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The development of high‐titre inhibitory antibodies (inhibitors) against factor VIII (FVIII) remains a challenge in the management of patients with haemophilia A (HA). Patients with high‐titre inhibitors are more likely to experience uncontrolled bleeding, physical disability from chronic arthropathy and premature death compared with those without this complication. Immune tolerance induction (ITI), utilizing repeated infusions of FVIII, is an effective therapeutic approach to eliminating inhibitory antibodies. This strategy can eradicate FVIII inhibitors, so that FVIII‐specific tolerance is induced. However, patients undergoing ITI are still vulnerable to the development of serious and/or repeated bleeding events. The efficacy of bypassing agents in preventing bleeding episodes has been widely proven in patients with HA and inhibitors to FVIII. Evidence suggests that reducing bleeding during ITI can also shorten the time to tolerance. There are concerns with the use of bypassing agents, including the cost of treatment, short half‐life, management of non‐responders and the risk of thrombosis. Despite these concerns, and the still limited evidence from prospective studies and consensus reports, the use of prophylaxis with bypassing agents during ITI has been gaining support. This review presents a rationale and current data supporting the use of prophylactic bypassing agents as effective and safe therapies to reduce the incidence of joint bleeding due to inhibitors and improve quality of life in patients with HA undergoing ITI. [ABSTRACT FROM AUTHOR]

Introduction: Outcome data on treatment of patients with haemophilia A spanning several years of real‐world evidence collection are currently very limited. Aim and methods: The global prospective long‐term Advate® Haemophilia A Outcome Database (AHEAD) cohort study collects real‐world data from patients with severe and moderate haemophilia. We report an interim data read‐out after three years of observation. Results: A total of 522 patients were enrolled from 21 countries: 334 completed year 1 follow‐up, 238 completed year 2 and 136 completed year 3, with an overall follow‐up of 811 patient‐years. Median annual bleeding rates (ABR) were 1.7 in the prophylaxis group and 8.9 in the on‐demand group at year 1 visit, 1.6 and 13.0, respectively, at year 2 visit and 2.2 and 10.3, respectively, at year 3 visit. Moreover, about 42% of patients on prophylaxis vs 12% of patients on on‐demand had zero annual joint bleeding rates (AJBR). Effectiveness of prophylaxis and on‐demand treatment was deemed excellent/good in the majority of cases. Octocog alfa (Advate®) was well tolerated. The inhibitors that developed in nine patients all disappeared spontaneously. Three patients had been previously exposed to FVIII for ≤50 exposure days (EDs), 3 for >50 EDs and 3 showed a borderline positive inhibitory activity (≤0.6 BU/mL). Conclusions: These data confirm that the goal of zero bleeds is achievable, although not yet achieved in all patients. Understanding reasons behind the lower response to standard prophylaxis regimens in some patients and personalizing prophylactic treatment may further improve outcome in patients with haemophilia A. [ABSTRACT FROM AUTHOR]

Introduction Contemporary haemophilia care demands Patient-Reported Outcomes. SO- FIT is a UK multi-centre study, assessing self-reported function, health-related quality of life ( HRQoL) and joint health in boys with severe haemophilia. Methods Subjective physical function (PedHAL, HEP-Test-Q) and HRQoL (Haemo-QoL Short Form [SF]) were assessed alongside joint health using the objective Haemophilia Joint Health Score (HJHS v2.1). Demographic and clinical data were collected. Results Data from 127 boys mean age 12.38 ± 2.5 (range 8-17) treated at 16 sites were analysed. One-hundred-and-thirteen had haemophilia A, 25/9 past/current inhibitor, 124 were treated prophylactically (46.8% primary) and three on-demand. In the preceding 6 months, boys reported median 0 joint bleeds (range 0-8) with a median HJHS score of 1 (range 0-30). Boys reported good physical functioning; HEP-Test-Q (M = 80.32 ± 16.1) showed the highest impairments in the domain 'endurance' (72.53 ± 19.1), in Ped HAL (M = 85.44 ± 18.9) highest impairments were in the domains 'leisure activities & sports' (M = 82.43 ± 23.4) and 'lying/sitting/kneeling/standing' (M = 83.22 ± 20.3). Boys reported generally good HRQoL in Haemo-QoL SF SF (M = 22.81 ± 15.0) with highest impairments in the domains 'friends' (M = 28.81 ± 30.5) and 'sports & school' (M = 26.14 ± 25.1). HJHS revealed low correlations with the Haemo-QoL SF ( r = .251, P < .006), the PedHAL ( r = −.397, P < .0001) and the HEP-Test-Q ( r = −.323, P < .0001). A moderate correlation was seen between HEP-Test-Q and Haemo-QoL SF of r = −.575 ( P < .0001) and between Ped HAL and Haemo-QoL SF r = −.561 ( P < .0001) implying that good perceived physical function is related to good HRQoL. Conclusions The SO- FIT study has demonstrated that children with severe haemophilia in the UK report good HRQoL and have good joint health as reflected in low HJHS scores. [ABSTRACT FROM AUTHOR]

Introduction Central venous access devices facilitate home treatment in boys with haemophilia. These are usually fully implanted lines, referred to as ports. Caregivers are taught to manage the port using sterile techniques and maintaining patency by flushing with saline or heparin solution. National and international guidelines for the home care of ports are lacking. Aim To evaluate if infection or occlusion rates differ between home care regimens used for ports in children with haemophilia. Methods Children with ports were identified from the PedNet registry. Data on the homecare policy were acquired from each centre. To ensure a complete data set for each port, only ports that had been removed were included in the study. Three care groups were defined: 'aseptic non touch technique', 'sterile technique' and 'fully sterile technique'. Outcomes within and between the groups were analysed. Results A total of 240 children with 352 ports were studied. Insertion occurred at a median age of 1.32 years. The median port duration was 2.94 years with a total of 215 688 port days in children without and 183 852 in children with inhibitors. Infection was the most common cause of port removal (34%); there was no significant difference with infection as reason for removal between the different care groups. Occlusion was not more frequent in centres that did not use heparin. Conclusion Use of sterile gloves and gowns did not reduce the risk of port infection. Using less stringent sterile techniques for accessing ports is easier for caregivers and in addition may have health economic benefits. [ABSTRACT FROM AUTHOR]

