WFH 2018 World Congress

Managing comorbidities

Haemophilia management means more than controlling bleeding and avoiding joint damage: like anyone else, people with haemophilia have comorbidities and the added risk of complications can present unique challenges. In this workshop, speakers discussed their approaches to managing acute and chronic disorders.

Obesity: Kuixing Li (Nurse, Pekin Union Medical College Hospital, China) said that 15% of adults and 10% of children in China are obese or overweight. In the general population, obesity increases the risk of many long term conditions. In people with haemophilia, the most immediate concern is the increased risk associated with surgery, which increases inactivity postoperatively. Conversely, effective prophylaxis improves mobility and the person’s capacity to be active.

The approach to management is the same for people with haemophilia as anyone else – promoting weight loss through a healthy diet, safe exercise and supporting good mental health and sleep habits. Haemophilia nurses should identify which of their patients are at risk due to being overweight or obese. They should encourage them to take responsibility for their own health and choose healthier lifestyles, and help them increase their knowledge and skills for healthy living.

There will be no progress unless the patient is motivated so it is important to explain the risks and benefits of weight loss and explore the person’s attitudes and readiness to change. A self-help strategy, goal setting and regular monitoring (including weight, BMI, waist circumference, muscle strength and joint condition) can be complemented by support groups and new technologies such as phone apps. The management of weight loss may come under one or more medical specialties depending on local arrangements; it is useful to identify who can be contacted for support.

Ms Kuixing described the case of a boy with severe haemophilia who, in 2011, weighted 100 kg. At that time, he was mainly treated with on-demand factor replacement. Over the next 6 years, haemophilia treatment was gradually switched to prophylaxis. The transition was not smooth because the number of bleeding episodes transiently increased and weight loss was modest and variable. By 2017, however, prophylaxis accounted for 86% of administered factor, the boy’s weight was 76 kg and the frequency of bleeding episodes had been halved. This case shows that tackling obesity requires commitment; it can be marred by periodic setbacks but optimising haemophilia management offers long term gains.

 

Long term issues of cerebral bleeding in a person with severe haemophilia: Robyn Shoemark (Clinical Nurse Consultant, Sydney, Australia) described the case of a boy whose moderate to severe haemophilia went unrecognised until age 3, during which time clinical attention was focused on the neurological legacy of intracranial bleeding in utero.

A droopy eye was the first evidence of neurological impairment but it was initially not thought suspicious because another family member had a similar characteristic. However, one-sided weakness and poor balance ultimately led to referral and a diagnosis of 3rdocular nerve palsy and right hemiplegia. At the age of 18 months, physiotherapists noted bruising on the shins and buttocks but, since the boy was only able to scoot around on his bottom, this also was not considered significant. At about 2 years of age, he was enrolled into a botulinum toxin study (for muscle spasm) then, at 3.5 years old, he developed compartment syndrome after an injection. It was at this stage that routine postoperative coagulation tests were noted as abnormal and a diagnosis of haemophilia was finally made.

At age 7.5, after a total of 26 exposure days to recombinant Factor VIII, he developed an inhibitor. Tolerisation eventually eradicated this after 5 weeks while botulinum toxin therapy continued; after 8 months, the dose of recombinant Factor VIII was reduced to 50 IU/kg on alternate days. He began venepuncture training at age 9.

Management had involved teams from ophthalmology/orthoptics, rehabilitation, occupational therapy, physiotherapy, speech therapy, orthopaedics, orthotics, neurology, dietetics, dentistry and haematology. The patient is now 20 years old and the transition to adult services means that he and his mother must travel to three centres spread across Sydney to access these specialties. He still has impaired mobility and vision and these present challenges to independent living.

 

Pain in people with haemophilia: a global snap-shot study: How do people with haemophilia manage their pain? Greta Mulders (on behalf of Novo Nordisk Global Haemophilia Nurses Support Committee, GHNSC) presented a cross-sectional study by 53 nurses from 24 haemophilia centres in 11 countries in Asia, Europe and the US. 209 patients attending a clinic for a routine appointment completed a questionnaire to determine the prevalence of pain and how they dealt with it.

Most (71%) had severe haemophilia and 13% had inhibitors. About half reported having pain, with three quarters saying this occurred in the previous 28 days and two-thirds describing pain affecting joints and muscles. There was no difference in pain severity experienced by patients using prophylaxis or on-demand therapy but patients with inhibitors reported 87% greater severity and frequency of pain than those without inhibitors. Patients in western developed economies, who have greater access to prophylaxis than non-western countries, reported twice as much pain as patients elsewhere.

Patients deployed a range of strategies to treat their pain. Paracetamol was used by 42%, of whom about two-thirds said it provided sufficient analgesia. Almost half of respondents used medication without involving health care staff. Other approaches to pain relief included rest (57% of patients), physiotherapy (40%), crutches (25%) and marijuana (15%).

Ms Mulders concluded that people with haemophilia have pain regardless of treatment regime, age, severity or ethnicity and more awareness is needed. Nurses should always ask their patients ‘How is your pain today?’ and address management in a structured way.

 

Haemophilia and sickle cell disease: Describing the impact of two genetic conditions – severe haemophilia A and sickle cell disease – on family life, Anica Phillott (Paediatric Haemophilia Nurse Manager and Specialist, London) pointed out that sickle cell disease is more common than haemophilia in the UK: it affects about 12,000 – 15,000 people, most of whom live in Greater London. It mostly occurs in people from South Asia, Africa and the Middle East because the mutation that causes the disorder confers a degree of protection against malaria and is therefore preserved in exposed populations.

In this instance, sickle cell disease was diagnosed at birth through routine screening and haemophilia was diagnosed following a bleeding episode at 18 days of age. Management involves chronic transfusion therapy (the mainstay of treating sickle cell disease to reduce the risk of long term vascular complications) plus treatment to reduce iron overload, and alternate day prophylaxis with Factor VIII.

