The UK Haemophilia Doctors Organisation triennial audit of UK Comprehensive Care Haemophilia Centres

Under the auspices of the United Kingdom Haemophilia Doctors Organisation (UKHCDO) the UK Comprehensive Care Haemophilia Centres (CCCs) have undergone a three yearly formal audit assessment since 1993. This report describes the evolution of the audit process and details the findings of the most recent audit round, the sixth since inception. The audit reports from the 2009 audit round were reviewed by the audit organizing group and a structured analysis of the data was compiled. CCCs in the UK offer a high standard of comprehensive care services. The main areas of concern were the state of the premises (seven centres), lack of dental services (seven centres), physiotherapy (seven centres) and social work support (11 centres). Major concerns were identified at eight centres requiring a formal letter from the chairman of UKHCDO to the chief executive of the host trust. Since inception of the triennial audit process centre report recommendations have resulted in major improvements in the services available at UK CCCs. The audit process is considered to be a highly effective means of improving the quality of care for patients with bleeding disorders and can be used as a model for the introduction of a similar process in other countries.     

Haemophilia Care in Europe: the ESCHQoL study

The aim of this study was to determine the clinical conditions of patients with haemophilia within Europe as recommended by the European Commission. In this multicentre, cross‐sectional, ambispective study, conducted within 21 European countries patients' clinical data were collected, amongst others haemophilia type, severity, treatment pattern, use of factor products, bleeding, orthopaedic joint scores and infections. A total of 1400 patients, 84.3% with haemophilia A and 15.7% with haemophilia B were enrolled by 42 centres between 2004 and 2006. Thereof, 417 were children (30.0%) and 983 were adults (70.0%). About 70% of patients had severe factor deficiency (<1%). More than half of the adults were carriers of chronic infections (12.6% HIV, 55.8% HCV), compared to only 3.8% children (no HIV, 2.9% HCV). Patients were grouped according to per capita amount of clotting factor used in patients' region of residence in 2005: region 1: >5 IU; region 2: 2–5 IU; region 3: <2 IU. Paediatric and adult patients in region 3 had median numbers of three and eight joint bleeds, respectively, with worse joint scores compared to region 1 with zero and one bleed. Prophylactic therapy was used in only 31.3% children and 8.9% adults with severe haemophilia in region 3 compared to 93.7% and 54.1%, respectively, in region 1. Statistical analysis revealed that residence in areas with low factor consumption/availability is the most prominent risk factor for joint disease. Access of European patients with haemophilia to optimal care with safe factor VIII concentrates is limited and depends on the region of residence.     

European principles of haemophilia care

Summary.  As the management of haemophilia is complex, it is essential that those with the disorder should have ready access to a range of services provided by a multidisciplinary team of specialists. This document sets out the principles of comprehensive haemophilia care in Europe. Within each country there should be a national organization which oversees the provision of specialist Comprehensive Care Centres that provide the entire spectrum of clinical and laboratory services. Depending upon the size and geographical distribution of the population, a network of smaller haemophilia centres may also be necessary. There should be arrangements for the supply of safe clotting factor concentrates which can also be used in home treatment and prophylaxis programmes. A national register of patients is recommended along with collection of treatment statistics. As comprehensive haemophilia care is multidisciplinary by nature, the need for education and research programmes for all staff members is emphasized: Members of the Interdisciplinary Working Group not represented in the list of authors are mentioned in Section 4 of this document.     

