Treatment © Haemophilia Alliance

Facilities

	there should be dedicated facilities for disabled car parking in the vicinity of the haemophilia treatment area.
	there should be appropriate disabled access facilities throughout the haemophilia treatment area.
	The clinical treatment of patients with haemophilia should take place in a dedicated clinical area which should be comfortable, quiet and appropriately equipped. These areas must allow confidential interviews between staff and patients, particularly for those with HIV and hepatitis virus infections.
	Routine treatment of patients with haemophilia in an accident and emergency department is not recommended.

On-call arrangements

Patients with haemophilia are often not treated appropriately when they present out of hours to an accident and emergency department. Effective treatment is more likely to be administered promptly and efficiently if the following measures are adopted:

	on-call arrangements for haemophilia should be clearly identified to junior hospital medical staff and triage nurses.
	there should be a consultant haematologist on-call at all times with responsibility for patients with haemophilia; appropriate mechanisms should be in place for meeting the training needs of such consultants.
	junior medical staff responsible for care of haemophilia out of hours should receive formal education about haemophilia and its treatmentt.
	a protocol for the management of patients with haemophilia out of hours should be available for junior medical staff.
	there must be appropriate laboratory back-up for the emergency care of patients with haemophilia and related disorders.
	patients should be given clear information as to who they should contact in the event of an emergency.
	the exact way in which on-call arrangements are delivered to the above standards will need to be interpreted at local level following an assessment of staff levels and facilities; this may involve the establishment of shared on-call arrangements between Haemophilia Centres and Comprehensive Care Centres.
	local ambulance controls should be instructed to direct patients with haemophilia and related conditions to the nearest Haemophilia Centre, as long as the clinical situation allows.

Treatment of children

The care of children with haemophilia and related disorders can be complex and should only be carried out by staff who are experienced and trained in the management of children.

The treatment of children should follow the guidance of The Welfare of Children and Young People in Hospital (DOH 1992):

	accommodation, facilities and staffing should be appopriate to the needs of children and adolescents and be separate from those provided for adults.
	children with haemophilia should have 24 hour access to a paediatric ward or setting for the purposes of acute treatment of bleeding episodes.
	there should be appropriate levels of dedicated paediatric support made available at all times.
	haemophilia centre staff looking after children with haemophilia will be responsible for implementing home therapy programmes, prophylactic care and community care for these families. This will involve not only education but liaison with a range of agencies working in the community.
	transfer from paediatric to adult care is a particularly sensitive time for the teenager with haemophilia, particularly if the adult centre is sited in a different hospital. There should therefore be seamless and sensitive transition to adult care at an appropriate age, including a period of joint registration between the paediatric and adult Haemophilia Centres.

Prophylaxis

Prophylaxis is the regular administration of factor VIII and factor IX concentrates to patients with haemophilia to prevent acute episodes of bleeding into joints and muscles. The basis underlying prophylaxis is the observation that children with moderate haemophilia - who have factor VIII/IX levels above 2 iu/dl - experience spontaneous episodes of bleeding only rarely. For patients with severe haemophilia therefore, the intention of prophylaxis is to maintain the basal factor VIII/IX level above 1 iu/dl at all times and to thereby prevent bleeds and preserve joint function.
The introduction of prophylactic therapy must be an individual decision and based on the patient’s - and the family’s - particular circumstances. These decisions are usually but not invariably related to the severity of the haemophilia and the frequency of serious bleeds in the child. UKHCDO guidelines (reference 3) recommend that prophylaxis should be introduced at the very least after two episodes of spontaneous bleeding.