Children with von Willebrand disease ( VWD) in whom DDAVP is ineffective or contraindicated require treatment with a coagulation factor concentrate containing von Willebrand factor ( VWF) and factor VIII ( FVIII). The aim of this study was to monitor the safety, efficacy and tolerability of Wilate® (a VWF: FVIII concentrate with a 1:1 ratio) used across the North London Paediatric Haemophilia Network since May 2010. In total, 47 children (aged 0.0-17.0 years) with type 1 ( n = 28), type 2 ( n = 7), type 3 ( n = 10) and acquired VWS ( n = 2) have been treated for bleeds, surgery and/or prophylaxis using 260 000 IU Wilate®. Analysis of dose and frequency of treatment show expected responses to treatment with mean doses of 55, 50 and 50 IU kg−1 for bleeds, surgery and prophylaxis respectively. Most bleeds responded to a single treatment. Surgical procedures were covered with clinician approved dosing schedules with 95% (39/41) reported as having excellent or good efficacy. There was no accumulation of FVIII or VWF and no thromboembolic events. This case series confirms the efficacy, safety and tolerability of Wilate® in neonates, children and adolescents when used on-demand, prophylactically and in the surgical setting. [ABSTRACT FROM AUTHOR]

Haemophilia carriers and women with inherited bleeding disorders ( IBD) experience menorrhagia, bleed following dentistry, surgery, injury or childbirth. Symptoms are easily treated leading to full and active lives. Nevertheless, some girls and women suffer with abnormal bleeding for many years before diagnosis. We explored the experiences of girls and young women (aged 9-34 years) with IBD by means of focus groups which consisted of moderated discussion addressing specific aspects of bleeding, management and coping strategies. Subsequently, these issues were explored further though a paper-based questionnaire distributed via five specialist haemophilia centres in the UK. The study suggested that young women with IBD who are managed at haemophilia centres receive appropriate care and feel well supported. Although the clinic-based literature available to these women is 'fit for purpose', it does not fully address the perceived needs specifically regarding sex, menorrhagia, conception and childbirth, the Pill, tattoos/piercings and so on, leading many to turn to other information sources. Most of those who responded to our survey are confident in their lives, able to manage their IBD and take pragmatic views towards the inherited nature of their condition. But there is a substantial subgroup of women who experience stigmatization, isolation and bullying and express concerns relating to fertility and conception. Overall, this cohort would benefit from opportunities for mutual support. This could be via Internet-based social networking and may be of particular value to those who are unable to seek help from traditional medical services due to religious or other cultural barriers. [ABSTRACT FROM AUTHOR]

Sport is nowadays perceived as beneficial for children with haemophilia, as good muscle strength supports joints and may reduce bleed frequency; by contrast psychological benefits are less known. This study introduces the impact of sport on health-related quality of life ( HRQoL) and physical performance in children with haemophilia. A cross-sectional, multi-site, study of boys aged 6-17 years with haemophilia A or B of any severity, current or past inhibitor, which assessed physical performance, sporting activity and HRQoL using age appropriate questionnaires including KINDL, Haemo-QoL and HEP-Test-Q. Eighty-four haemophilic boys (23 mild, 19 moderate, 42 severe) with a mean age of 11.52 years ( SD = 3.4) were enrolled from two haemophilia centres in the United Kingdom. 28.4% were overweight/obese according to their BMI/age and had a good orthopaedic status (M = 1.55, SD = 3.3). Boys watching < 1-2 h of TV/ PC/day had fewer days lost (M = 3, SD = 3.2) than those with a more sedentary lifestyle (M = 9.40, SD = 7.1) ( P < 0.032). 90.5% participated in regular sporting activity; 79.9% at least twice a week. HRQoL in children was generally good, with highest impairments in boys aged 8-12 years. Boys aged 8-16 years reported good physical performance (M = 80.0, SD = 16.0) with highest impairments in the dimensions 'endurance' and 'mobility'. Boys doing sport had a significant better physical performance and HRQoL than boys not doing sport. Sedentary life styles had a negative impact on the subjective physical performance and number of days lost of children. Encouraging haemophilic boys to participate in sport will have a direct impact on their overall HRQoL. [ABSTRACT FROM AUTHOR]

. Clinical research should form a core component of the role of haemophilia nurse specialists. The UK Haemophilia Nurses Association sought to determine the barriers that prevent nurse specialists from engaging in research and to seek ways to promote clinical research by haemophilia nurses in the UK. Web-based survey with subsequent workshop discussion was conducted. Responses were received from 32 nurses (a 50% response rate), all of whom agreed that haemophilia nurses should be actively involved in nursing research although only 21 had actually participated in research specifically related to haemophilia practice. Of these, most research had been related to educational programmes or (less commonly) was limited to data collection as part of multidisciplinary studies. Involvement in research rarely resulted in publication. Some barriers to involvement in nursing research and subsequent publication were suggested by survey respondents. They also indentified key practice areas that warranted nurse-based research including carriership and antenatal decision-making, along with the role and impact on care of the specialist haemophilia nurse, education and empowerment. To overcome the barriers to engaging in research and publishing, nurses require dedicated research time, mentorship and collaboration with more experienced haemophilia nurse researchers. [ABSTRACT FROM AUTHOR]