The young mother was an only child of African origin; she had limited English. Her mother had died shortly after delivery and she’d had only a short relationship with the boy’s father. There had been no known history of either haemophilia or sickle cell disease in the family, though mild epistaxis had been a lifelong problem. The family was evicted from home when the boy was 3 years old due to lack of money.

The mother was keen to have the boy circumcised for cultural reasons. The medical team was reluctant to carry out the procedure because of the high risk of complications but there was a real risk that circumcision would be carried out outside the NHS. By chance, the boy developed phimosis and circumcision was performed on medical grounds.

Although haemophilia is now managed well and the outlook is good, the boy faces a future of disruptive treatment for sickle cell disease and serious long term complications. It can be difficult to distinguish between sickle cell crisis and a joint bleed, and both are painful. The impact on the family is made worse by a lack of understanding of both conditions among health care providers and transition raises the risk that treatment may become disorganised.

 

Ageing well

In countries with access to factor replacement therapy, life expectancy among people with haemophilia has improved greatly in recent years. But this brings the expectation that they will suffer the same age-associated disorders as other older adults – with the added burden of complications directly attributable to haemophilia. This presents new challenges for clinicians, said Dr Farooq Ahmad (Clinical Lead, Healthy Ageing Theme, Health Innovation Network, South London).

Since the 1970s, the proportion of older people in each category of severity of haemophilia has increased and this trend is expected to continue. Consequently, more are living with joint disease, which will affect mobility; bone density is lower than in the general population and there is a higher risk of chronic kidney disease; the risk factors for cardiovascular disease will match those of the population as a whole; and there is growing awareness of the emergence of psychiatric (dementia, depression) and neurological (Parkinson’s disease) disorders in the haemophilia population. The strategies for healthy ageing in people with haemophilia are the same as for anyone else: promotion of healthy living and prevention and management for illness and disability though good diet and exercise, reduced isolation and loneliness, and preventative medication and activity.

Ageing brings with it an increasing risk that small things can develop into big problems that make life less easy. Contributory factors include psychological problems, long term conditions that threaten independence, social challenges and acute health problems such as infection and injury. The combined and cumulative impact of each of these depends on the individual, varying with time and in relation to external and intrinsic factors but it may be possible to alter some aspects of life so that a balance between vulnerability and resilience can be restored. The difficulty in maintaining this balance is what defines frailty.

Frailty increases with ageing but it is distinct from age, comorbidity and disability. It is a state of reduced resilience and increased vulnerability in which minor events can trigger disproportionate adverse outcomes in health, wellbeing or functional ability. In other words, the impact of the problems of daily living is greater for someone who is frail compared to someone who is not. Frailty can be measured objectively – examples of validated tools include the electronic frailty index (www.improvementacademy.org/improving-quality/healthy-ageing.html), which is part of NHS England’s GP toolkit for supporting older people (www.england.nhs.uk/publication/toolkit-for-general-practice-in-supporting-older-people-living-with-frailty); the Dalhousie Clinical Frailty Scale (http://camapcanada.ca/Frailtyscale.pdf); and the Timed Get Up and Go test (www.csp.org.uk/publications/get-go-guide-staying-steady). Fortunately, frailty can be modified through appropriate interventions using assistive technology and community activation.

Most older people have more than one long term condition, for which they receive care from different specialties in different settings. Many find it difficult to navigate the care system and to cope with multiple medication regimens. NICE guidance on managing multimorbidity (www.nice.org.uk/guidance/ng56) recommends that older people are treated holistically, as an individual with multiple needs rather than as a disparate set of conditions. This means assessing the burden imposed by their morbidities and treatments and agreeing with them a single management plan that covers all aspects of their care.

Loneliness is a major problem for older people – such a concern, in fact, that the Government appointed a Minister for Loneliness in January 2018 in response to recommendations by the Jo Cox Commission (www.jocoxloneliness.org). About half of the over-75s live alone and many say they can go for days or weeks without social interaction. They may present to primary care with non-medical conditions, providing an opportunity for referral to community groups or social support through social prescribing (www.kingsfund.org.uk/publications/social-prescribing). A 24-hour free helpline is available offering support and advice (www.thesilverline.org.uk) and online support can be accessed at HealthUnlocked (https://healthunlocked.com).

Delivering this care model means thinking in new ways. GPs’ practice systems need to identify patients who are frail and health professionals should be proactive in planning management reviews. The existence of a single holistic care plan means that medical data must be integrated and this requires clear communication between the disciplines involved. Further, the care plan must be accessible to different agencies. Dr Ahmad described the Coordinate My Care initiative (http://coordinatemycare.co.uk), an ‘NHS clinical service sharing information between your healthcare providers, coordinating care, and recording wishes of how you would like to be cared for’. This scheme would go a long way to meeting the complex needs of older people with haemophilia.

Turning to mental well being, Dr Ahmad said that depression and anxiety are underdiagnosed among older people because of stigma, fear of medication and reluctance on the part of clinicians. But mental health problems are common – 20% of older people have depression – and long term conditions can themselves cause poor mental health, as is the case with the sense of defeat and being overwhelmed due to diabetes distress. More positively, older people tend to do well with psychological therapies; they and clinicians should be encouraged to follow this route.

Dementia is increasingly common with age, the risk rising from 1 in 14 at age 65 to over 1 in 6 by age 80. Like haemophilia, dementia has a profound impact on both the patient and carer and sustained support is needed to ensure both are able to live better quality lives. It is essential to recognise this early because access to support and management is available only when a formal diagnosis is made. The DeAR-GP assessment (www.nice.org.uk/sharedlearning/dementia-assessment-referral-to-gp-dear-gp) is a simple tool to help primary care physicians to refer promptly.

