Care of Bleeding Disorder Patients
The primary aim of care is to prevent and treat bleeding with the deficient clotting factor but optimal care requires more than the treatment of acute events. The following recommendations are based on WFH guidelines [WFH, 2013] but the principles of management are similar for VWD [Laffan et al, 2014].
People with bleeding disorders are best managed in a comprehensive care setting that promotes physical and psychosocial health and quality of life while decreasing morbidity and mortality.
To improve health and quality of life, the priorities of management are:
- prevent bleeding and joint damage
- prompt management of bleeding
- manage complications including:
- joint and muscle damage and other sequelae of bleeding
- inhibitor development
- viral infection(s) transmitted through blood products
- attention to psychosocial health.
What is a comprehensive care team?
A comprehensive care team is a multidisciplinary group that offers the expertise and experience needed to meet the physical and psychosocial needs of patients and their families. Its core membership should be:
- a paediatric and/or adult haematologist, or a physician with interest and expertise in haemostasis)
- a nurse with relevant expertise
- a musculoskeletal expert (physiotherapist, occupational therapist, physiatrist, orthopaedic specialist, rheumatologist)
- a laboratory specialist
- a social worker or a psychologist.
All members of the core team should have expertise and experience in treating bleeding disorders. The WFH recommends that the team director should be a doctor but acknowledges that roles within the team will depend on the availability and expertise of its members and the how services are organised locally.
The comprehensive care team needs to involve other specialists in care delivery, in particular:
- chronic pain specialist
- infectious disease specialist
- vocational counsellor.
Delivering comprehensive care
The team coordinates the delivery of care and services to patients and their families by developing and regularly reviewing an individual management plan that covers all aspects of care in hospitals (inpatient and outpatient), primary care and the community. It is also the team’s responsibility to deliver training for home therapy and educate family members to ensure that the patient’s needs are met. The team should also monitor outcomes, audit services and participate in research initiatives that may improve the quality of care. With so many disciplines involved, it is essential that different services and centres communicate well.
Patients should be supported to manage their haemophilia at home if at all possible. Home therapy is associated with decreased pain, dysfunction and long-term disability and significantly reduces hospital admissions for complications. It improves quality of life by offering greater freedom to travel and participation in physical activities, less absenteeism, and greater employment stability. It is feasible for young children provided venous access is good enough and the parents are motivated; family support is important for older children and young people.
To achieve this, home therapy must be supervised closely by the comprehensive care team and should only be initiated after adequate education and training. The components of an education programme should include:
- general knowledge about haemophilia
- recognition of bleeds and common complications
- first aid measures
- dosage calculation
- preparation, storage, and administration of clotting factor concentrates
- aseptic technique
- performing venepuncture (or access of central venous catheter)
- record keeping
- proper storage and disposal of needles/sharps
- handling blood spills.
For their part, patients or parents should monitor and document their treatment, keeping a record of the date and site of bleeding episodes, dosage and lot number of product used, and adverse effects. These records should be reviewed at follow-up visits and care adapted accordingly.
Intravenous access is easier with a Port-ACath or other implanted access device. This may be the only way that early prophylaxis is possible for younger children but the benefit must be weighed against the risks of surgery, local infection and thrombosis. The catheter must be kept scrupulously clean and maintained to prevent clotting.
Physiotherapy is an integral part of the management of haemophilia [Strike et al, 2014]. Its aims are to:
- promote normal neuromuscular development
- preserve or restore joint range of motion and muscular flexibility
- increase muscular strength and endurance
- maintain or improve co-ordination and balance
- maintain a healthy body weight, decreasing stress on joints
- promote development and maintenance of bone density
- improve aerobic conditioning
- improve function, participation and improve quality of life
- reduce health risks associated with a sedentary lifestyle
Few clinicians doubt the value of physiotherapy in the management of pain, preserving joint function and reducing disability but the various interventions are not supported by strong evidence [Strike et al, 2014], although many studies not meeting strict methodological criteria are supportive [Blamey et al, 2010]. Consequently, there are no formal evidence-based guidelines on best practice.