	Prophylaxis should be delivered according to the recommendations of UKHCDO.
	Prophylactic therapy usually involves the regular administration of factor VIII or factor IX 2-3 times per week.
	Effective prophylactic therapy can prevent long term damage to muscles and joints (level IIa evidence, recommendation B, references 1,2) avoiding disability and the need for subsequent treatment later on in life.
	Prophylaxis is also perceived as being beneficial for children with haemophilia as it minimises disruption to the patient and his family.
	An effective prophylactic dose is the minimum dose which prevents spontaneous breakthrough bleeding. This will vary according to clinical circumstances and will also vary significantly between patients. The exact dose may need to be determined by formal recovery and half life studies in which the decay of injected factor VIII/IX is monitored.
	Prophylactic therapy - and home therapy - represents a major responsibility for the parents of a child with haemophilia and should only be embarked upon when there is clear evidence that they are prepared to accept responsibility for these treatments, are competent at delivering them and will undertake to provide the Haemophilia Centre with the relevant clinical information concerning the use of coagulation factor concentrates in the home setting.
	Prophylactic therapy is administered in the home setting and the Haemophilia Centre will provide appropriate clinical and psychosocial support, in liaison with community based services.
	The duration of prophylactic therapy will depend upon individual clinical circumstances and may need to be continued into adulthood.
	Prophylaxis is also recommended for adults in the setting of surgical procedures and where there has been recurrent bleeding into a single joint (target joint).

Home and community care

	Wherever appropriate, the care of patients with haemophilia and their families should be delivered in the home setting which will minimise absence from school and work and help patients to live more effectively with their life long bleeding disorder.
	Under usual circumstances, a patient with severe haemophilia should be on home treatment by the age of four years at the latest, depending on venous access and family circumstances.
	Haemophilia centres will liaise with patients and their families on home therapy and will monitor the usage of coagulation factor concentrates.
	Haemophilia Centres will liaise with General Practitioners, Primary Care Groups and Trusts, together with other community agencies.
	Wherever possible, coagulation factor concentrates should be delivered to the patient’s home as this minimises the number of occasions when the patient must travel to the Haemophilia Centre.
	Patients and their families will be educated as to the importance of keeping formal records of all treatments and episodes of bleeding, to enable them to provide the Haemophilia Centre with essential outcome data; the keeping of appropriate records in the home setting will be monitored by the Haemophilia Centre.

Outpatient review

	All registered patients should be offered a regular clinical and multi disciplinary review, with records kept of non-attendance. The frequency with which patients will need to be seen will depend on a number of factors including: the severity of the haemophilia the frequency of episodes of bleeding the presence of any viral complications of previous haemophilia treatment long term complications of previous episodes of bleeding
	At a minimum, patients with mild haemophilia should be seen yearly and patients with severe/moderate haemophilia should be seen six monthly.
	Some patients will need to be seen more frequently than this, particularly those with inhibitors and those with viral complications of their haemophilia treatment
	Patients with haemophilia should be screened on a regular basis for the presence of an inhibitor, as recommended by UKHCDO (reference 4).
	All patients with inherited bleeding disorders who are likely to require blood and coagulation factor concentrates should be vaccinated against hepatitis A and hepatitis B, if not already immune.

Patient education and support

	Haemophilia has a significant impact on the patient and family and leads not only to physical disability but also to problems with schooling, employment and relationships.
	Commissioners should ensure that there are appropriate mechanisms in place for the psychosocial support of the patient and his family, particularly in terms of the provision of social welfare and counselling services. This may require joint commissioning with social services.
	Haemophilia and related disorders are likely to be particularly stressful: around the time of diagnosis whilst the child is very young and reliant on demand therapy at the introduction of home therapy and prophylaxis when starting or changing school at times of inter-current illness and personal stress following bereavement
	The establishment of self help groups is recommended and can be facilitated by the Haemophilia Society.

Patient participation

	Patients and their carers should be encouraged to be active participants in the delivery of care and to assume appropriate responsibility.
	Effective haemophilia care can be facilitated by the establishment of a close dialogue between the Haemophilia Centre and the patient group.
	It is therefore recommended that local patient consultative groups be established and used as a sounding board for all developments in relationship to haemophilia services; the establishment of such groups can be facilitated by the Haemophilia Society.
	Patients should be involved in the design of Haemophilia Centre audits and should have access to the results of Haemophilia Centre audits.