In conclusion, Dr Ahmad said simple things like companionship and social prescribing can often make a big difference to quality of life for older people. He highlighted the need to identify those who at increased risk of hospitalisation or complications and the importance of being proactive about developing an integrated care plan. Outcomes are improved when health professionals recognise the complexity of caring for older people and the value of good communications. Haemophilia nurses can help by finding evidence of what works locally and promoting integrated and joined up care.

 

Agreeing outcomes in trials of haemophilia therapy

In an ideal world, all clinical trials would use the same set of outcomes and endpoints so that their findings could be pooled and confidence in the results increased. Professor Alfonso Iorio (McMaster University, Canada) explained that this doesn’t happen because the creativity of investigators and the need for trial sponsors to differentiate their product from those of competitors create a range of endpoints that may or may not be compatible. For example, it is clear that trials and reviews of treatments for HIV/AIDS have not agreed about which outcomes are important (J Clin Epidemiol 2017;84:85-94).

As an epidemiologist, Professor Iorio is part of a team responsible for health technology assessments – the final step of drug assessment before marketing access is granted. This step is all about assessing value for money and, in the context of innovative treatments for haemophilia, the question is what premium value should be placed on such premium products? If all the outcomes relevant to patients are not considered in a trial, further studies have to be carried out to measure them.

An analysis of 63 submissions considered by Canadian regulators for marketing approval of drugs for rare diseases found that 45% were rejected (Orphanet J Rare Dis 2016;11:164). Of these, only 8% were rejected due to cost; by contrast, almost 70% were refused because of insufficient or lack of evidence.

Agreeing a common set of endpoints has become a priority as trials of gene therapy for haemophilia get underway. In 2016, US health economists proposed a three-tier value framework of patient-centred outcomes for medicines assessment (NEJM 2016;374:504-6). For haemophilia, this might mean:

  • Health status achieved or retained
    • Function/activity/joint status
    • Bleed severity
    • Pain
    • Health-related quality of life
  • Process of recovery
    • Time to recover from a bleed
    • Missed days off work/school
    • Inhibitors, pathogens, orthopaedic interventions…
  • Sustainability of health
    • Bleeding frequency, joint preservation
    • Lifelong productivity, good health

Which of these should form a core set of outcomes that can be included in every trial to make their findings compatible? Those selected should preferably be relevant to clinicians and patients; objective and validated; patient-reported (though there are problems relying on these); and relevant to health technology assessment. Each outcome meets several of these criteria but, Professor Iorio suggested, pain and quality of life are the two that should be at the heart of every trial.

The Core Outcome Set-STAndards for Development (COS-STAD) project aimed to identify minimum standards for study design agreed upon by an international group (PLoS Med 2017; 14: e1002447). A consensus discussion by multiple stakeholders including patients identified 11 essential standards, of which 4 were deemed critical to ensuring that patients’ interests are represented in trial design:

  • Stakeholders should include health professionals with experience of patients with the condition…
  • … and patients with the condition or their representatives
  • The initial list of outcomes should consider the views of both patients and health professionals
  • Care should be taken to avoid ambiguity of language in the list of outcomes

In conclusion, Professor Iorio pointed out that it is not enough solely to define trial outcomes. It important to agree how to measure them reliably – for example, how to report an improvement in quality of life in the way that is most relevant to stakeholders. The COS-STAD recommendations are now ready to be incorporated into clinical trials – with one exception: it is not clear how best to measure emotional functioning as a component of quality of life. There is no shortage of tools to measure outcomes but there is a lack of evidence to show which is best.

 

Insight into the complexities of pain in people with haemophilia

Half of people with haemophilia have constant pain and one-third have pain affecting at least 5 locations. But pain management is not well developed and there is no consensus among haemophilia centres about treatment, said Nathalie Roussel (University of Antwerp, The Netherlands).

The definition of pain, according to the International Association for the Study of Pain, is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. The consequences of pain are physical (spasm, restricted movement, muscle guarding), physiological (inflammation), emotional (anger, frustration, helplessness) and functional (muscle weakness and loss of function) and all affect quality of life. It is very important to explain to patients that there is no requirement for physical damage to experience pain, and to emphasise that pain can affect many aspects of daily life – in fact, it can take control of one’s life.

The first priority is always to exclude acute bleeding as a cause of pain. Pain assessment should include both physiological and psychological components. Clinically, we talk about acute and chronic pain as if they are distinct but for patients the difference is solely one of duration: people with haemophilia find it difficult to distinguish between the two and signs and symptom are not reliable indicators.

Pain assessment should include the evaluation of the predominant pain mechanism (i.e. nociceptive, neuropathic pain or altered central pain processing) because the treatment approach will be different. It is helpful to explain the neurological pathways of pain perception to patients, pointing out that the sensation of pain may be perceived in the absence of an obvious cause. Different parts of the brain have a role in pain perception beyond those immediately involved in processing noxious stimuli. For example, the amygdala modulates the emotional response to pain and the prefrontal cortex modulates the cognitive response. Patients may not realise that the brain exhibits neuroplasticity – for example, chronic back pain is associated with a reduction in gray matter.

Pathways descending from the brain to the periphery inhibit or facilitate pain perception. Physical activity restores the inhibitory function, even though it may hurt. Stress, fear of movement and hypervigilance can be facilitatory, so it is useful to explain to patients that they can do something to influence this. Increased activity of ascending pathways can alter central pain perception. This may be caused by a reduced nerve threshold for triggering the action potential or, in the long term when persistence of pain outlasts the original cause, modification of ascending pathways can cause sensitisation. This may be clinically evident as pain perceived in sites other than the joint in which pain originates.