The activities of a physiotherapy service fall into three categories [Nordic Hemophilia Council, 2015]:
Inform parents and teenagers about the value of physical activity and sports for developing and maintaining bone mineralisation, muscle strength, mobility endurance and coordination. Demonstrate to parents how to assess joint mobility in young children for early detection of joint bleeding.
Joint mobility, muscle strength, pain, joint and muscle contractures, axial changes in the joints, balance and gait functions. Differentiate between joint and muscle bleeding and synovitis together with the physician.
The assessment may utilise formal tools such as the Haemophilia Joint Health Score (for children aged 4 – 16 but may be used for older people after adjustment for comorbidities), visual analogue scale for pain and the Haemophilia Activities List for the patient’s perspective. An occupational therapist may assess activities of daily living.
Exercise program to restore lost function during an acute bleeding episode is associated with more rapid normalisation of function and a lower risk of disability.
Early active exercise in combination with intensive treatment with factor concentrate can reverse early haemophilia arthropathy.
In a person with arthropathy who experiences an acute bleeding episode, the purpose of physiotherapy is to reduce pain and restore joint mobility and muscle strength. Treatment may include different types of mobility exercises (active, active unloaded, passive), instruction about posture, strength and endurance exercise and coordination training. Other options include exercise in warm water, transcutaneous electrical nerve stimulation, and the application of heat or cold.
Physiotherapy should be offered before and after orthopaedic surgery such as synovectomy or joint replacement according to protocols in the orthopaedic service. Physiotherapists have a role in prescribing orthotics and orthopaedic devices in cases of joint misalignment, stiffness and pain; they may also help with walking aids and other appliances.
Pain is common among people with haemophilia and individuals with more severe forms of VWD [Nordic Hemophilia Council, 2015, 2008]. Bleeding into a joint or muscle causes acute pain; the arthropathy resulting over time from repeated bleeding events caused is associated with chronic pain and disability. Unlike acute pain, chronic pain is associated with neurobiological, psychological and social changes that serve to maintain the pain and alter an individual’s behaviour; it may not be amenable to conventional analgesics and may require treatment with a centrally-acting agent (e.g. an anti-epileptic agent or an antidepressant) and specialist techniques.
Therefore [Young et al, 2014]:
- an individualised approach to management is essential
- drug treatment, physiotherapy, surgery and possibly complementary therapies are all essential components of management
- ongoing psychosocial assessment is needed to address factors contributing to a person’s pain experience
Several surveys have shown that, in patients with severe haemophilia:
- In a sample with an average of four painful joints [Humphries et al, 2015]
- activities of daily living were limited in 89%
- mood was negatively affected in 85%
- untreated persistent pain was reported by 50%
- two-thirds suffered from more than one painful joint, with the ankle being the most common site of pain
- pain was a significant factor contributing to functional limitation
- patients with haemophilia and haemophilic arthropathy experience substantially more disability and morbidity than the general population
- in patients with inhibitors:
- 81% were disabled
- 27% had chronic synovitis
- quality of life assessments identified pain in 71% of patients and extreme pain in 4%.
- physical functioning, bodily pain and role-physical scores were lower than in the general population
- more frequent pain correlates with negative thoughts about pain (e.g. anger, fear, isolation-seeking behaviour and anticipating catastrophes) and increased concern about using pain medication
- intensity of pain is the primary influence on physical quality of life, and negative thoughts about pain affect mental quality of life
In a survey of patients with moderate haemophilia:
- 73% reported a joint bleed in the past year
- 43% had joint impairment
- 27% were disabled and 15% reported chronic pain
It is important to take an holistic perspective when assessing pain. Patients should be reassured that their pain can be managed. Chronic pain should normally be tackled by a multidisciplinary team working with pain specialists. Physiotherapy has an essential role in the diagnosis and management of disability and preventing deterioration. It can be useful to measure pain severity periodically using a visual analogue scale or similar tool to determine the effectiveness of treatment
Prompt cessation of bleeding [Srivastava et al, 2013]
- Early treatment is important to resolve bleeding and reduce pain; acute bleeding should be treated at home as soon as possible, ideally when the patient experiences an aura
- Factor concentrate should be administered promptly; if bleeding does not stop, a second infusion may be required (half the initial dose after 12 hours in haemophilia A or after 24 hours in haemophilia B
- Patients with inhibitors have poorer outcomes than non-inhibitor patients; early initiation of a bypassing agent is needed to stop bleeding and reduce complications
There is not a strong evidence base for pain management specifically in people with haemophilia and current strategies are unsatisfactory Humphries et al, 2015; Auerswald et al, 2016]. Pain management protocols, including the choice of analgesics, vary between hospitals and local guidance should be followed. In this respect, some aspects of NICE guidance, such as the guideline on the management of osteoarthritis [NICE, 2014], will be relevant. SIGN has published a guideline on the management of chronic pain summarising best practice SIGN, 2013].