. It is well known and often reported that patients with long-term health conditions have problems adhering to treatment regimens. This is often reportedly worst in adolescents who struggle with the physical and psychological impact of adolescence as well as with the limitations that treatment regimens impose on their day-to-day activities. This article presents results from a larger study that aimed to discover what living with haemophilia in the 21st century was like for boys with severe haemophilia. The overall study was a multi-method, cross-sectional interview based study of 30 boys with severe haemophilia, treated with prophylaxis at a single site in the UK. Although not specifically asked in the interview schedule, opinions about treatment (prophylaxis) were given by 66% of the boys. These boys recognized that prophylaxis offered them protection from bleeding, the older and more sporty boys understood the need for tailored prophylaxis around 'risk' activities such as sport or events away from home. For some boys this meant low dose daily prophylaxis, and this further enhanced treatment adherence, as it became firmly embedded in their daily ritual of health care. This study shows that adolescent boys are in fact adherent with treatment, possibly at a schedule decided upon by them rather than one directed by the haemophilia centre. They are able to comprehend complex treatment decisions and make treatment plans that offer them maximum protection with minimal interference in their day-to-day activities. [ABSTRACT FROM AUTHOR]

. Access to modern treatments allows adolescents with haemophilia to manage their haemophilia at home, with improved treatment outcomes and quality of life, but has reduced peer support and the potential for experiential learning from older peers. Social networking, aided by modern communication technologies, may offer health benefits through peer support. We sought to assess whether or not disease-specific social networking could benefit adolescents with severe haemophilia. A total of 150 adolescents (aged 10-18) with severe haemophilia A or B from 11 UK treatment centres or those who had attended focus groups to explore the potential for a social network designed specifically for their use were surveyed. Teenage boys with severe haemophilia in the UK who responded to an online and paper questionnaire ( n = 47; 31% response rate) rarely knew of or socialized with others with haemophilia outside their families. Two-thirds of respondents said they would like to meet others. For 70% of boys, parents were the major source of information about haemophilia, yet more than half said they often had trouble finding answers to their questions. These boys frequently used online social networks to chat with friends. Adolescents with severe haemophilia frequently have limited contact with others and many wish to have greater contact. They may benefit from peer support and experiential learning gained through online social networking. The SixVibe restricted access social network is to be launched in 2011. It includes features designed to promote and facilitate the development of peer-to peer disease management skills for adolescents with severe haemophilia. [ABSTRACT FROM AUTHOR]

This paper presents the results of a study talking to children and young people affected with severe haemophilia A and/or haemophilia B about their knowledge and understanding of genetics and inheritance. These data were gathered in a qualitative study using semi-structured interviews with thirty boys aged four to sixteen discussing the impact of haemophilia on their lives. Responses were tape recorded, transcribed and analysed, using thematic analysis; one of the themes identified was genetic knowledge which is presented in this paper. Genetic knowledge was formed within the context of normal day-to-day lives within families affected by haemophilia, with parents and haemophilia centre staff being sources of information about individual inheritance patterns as well as providers of information about the future genetic impact of having haemophilia. [ABSTRACT FROM AUTHOR]

Intracranial haemorrhages (ICH) in children with haemophilia are rare, and the outcome is variable, ranging from no apparent impairment to death. The aim of this investigation was to identify if children with haemophilia and ICH, have any long-term problems with motor function, visual motor integration or strengths and difficulties compared with a control group. A review of the Haemophilia Database at Great Ormond Street Hospital for Children NHS Trust was undertaken to identify boys with haemophilia and a history of ICH, as well as a control group of peers with no such history. Boys were born between January 1994 and December 2002. All boys were assessed using the movement Assessment Battery for Children, the Developmental Test of Visual Motor Integration and The Strengths and Difficulties Questionnaire as standardized assessments of motor competence, visual motor integration and behavioural difficulties. Six boys with haemophilia and ICH and 11 controls (mean age: 7 years; range: 4–12 years) were assessed. Children with ICH were significantly more likely to have problems with motor function and visual motor integration (Fisher’s exact: P < 0.05). In addition, they had a tendency towards more problems with strengths and difficulties than their peer group (Fisher’s exact: P = 0.06). Five of the six boys who had sustained an ICH were in mainstream schools; four requiring assistance with their education. The results of this small study suggest that ICH may signify long-term consequences for boys with haemophilia. The multidisciplinary team need to be aware of the rare but potentially important impact on motor function, visual motor integration and behaviour, which may inhibit the child from functioning optimally. An agreed comprehensive battery of assessments in collaboration with schools and healthcare workers is required to identify impairments to enable prompt interventions to be co-ordinated. [ABSTRACT FROM AUTHOR]

The past decade has seen the introduction of a number of needleless transfer devices for the reconstitution of coagulation factors. This study investigated the use of four commercially available transfer devices by children with bleeding disorders, and assessed their preferences for the devices. Fifteen children with bleeding disorders requiring prophylactic home treatment with coagulation factors were recruited to the study. The participants tested reconstitution with four dummy transfer devices: BAXJECT, BIOSET, ReFacto R2 and Mix2Vial. Participants did not infuse the factors reconstituted using the devices. Each participant then answered a series of questions on each device; answers were based on a five-point Likert scale and the devices were ranked in order of preference. All participants were able to use the devices within 5 min and 78% of participants ranked all devices as ‘fairly easy’ or ‘very easy’ to use. The most popular device was Mix2Vial, which was the most preferred by seven participants (46.7%). BAXJECT was the preferred device of four participants, but was also the least, or least but one, favourite of nine participants. Pre-filled syringe transfer devices, BIOSET and ReFacto R2, were preferred by only 26% of participants. This is the first published study comparing children’s preferences for transfer devices. All children were able to manage the devices readily, and Mix2Vial was the preferred device of the majority of participants. Newer, advanced transfer devices offer a user-friendly and more convenient and effective way for children to reconstitute factors. [ABSTRACT FROM AUTHOR]

