Haemophilia A

Published on 02/04/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

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244 Haemophilia A

Instruction

Examine this patient’s knee (or elbow) joint; he has a bleeding disorder.

Salient features

History

• Family history of bleeding (X-linked recessive disorder): draw the family tree

• Recurrent bleeding into the joints

• Intramuscular haematomas (after trauma, such as injections)

• Retroperitoneal bleeds

• Bleeding from mucous membranes

• Haematuria, haemospermia

• Intracranial bleeds (second most common cause of death in haemophiliacs after HIV)

• History of spontaneous bleeds (suggests severe disease).

Examination

• Male patient

• Fixed deformity of the joint (haemarthrosis causes bone and joint destruction).

Proceed as follows:

Diagnosis

This patient has a fixed deformity of the elbow (lesion) caused by bleeding into the joint as a complication of haemophilia A (aetiology). The joint is now undergoing osteoarthritic changes (functional status).

Note: Be prepared to discuss the coagulation cascasde.

Questions

What is the inheritance of haemophilia?

One-third are sporadic and the rest are X-linked (defects include deletions, point mutations and insertions on the X chromosome).

What is deficient in haemophilia?

It is factor VIII:C, the clinical manifestations depend on its level. Levels <1% are associated with spontaneous bleeding, whereas patients with levels <5% have severe bleeding after trauma and occasionally spontaneous bleeding. When levels are >5%, bleeding occurs after trauma.

Advanced-level questions

How are bleeding episodes treated?

• Factor VIII concentrates:

• For minor bleeding, factor VIII concentrates should be raised to 20–30% of normal
• For severe bleeding factor VIII is raised to at least 50%
• For major surgery, factor VIII should be raised to 100% and maintained at over 50% until healing has occurred.

• Patients can stock Factor VIII in domestic refrigerators for self-administration to start treatment immediately on bleeding. It is given twice daily and intravenously.

• Desmopressin (DDAVP), administered intravenously, can increase factor VIII levels depending on the initial level.

What are the complications of haemophilia?

Complications of the disorder

• Recurrent joint bleeding:

• Chronic arthropathy, pain and loss of function
• Crippling arthritis: recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other haemorrhages in young boys with severe haemophilia A (N Engl J Med 2007;357:535–44).

• Death from haemorrhage.

Complications related to treatment

• Transfusion-transmitted infections (risk reduced with virally inactivated concentrates; risk probably eliminated with recombinant products)

• Development of antibodies (inhibitors). Black patients with haemophilia A (factor VIII deficiency) are twice as likely as white patients to produce inhibitors against factor VIII proteins given as replacement therapy.

What is the commonest cause of death?

Currently, it is HIV infection, transmitted by contaminated factor VIII concentrate administered in the past. HIV-associated immune thrombocytopenia may worsen the bleeding tendency.

In 1803, John Conrad Otto emphasized its inheritance as an X-linked disorder in his description of a New Hampshire family.

Queen Victoria’s descendants are said to have suffered from haemophilia (BMJ 1995;311:1106–7). She was a clinically normal carrier; she had one son, Leopold, who had haemophilia, and two daughters, Alice and Beatrice, who were carriers and who, in turn, transmitted the disease to the Russian, Prussian and Spanish royal families.

In 1964 Pool and co-workers discovered that factor VIII is concentrated in cryoprecipitate.

In 1984 the gene for factor VIII was cloned and expressed in tissue culture.

Robert Gwyn Macfarlane, Professor at Oxford, did pioneering work on the care of haemophiliacs and was the first to propose the cascade hypothesis of blood coagulation.

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