Haemophilia Experiences,Results and Opportunities (HERO) study: treatment‐related characteristics of the population

The HERO (Haemophilia Experiences, Results and Opportunities) quantitative surveys collected information on characteristics and perceptions of adult persons with haemophilia (PWH) and parents of children with haemophilia. The aim of this article is to describe the perceptions of PWH and parents on psychosocial aspects related to treatment. Two online surveys (one for PWH, one for parents) were conducted in 10 countries. Among 675 PWH respondents, 77% reported having responsibility for their own care; 72% of 561 parent respondents had the main responsibility for their son. PWH were most commonly treated on demand (45% of 648 adults using factor concentrate), with 32% on regular prophylaxis and 23% treated on demand with short‐term prophylaxis (e.g. for sports/physiotherapy). Children were most often treated with prophylaxis (65% of 549 children using factor concentrate), with 26% treated on demand and 8% treated on demand with short‐term prophylaxis. Factor was generally used as instructed at home. Some respondents (41% PWH; 30% parents) had difficulties/concerns with factor availability/affordability. PWH reported more bleeds in the last 12 months than parents reporting their son's bleeds (mean 17.8 vs. 8.7). Both PWH and parents generally perceived that overall, their (their son's) haemophilia was well controlled. Results differed by country. The HERO study captured new, patient‐based data regarding many facets of life relevant to PWH, including treatment. The information conveyed in this article largely represents new insights regarding perceptions of treatment and provides initial benchmark statistics for further research.     

Haemophilia care in Europe: a survey of 19 countries

Summary. In 2009, a questionnaire was circulated to 19 national haemophilia patient organizations in Europe affiliated to the European Haemophilia Consortium (EHC) and the World Federation of Hemophilia (WFH) to seek information about the organization of haemophilia care and treatment available at a national level. The responses received highlighted differences in the level of care despite the recent promulgation of consensus guidelines designed to standardize the care of haemophilia throughout the continent of Europe. There was a wide range in factor VIII consumption with usage ranging from 0.38 IU per capita in Romania to 8.7 IU per capita in Sweden (median: 3.6 IU per capita). Despite the specific inclusion of coagulation factor concentrate in the WHO list of essential medications, cryoprecipitate is still used in some eastern European countries.     

Haemophilia in the developing world: the Brazilian experience

The success of haemophilia treatment is based on well-established criteria, and the use of clotting factor concentrates is fundamental. These strategies are seen in the developed world when measures of quality of life are studied or when disabilities are evaluated among haemophilic patients. At the same time, countries in the developing world, with almost 80% of the haemophilia population, are making tremendous efforts to change their diagnosis and treatment methods, in order to improve their healthcare and therefore be able to promote better life for haemophiliacs. However, these goals are threatened when there are many social needs and few economic resources. There is wide variation in conditions in these countries, depending on what has already been done, how many patients the country has, how the blood banking services are planned and obviously, what are the interested parties. Even with so many difficulties, there are ways to work towards and reach the most important goal, which is to prepare the haemophiliacs to be citizens that are as productive and capable of working as are the nonhaemophiliacs. Each country has to take its part; the commitment of the community, physicians and government will be needed to design a model that is compatible with all the necessities and possibilities, and is understood by all the persons involved.     

A survey of adherence to haemophilia therapy in six European countries: results and recommendations

Summary. Very few studies have addressed the question of adherence of haemophiliacs to their treatment. The aim of our study was to compare their levels of adherence to therapy and also to provide recommendations. Professionals of an international research company performed individual interviews with 30 patients in each of six European countries (France, Germany, Italy, Spain, Sweden and UK) resulting in a total of 180 patients. Twenty‐eight interviews with haemophilia physicians and specialist nurses were also undertaken. Overall adherence to treatment was high (80–87% in each country). There was a positive correlation between greater adherence and younger age, prophylactic treatment, time spent with a haemophilia treatment centre (HTC) and the quality of the relationship with the haematologist and nurse. The four leading reasons for not using the prescribed amount of clotting factor or skipping the administration interval were reduction, fluctuation or disappearance of symptoms, forgetfulness, lack of time for treatment and convenience. These reasons differed according to the country and the age of the patient. The main suggestions made by patients to improve adherence related to HTC, environment and factor concentrates. Patients considered also that internet and electronic patient diaries were likely to improve adherence. In this selected group of European haemophilia patients, adherence to treatment appears higher than for most patients with other chronic diseases. However, it remains important to be aware of the possibility of non‐adherence given the serious implications, particularly when considering a differently selected group of patients.     