From the patient’s perspective, some people are concerned about becoming dependent on analgesics and may be reluctant to take them. It is therefore important to inform people about the risks and benefits of treatment and to discuss their beliefs about medication.
Analgesics are divided into three classes:
- Simple analgesics
- Anti-inflammatory drugs
- COX-2 selective NSAIDs
- Intra-articular steroids
- Weak for mild to moderate pain: codeine
- Stronger for moderate to severe pain: tapentadol, tramadol
- Strong for severe pain: morphine.
Summary of the pros and cons of standard analgesics (adapted from Humphries et al, 2015])
|Paracetamol||Generally well tolerated
May be effective combined with other analgesics
|Doubtful effectiveness as monotherapy for pain associated with inflammation
Liver function abnormalities at normal doses
|Selective COX-2 inhibitors||Small to moderate analgesic effect, anti-inflammatory
|Adverse systemic effects include dyspepsia, gastrointestinal bleeding, nephrotoxicity, risk of serious adverse cardiovascular effects in older people
Important prescribing cautions and contraindications
|Codeine||Readily available combined with paracetamol (though dose may be too low in fixed dose combinations)||Weak analgesic suitable for mild to moderate pain only
Constipation common; shares adverse effects of other opioids
Variable conversion to morphine; marked increase in toxicity in ultra-rapid metabolisers (5 – 10% of people) and reduced therapeutic effect in poor metabolisers (also 5 – 10%)
|Tramadol||Greater analgesia than NSAIDs but still weak compared with other opioids
Less abuse potential than strong opioids
May affect platelet function
Caution with other drugs affecting serotonin function and digoxin, warfarin
|Strong opioids||Most effective oral analgesics
Short- and long-acting formulations
Parenteral administration possible
|May be poorly tolerated
Serious adverse effects include constipation, nausea/vomiting, sedation and respiratory depression
Risk of abuse and dependence
No anti-inflammatory activity
Paracetamol is the only simple analgesic suitable for people with bleeding disorders. It is most effective when taken regularly and can be combined with an opioid. Aspirin and low-dose ibuprofen are familiar household analgesics but both inhibit platelet function.
NSAIDs have both analgesic and (with repeated administration) anti-inflammatory activity. COX-2 selective agents are preferred because they have least impact on platelet function and they are less likely to cause adverse gastrointestinal effects than non-selective agents (e.g. naproxen, high-dose ibuprofen). NICE recommends that treatment with an NSAID, including a COX-2 selective inhibitor, should be co-prescribed with a proton pump inhibitor for gastroprotection [NICE, 2014]. Older people are particularly at risk of gastrotoxicity.
COX-selective NSAIDs are associated with an increased risk of thrombosis and there is uncertainty whether haemophilia confers any protection against this risk [Boban et al, 2016]. The patient’s risk factors and the product’s precautions and contraindications should therefore be reviewed before prescribing.
COX-2 selective NSAIDs include celecoxib, diclofenac, etoricoxib, meloxicam, nabumetone and tenoxicam.
Strong opioids have a role in the management of chronic pain but there is concern about the risk of adverse effects [Volkow et al, 2016]. Guidance has been developed for clinicians in the UK [RCA]. The most recent management guideline was published in the US; it states: ‘Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks,’ [Dowel et al, 2016].
SIGN recommends [SIGN, 2013]:
- Strong opioids should be considered as an option for pain relief for patients with chronic low back pain or osteoarthritis, and only continued if there is ongoing pain relief. Regular review is required.
- Patients prescribed opioids should be advised of the likelihood of common side effects such as nausea and constipation.