Glanzmann thrombasthenia (GT) is a rare autosomal recessive platelet function disorder. Stem cell transplantation (SCT) is curative, but it is only indicated in selected patients with a severe clinical phenotype or who develop anti-platelet antibodies. SCT have previously been limited to full intensity myeloablative conditioning regimens. This study details the successful outcome of SCT in five consecutive patients with GT, three of whom received reduced intensity conditioning (RIC) with stem cells from non-sibling donors. This is the first time RIC SCT has been reported in GT, and offers the possibility of curative therapy with reduced late effects. [ABSTRACT FROM AUTHOR]

The unpredictable nature of bleeding and complications, and the highly variable nature of haemophilia A, necessitate that each patient be dealt with on an individual basis with treatment tailored to specific needs. Safety of treatment is paramount and, due to concerns over viral safety, the use of recombinant factor VIII products has increased across Europe. Prophylaxis treatment has also increased, as recent studies have shown reductions in number of joint bleeds, fewer days lost from work, less need for surgery and fewer emergency hospital visits compared with on-demand regimens. Other factors that need to be considered include convenience for the patient, consistency of supply and cost. Consequently, management of haemophilia involves complex interrelationships between the patient, family and healthcare team. [ABSTRACT FROM AUTHOR]

Desmopressin (1-deamino-8-D-arginine vasopressin (DDAVP)) has been shown to be an effective treatment option when administered both intravenously [ 1,2 ] and subcutaneously [ 3 ] to children with inherited bleeding disorders. We demostrate here, both the efficacy and acceptability of a new intranasal DDAVP preparation, providing a cost effective treatment with good outcomes for children with bleed disorders. [ABSTRACT FROM AUTHOR]

Children horn with severe homozygous protein C deficiency do not survive beyond the neonatal period unless they receive protein C replacement. Protein C concentrate (Baxter Biosciences, Vienna) is usually given intravenously via a central venous catheter. The authors describe 2 children in whom protein C concentrate was successfully administered by subcutaneous infusion after they had had recurrent central line infections. Alternate daily doses of 250–350 IU/kg resulted in trough protein C levels of >25 IU/dL. In the follow-up period of 1–2 years neither child has had a thrombotic episode or purpuric skin lesions, and infusions are managed in the home by their parents. [ABSTRACT FROM AUTHOR]

The government is backing the widening of nurse prescribing. Faith Gibson and colleagues surveyed nurses to discover their perceptions of this expanded role. [ABSTRACT FROM AUTHOR]

Hermansky-Pudlak syndrome (HPS) is a rare disorder characterised by oculocutaneous albinism, a bleeding tendency, and lipofuscinosis. This retrospective study reviews the clinical history and haematological features of 23 cases of HPS. Information was gathered from patient notes and by direct interview. Thirteen of the 23 children were of Turkish origin, 12 being members of four kindreds from the Turkish/Kurdish border. Four children originated from Pakistan. Haemorrhage was uncommon; two experienced significant bleeding (intracranial and retinal haemorrhage in one and menorrhagia in another), and twelve minor symptoms. Results of laboratory evaluation of platelet function were not predictive of bleeding; in particular the PFA-100 analyser was not sensitive to the HPS defect. The most sensitive test of platelet fuction was quantitation of platelet nucleotides. The occurrence of Turkish and Pakistani kindreds with HPS is novel and follow up for long term complications described in Puerto Rican patients as well as genetic analysis is ongoing. [ABSTRACT FROM AUTHOR]

Adherence or compliance to prescribed treatment regimens is an important and much debated area of haemophilia care. Many patients are labelled as ‘non-adherent’ because they don’t do what we say in terms of self- treatment and factor administration. However, do we engage patients in developing mutually acceptable treatment programmes which work for them as individuals? If we do, does this affect self-care and treatment uptake through a supportive relationship which enhances treatment concordance? Once we have agreed treatment regimens, how do we measure the success or outcomes of them? This paper discusses these issues, and some of the tools that are available to assess adherence in a systematic way. [ABSTRACT FROM AUTHOR]

Summary. Factor XIII deficiency is a rare inherited bleeding disorder that is often difficult to diagnose. The standard screening tests are normal in these patients and their bleeding phenotype may be variable. We report the case of a 3-year-old girl who presented with an intracranial haemorrhage. Several confounding factors, such as the suspicion of an arteriovenous malformation and the development of a deep venous thrombosis, led to a delay in the diagnosis of factor XIII deficiency. Subsequently, her brother was also found to have severe factor XIII deficiency. This case highlights the importance of a detailed history and of screening families in which index cases have been identified. It should also remind physicians that bleeding disorders may have unusual presentations and should be sought when investigating unexplained bleeding. [ABSTRACT FROM AUTHOR]

Although prophylactic treatment of boys with severe haemophilia has progressed significantly, there has been very little change in the way that coagulation factors are reconstituted and administered. Most boys with severe haemophilia can self infuse by the age of eight and most are totally self sufficient by the age of 14. This small study evaluated a product developed to improve the reconstitution and administration process by seeking the views of ten boys who self infuse recombinant coagulation factor. The boys completed a simple questionnaire related to the current method and after the introduction of new method of reconstitution using the ReFacto Rapid Reconstitution[TM] (R2) device. The R2 device was reported by most boys to be advantageous in terms of time and safety in reconstitution as well as being acceptable to all but one. Even relatively young children can be successfully included in research and their opinions about their health care should be sought before introduction of changes, especially when proposed changes could affect their ability to perform their own treatment. [ABSTRACT FROM AUTHOR]