Treatment acquired infections

	The epidemic of treatment acquired infections (HIV, hepatitis B and C) that occurred in patients with haemophilia in the late 1970s and early 1980s as a result of contaminated coagulation factor concentrates has had a profound effect on the haemophilia community.
	Patients and families with HIV and hepatitis infection experience particularly complex needs, both medically and psychosocially.
	Nearly all patients with HIV have been co-infected with hepatitis B and/or C and this may accelerate the clinical course of both disorders.
	It is essential that patients with HIV and hepatitis infection - and their families - have appropriate access to psychological and social welfare support services; these should be provided by both statutory and voluntary sector agencies.
	It is essential that patients with HIV infection are reviewed regularly by an HIV specialist and that treatment strategies are in accordance with published guidelines (reference 5).
	It is essential that patients with hepatitis infection are reviewed regularly by a hepatitis specialist and that treatment strategies are in accordance with published guidelines including NICE (National Institute for Clinical Excellence) issued guidelines on the use of ribavirin and interferon alpha for hepatitis C (references 6,7,8).

Use of coagulation factor concentrates

	All patients should be treated according to recommendations produced by UKHCDO (reference 9)
	Over the past 25 years the treatment of patients with haemophilia with plasma derived blood products has resulted in outbreaks of infection with HIV and hepatitis viruses.
	Plasma derived concentrates are derived from the pooled plasma of thousands of donors, who are all screened for the presence of any known viruses. The concentrates are also extensively inactivated during the fractionation process. Despite this, it is apparent that plasma derived concentrates still have the ability to transmit known viruses such as hepatitis A and parvovirus and real concern therefore exists about the possibility of the transmission of currently unrecognised infectious agents through the use of plasma derived concentrates.
	for these reasons, recombinant coagulation factor concentrates are the treatment of choice for patients with inherited bleeding disorders and should wherever possible be used in preference to plasma derived blood products, (level IV evidence, grade C) in accordance with the recommendations of UKHCDO (reference 9).
	in the absence of any suitable recombinant preparations, patients with severe von Willebrand’s disease, and those with rare types of severe haemophilia (deficiencies of factor V, X, XI etc) are likely to be treated with plasma derived coagulation factor concentrates for the foreseeable future.

Management of inhibitors

	around 30% of patients with haemophilia develop an antibody against factor VIII; this is known as an inhibitor and there is significant morbidity and mortality associated with its development. Inhibitors against factor IX are less common and occur in 1-3% of patients. In approximately half of these patients the inhibitor is transient and of low titre (less than 5 Bethesda units) and therefore of little clinical significance. In other patients the inhibitor is of high titre (more than 5 Bethesda units) and these patients do not respond to factor VIII therapy, requiring alternative and complex by-pass treatments.
	the clinical care of patients with inhibitors is particularly expensive; furthermore inhibitor development is wholly unpredictable. For these reasons, commissioners may wish to participate in risk reduction strategies as a consortium with other commissioning agencies for the management of these patients.
	The management of patients with inhibitors is complex and should be carried out only in centres that are experienced in this form of therapy and that have appropriate clinical and laboratory resource.
	Acute episodes of bleeding in patients with inhibitors should be treated according to the published recommendations of UKHCDO (reference 4).
	Every confirmed incident of inhibitor development should be reported to the Inhibitor Working Party of UKHCDO, the MCA and the manufacturer.
	The care of patients with low titre inhibitors should be discussed with a Comprehensive Care Centre that is experienced in the management of patients with inhibitors.
	The care and management of patients with a high titre inhibitor should be under the supervision of a Comprehensive Care Centre. The extent of treatment that can be performed at a local Haemophilia Centre will be determined by local discussions and informed by external audit.

Immune tolerance

	Immune tolerance involves the regular administration of high doses of factor VIII/IX over an extended period which eventually may lead to the patient being tolerant of the injected coagulation factor and the disappearance of the inhibitor.
	There are substantial advantages in being able to eradicate the inhibitor if at all possible, thus allowing the patient to be treated with factor VIII/IX (reference 10).
	Immune tolerance programmes should follow the recommendations of the UKHCDO (reference 4).
	It is generally agreed that all patients with a newly diagnosed inhibitor - particularly children - are likely to benefit from immune tolerance programmes if given at an early stage. These programmes are less likely to be successful when the inhibitor is long established and of high titre.
	The management of patients with immune tolerance is complex and should be carried out only in those centres that are experienced in this therapy and that have appropriate clinical and laboratory resources.
	Immune tolerance programmes are very expensive; they should be discussed in full with commissioners and Public Health Consultants/Specialists prior to commencement, including a detailed breakdown of treatment proposals and costs. Commissioners may find it relevant to take independent and expert advice before agreeing to fund an immune tolerance programme.
	Scientific information concerning immune tolerance programmes is relatively scanty and it is strongly recommended that wherever possible patients undergoing immune tolerance programmes should be entered into clinical trials and the results reported to national or international databases as appropriate.