- All patients on strong opioids should be assessed regularly for changes in pain relief, side effects and quality of life, with consideration given to a gradual reduction to the lowest effective dose.
- It may be necessary to trial more than one opioid sequentially, as both effectiveness and side effects vary between opioids.
- Opioid rotation should be considered for chronic pain that is likely to respond to opioids, if there are problems with efficacy or side effects.
- Signs of abuse and addiction should be sought at re-assessment of patients using strong opioids.
- Routine urine drug testing, pill counts or prescription monitoring should not be used to detect problem use.
- Currently available screening tools should not be relied upon to obtain an accurate prediction of patients at risk of developing problem opioid use before commencing treatment.
- There should be careful assessment of pre-existing risk factors for developing opioid misuse. In patients where opioid therapy is indicated, but there is an increased risk of iatrogenic opioid misuse, specialist advice should be sought. The minimal effective dose should be used to avoid increased problems of fracture and overdose that may occur on higher doses.
- Specialist referral or advice should be considered if there are concerns about rapid-dose escalation with continued unacceptable pain relief, or if >180 mg/day morphine equivalent dose is required.
Intra-articular injection of a steroid provides long-lasting (4 weeks to several months) pain relief. The injection should be administered by an appropriately trained clinician under cover of factor concentrate prophylaxis to reduce the risk of bleeding. The injected joint should not be loaded for 24 hours after treatment.
Adverse effects associated with the procedure include local pain (common) and facial flushing (this may also affect the trunk) [Peterson and Hodler, 2011]. Two per cent of patients with arthritis experience worsening of the pain for the following 24 hours. Systemic absorption of the steroid raises blood glucose for up to 5 days after the procedure; patients with diabetes should therefore monitor their glucose levels. Severe joint destruction with bone necrosis may occur if intra-articular injections are repeated over a long period. Infection is a serious but rare complication.
Psychosocial impact of haemophilia
Haemophilia has a substantial impact on individuals and their families or carers. A 2010 review [HERO, 2010] categorised its effects into three parts:
- Challenges of diagnosis and treatment
- early prophylaxis and treatment at home
- access to factor concentrates and high quality blood products has reduced anxiety about treatment safety
- the responsibility of home treatment can be daunting for parents
- parents can be distressed by difficulties of venous access in young children
- acceptance of initial diagnosis and early management of disease
- the diagnosis of haemophilia is life-changing
- parents feel shock and guilt, causing loss of self esteem
- mothers feel guilty about being a carrier, leading to passivity, despair and depression that interferes that potentially impairs the care of their child
- fathers may withdraw or seek control through information
- a child may use their haemophilia to avoid responsibility and challenge
- effective communication between parents is essential
- providing appropriate information at this stage is highly effective
- early prophylaxis and treatment at home
- Social and family challenges
- impact on family life
- near-normality is achievable but disruptive setbacks occur, leaving the family feeling vulnerable
- there is no respite from the pressure to be mindful of haemophilia
- focusing attention on the affected child may risk siblings being neglected
- fostering independence
- finding the balance between autonomy and overprotectiveness is difficult
- children need to learn how to manage their haemophilia
- parents’ quality of life is improved when children are independent
- adolescents with haemophilia are otherwise no different from others of their age
- increased bleeding due to neglecting treatment risks joint damage and disability
- during transition to adult health care, parents are more fearful of the future than their children
- secrecy through fear of social stigma
- children may conceal their diagnosis from their peers, as may fathers with haemophilia
- poor public understanding of haemophilia means affected individuals are treated inappropriately or risk being denied opportunities
- participation and isolation
- exclusion from activities such as sports may isolate a child
- people with haemophilia are less involved in full time paid work and suffer more from occupational disability
- isolation is greater if there is no access to prophylaxis
- time off work to manage haemophilia reduces the family income
- impact on family life
- Psychological challenges
- fear of pain and pain management
- dealing with chronic pain and joint dysfunction is difficult
- psychological therapy can reduce stress and anxiety and encourage adherence with treatment
- long term complications threaten independence
- anxiety and depression, anger and frustration
- anger and frustration, anxiety and depression are common
- coping strategies mean these feelings may not be apparent when assessing quality of life
- there is some evidence that suicidal ideation is increased
- fear of pain and pain management
In addition, compared with others with haemophilia, people with inhibitors are (duTreil, 2014]:
- more likely to have problems with mobility, more frequent admission to hospital, time off school or work, and difficulty maintaining a job; this is associated greater impairment of quality of life
- more likely to have poor mental health
- at greater risk of low adherence to treatment
Older people with haemophilia rate their physical health and psychosocial well being as worse than that of people without haemophilia of a similar age. This is associated with joint damage, daily functioning, gait and balance, and more frequent depression [von Mackensen, 2012].