Pain mechanisms appear to be altered in people with haemophilia: they have increased pain sensitivity, especially in large joints, and there is some evidence that they have hypersensitivity at multiple sites. They do not develop hypoanalgesia after exercise, by contrast with people who do not have haemophilia. However, although the importance of assessing psychosocial aspects of pain is widely recognised, there is a lack of evidence about the effect of stress, negative emotions and catastrophising on pain perception.

It is time for a change in how we manage pain in people with haemophilia – we can do better, Ms Roussel concluded. It is no longer sufficient to assess pain using only a visual analogue scale: the full range of the patient’s cognitive and emotional reactions must be taken into account when formulating a treatment plan.

 

Nurse- and physio-led clinics – is it the future?

What should a haemophilia clinic offer its patients?: The standards for care of haemophilia in The Netherlands are set by official management guidelines, explained Katrien de Rooij (Nurse Practitioner, Maastricht). Among the most important of these is a requirement for haemophilia centres to serve a minimum of 40 patients. This has resulted in the smaller centres affiliating with larger ones, a system that provides good access for patients while meeting the criterion for service quality. How well does this work for people with haemophilia?

Ms de Rooij sought the views of 9 patients with severe haemophilia A, all of whom were able to self treat a bleed at home using a small supply of factor and haemostatics. The patients considered themselves experts in the management of their condition. All said they were satisfied with access to a centre during working hours but out of hours support was lacking. Patients were more likely to contact a centre in the evening than during the working day but they said the staff knew less than they did about managing haemophilia. Two patients didn’t bother reporting bleeds because they could manage themselves. No-one thought that going to A&E was an option. Patients preferred to access a haemophilia centre without having to go through other departments and they would value 24-hour access. This would be achievable of nurses could exercise professional autonomy, Ms de Rooij concluded.

Multidisciplinary teamwork in haemophilia care. Challenges of a MDT clinic: Everyone acknowledges that a haemophilia service should be provided by a multidisciplinary team, said Wypke de Boer (Pediatric Physical Therapist, Amsterdam). Centres tend to agree that one of the roles of the haemophilia nurse is to coordinate the team but there is less agreement about how best to use the skills of physiotherapists. A working group on physiotherapy services in haemophilia care has been established in The Netherlands with the aim of creating a large network of physiotherapists and establishing greater concordance about their role. There is a strong case for leadership to come from nurses and physiotherapists.

Physiotherapy contributes to both acute and chronic care. Acute care involves assessment (differentiating between bleeds and/or other problems), treatment (of acute bleeds, synovitis or haemophilic arthropathy), advice (to physiotherapists in the community until function is fully recovered) and postoperative rehabilitation. Chronic care is about education in identifying and preventing bleeds, evaluating joint status, preventing musculoskeletal deterioration and helping patients to remain active and join in.It is estimated that the cost of optimal physiotherapy services would amount to about 1% of the total cost of care.

The challenges to effective team working are familiar to everyone. There is never enough time. Education and prevention are limited by lack of funds even though they have the potential to reduce spending in the long term. Management guidelines don’t always provide consistent messages. Good logistic skills are needed to implement innovations such as video consultations and home training programmes. The roles of team members need to be clearly defined – a challenge for the professions and one that requires good communication and organisation. Members of the team should have an equal say and agree the messages they offer patients.

Nurse- and physio-led clinic: how can this run well? The evolution of a nurse-coordinated clinic: Jan Martin (Senior Clinical Nurse, Cleveland) described 8 years of experience of a menorrhagia clinic as an example of how nurse leadership can be a success. First, she pointed out that there is policy support for a nurse-led multidisciplinary team from the  American Academy of Ambulatory Care Nursing, which has unequivocally stated that registered nurses are ‘the team members best prepared to facilitate the functioning of interprofessional teams across the care continuum, coordinate care with patients and their caregivers, and mitigate the growing complexity of transitions in care’. Second, the nurse already plays a central role by coordinating the various team members, acting as a ‘referral pivot’ for patients.

Clinics need to be designed and run creatively if they are to meet patients’ needs. This means extended hours, bases in different locations, shared appointments with medical staff, opportunities for patients to socialise and age-appropriate clinic times.Physical therapists see patients on their own and in the clinic setting, able to provide advice and to prescribe therapies as needed.

It took 6 months to establish the menorrhagia clinic. Based in the women’s hospital, the initiative was originally driven by a physician as away to provide for an underserved, underdiagnosed group of patients. A&E is a major source of referrals to the clinic. All patients are screened by a nurse, who then refers them to a paediatric haematologist and/or an obstetrician/gynaecologist. Patients receive a thorough workup and normally have a diagnosis without the delay associated with inter-departmental referrals. To date, 386 young women have received personalised, specialised care with education and follow-up.

Nurse- and physio-led clinics. Is this the future of haemophilia clinics and how can we collect outcomes data with minimal burden to our patients?: Haemophilia is fundamentally a bleeding disorder but, with the advent of effective factor replacement therapy, it is the impact on joints and muscles that now present a major problem for patients, said David Stephensen (Physiotherapist, Canterbury and London). The assessment of musculoskeletal function is a core function of the multidisciplinary team and evaluation using standard tools at least annually is recommended for early identification of problems.

This imposes a considerable burden on patients – one that is not lightened by the way that many haemophilia centres organise their clinics. The one-stop clinic aims to help patients avoid multiple visits to access different services. Traditionally, the patient first sees the physician before going on to see other professionals; consultations inevitably run over time, causing disorganisation and delays further down the line. Physiotherapists are not alone in having a morning clinic wasted because patients are held up in the queue.

