Haemophilia is a group of hereditary genetic disorders that result in impaired coagulation. There are two main types of haemophilia:
- Haemophilia A
- Haemophilia B
Haemophilia A is a bleeding disorder caused by a deficiency of clotting factor VIII. It is the commonest form of haemophilia, affecting 1:4,000 to 1:5,000 live male births globally.
The vast majority of cases are inherited in an X-linked recessive fashion, affecting males born to carrier mothers. Females born to affected fathers can also, rarely, be affected due to homozygosity for the gene, where there is marriage to close relatives. Very rarely, acquired forms do exist, mostly in older patients due to autoantibodies directed against factor VIII or haematological malignancy.
The first presentation is usually around 6-months of age when infants begin crawling, but it can present later. Bleeding can follow trauma or occur spontaneously. Haemorrhage into muscles and joints (haemarthrosis) is very indicative of haemophilia. Gastrointestinal and cerebral haemorrhage can also occur but is much less common.
Untreated patients with severe disease may develop:
- Arthropathy and joint deformity
- Soft tissue haemorrhages (can cause compartment syndrome and neurological damage)
- Extensive retroperitoneal bleeds
- Haematoma formation (may require fasciotomy)
Haematological investigations typically reveal:
- Full blood count – low haematocrit and reduced haemoglobin if any recent bleeding
- Prothrombin time, bleeding time, fibrinogen levels and von Willebrand factor are all normal
- Activated partial thromboplastin time (APTT) is usually prolonged but can be normal in mild disease. Mixing the patient’s plasma 1:1 with donor plasma should normalise APTT.
- Factor VIII:C is reduced, and percentage activity represents the severity of disease
Management is with the use of intravenous factor VIII concentrate. This has dramatically improved haemophilia A treatment, preventing joint bleeding and halting the deterioration of joints.
Haemophilia B is a bleeding disorder caused by a deficiency of clotting factor IX. It is the second commonest form of haemophilia and is rarer than haemophilia A, affecting approximately 1:30,000 live male births globally.
Haemophilia B is inherited in an X-linked recessive fashion, affecting males born to carrier mothers. There is also a variation called Leyden, in which factor IX levels are below 1% until puberty, when they rise, potentially reaching as high as 40-60% of normal. This is thought to be due to the effects of testosterone at puberty.
The clinical presentation and haematological investigations are similar to those seen in haemophilia A. Factor IX activity is reduced. Management is with the use of intravenous factor IX concentrate.
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