Health-related quality of life is more affected by menorrhagia in women with haemophilia or von Willebrand disease than those who do not have a bleeding disorder [Von Mackensen, 2011].
Important aspects of psychosocial support include [HERO, 2010; Von Mackensen, 2007; Negrier et al, 2013]:
- counselling to address the concerns of children, their families and adults so they can better manage their bleeding disorder
- counselling for women who are potential carriers
- encouraging effective communication within the family and wider social circles so that those affected can talk about haemophilia more freely
- developing support networks to encourage sharing of experiences and feelings
- families should be provided with information and educated about haemophilia and its management; there is also a need to inform others in the workplace and at school
- physical activity and sports participation improve quality of life and improve physical strength, balance and flexibility
- strategies to ensure adherence (e.g. distraction techniques, role playing and support for parents) should be implemented from childhood.
Ideally, this approach would be integrated in the work of the multidisciplinary team.
Good dental care is important for the usual reasons of preserving teeth and gums and to avoid the need for surgery. People with a bleeding disorder should receive standard dental care with additional measures to tackle the risk of bleeding.
The WFH guideline recommends a level of preventative dental care that is routine in the UK (i.e. regularly twice daily brushing, fluoride toothpaste, flossing, regular check ups), beginning with check ups from the time the baby teeth start to erupt. The UK Haemophilia Centres Doctors Organisation (UKHCDO) has published detailed guidance on managing dental care for people with bleeding disorders. It recommends similar care for people with haemophilia or VWD.
Treatment planning and close liaison between the dentist and the haemophilia centre are essential. Invasive dental procedures should be scheduled to minimise re-exposure to factor concentrate.
- Standard advice on post-extraction precautions apply (e.g. avoid hot drinks, rinse with salt water).
- In addition, there should be a plan to manage haemostasis before dental extraction or surgical procedures are carried out within the oral cavity.
- Normal local anaesthetic injections are often carried out without factor cover in adults (but not children) but inferior alveolar nerve block or lingual infiltration require prior treatment.
- For invasive dental procedures, a single dose of a clotting factor concentrate should achieve a minimum level of 50% (although each patient should have an individual plan and a repeat dose may be required).
- Tranexamic acid, taken orally and/or as a mouthwashshould be prescribed before and post dental extraction for up to seven days.
- Local haemostatic measures should also be used.
Patients should report any prolonged bleeding and/or difficulty in speaking, swallowing, or breathing immediately.
Surgery and invasive procedures
Careful planning is needed to minimise the risk of bleeding associated with surgery in people with bleeding disorders and this requires cooperation between the surgical and haemophilia care teams. Cover with a factor concentrate or haemostatic agent is needed for invasive diagnostic procedures such as lumbar puncture, arterial blood gas determination or any endoscopy involving a biopsy.
When planning for surgery:
- The anaesthetist should have experience of treating people with a bleeding disorder
- The procedure should be scheduled early in the week and early in the day to ensure optimal laboratory and blood bank support
- Preoperative assessment should include inhibitor screening and inhibitor assay
- Sufficient clotting factor concentrate should be available during the procedure and postoperatively to cover the period of healing and rehabilitation (alternatively, plasma components should be available)
- The dose and duration of clotting factor concentrate cover depends on the type of surgery (specifics are provided in the WFH guideline1)
There is a risk that exposure to clotting factors may induce inhibitor development in patients with mild haemophilia A and in those receiving intensive factor replacement for the first time. These patients should be re-screened 4 – 12 weeks postoperatively. Patients with non-severe haemophilia A who receive continuous infusion after surgery should also be monitored for inhibitors.