There is a better way. In Canterbury, patients see the physiotherapist first, allowing time for a full appointment and a comprehensive assessment. In the London centre, the musculoskeletal clinic is separate from the main clinic; the patient sees the physiotherapist first and the physician is then better informed about the musculoskeletal assessment. The physiotherapist collects a core set of outcomes routinely (strength, balance, joint motion) but can widen the scope of the assessment according to individual need (e.g. endurance, physical activity).

Both models ensure that the service is led by musculoskeletal outcomes rather than haematological ones. As a result, patients are more satisfied and the number of unplanned visits to the haemophilia centre or emergency services is reduced.

 

Sports and exercise

The idea that people with haemophilia should not play sports, or at least confine themselves to non-contact activities, is outmoded. Children and young people want to be like their peers; adults won’t be denied fulfilling experiences. Now that survival among people with haemophilia is increasing to an age where the risk of cardiovascular and other age-related disorders becomes real, remaining fit and active both physically and psychosocially has become more important.

 

Sports therapy in haemophilia: Professor Thomas Hilberg (Bergische Universität Wuppertal, Germany) emphasised the benefits of maintaining an active lifestyle, pointing out that moderate physical activity is associated with a 50% reduction in cardiovascular death in the over-65s and a reduction in knee pain in people with osteoarthritis. People with haemophilia are no exception: a 2016 Cochrane review concluded that most exercise interventions improved one or more outcomes including pain, range of motion, strength and walking tolerance.

There are obstacles: haemophilia in adults is associated with impaired coordination and reduced endurance, strength and flexibility. This is where sports therapy has a role. Defined as ‘an exercise therapy based on behaviour-orientated components… planned, dosed and supervised by sports therapists and performed by the patient alone or in a group’ and delivered as a tailored programme, it has been shown to increase muscle strength and measures of endurance, mobility and coordination in people with haemophilia. Sports therapy also increases measures of quality of life with a small increase in overall costs (Orphanet J Rare Dis 2018;13:38. doi: 10.1186/s13023-018-0777-7;Haemophilia 2018 Mar 30. doi: 10.1111/hae.13459). More details are available at www.haemophilia-exercise.de/en.

We now need to determine how best to optimise sports therapy by tailoring intensity, duration and frequency to individual need; and how to manage treatment to minimise the risk of bleeding while maximising opportunities for activity.

 

Feeling better: psychosocial perspective: The mental benefits of physical activity include reductions in anxiety and feelings of stress; in the long term, daily physical activity is associated with reduced risks of dementia and depression. Continuous physical activity is more important than the type of exercise undertaken. Active people report clearer thinking, a greater sense of calm, increased self-esteem and happier moods, said Sylvia von Mackesen (Clinical Psychologist, University of Hamburg). Prophylaxis with factor replacement has provided greater access to sports participation than previous generations enjoyed. Physical activity brings many benefits to children with haemophilia. It is essential to healthy development and improves physical, social and psychological wellbeing. It has a greater effect on health-related quality of life in children than adults.

Dr von Mackeson presented evidence consistently showing a link between physical inactivity and impaired functioning, though few studies had considered psychosocial functioning. Sport is undoubtedly popular among boys with haemophilia: the EIS study, led by Kate Khair (Haemophilia 2012;18:898-905), showed that 95% of participants rated sport as ‘good’, 93% wanted to continue sport when older and 68% would like to try a new sport, including rugby, boxing, hockey and cricket. Only 10% of boys considered sport was bad or dangerous. But a sedentary lifestyle is associated with worse scores of physical functioning and more school days missed; in adults, worse physical functioning correlates with chronic pain.

Physical performance should be assessed using subjective and objective measures, using tools such as the Hep Test-Q (www.hep-test-q.org). Supervised sport activities should be considered part of the aims of an holistic global approach to haemophilia management

 

How to choose? Sport for people with haemophilia: Axel Seuser (Centre for Prevention, Rehabilitation and Orthopaedics, Bonn) took a cautious approach to recommending sports for people with haemophilia. He pointed out that children with haemophilia have more ‘silent symptoms’ (demonstrable on joint thermography) and tender spots than other children, suggesting the hidden presence of synovitis and inflammation. It is important that haemophilia management is optimised before commencing sporting activity. This means ensuring good adherence with prophylaxis, a factor level greater than 15% (though there is no evidence to support this widely-quoted figure), and coordinating prophylaxis with the activity (e.g. self-treating before the event). Individuals should prepare for their sport as any athlete does: warm up, start slow, finish early, train regularly and stretch after exercise but Dr Seuser also suggested that people with haemophilia should get professional advice and work with a coach. How feasible such an approach would be for day-to-day sports participation is not clear.

Statistics on the risk of injury associated with different sports are unreliable and no sport is completely safe. Sports associated with low acceleration or low joint loading, such as swimming and surfing, carry lowest risk; contact sports are the most risky. But sports participation is clearly beneficial, improving balance, strength and body awareness in people with haemophilia.

 

A revolutionary experience: Clive Smith (Haemophilia Society, UK) is living proof that having haemophilia does not prevent participation at the highest level of sports for individuals with sufficient will and commitment. He has severe haemophilia A. Between the ages of 7 and 9, he had target joints in his elbow and ankle and he could walk for only one week in every four due to severe pain; he lost muscle mass in one leg, a problem that would continue into adulthood. Beginning prophylaxis, he was able to play football and basketball and would compete against his two brothers who also have haemophilia. University and young adulthood saw a fall in sports participation and it wasn’t until his late twenties that he began running. This ended when the restricted mobility of the target ankle joint caused severe pain. By now he was undergoing regular physiotherapy and, with his therapist’s support, he decided to run the Brighton marathon in 2013. To say he never looked back would be to underplay the tremendous effort that has gone into his training and therapy in intervening the years but Clive was the first person with haemophilia to complete an Ironman event (an extreme triathlon consisting of a 2.4-mile swim, a 112-mile bike ride and a 26-mile marathon) and he has now completed three with very competitive times. Underpinning this elite performance is an intensive training schedule that involves three bike rides, three runs and three swims over 6 days per week. He administers prophylaxis at home with 3,000 units three times weekly (he weighs 74 kg) on the night before a run (because this is potentially the most damaging activity).

