1st June 2023

Haemophilia

A deficiency of clotting factor VIII or IX can result in Haemophilia, an X-linked recessive bleeding disorder. Factor VIII or Factor XI deficiency results in Haemophilia A and B, respectively. Due to genetic inheritance, inherited haemophilia occurs almost entirely in males, but females can also be affected.

Acquired haemophilia is a much rarer, non-genetic bleeding disorder. It has an autoimmune component and is due to the presence of a coagulation factor inhibitor, such as a lupus anticoagulant.

Haemophilia A

Haemophilia A is caused by the deficiency of the coagulation factor VIII. This disorder encompasses three categories: mild, moderate, and severe; the severity is based on factor VIII levels.  In the normal population, the factor VIII levels are between 50% and 100%. In mild, moderate, and severe Haemophilia A, the factor VIII levels are between 6 – 40%, 1 – 5% and <5%, respectively.

The symptoms of Haemophilia A depend on whether the disorder is mild, moderate, or severe. Symptoms range from instances where bleeding only occurs following an injury, procedure or childbirth to spontaneous bleeding such as into muscles and joints and intracranial bleeds.

Haemophilia B

Haemophilia B is caused by the deficiency of the coagulation factor IX, Haemophilia B is also known as Christmas Disease. Depending on the level of factor IX, it can be classified as mild, moderate, or severe. Again, the symptoms, like Haemophilia A, vary depending on the classification of the disorder.

Haemophilia inheritance

Image Source: Public Health Image Library (2022). Haemophilia. Available for free at: https://www.cdc.gov/ncbddd/hemophilia/facts.html (Accessed on: 30 January 2023).

Investigations

If a patient has a family history of haemophilia or signs and symptoms that could suggest haemophilia, then the investigations below should be performed:

• APTT – usually prolonged
• APTT mixing studies – APTT corrects
• Factor VIII or factor IX assay – decreased levels of VIII in haemophilia A or decreased levels of IX in haemophilia B
• FBC – usually normal, but anaemia can exist due to chronic bleeding
• PT – normal
• Von Willebrand factor assay – normal
• Bleeding time – normal
• Liver function tests – normal

Management

Broadly, management can be divided into management in the acute setting and prophylaxis.

In the acute setting of severe bleeding, patients should be managed with high-dose clotting factor concentrate of either factor VIII or factor IX (depending on whether they have haemophilia A or B). Some patients may require emergency surgery or procedures, for example if there is compartment syndrome caused by a severe muscular haematoma. Some patients can be treated with tranexamic acid. In mild Haemophilia A, desmopressin can be used to increase the factor VIII and von Willebrand factor (VWF) levels both as treatment and prophylactically prior to a procedure.

Occasionally patients who receive clotting factor concentrates can develop antibodies, called inhibitors, which make the factor concentrates less effective when they are next given. Patients should be regularly tested for inhibitors.  If high-titre factor inhibitors are present, bypassing agents should be used instead of the clotting factor concentrates.

In the prophylactic setting, if the haemophilia is severe and there are no factor VIII/IX inhibitors, prophylactic recombinant or plasma-derived factor VIII or factor IX should be administered. If patients have factor VIII/IX inhibitors, then immune tolerance induction can be used to eliminate the inhibitor. Emicizumab, a monoclonal antibody, has now been approved for prophylaxis in haemophilia A (irrelevant of the inhibitor status).