24th July 2024

Bleeding disorders

Von Willebrand disease (vWD)

This is the most common inherited bleeding disorder. It is inherited via an autosomal pattern with variable penetrance.

There is deficiency or poor function of von Willebrand factor (vWF), which is critical for platelet aggregation at sites of vascular injury. It is also bound to factor VIII, a key component of clotting, which degrades when not bound.

Clinical features of vWD

Presentation is often with mucocutaneous bleeding. Females are more likely to present, commonly with menorrhagia or postpartum bleeding.

Investigations include:

• FBC: anaemia may be present; platelet counts are often normal, although can be reduced
• Coagulation studies: PT is normal; APTT is either prolonged or normal
• vWF antigen level: low

Management of vWD

For minor bleeding, antifibrinolytic treatment such as tranexamic acid can be used, as well as desmopressin, which can stimulate the release of vWF and factor VIII. vWF-containing concentrates are given prior to major procedures or in severe bleeding.

Haemophilia A and B

These are X-linked recessive disorders, and therefore affect males. Haemophilia B is also called Christmas disease.

There is a deficiency or absence of factor VIII (haemophilia A) or factor IX (haemophilia B), which are important in the amplification of thrombin and thus fibrin production.

Clinical features of haemophilia

Symptoms include frequent bruising and bleeding into muscles and joints. Patients with complete absence of the factor present at an earlier age than those with milder disease.

Coagulation studies will show a prolonged APTT that normalises on mixing with normal pool plasma, suggesting factor deficiency rather than inhibition. Factor VIII and IX levels confirm the diagnosis.

Management of haemophilia

Factor replacement remains the cornerstone of treatment. It can be used prophylactically to prevent bleeding, both before procedures and in general to prevent major joint bleeds, which can lead to debilitating haemophilic arthropathy.

Repeated doses of factor concentrate can lead to inhibitor formation, reducing the efficacy of treatment. In these cases, bypassing agents are required. Desmopressin may be used for haemophilia A.

References

• Berntop E, Fischer K, Hart D. Haemophilia. Nature Reviews Disease Primers. 7, 45 (2021).[cited 16 December 2021] https://doi.org/10.1038/s41572-021-00278-x
• Laffan M. Von Willebrand disease [Internet]. BMJ Best Practice. BMJ Publishing Group; 2021 [cited 16 December 2021]. Available from: https://bestpractice.bmj.com/topics/en-gb/365
• Poon MC, Lee A. Haemophilia. In: BMJ Best Practice. [Internet]. London: BMJ Publishing Group, 2021 [cited 16 December 2021]. Available from: https://bestpractice.bmj.com/topics/en-gb/468