This level of performance was not achieved overnight but earned over several years of gradually increasing training load and the support of his family. Not everything went smoothly – ‘ups and downs are not part of the journey, they are the journey’, Clive says – but he was determined that haemophilia would not limit his aspiration. Everyone has different goals, he said, don’t let haemophilia stop you achieving your own personal Ironman.

 

Treating and bleeding: healthcare professionals living with a bleeding disorder

Does having a bleeding disorder affect how a healthcare professional fulfils their role as a carer for people with haemophilia? The answer is yes – but in different and unexpected ways.

Gaetan Duport, who worked as a physiotherapist in Orleans, France, and is now an adviser to the French Haemophilia Society (FSH), said that having severe haemophilia A means he has a strong understanding of how his patients feel. He can be empathetic and, in his role with the FSH where people are aware of his diagnosis, he connects well with people and establishes a strong peer relationship. But in his clinical work he maintained a professional barrier – difficult at times but, he said, personal experience is not the same as professional expertise.

In France, health professionals are not keen on involving a patient in a health care role but being a patient or caregiver is a strength when providing education. The Parent Resource Programme aims to equip parents and caregivers with the skills they need to play an effective role in haemophilia management. To participate, they must have the support of the treatment centre and their local haemophilia group, and be facing the prospect of at least 3 years of prophylaxis.

Mr Duport was clear that his 30 years’ experience of living with haemophilia has not made him a better therapist than colleagues who do not have a bleeding disorder. As is the case with a professional qualification, having haemophilia doesn’t help if you don’t know how to build relationships with patients, he said.

By contrast, Shaun Emmitt, Haematology Nurse Specialist at Sheffield Children’s Hospital, decided not to disclose to his patients the fact that he has severe haemophilia and arthropathy. His experience of growing up with a bleeding disorder in an era of on-demand treatment with plasma-derived products bears little resemblance to the environment children experience nowadays. He was strongly discouraged from sports other than swimming whereas children are now encouraged to join in as much as possible. Similarly, he feels that having a bleed is a personal experience that should not be influenced by expectations based on how someone else dealt with the problem. There is also a risk that a needy family – one with a newly diagnosed child, for example – might latch on to his diagnosis rather than find their own way forward.

That said, Shaun felt that his first hand knowledge of haemophilia means he understands how others feel and what kind of support they need. Recalling having to endure multiple unsuccessful attempts at venepuncture, he has made it his mission to refine his technique as best he can. He agreed that having haemophilia doesn’t make him a better nurse than his colleagues but it does offer ‘a different way in’. His goal, he concluded, is to treat patients as he’d wanted to be treated.

Tony Roberts believes that sharing his diagnosis of haemophilia with teenagers and older men can provide encouragement and help people when they find themselves in a dark place. As an educational psychologist and adviser to the South Africa Haemophilia Foundation, he coordinates psychosocial outreach and organises camps for boys. Born in the 1950s, he experienced treatment with fresh frozen plasma, cryoprecipitate and Factor VIII. Severe damage to his knees and ankles disrupted schooling and left him with low self-esteem but, with support from family and friends, he took up education again and qualified as a teacher before becoming a psychologist. As a ‘bleeder-treater’, Tony believes he can empathise with parents and be a role model to show that it is possible to have a normal life and be self-sufficient while living with haemophilia. The main difficulty about being so open about his haemophilia is that he finds it difficult to ‘bracket’ his feelings when working with a client: that person is the healer and it is the therapist’s task to create the space in which healing can take place without influencing the process with his or her own story. This is a constant challenge, he said.

 

Free papers

Several sessions of the Congress were devoted to rapid fire presentations of small studies addressing a wide range of topics. Ellis Neufeld (Memphis, USA) opened the first session, devoted to late-breaking studies, with an analysis of 20 years of safety data for recombinant Factor VIII (1996 – 2016), equivalent to more than 5 million doses of 90 mcg/kg. Venous thrombotic events were the most frequently reported in most types of haemophilia, with 249 events occurring in 217 patients. The exception was acquired haemophilia, in which arterial events were more frequent. Although some level of under-reporting of adverse events was likely, it was not considered to be substantial and the analysis revealed no new safety concerns.

Marijke van den Berg (World Federation of Hemophilia) presented data from PedNet on inhibitor incidence in previously untreated patients with severe haemophilia A who had been treated with recombinant or plasma-derived products. The study followed up 1,083 patients from 33 centres in 18 countries over the first 50 exposure days (ED). Children receiving plasma-derived products had a slightly greater intensity of treatment, beginning younger (8.0 vs 9.5 months) and reaching 50 ED earlier (18.8 vs 20.2 months). The incidence of inhibitors associated with the two product classes was similar (28% and 27% respectively), with high titre inhibitors present in 21% and 20%.

Two speakers presented data from the HAVEN trials of emicizumab. Johnny Mahlangu (South Africa) said that, in HAVEN 3, 152 young people and adults previously treated with episodic or prophylactic Factor VIII but who had not developed inhibitors received one of two doses of emicizumab or placebo. After 6 months, the annualised bleeding rate (ABR) was 1.3 and 1.5 with emicizumab and 38.2 with placebo; 56% – 60% of those receiving active treatment had no bleeds. A within-patient comparison showed that the ABR during prior Factor VIII prophylaxis had been 4.8 compared with 1.5 with emicizumab. Professor Mahlangu noted that 215 patients accidentally received both Factor VIII and emicizumab but there was not evidence of thrombotic events in this group.