Introduction Intracranial haemorrhage (ICH) is the most serious bleeding event for patients with inherited bleeding disorders (IBD). The risks and long-term consequences remain unknown. Aim This single-centre service evaluation aimed to identify the incidence, risks and long-term outcomes following ICH in patients with IBD. Methods The IBD database and medical notes between 1987 and 2013 were reviewed. Children without apparent neurological deficit following ICH completed standardized assessments and supplementary information sheets. Results ICH was confirmed in 38/1111 children with IBD. The overall risk of ICH amongst children with IBD was 3.4% (95% CI: 2.5, 4.7%). However, 27/38 had an ICH in the first year of life, 18 of which were in the neonatal period. In children with IBD who had an ICH, the risks of ICH in the neonatal period or first year of life were 18/38 (47%) (95% CI: 32, 63%) and 27/38 (71%) (95% CI: 55, 83%) respectively. Mortality risk from ICH in children with an IBD was 5/38 (13%) (95% CI: 5.8, 27.3 %). Ten of 32 survivors had known neurological sequelae including motor disorder deficits (MDD) while 22 had no documented evidence of neurological impairment or MDD. Re-evaluation was possible in 17/22 children, 8 of whom demonstrated evidence of MDD. After re-evaluation, the risk of significant neurological MDD from ICH increased from 31% CI (95% CI: 18, 49%) to 56% CI (95% CI: 39, 72%). Conclusion Risks and consequences of ICH in IBD were highest within the neonatal period and first year of life. MDD after ICH was not reliably identified in early life and ongoing monitoring in the first decade of life will facilitate educational support or physical rehabilitation. [ABSTRACT FROM AUTHOR]

To explore the life experiences of pain in people with severe haemophilia and understand how such experiences influence beliefs and sensation of pain in adulthood. A qualitative inquiry approach using focus groups and semi-structured individual interviews was used. Participants included people with severe haemophilia living with chronic pain. Data were analysed using reflexive thematic analysis. Fourteen men with a median age of 47 (range 23–73) agreed to take part. Eleven participated in two focus groups and three were interviewed over telephone. Two themes were conceptualised from the data: (i) haemophilia and pain – an evolving life biography (the personal narrative, historical, social, and medical context, continuous adaptation of activity choices, surveillance of pain and its meaning); (ii) "My normal isn't normal" – identity and self-agency (pain as a feature of life and identify with severe haemophilia, loss of enjoyable activities balanced against staying active, barriers to participation). Pain is a constantly evolving, lifetime feature for many adults with haemophilia and it is viewed as part of their identity with their condition. Healthcare professionals working in haemophilia should try to better understand the influence of an individuals lived experience with their haemophilia on beliefs and behaviours of pain. Severe haemophilia is a rare bleeding disorder that results in musculoskeletal joint disease. Adults with severe haemophilia have experienced multiple episodes of bleeding related musculoskeletal pain since childhood. Pain beliefs and behaviours in adulthood appear to be influenced by a lifetime of painful experiences associated with haemophilia. In order to better support people with haemophilia and chronic pain, healthcare professionals in haemophilia need to better understand how an individuals lived experience of pain helps inform their beliefs about it. [ABSTRACT FROM AUTHOR]

To explore the experiences, views and beliefs of people with severe haemophilia and healthcare professionals (HCPs) on approaches for pain management, as well as their views on exercise being used as an aspect of management. Taking a qualitative inquiry approach using focus groups and semi-structured interviews, participants included people with severe haemophilia living with chronic pain and haemophilia HCPs. Data were analysed using reflexive thematic analysis. Fourteen men with haemophilia with a median age of 47 (range 23–73) and six haemophilia HCPs agreed to participate. Of the people with haemophilia, 11 attended two focus groups and three were interviewed over telephone. Healthcare professionals were interviewed face-to-face. Two themes were conceptualised from the data: (i) haemophilia management and pain management is discordant (imbalance between good haemophilia care but poor pain management, historical medico-social influences on pain management, the need for trust); (ii) uncertain about exercise but clear on what matters (conflicting views on exercise, the need for proof of safety, personalised care). Options for effective pain management remain limited and what is used is heavily influenced by beliefs and experience. Exercise as a treatment option in pain management is conceptually acceptable for people with haemophilia. Effective pain management requires understanding of individual beliefs and fears, and a personalised approach supported by knowledgeable, trusted clinicians. Musculoskeletal joint pain and its relationship with bleeding in people with haemophilia continues to be a management challenge. Current pain management strategies are of limited effectiveness with little evidence of an approach that reflects the multi-modal pain experience. Whilst exercise and rehabilitation approaches are conceptually possible for people with severe haemophilia, barriers remain regarding perception of overall safety and effectiveness. People with severe haemophilia may consider exercise as part of a pain management strategy if it is individualised, and they are supported to do it by clinicians who understand them and their haemophilia. [ABSTRACT FROM AUTHOR]

Development of haemophilic arthropathy has long-term implications for functional mobility in people with haemophilia, but early manifestations are often asymptomatic and difficult to identify. Earlier identification of joint damage may improve outcomes. The aim of this case note review was to determine whether the GAITRite® system (electronic pressure sensitive walkway) could identify early changes in gait patterns in boys with haemophilia compared with their peers. Clinic data from medical and physiotherapy notes of boys with severe haemophilia were compared with data from age and leg length-matched controls. Data from two consecutive walks at preferred speed were collected on all participants using the GAITRite® system. Clinic assessment notes from 26 boys (aged 7–17 years) with severe haemophilia were identified. Of these, 20 boys had no evidence of joint pathology on assessment and six boys had radiographic evidence of arthropathy. When these data were compared with normal controls, there were statistically significant increases in swing time, stance time, single support and double support in the asymptomatic group ( P < 0.01) suggesting subtle early compensatory changes in gait pattern. The children with arthropathy had additional significant differences in their gait compared with matched controls. These differences included normalized velocity, step length, stride length, step time and base of support ( P < 0.01). The GAITRite® system appears sensitive enough to identify early subtle changes in gait and differentiate between asymptomatic boys with haemophilia and those with arthropathy in comparison with a matched control group. The electronic walkway is an accessible and portable means of providing quantitative gait analysis in the clinical environment. This is an important finding as early identification of gait changes may provide clinicians with the opportunity to intervene with the aim of arresting progression of joint damage. [ABSTRACT FROM AUTHOR]

