[2][8] Other types include haemophilia C, which occurs due to low levels of factor XI, Von Willebrand disease, which occurs due to low levels of a substance called von Willebrand factor, and parahaemophilia, which occurs due to low levels of factor V.[9][10] Haemophilia A, B, and C prevent the intrinsic pathway from functioning properly; this clotting pathway is necessary when there is damage to the endothelium of a blood vessel.

Females who are carriers usually have enough clotting factors from their one normal gene to prevent serious bleeding problems, though some may present as mild haemophiliacs.

Complications may arise from the disease itself or from its treatment:[24] Haemophilic arthropathy is characterised by chronic proliferative synovitis and cartilage destruction.

The hypertrophied and fragile synovial lining while attempting to eliminate excessive blood may be more likely to easily rebleed, leading to a vicious cycle of hemarthrosis-synovitis-hemarthrosis.

In addition, iron deposition in the synovium may induce an inflammatory response activating the immune system and stimulating angiogenesis, resulting in cartilage and bone destruction.

Since the mutations causing the disease are X-linked recessive, a female carrying the defect on one of her X-chromosomes may not be affected by it, as the equivalent dominant allele on her other chromosome should express itself to produce the necessary clotting factors, due to X inactivation.

[31] The most common mutation that causes severe cases of haemophilia A is an inversion within intron 22 of the factor VIII gene (F8) which is located near the tip of the X chromosome, leading to an abnormal crossover during meiosis.

Such tests include: There is a small risk of these procedures causing problems such as miscarriage or premature labour, so the woman may discuss this with the doctor in charge of her care.

[40][41][42][43] Haemophilia A is a recessive X-linked genetic disorder resulting in a deficiency of functional clotting Factor VIII.

[15] It is a rare but potentially life-threatening bleeding disorder caused by the development of autoantibodies (inhibitors) directed against plasma coagulation factors.

While recombinant clotting factor products offer higher purity and safety, they are, like concentrate, extremely expensive, and not generally available in the developing world.

In rare cases a third route or treatment is used, high doses of intravenous immunoglobulin or immunosorbent that works to help control bleeding instead of battling the auto-antibodies.

Popular sports with very high rates of physical contact and injuries such as American football, hockey, boxing, wrestling, and rugby should be avoided by people with haemophilia.

[55][56] Other active sports like soccer, baseball, and basketball also have a high rate of injuries, but have overall less contact and should be undertaken cautiously and only in consultation with a doctor.

People with severe haemophilia who do not receive adequate, modern treatment have greatly shortened lifespans and often do not reach maturity.

[57] Since the 1980s the primary leading cause of death of people with severe haemophilia has shifted from haemorrhage to HIV/AIDS acquired through treatment with contaminated blood products.

[60] About seventy or eighty years ago, a woman by name of Smith, settled in the vicinity of Plymouth, New Hampshire, and transmitted the following idiosyncrasy to her descendants.

(...) So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation.

Several similar references to the disease later known as haemophilia appear throughout historical writings, though no term for inherited abnormal bleeding tendencies existed until the nineteenth century.

[64] In 1803, John Conrad Otto, a Philadelphian physician, wrote an account about "a hemorrhagic disposition existing in certain families" in which he called the affected males "bleeders".

The idea that affected males could pass the trait onto their unaffected daughters was not described until 1813 when John F. Hay published an account in The New England Journal of Medicine.

[66][67] In 1924, a Finnish doctor discovered a hereditary bleeding disorder similar to haemophilia localised in Åland, southwest of Finland.

In Russia, Tsarevich Alexei, the son and heir of Tsar Nicholas II, famously had haemophilia, which he had inherited from his mother, Empress Alexandra, one of Queen Victoria's granddaughters.

It is believed that, by simply advising against the medical treatment, Rasputin could bring visible and significant improvement to the condition of Tsarevich Alexei.

[76] Her youngest son, Infante Gonzalo, died at age 19 from abdominal bleeding following a minor car accident in which he and his sister hit a wall while avoiding a cyclist.

[77] The method for the production of an antihaemophilic factor was discovered by Judith Graham Pool from Stanford University in 1964,[78] and approved for commercial use in 1971 in the United States under the name Cryoprecipitated AHF.

[80] Up until late 1985 many people with haemophilia received clotting factor products that posed a risk of HIV and hepatitis C infection.

[citation needed] Tens of thousands worldwide were infected as a result of contaminated factor products including more than 10,000 people in the United States,[81] 3,500 British, 1,400 Japanese,[82] 700 Canadians,[83] 250 Irish,[84] and 115 Iraqis.

[16] In July 2022 results of a gene therapy candidate for haemophilia B called FLT180 were announced, it works using an adeno-associated virus (AAV) to restore the clotting factor IX (FIX) protein, normal levels of the protein were observed with low doses of the therapy but immunosuppression was necessitated to decrease the risk of vector-related immune responses.

[91][92][93] In November 2022, the first gene therapy treatment for haemophilia B was approved by the U.S. Food and Drug Administration, called Hemgenix.