HAVEN 4 evaluated the efficacy and safety of monthly administration of emicizumab 6 mg/kg (after a loading dose phase) in 41 adults with haemophilia A with (5 patients) and without inhibitors. Steven Pipe (USA) reported that after 6 months the estimated ABR was 2.4, with 56% of patients reporting no bleeds and 90% reporting no more than 3 bleeds. Blood levels of emicizumab were slightly lower during monthly administration compared with standard dosing at a mean of 41 ng/ml. The most frequent adverse events were injection site reactions, reported by 22% of patients.

Alison Dougall (Chair, WFH Dental Committee) pointed out that haemophilia services don’t routinely collect information about dental health unless bleeding is prolonged (>10 minutes with evidence of blood in the saliva). What evidence we have suggests that people with haemophilia do not understand how best to maintain oral health – they tend to stop brushing if their gums bleed but this is most likely the result of periodontitis rather than failure of coagulation. Analysis of data gathered in the PROBE study (www.probestudy.org) shows that self-reported gum bleeding (a proxy for gingivitis and periodontitis) occurred in 85% of people with haemophilia compared with 15% of controls. This places the oral health of people with haemophilia on a par with that of 65 – 80 year-olds. Of the 1,170 PROBE participants with haemophilia, 163 (14%) reported a life-threatening bleed, of which one quarter were associated with a dental disorder. Periodontal disease also has a psychosocial and emotional impact due to the appearance of the gums, halitosis and the effect on personal relationships. Ms Dougall concluded that more data are needed on oral health in people with haemophilia to guide interventions.

It is widely acknowledged that caring for a child with haemophilia places a great burden on caregivers but until recently there has been little quantitative analysis of the challenges faced by parents and carers. The BBC study, coordinated by Haemnet and conducted in France, Germany, Italy, Poland, Sweden, Turkey and UK, used the recently developed HEMOphilia associated CAregiver Burden scale (HEMOCAB) to assess caregivers’ burden and evaluate the impact of bleeding. Sylvia von Mackensen (Germany) reported on the results obtained to date from 144 participants. Their mean age is 40 and 80% are currently married; 40% are in full time work and 18% had a long term condition themselves. Of those not working full time, 40% said this was due to their child’s haemophilia and 12.5% had changed employment to make management easier. Infusing factor replacement required an average of 8 hours a month in addition to the 8 – 9 hours a month taken up by clinic visits. Two thirds of participants said that haemophilia has a negative impact on the family due to stigma and anxiety about the child’s health, though there were also positive aspects such as drawing the family closer together. One-third reported an economic impact with average personal expenditure on haemophilia care of 275 Euros per year, mainly on transport. These data show that the main impact of haemophilia on parents and carers is in the domains of ‘Perception of your child’ and ‘Emotional stress’ and that caregiver burden is increased by the occurrence of joint bleeds.

In a session devoted to the expanding role of physiotherapists in the management of haemophilia, themes ranged from preventing joint infection to muscle function in Costa Rican children. James Luck (USA) pointed out that late infection of joint prosthesis is expensive – he cited an average of $450,000 per patient and cited the example of one patient whose problems had persisted for 4 – 5 years had (so far) cost the insurer $11 million. He suggested that self-infusion was the source of bacterial joint infection occurring 5 years after surgery or later. His study had shown that educating patients about the risk and improving technique could substantially reduce the rate of infection, though not abolish it.

Hannah Harbidge (Bristol) presented a study of the impact of a training course on assessing global gait score using HJHS criteria. The course reduced variability between physiotherapists in the assessment of adults and showed that longer clinical experience was associated with greater concordance between the physiotherapist and expert evaluation. She suggested this was probably because their greater clinical expertise enabled them to distinguish the subtle changes that affect children with haemophilia.

Presenting a single centre’s preliminary evaluation of results from the HEAD US study evaluating ultrasound in the early detection of joint damage, Stephen Classey (London) said that this technique moderately correlated with clinical assessment and the two modalities were complementary. There was some dissent among the audience about whether ultrasound might be useful for detecting change in cartilage and bone as well as picking up synovitis. Some of the more experienced speakers strongly felt that this was possible if the user had sufficient expertise.

Axel Seuser (Germany) reported a study in 34 children in Costa Rica in whom muscle function had been assessed in 2009 and 2011. The 2-year period saw little change overall though some differences in individual children were large. There was, however, a significant average deterioration in the gluteus medius muscle strength and some evidence that bicep strength had fallen. There was no change in SJHS score.

People with haemophilia are more likely than the general population to have low bone mass but there is a lack of long term data about the risk, said Andreas Strauss (Germany). He presented a retrospective study of 33 people with severe haemophilia (mean age 33), showing that vitamin D levels were low but there had been no change in bone mineral density during the 10-year study period. However, low bone mineral density correlated with higher joint score.

Kathelijn Fischer (Netherlands) wondered whether the paediatric Hemophilia Activities List couldn’t be made a bit shorter. This tool contains 53 questions covering 7 domains, taking about 10 minutes to generate a score between 1 and 100. Experience in her department showed that its discrimination was poor because most children have a high score. Analysis of the responses to individual questions showed that some were barely relevant to children – climbing stairs and self care being two examples. There is potential to shorten the questionnaire, she concluded, though the changes need to be tested in different patient populations and with input from patients.

Patients are moderately enthusiastic about a clinic model that offers a protected hour-long appointment with a physiotherapist, said Vishal Patel (London). His survey of 24 patients (51% of those asked) found that 95% said they found this approach at least useful, with about half of these describing it as very useful. Almost all welcomed the appointment and two thirds left with a better understanding of their condition. 41% improved their awareness of the consequences of low adherence and one-third said they would modify their treatment as a result.