Economic and political factors have led to the increased use of home therapy programmes for patients who have traditionally been treated in hospital. Many patients with hereditary angioedema (HAE) experience intermittent severe attacks that affect their quality of life and may be life-threatening. These attacks are treated with C1-inhibitor concentrate which, for most patients, is infused at the local hospital. Home therapy programmes for HAE are currently being established. This paper reviews the extent of use of these programmes and summarizes the advantages and potential disadvantages of the concept so far. [ABSTRACT FROM AUTHOR]

Reliable venous access is essential to facilitate the administration of prophylactic factor concentrate or blood products in children with congenital coagulation disorders and immune tolerance therapy (ITT) regimens in those who develop high responding inhibitors. Poor venous access is even more problematic in very young children, the vast majority of whom will require the insertion of central venous access devices (CVADs). Previous studies have suggested that infection rates are low and that there are few long-term complications associated with CVAD usage. We have reviewed 86 CVADs that have been inserted, since 1988, in 58 children with congenital bleeding disorders, aged 6 d to 16·5 years, attending Great Ormond Street Hospital, London, and the National Children's Hospital, Dublin. The devices have remained in situ for 2 weeks to 92 months (median 22·5 months). Early (0–2 weeks) complications of CVAD insertion included nine bleeding episodes, one extravasation of factor concentrate, three allergic reactions to factor concentrate and five catheter infections. Overall, CVAD infection was the commonest problem encountered, with 52 devices (60%) becoming infected. Twenty-seven CVADs (31%) required removal. Infection rates in children without inhibitors (29/68) were 1/20 patient–months or 1·6 infections/1000 patient–days, but infection rates for those with inhibitors were 1/8·5 patient–months or 4·3/1000 patient–days. Staphylococcus epidermidis was the predominant organism (25/52) isolated. Blockage of CVAD (four) and catheter disconnection (four) were the most frequently occurring non-infectious long-term complications. Skin erosion of the port was also seen in three children, in one child at 20 months, in one at 29 months and in one at 34 months after insertion. This study demonstrates a high CVAD infection rate and highlights the long-term complications of CVAD usage. [ABSTRACT FROM AUTHOR]

Homozygous severe factor V ( FV) deficiency has a prevalence of around one per million. Even in patients with FV levels of <0.01 IU mL−1 there appears to be a variation in bleeding phenotype in that there is a subgroup of affected individuals who present in later childhood and have a relatively mild bleeding phenotype, but there are children who present as neonates with intracerebral bleeding events and who have a much more severe bleeding phenotype. The only available current FV replacement is in the form of fresh frozen plasma ( FFP) or solvent detergent FFP. We present here our experience with surgical haemostatic cover for 13 surgeries in three children with severe FV deficiency. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the use of prothrombin complex concentrate.

Summary: Overweight and obesity may carry a significant disease burden for patients with haemophilia (PWH), who experience reduced mobility due to joint inflammation, muscle dysfunction and haemophilic arthropathy. This review aimed to define the prevalence and clinical impact of overweight/obesity in the global population of PWH. A detailed literature search pertaining to overweight/obesity in haemophilia in the last 15 years (2003–2018) was conducted, followed by a meta‐analysis of epidemiological data. The estimated pooled prevalence of overweight/obesity in European and North American PWH was 31%. Excess weight in PWH is associated with a decreased range in motion of joints, accelerated loss of joint mobility and increase in chronic pain. Additionally, the cumulative disease burden of obesity and haemophilia may impact the requirement for joint surgery, occurrence of perioperative complications and the prevalence of anxiety and depression that associates with chronic illness. Best practice guidelines for obesity prevention and weight management, based on multidisciplinary expert perspectives, are considered for adult and paediatric PWH. Recommendations in the haemophilia context emphasize the importance of patient education and tailoring engagement in physical activity to avoid the risk of traumatic bleeding. [ABSTRACT FROM AUTHOR]

Introduction: Contemporary haemophilia management recommends sport and physical activity in children with haemophilia. Assessment of subjective physical functioning requires standardized and validated instruments. Aims: To adapt and psychometrically test the adult Haemophilia & Exercise Project‐Test‐Questionnaire (HEP‐Test‐Q) for children (aged 6‐17 years). Methods: In discussion rounds with children, single items of the adult HEP‐Test‐Q were reformulated to make them understandable without changing the item concept. The validation of the child‐adapted version in children with haemophilia (n = 228) included pre‐testing with feasibility testing, cognitive interviewing (n = 34), pilot‐testing of the revised version in the EIS Study (n = 67) and field‐testing in the SO‐FIT Study (n = 127). Results: Pre‐testing revealed a completion time of 8.2 ± 4.1 minutes and children liked the instrument. Cognitive interviews demonstrated that most items were easy to understand; 9 items were reformulated. Pilot‐testing demonstrated good psychometric characteristics in terms of reliability (α = .94 Total Score) and validity. Convergent validity testing showed moderate correlations with the Haemo‐QoL (r = −.491), but low correlations with the Petrini Score (r = −.293). Known groups' validity revealed significant differences in clinical subgroups; chronic pain (P < .002) and target joints (P < .021). Field‐testing confirmed psychometric characteristics; Cronbach's alpha ranged from α = .80 ("endurance") to α = .94 (Total Score). The child‐adapted HEP‐Test‐Q showed moderate correlations with the PedHAL (r = .634, P < .0001) and the Haemo‐QoL SF (r = −.575, P < .0001). Known groups' validity testing proved that the HEP‐Test‐Q could discriminate between clinical subgroups. Conclusion: The child‐adapted HEP‐Test‐Q is a short, practical and acceptable instrument for the assessment of subjective physical functioning. Outcomes can be compared to adults because item concepts are identical to the adult version. [ABSTRACT FROM AUTHOR]

