Kate Khair, MSc, RN, RSCN.
Clinical Nurse Specialist, Great Ormond Street Hospital for Children NHS Trust, LondonHaemophilia is an inherited condition that is characterised by a reduction or absence of the clotting factors VIII (haemophilia A) or IX (haemophilia B), which are necessary for effective haemostasis. There are thirteen clotting factors in total, and if one of the other factors is reduced or absent, the condition is named after that deficiency - for example, 'Factor V deficiency'. The 'true' haemophilias are X-linked - thus males are usually clinically affected, while females only carry the condition. The other factor deficiency disorders affect males and females equally.
Haemophilia is an inherited condition that is characterised by a reduction or absence of the clotting factors VIII (haemophilia A) or IX (haemophilia B), which are necessary for effective haemostasis. There are thirteen clotting factors in total, and if one of the other factors is reduced or absent, the condition is named after that deficiency - for example, 'Factor V deficiency'. The 'true' haemophilias are X-linked - thus males are usually clinically affected, while females only carry the condition. The other factor deficiency disorders affect males and females equally.
In about two-thirds of people with haemophilia there is a previous family history of the condition, leading to a high probability that 'at risk' males may have the condition. These infants will be diagnosed either antenatally or shortly after delivery.
In the remaining third of people with haemophilia, who have no previous family history of the condition, children are usually diagnosed at around 10 months of age, when they are beginning to become mobile and bruising and/or bleeding becomes apparent. Children may be diagnosed earlier than this if there is a history of birth trauma, injury or surgery (for example, religious circumcision). Parents are occasionally under suspicion of non-accidentally injuring their child before a diagnosis of haemophilia is made. This can cause a breakdown in relationships between health-care workers and parents.
Cerebral haemorrhage remains the most common cause of bleed-related death in children with haemophilia. Many of these bleeds occur as a result of birth trauma - particularly if ventouse extraction has been undertaken (Nelson et al, 1999). If a person with haemophilia suffers from even mild head trauma, there is a high risk of cerebral bleeding and appropriate investigations and treatment should be undertaken.
The severity of haemophilia varies according to the level of Factor VIII or IX that the person has. Severe haemophilia causes the most bleeding problems, while milder forms of the disease may not present until later in life, usually as a result of trauma or surgery (Box 1).
Contemporary treatment of children in the UK is with recombinant (genetically engineered) products that reduce the exposure to - and thus the risk of - blood-borne viruses. Children who are severely clinically affected can be treated prophylactically (two to three times per week) to prevent bleeds occurring (Liesner et al, 1996). If necessary, an implantable port may be used to facilitate administration.
Alternatively, in children and adults who bleed infrequently, treatment may be given 'on demand' to treat a bleed once it has occurred.
Recombinant products have been available only since 1994 and are still in limited supply. Therefore many adults were and still are treated with plasma-derived factor concentrates. Sadly, many were infected with HIV and/or hepatitis C before it was realised that these products presented a risk. Since 1985 all plasma products have been treated (by, for example, heat or solvent detergents) to reduce the risk of further viral transmission (Lee, 1996).
Some people (usually children) with haemophilia recognise factor VIII/IX as a foreign protein and develop an antibody to it. These antibodies are called inhibitors because they inhibit the way in which the factor works. The presence of an inhibitor is suspected when the clinical response to treatment is less than expected. As many as 15-25% of children with haemophilia may develop an inhibitor - the inhibitors are often transient and disappear without causing major clinical problems.
Inhibitors can also occur in people who do not have haemophilia - this is 'acquired haemophilia' and occurs most commonly in adults with auto-immune disease, cancer or, occasionally, following pregnancy. In both situations, factor replacement therapy is either not fully effective or is only partially effective. In congenital haemophilia, 'immune tolerance' treatment is undertaken, in which factor VIII/IX is given frequently in very large quantities, for months to years to eradicate the inhibitor. In acquired haemophilia steroids, immune suppression and/or chemotherapy may be used as treatment options.
