. Prolonged bleeding from a venepuncture or heelprick is another common early sign of haemophilia, these signs may lead to blood tests which indicate haemophilia. In other people, especially those with moderate or mild haemophilia, any trauma will lead to the first serious bleed. Haemophilia leads to a severely increased risk of prolonged bleeding from common injuries, or in severe cases bleeding may be spontaneous and without obvious cause. Bleeding may occur anywhere in the body, superficial bleeding such as those caused by abrasions, or shallow lacerations may be prolonged and the scab may easily be broken up due to the lack of fibrin, which may cause re-bleeding. While superficial bleeding is troublesome, some of the more serious sites of bleeding are: Muscle and joint haemorrhages – or haemarthrosis – are indicative of haemophilia, while digestive tract and cerebral haemorrhages are also germane to other coagulation disorders. Though typically not life-threatening, joint bleeding is one of the most serious symptoms of haemophilia. Repeated bleeds into a joint capsule can cause permanent joint damage and disfigurement resulting in chronic arthritis and disability. Joint damage is not a result of blood in the capsule but rather the healing process. When blood in the joint is broken down by enzymes in the body, the bone in that area is also degraded, this exerts a lot of pain upon the person afflicted with the disease. One therapeutic conundrum is the development of inhibitor antibodies against factor VIII due to frequent infusions. These develop as the body recognises the infused factor VIII as foreign, as the body does not produce its own copy. In these individuals, activated factor VII, a precursor to factor VIII in the coagulation cascade, can be infused as a treatment for haemorrhage in individuals with haemophilia and antibodies against replacement factor VIII. Haemophilia A is inherited as an X-linked recessive trait. It occurs in males and in homozygous females (which is only possible in the daughters of a haemophilic male and a carrier or haemophiliac female). However, mild haemophilia A is known to occur in heterozygous females due to X-inactivation, so it is recommended that levels of factor VIII and IX be measured in all known or potential carriers prior to surgery and in the event of clinically significant bleeding. About 5-10% of people with haemophilia A are affected because they make a dysfunctional version of the factor VIII protein, while the remainder are affected because they produce factor VIII in insufficient amounts (quantitative deficiency). Of those who have severe deficiency (defined as <1% activity of factor VIII), 45-50% have the same mutation, an inversion within the factor VIII gene that results in total elimination of protein production. Since both forms of haemophilia can be caused by a variety of different mutations, initial diagnosis and classification is done by measurement of protein activity rather than by genetic tests, though genetic tests are recommended for testing of family members once a known case of haemophilia is identified. Approximately 30% of patients have no family history; their disease is presumably caused by new mutations.