Handwriting analysis could be a useful tool to assess elbow function in children with haemophilia, said Gianluigi Pasta (Italy). His study of 20 children (median age 12) with severe haemophilia had shown that 74% had dysgraphia. This could not be attributed to learning difficulty, which is much less common (up to 10%). Having dysgraphia did not correlate with bleeding frequency, symptoms or joint score, though there was an imbalance in muscle strength, with raised bicep strength and triceps weakness. Dr Pasta suggested that dysgraphia could be used as a broad measure of the composite effect of several factors affecting limb mobility. He acknowledged a point from the audience that adults say all children have bad handwriting but disagreed that this explained his findings.

 

Inhibitor management

Inhibitors to Factor VIII are perhaps the most serious complication of haemophilia management in current times, said Christine Guelcher (US Children’s National Health System).

Risk factors for inhibitor development are patient-related (family history, mutation type, severity of haemophilia, ethnicity) and treatment-related (exposure days, age at first exposure, intensity, infection, type of factor). Careful treatment may reduce the risk associated with modifiable treatment factors but the overall prevalence of inhibitors is 5% – 7% and they are twice as common in people with severe Factor VIII deficiency (12% – 13%). Estimates of the incidence of new inhibitors range from 1 in 10 to 1 in 3 patients. Immune tolerance induction (ITI) is successful in about 80% of patients with a titre ≤10 BU but in 40% – 60% at higher titres.

We now recognise that the outcome is improved when ITI begins as early as possible after inhibitors have been diagnosed but there is scope for confusion as treatment guidelines emerge. The future brings hope and uncertainty: a new generation of agents for prophylaxis means we may one day see a time when ITI is no longer necessary.

Inhibitor Management: Waiting for 10: Focusing on ITI in previously untreated patients with severe Factor VIII deficiency with newly diagnosed inhibitors, Julia Hews-Girard (Calgary, Canada) said guidelines recommend delaying ITI until the inhibitor titre falls below 10 BU (except when the inhibitor was detected within the previous 1 – 2 years and when bleeding is difficult to control or frequent). But ITI can be successful when initiated at a higher titre, so should we be treating the number or the patient?

The advantages of delaying ITI are a higher success rate at lower titres (83% vs 40%), a shorter time to tolerisation, lower doses are effective and the patient is likely to need fewer high volume infusions. Conversely, that delay puts the patient at greater risk of bleeds that are difficult to manage and an increased risk of developing joint arthropathy, with a consequential impact on quality of life and treatment costs. Finally, the titre may not fall below 10 BU and, after this wasted time, the patient may ultimately need a high-dose regimen.

There is also uncertainty about managing inhibitors in other settings. Inhibitors against Factor IX are less frequent but often difficult to manage. Inhibitors in people with mild or moderate haemophilia behave differently from those associated with the severe disorder. And it is not known why inhibitors suddenly develop in patients who have a long, previously uneventful history of prophylaxis.

Prompt ITI: It’s not always clear how quickly to begin ITI after inhibitors have been diagnosed. Jennifer Maahs (Indiana, USA) described the case of a 10-month old boy who developed a low titre inhibitor (3 BU) after 14 exposure days of Factor VIII prophylaxis. Central venous access was in place so continuing prophylaxis or beginning ITI were both options. It was decided to start ITI but, after one month, he had converted to a high responder with a titre of 13 BU.

Ms Maahs said this case illustrated the dilemma presented by inhibitors: is it better to start ITI soon or wait to see whether the titre falls and manage the increased bleeding risk? Evidence favours earlier treatment, she said, because it may intervene in the pathways causing immune response before they become entrenched and it induces tolerance before a stable population of plasma cells in the bone marrow is established. It also decreases the duration of high risk of bleeding episodes. However, success depends starting within a very short time from diagnosis – as little as one month. The latest guidelines from the UK Haemophilia Centre Doctors’ Organisation recommends initiating ITI as soon as an inhibitor is confirmed, regardless of starting titre (Haemophilia 2017;23:654-659).

ITI may require multiple strategies over a long period, Ms Maahs concluded. In the case of the toddler she cited, inhibitors were eventually eradicated by treatment with rituximab and, during the 9 months of ITI, he experienced four bleeds in his left knee.

 

New Products = Control Over Inhibitors: ITI can be challenging for clinicians, patients and carers alike. Difficulties with ITI often occurred in children, the need for venous access increased the risk of infection, and treatment required considerable commitment from patients and parents. There is uncertainty about the best time to start ITI and the risk that this burdensome strategy could fail. Is there an alternative, asked Mary Jane Frey (Detroit, USA)?

Citing the case of a 23 month-old boy who developed a low responding inhibitor after relatively little exposure to Factor VIII prophylaxis, she said initiation of ITI had been cancelled several times because of minor infections. Reluctant to continue risking a bleed, he was treated with emicizumab, which acts by bridging activated factor IX and factor X to restore the function of missing activated factor VIII. The nursing implications of this approach arise mainly from its route of administration: nurses should check local policies on subcutaneous injection, noting the need for a weekly loading dose for the first 4 weeks. The dose volume can be minimised by using the more concentrated solution (it is supplied in vials of 30 mg/ml and 150 mg/ml).

Emicizumab is the first of a new generation of agents that have the potential to reduce bleeding other than by factor replacement. Novel molecules include concizumab, which blocks tissue factor pathway inhibitor, and fitusiran, which inhibits antithrombin. It is hoped such agents will reduce the need for venous access and overcome the challenges associated with inhibitors and ITI. However, their introduction is likely to have a disruptive impact on clinical practice and may bring about a decline in the skills currently used by patients and carers to manage their treatment.