Background There is increasing recognition that sport is important for individuals with haemophilia; however, there remains a paucity of data of the importance of this in adults, many of whom already have joint pathology related to childhood bleeds and treatment access. This multicentre, cross-sectional study presents the impact of sport on health-related quality of life ( HRQoL), physical performance and clinical outcomes in adults with haemophilia. Results Fifty adults aged 35.12±14.7 with mild ( n = 12), moderate ( n = 10), or severe ( n = 28) haemophilia A (70%) or B (30%) from four haemophilia centres across the United Kingdom participated in the study. A total of 64% were overweight/obese according to their BMI; median orthopaedic joint scores using the WFH Orthopaedic Joint Score ( OJS) were 6 (range 0-48). On a VAS pain scale (range of 0-10), patients reported mean score of 5.66 ± 2.4. 36% of participants reported not doing any sport, mainly due to their physical condition. However, 64% of participants reported undertaking sporting activity including contact sports, mostly twice per week in average 4 h week−1. Participating in sport did not have a statistically significant impact on HRQoL; except in the domain 'sport and leisure' of the Haem-A-QoL. Patients doing more sport reported significantly better HRQoL than those doing less sport ( P < 0.005). Those doing sport for more than 4 h week−1 had a significantly better physical performance than patients doing less sport (assessed with Hep-Test-Q). Encouraging physical activity and sport in older patients with haemophilia may have a direct impact on their HRQoL; thus, education about sport activity should be incorporated into routine haemophilia care. [ABSTRACT FROM AUTHOR]

Introduction Pain is a major clinical problem in patients with bleeding disorders. This study aimed to determine the level of pain and how it is managed in children and adolescents with bleeding disorders. Methods This cross-sectional study was performed in three haemophilia centres (one in Shiraz and two in London).The data were collected using questions about pain management and Wong-Baker Faces Pain Rating Scale at routine clinical review as well as attendance for bleed treatment in summer 2014. Results This study indicated no difference among the three haemophilia centres regarding having pain, however, a significant difference was found among them concerning the mean score of pain intensity. Among the 154 subjects, 20.8% had pain on the study day, most reporting moderate levels of pain. The study participant's most frequently described their pain as aching, dull, throbbing and stabbing. Moreover, 84.38% of pain was experienced in joints and the most common painful joints were knees, ankles, elbows, hands and hips. The most common pain relief strategies included factor administration, immobilization and rest, ice packs and analgesia. Pain was significantly associated with disease severity and age. Conclusion As the intensity of pain in on-demand patients was highest, using prophylaxis treatment is suggested. Moreover, adolescent patients reported more pain; giving more self-care information to them and their parents is recommended. Since little evidence was published for pain assessment and management in children and adolescents with bleeding disorders, more research is recommended. [ABSTRACT FROM AUTHOR]

Inhibitor development is the most serious and challenging complication in the treatment of severe haemophilia A. Up to 38% of such patients develop inhibitors with current recombinant factor VIII (rFVIII) products produced in hamster cell lines. Human-cl rhFVIII is a new generation fully sulfated B-domain-deleted FVIII coagulant glycoprotein, which is generated from a human cell line. Thus, there are no non-human epitopes which would be potentially immunogenic. This molecule has significantly higher VWF-binding affinity compared with existing full-length rFVIII produced in hamster cell lines. The development aim of Human-cl rhFVIII is to address the challenges of FVIII inhibitors and frequent infusions during prophylaxis. Human-cl rhFVIII's mean half-life is very comparable to some of the newer products which involve modification of the FVIII molecule to extend the circulating half-life. There are promising data concerning the use of a personalized prophylaxis regimen with Human-cl rhFVIII. Preliminary data indicate a median dosing interval of 3.5 days with 66.7% of the patients on a twice per week or fewer infusions schedule combined with a low bleeding rate and no increased FVIII consumption when compared to standard prophylaxis. No product-specific laboratory assay is required to monitor the coagulation activity for Human-cl rhFVIII. The results of registration clinical trials with Human-cl rhFVIII as well as the ongoing studies in previously untreated patients (NuProtect) and personalized prophylaxis study in previously treated patients (NuPreviq), will be discussed. The manufacturer has received marketing authorization for Human-cl rhFVIII in Europe and Canada under the name Nuwiq® and plans to launch it in the USA and globally in 2015. [ABSTRACT FROM AUTHOR]

Link nurses are practising nurses with an expressed interest in a given specialty, with formal links to clinical nurse specialists and other specialist staff. The role involves attending meetings to discuss ideas and new developments, and relaying findings to other ward nurses to improve their practice. Such nurses are common in many specialties such as diabetes and tissue viability. In haemophilia, the role has the potential to enhance the care of haemophilia patients on general hospital wards. In April 2012, a focus group of five haemophilia nurses was convened to discuss their experiences of 'link nurse' programmes within district general hospitals and the potential value of developing the haemophilia link nurse role, and to consider the materials needed to support such role development. It was agreed to test whether other haemophilia nurses perceived such a need by means of a short five-item questionnaire devised by the group and made available to all members of the UK's Haemophilia Nurse's Association via Survey- Monkey. Final responses from 59 haemophilia nurses across the UK have been analysed. Most nurses agreed that there was value in the development of a haemophilia link nurse role within UK hospitals and thought their trusts would support it. While barriers and potential downsides were acknowledged, this was seen as a useful way of sharing information and knowledge with colleagues from different specialties and of raising awareness of bleeding disorders among the general nursing community. Haemophilia nurses should coordinate the development of a Haemophilia Link Nurse training and education pack. [ABSTRACT FROM AUTHOR]