Prophylactic treatment of haemophilia patients with inhibitors: clinical experience with recombinant factor VIIa in European Haemophilia Centres

Many patients with haemophilia develop inhibitors to factor VIII and require bypassing agents to provide haemostatic cover for limb- or life-threatening bleeding episodes. Due to the reduced risk of blood-borne pathogen transmission with recombinant products, on-demand recombinant factor VIIa (rFVIIa; NovoSeven is the treatment of choice for children with inhibitors. In haemophiliac patients without inhibitors, primary prophylaxis has been clinical practice for several years. This paper summarises 13 case histories of rFVIIa secondary prophylaxis for haemophilia patients with inhibitors. This was a retrospective survey of adult and paediatric severe haemophilia patients with inhibitors treated with rFVIIa from ten European Haemophilia Centres. There was a wide variation in administered rFVIIa dose, from 200-250 microg kg(-1) per week to 220 microg kg(-1) daily. In many cases, this was lower than the recommended on-demand dose of rFVIIa. In 12/13 cases, prophylaxis with rFVIIa considerably reduced the number of bleeding episodes compared with previous treatment. Eight/nine patients were satisfied or very satisfied with rFVIIa treatment, and in cases reporting subjective quality of life (QoL), all were improved, much improved, or significantly improved. In haemophilia patients with inhibitors, prophylaxis with rFVIIa is highly effective in reducing the number of bleeding episodes and results in good patient compliance and improved QoL. Randomised controlled trials are needed to confirm these findings. Results of a recently completed clinical trial on secondary prophylaxis with rFVIIa in frequently bleeding haemophilia patients with inhibitors are expected in late 2006.     

The WFH Haemophilia Centre Twinning Programme: 10 years of growth, 1993–2003

The World Federation of Haemophilia (WFH) Twinning Programme celebrates its tenth anniversary this year. Twinning is one of several international WFH programmes designed to improve haemophilia care at a global level. There are two types of twinning, and the haemophilia treatment centre twinning programme should be distinguished from the WFH haemophilia organization twinning involving national member organizations. The WFH Haemophilia Treatment Centre Twinning Programme helps emerging haemophilia treatment centres develop partnerships with well-established and experienced centres. Twinning can improve diagnosis and clinical care through coaching, training and transfer of expertise, ultimately leading to improved quality of life for patients. Twinning can also enhance the profile and recognition of treatment centres in emerging countries, which can be valuable in raising awareness among politicians and the media. Examples of activities include consultation on the management of specific cases, clinical and laboratory training, donation of equipment and publications as well as research projects. The centre twinning programme also benefits centres in developed countries by giving them the opportunity to gain exposure to clinical problems no longer encountered in their own countries, as well as experience of new cultures. Currently, a total of 23 treatment centres around the world are linked through the twinning programme and applications for new partnerships are welcome. Twinning links are not permanent, but are reviewed on an annual basis and typically remain in place for periods of 3-5 years. Limited financial support from WFH is available to twinned centres in the form of money for an initial assessment visit, as well as regular annual grants to established partners and the possibility of applying for additional funding to support specific projects. In addition, continuing support and advice are available from the WFH regional programme officers.     