Acquired haemophilia

	Acquired haemophilia is due to the development of an inhibitor against factor VIII (or rarely factor IX or von Willebrand factor) in a previously normal individual. It is rare, and affects both males and females. It is sometimes associated with drug therapy, auto immune conditions and pregnancy but most cases arise spontaneously.
	Acquired haemophilia is a particularly severe and often life threatening condition which needs emergency care to secure haemostasis, usually involving treatments such as factor VIIa, FEIBA, porcine factor VIII, chemotherapy and intravenous immunoglobulin.
	The management of patients with acquired haemophilia is particularly complex and should be carried out only in Comprehensive Care Centres that are experienced in this therapy and that have appropriate clinical and laboratory resources.
	The treatment of acquired haemophilia should follow the guidelines of UKHCDO (reference 4).
	All cases of acquired haemophilia should be notified at the earliest opportunity to the relevant commissioning authority, together with information about proposed treatment plans.

von Willebrands disease

	Von Willebrands disease is the most common inherited bleeding disorder, and affects both males and females.
	Tthere are a number of different subtypes of von Willebrands. Whilst many patients have only mild clinical problems, a relatively small number of patients are severely affected - these patients experience the same medical and psychosocial problems as patients with severe haemophilia and they should be treated with similar comprehensive care programmes.
	In contrast to haemophilia, the major clinical problems in von Willebrands are mucocutaneous in nature, so that patients experience nose bleeding and gum bleeding, together with prolonged bleeding after trauma, dental and surgical procedures.
	Many female patients with von Willebrands disease experience significant problems with menorrhagia and bleed heavily after childbirth. These patients should have access to appropriate obstetric and gynaecological support.
	All patients with severe von Willebrands disease should have access to comprehensive care, as described for patients with severe haemophilia.
	Wherever possible, all patients with mild von Willebrands disease should be offered clinical review at least annually by a Comprehensive Care Centre or Haemophilia Centre.
	A relatively small number of patients with von Willebrands disease were infected by hepatitis C or HIV. These patients will require access to the same services as virally infected patients with haemophilia.
	The delivery of care at a local level to patients with von Willebrands must be determined by discussions between the local Haemophilia Centre and its Comprehensive Care Centre and will depend upon clinical circumstances and the degree of expertise available in the Haemophilia Centre, as determined by external audit.

Rarer coagulation defects

	Other types of inherited bleeding disorders - deficiencies of factor XI, factor X, factor XIII, factor V etc - exist and are usually very rare, although they are occurring in increasing frequency in various ethnic groups. These bleeding disorders affect women as well as men.
	Severely affected patients with these rare types of haemophilia should be registered with a Comprehensive Care Centre and offered the same access to comprehensive care as patients with severe haemophilia A and B.
	The delivery of care at a local level to patients with rarer defects must be determined by discussions between the local Haemophilia Centre and its Comprehensive Care Centre and will depend upon the degree of expertise available in the Haemophilia Centre, as determined by external audit

Inherited platelet disorders

	Although rare, patients with severe inherited platelet disorders such as glanzmann's thrombasthenia have a profound bleeding tendency.
	These patients should be registered with a Comprehensive Care Centre and offered the same access to comprehensive care as patients with severe haemophilia.
	The delivery of care at a local level to patients with inherited platelet disorders must be determined by discussions between the local Haemophilia Centre and its Comprehensive Care Centre and will depend upon the degree of expertise available in the Haemophilia Centre, as determined by external audit.

Adverse events

Any adverse events should be reported through the existing red card scheme of UKHCDO and the yellow card scheme of the Committee for Safety of Medicines.

Clinical trials products

A Haemophilia Centre treating patients with coagulation factor concentrates on a clinical trials programme must inform commissioners of the use of these products and of the intended duration of the trial.