With both types of inhibitor, bleeding can become life- or limb-threatening, is difficult to manage, expensive to treat and requires highly specialist medical and nursing care.
VON-WILLEBRAND's DISEASE (vWD)
vWD affects males and females equally; its inheritance may be either autosomal recessive or dominant. It may be mild (Type 1) to severe (Type 3). Bleeding varies within these subtypes; those with Type 1 usually suffer from bruising and minor bleeding, commonly from mucous membranes. Nose bleeds and heavy periods are very common, as is post-partum bleeding.
Von-Willebrand factor (vWF) - a clotting factor in the blood - binds with factor VIII to carry it to the site of bleeding. Those with Type 3 vWD often have very low levels of both vWF and factor VIII and experience potentially life-threatening bleeding.
Treatment of vWD may be either through administration of intermediate-purity, plasma-derived factor VIII concentrates that contain vWF or, in milder cases, by using DDAVP or anti-fibrinolytic agents such as tranexamic acid. In women with menorrhagia, the oral contraceptive pill may reduce symptoms.
Specialist care centres
All people with haemophilia should be registered at a haemophilia 'comprehensive care centre'. There are 26 of these centres across the UK, usually in large teaching hospitals. They provide a full range of haemophilia care, including genetic counselling, diagnosis, treatment, management of complex cases, community outreach and shared care with local hospitals, as well as undertaking research and development (DoH, 1993).
Gene technology now allows antenatal diagnosis, whereby women can choose to terminate affected pregnancies or to undergo pre-implantation diagnosis following in vitro fertilisation.
The production of recombinant (genetically engineered) factors has provided the theoretical ability to perform gene therapy for haemophilia. Although this procedure has not yet proved 100% successful, the technology does mean that a cure is now a future possibility.
Factor VIII deficiency, also referred to as classical haemophilia or haemophilia A, has an incidence of 1:10 000 males. Factor IX deficiency, also referred to as Christmas disease or haemophilia B, has an incidence of 1:50 000 males.
SIGNS AND SYMPTOMS
- Most bleeding episodes occur in people with severe haemophilia
- Bleeding is usually internal - mainly into the major weight-bearing joints (knees, ankles and hips) and the elbows - and may occur spontaneously or following trauma
- Bleeding produces a feeling of 'bubbling' or 'tingling' which, if left untreated, causes pain, swelling and a reduction in range of movement
- Recurrent joint bleeds result in chronic synovial thickening and bleeding, which in turn leads to joint deformity, arthritic changes and further reduced mobility
- Generally these changes are now seen only in adults with haemophilia because most children with severe haemophilia are treated prophylactically to prevent bleeds occurring.
The Haemophilia Society provides patient and parent support as well as financial and treatment advice. They are based in London but have local groups and hold 'family days' and hepatitis and HIV days outside London, as well as outward-bound events for children in school holidays. For more information contact firstname.lastname@example.org or telephone: 020-7380 0600.
The World Federation of Haemophilia provides information and support to members and countries who treat haemophilia. It is active in promoting diagnosis and safe treatment in developing countries and can be contacted at: www.wfh.org
An ENB course, 'The Essentials of Haemophilia Care', is taught at levels 2 or 3 at Christ Church College, Canterbury, and Sheffield Hallam University. For more details contact Martin Bedford (Canterbury) at email@example.com or Vicky Vidler (Sheffield) at Vicky.firstname.lastname@example.org
Department of Health. (1993) Provision of Haemophilia Treatment and Care (Health Service Circular 93/30). London: The Stationery Office.
Lee, C.A. (1996)Transfusion transmitted disease. Baillieres Clinical Haematology 9: 2, 369-394.
Liesner, R.J., Khair, K., Hann, I.M. (1996)The impact of prophylactic treatment on children with severe haemophilia. British Journal of Haematology 92: 973-978.
Nelson, M.D., Maeder, M.A., Usner, D. et al. (1999)Prevalence and incidence of intracranial haemorrhage in a population of children with haemophilia. Haemophilia 5: 306-312.