Principles of haemophilia care: The Asia‐Pacific perspective

Optimal haemophilia care is best established and implemented through a well‐coordinated plan guided by clearly defined principles and priorities. A document which enunciates those details is therefore important. A successful example of this approach is the definition of principles of haemophilia care (PHC) outlined by the European Association for Haemophilia and Associated Disorders (EAHAD) and also the World Federation of Hemophilia. A similar document applicable to the Asia‐Pacific region must take into account not only the highly varied healthcare systems but also the tremendous socio‐economic and cultural diversities which impact provision of such care. The Asia‐Pacific Haemophilia Working Group (APHWG), representing the countries in this region, has prepared this perspective of the PHC. While endorsing the overall framework outlined by EAHAD, this APHWG document emphasizes regional priorities on education and training of healthcare personnel in the diagnosis and management of hereditary bleeding disorders. Central coordinating agencies with wide stakeholder input, networks of haemophilia treatment centres and national registries as well as robust processes for procurement and distribution of safe and effective clotting factor concentrates (CFCs), implementation of prophylaxis programmes and management of patients with inhibitors should also be developed. The implementation of these strategies should lead to establishment of good comprehensive care programmes. This document should also be an advocacy tool to lobby for improved care for people with haemophilia (PWH) in the region. We urge national healthcare policy makers to consider these principles and initiate strong and decisive action to reach these goals.     

Inherited bleeding disorders: results from the Italian Regional Haemophilia Centre of Pescara

Backgorund

Inherited bleeding disorders registries can be useful to improve health care of these rare disorders and document their natural history.

Material and methods

We analysed the epidemiological, diagnostic and therapeutic aspects of patients managed at an Italian Regional Haemophilia Centre, based in Pescara (in the Region of Abruzzo).

Results

This Regional Haemophilia Centre currently follows 376 patients: 248 with rare clotting factor defects, 33 with von Willebrand’s disease, 75 with haemophilia A and 20 with haemophilia B. Three patients with severe haemophilia A have developed inhibitors. Among all the haemophiliacs, the prevalence of hepatitis C virus infection is 21% while the prevalence of human immunodeficiency virus infection is 5.3%. Among the whole haemophilic population referring to the Pescara Haemophilia Centre, 87.4% are treated with recombinant factors while 12 patients with severe haemophilia are receiving primary prophylaxis.

Conclusion

In brief, an analysis of the epidemiological, clinical and therapeutic data collected at the Regional Haemophilia Centre of Pescara is a useful tool for monitoring and continuously improving the quality of care of patients with inherited bleeding disorders.     

VERITAS‐Pro: a new measure of adherence to prophylactic regimens in haemophilia

Summary. Prophylactic treatment is recommended for severe haemophilia. Non‐adherence to a prophylactic regimen can limit treatment effectiveness and compromise outcomes. The aim of this study is to validate a new prophylactic treatment adherence scale entitled Validated Hemophilia Regimen Treatment Adherence Scale – Prophylaxis (VERITAS‐Pro), a self‐/parent‐report questionnaire consisting of 24 questions on six (four‐item) subscales (Time, Dose, Plan, Remember, Skip, Communicate) that takes approximately 10 min to complete and is currently available in English only. Participants were recruited to complete the VERITAS‐Pro for validation and reliability analysis; and observers were recruited for inter‐rater reliability analysis. Validation measures included subjective adherence ratings from participants and providers and the total number of recommended infusions administered as obtained from infusion logs. Data were evaluated for the entire sample and for parent‐report and self‐report subsamples. The study sample included 67 males, 53 (79.1%) diagnosed with severe FVIII deficiency. Internal consistency for the total VERITAS‐Pro score and all subscales was good to excellent; test‐retest reliability correlations were very strong. Validation measures were strongly correlated with VERITAS‐Pro scores. The VERITAS‐Pro is a reliable and valid measure of adherence to prophylactic treatment of haemophilia. The VERITAS‐Pro has greater utility than a global or informal rating of adherence because it represents a quantified and validated measure of adherence from the patient’s perspective and it divides adherence into specific areas, allowing insight into particular issues underlying non‐adherence. This tool may increase sensitivity to adherence problems and allow more targeted interventions to enhance adherence.     