Joint damage from bleeding episodes leads to physical or functional limitations in people with haemophilia. Various factors may influence the frequency and severity of joint damage. This study examined whether age, prophylaxis, history of high-titre inhibitors ( HTI) and bleeding events influenced the Haemophilia Joint Health Score ( HJHS) in children. Medical and physiotherapy notes of boys with severe haemophilia, aged 4-18 years, were reviewed to identify factors associated with increased HJHS. The HJHS of 83 boys (median age: 11) ranged from 0 to 25, with 44/83 (53%) having a score of zero. The median HJHS was 0 (mean 2.6). In the non- HTI group, the HJHS for boys on late prophylaxis was 2.68 times higher than those who started early and the HJHS was on average 10% higher for every additional recent bleed. In this group the odds of having a zero score fell by 30% for every year increase in age. Boys with a history of HTI had higher HJHS scores than the non- HTI group, and age, number of recent bleeds and tolerized status were positively associated with HJHS. The score rose on average by 28% for every year of age and by 76% for non-tolerized boys. This study provides further evidence supporting early prophylaxis use and the importance of immune tolerance therapy. The HJHS is a useful tool for identifying and tracking changes in joint health with respect to therapy or disease progression. With improvements in haemophilia treatment, the disproportionate number of zero scores will continue to make interpretation of the HJHS challenging. [ABSTRACT FROM AUTHOR]

Alloimmune FVIII and FIX inhibitors are the most serious complication of haemophilia in the postviral contamination era and their optimal management remains controversial. We present 15 boys with severe haemophilia (14 with haemophilia A and 1 with haemophilia B) who have received immune tolerance at our centre over a 9-year period. Twelve of them (80%) were successfully tolerized with varying dose intensities, but three of them (including the boy with haemophilia B) failed tolerization. The factors, which were associated with successful tolerance in our group, were a low maximum inhibitor titre and a short interval between diagnosis of the inhibitor and the start of immune tolerance. The time taken to achieve immune tolerance varied from 1 to 27 months and none of the inhibitors have recurred. Two of the three boys who failed immune tolerance had had their inhibitor for 72 and 69 months, respectively before tolerance was attempted. [ABSTRACT FROM AUTHOR]

A multicentre, international, cross-sectional study was carried out in the frame of field testing of the first haemophilia-specific quality-of-life (QoL) questionnaire (Haemo-QoL). The aim of this paper is to describe health status and health care and their impact on QoL in haemophilic children in Western Europe. Children aged 4–16 years with severe haemophilia without inhibitors were enrolled by 20 centres in France, Germany, Italy, the Netherlands, Spain and the United Kingdom. Clinical information was collected by the physicians with a medical documentation form. Health-related QoL (HRQoL) of children was assessed with Haemo-QoL, available for three age groups. Clinical data were available in 318 patients, 85.5% with haemophilia A. The mean age at first bleeding was 11 months, at first joint bleed 25 months. Functional joint impairments were found in 11.3%. Prophylaxis treatment was given to 66.7% of children in whom breakthrough bleeds occurred 0.4 times a month compared to 1.1 bleeds in children receiving on-demand treatment. A significantly higher factor consumption was found only in the two younger age groups of prophylaxis patients compared to on-demand patients. HRQoL was satisfactory in this cohort: young children were impaired mainly in the dimension ‘family’ and ‘treatment’, whereas older children had higher impairments in the so-called ‘social’ dimensions, such as ‘perceived support’ and ‘friends’. Health care of children in Western Europe is progressively improving with a large diffusion of home treatment and prophylaxis. This provides a high level of health status and HRQoL, being better in haemophilic adolescents on prophylaxis. [ABSTRACT FROM AUTHOR]

Summary The PFA-100® is a device that simulates high shear dependent platelet function in vitro and thus is particularly useful for screening for von Willebrand's disease (VWD). The aim of this study was to assess the overall potential of the PFA-100® as a primary clinical screening tool using the wide spectrum of clinical samples assessed for platelet function within our institution. The PFA-100® test was performed using both collagen/ADP (CADP) and collagen/epinephrine (CEPI) cartridges on samples from 337 patients with a wide variety of haemostatic defects. One hundred and eighty-two patients were defined as having normal platelet function based on classical laboratory tests and von Willebrand factor levels. The overall clinical sensitivity of the PFA-100® for platelet abnormalities (including VWD) was 81% for CADP and 86% for CEPI. The overall specificity was found to be 82% for CADP and 80% for CEPI. When utilizing both cartridges in combination (with both results either higher or lower than the upper cutoff of the normal ranges), the overall false positive and false negative rates were 12% and 6%, respectively. The PFA-100® proved to be sensitive in detecting classical defects by giving prolonged closure times in samples from patients with major platelet function defects (e.g. von Willebrand's disease, Glanzmann's thrombasthenia and Bernard Soulier syndrome). However, there were a small number of false negative results (6%) obtained with various milder platelet defects (e.g. Hermansky Pudlak syndrome, storage pool and release defects, type I VWD and macrothrombocytopenia). The PFA-100® test provides a useful rapid screening tool and should increase the efficiency and reduce the cost of the routine diagnosis of platelet dysfunction. [ABSTRACT FROM AUTHOR]

Summary. In a multinational working group, an instrument (Haemo-QoL) to assess quality of life in children/adolescents with haemophilia and their parents has been developed. In co-operation with haemophilia treatment centres in six European countries, approximately 10 children/adolescents with haemophilia per country and their parents were asked to participate in the pilot-testing. Both self-reported and parent-reported questionnaires were provided for two age-groups of children (4–16 years). Medical data was collected from physicians from patient files. Answers to open questions from participants (58 children and 57 parents) confirmed the content of 116 of the preliminary items. Cognitive debriefing revealed that the majority of the Haemo-QoL was rated favourably, but 29 questions were recommended to be omitted and several items to be reformulated. Preliminary psychometric testing of the revised 77 item questionnaire in the same sample showed acceptable reliability and validity, which will be examined in a subsequent study with a larger patient sample. [ABSTRACT FROM AUTHOR]