Haemophilia
Haemophilia A (Factor VIII deficiency) and haemophilia B (factor IX deficiency or Christmas Disease) are the most well known examples of genetic bleeding disorders. There are other, rarer, inherited bleeding disorders affecting the coagulation pathway.
A spectrum of severity exists depending on remaining levels of Factor activity and this accounts for the occasional diagnosis at a later age.
Inheritance is usually X-linked, affecting males born to carrier mothers, although sporadic cases do occur.
Presentation depends on the severity of the disease and includes neonatal bleeding, spontaneous haemarthrosis, severe bleeding following trauma or surgery (sometimes delayed). Prophylaxis for severe disease is with recombinant Factor.
If a diagnosis is considered in Primary Care, blood tests should be sent for FBC and coagulation screen prior to referral to haematology.
Von Willebrand’s Disease
This is the most common inherited bleeding disorder and is caused by low levels or dysfunction of Von Willebrand’s Factor. Usually the condition is mild without spontaneous bleeding, although there is a rarer subtype which is more severe and has a similar presentation to haemophilia.
Often the condition remains undiagnosed, but patients may present to the GP with prolonged and severe nose bleeds, and women with persistent menorrhagia sufficient to cause anaemia, despite a normal uterus. Patients often bleed profusely from small cuts or surgery, and GI bleeding is common. Spontaneous haemarthroses do not occur, unlike in haemophilia.
It is an autosomal dominant condition affecting men and woman, and is present in about 1% of the population.
Treatment is available in the form of desmopressin, tranexamic acid, or the combined pill for menorrhagia. Severe cases may need treatment with von Willebrand’s Factor. It is beneficial to be aware of the condition prior to surgical operations, to enable appropriate prophylaxis to be considered.
If a GP suspects von Willebrand’s disease they should perform a screening test by checking a FBC and coagulation screen as this may often be helpful to the haematologists in making the diagnosis. However, if there is a significant family or personal history suggesting this condition, even if the FBC and coagulation screen are normal, the patient should be referred to haematology for consideration and possibly further specialised tests.
Thrombophilia
Individuals with a hereditary clotting disorder (thrombophilia) are more likely to develop a venous thrombosis.
Essentially there are the acquired thrombophilias e.g. antiphospholipid syndrome, lupus, cancer etc., and there are hereditary thrombophilias.
Situations which might alert you to the possibility of an inherited thrombophilia would be:
- Strong family history of venous thromboembolism
- Thrombosis in an unusual site (e.g. portal or mesenteric vein)
- Age under 45yrs at presentation
- Recurrent episodes of thrombosis
- Recurrent miscarriage (3 or more)
- A family history of pregnancy induced hypertension
Current guidance suggests that only physicians with specialist knowledge should undertake screening tests for hereditary thrombophilia, so the majority of patients in whom the diagnosis is considered in Primary Care should be referred to the local haematology services, or to obstetrics in the case of recurrent miscarriage.
The current exception to this is the case of a woman wishing to commence the combined oral contraceptive (COC). If she has a positive family history then she should be counselled regarding the increased risk to herself of a thrombosis and alternative methods of contraception considered.
If the woman still wishes to use a COC then a thrombophilia screen may be checked by the GP before initiating the COC. This woman must be counselled that she is at high risk of a venous thromboembolism, whether or not she has a positive or negative thrombophilia screen, in light of her positive family history. However, her risk of thromboembolism on the COC remains less than if she were to become pregnant.
Thrombophilia Screening
A lab request for a thrombophilia screen should be sent to haematology in two blue topped bottles, and one gold topped bottle. The lab will undertake the following tests;
- Basic coagulation screen
- Antithrombin level
- Protein C&S level
- Factor V Leiden (commonest genetic risk factor for venous thrombosis)
- Prothrombin gene mutation
- Lupus anticoagulant