Acquired Haemophilia A in four north European countries: survey of 181 patients

Acquired haemophilia A (AHA) is a rare bleeding disorder caused by acquired antibodies against coagulation factor VIII. In the Nordic countries, treatment and outcomes have not been studied in recent times. To collect retrospective data on patients diagnosed with AHA in the Nordic countries between 2006 and 2018 and compare demographic data and clinical outcomes with previously published reports, data were collected by six haemophilia centres: three Swedish, one Finnish, one Danish and one Estonian. The study included 181 patients. Median age at diagnosis was 76 (range 5–99) years, with even gender distribution. Type and severity of bleeding was comparable to that in the large European Acquired Haemophilia Registry study (EACH2). Bleedings were primarily treated with activated prothrombin complex concentrate (aPCC) with a high success rate (91%). For immunosuppressive therapy, corticosteroid monotherapy was used most frequently and this may be the cause of the overall lower clinical remission rate compared to the EACH2 study (57% vs. 72%). Survey data on 181 patients collected from four north European countries showed similar demographic and clinical features as in previous studies on AHA. aPCC was used more frequently than in the EACH2 study and the overall remission rate was lower.     

The evolution of comprehensive haemophilia care in the United States: perspectives from the frontline

The establishment of dedicated comprehensive treatment centres more than a half century ago transformed the management of haemophilia in the United States. Formerly, a disease associated with crippling disability and premature death, today, persons with haemophilia who are treated appropriately from infancy and do not develop inhibitors can expect a normal life expectancy and relatively few bleeding episodes. The evolution of the comprehensive haemophilia care, while chastened by the viral epidemics of the 1980s, has been marked by ongoing advances, including prophylaxis, immune tolerance induction, new drugs and gene therapy research. Current challenges include sustaining the comprehensive care model despite decreased funding and expanding the delivery and affordability of comprehensive haemophilia care.     

Joint outcomes in patients with haemophilia: the importance of adherence to preventive regimens

Summary.  In patients with severe haemophilia, spontaneous bleeding into joints initiates a sequence of events culminating in disabling arthropathy. Early evidence from Sweden suggested that clotting factor prophylaxis improved patient outcomes. Recent randomized, controlled trials comparing prophylaxis with on-demand treatment have definitively shown that prophylaxis reduces bleeding and improves joint outcomes in patients with severe haemophilia A. Available evidence also supports the effectiveness of prophylaxis in patients with haemophilia B. In the United States, fewer than half of all patients with severe haemophilia A or B are treated with prophylaxis, and in those receiving such treatment, adherence to prophylactic treatment regimens is low in many age groups. Barriers to prophylaxis include cost, difficulties associated with venous access and the time required for prophylactic infusions. Although concerns around adherence play an important role in the willingness of physicians to prescribe prophylaxis, individualized prophylactic regimens may help increase patient adherence. Clotting factors that are more convenient and less time-consuming to infuse also may improve adherence to prophylactic therapy. By promoting rigorous adherence to prophylactic clotting factor therapies, physicians may be able to help preserve joint function in patients with severe haemophilia.     

Haemophilia care in the developing world: benchmarking for excellence

Seventy-five percent of patients with haemophilia receive no or inadequate treatment, and often do not survive to adulthood. With efficient organization, the disorder is treatable and becomes part of normal life. In developing countries there is a large discrepancy in haemophilia care. Some have zero treatment levels, while others already have comprehensive care centres. This paper attempts to assess and standardize the levels of haemophilia care for developing countries, setting up benchmarks or guidelines for future development. Four major areas are emphasized: clinical care, laboratory, blood products and patient organization. For each country or community, development work begins after the assessment of competency level in each area. The next step is then to plan, organize, improve and move up to the next level. To become successful, a sound and realistic strategy should be employed, starting from the identification of key leaders and the recruitment of an expert team. To obtain recognition and support from health authorities, the haemophilia care programme should not limit itself to haemophilia care but should also include medical care for all bleeding disorders, including the improvement of blood banks, blood products, coagulation laboratories and other medical facilities. This would directly improve the overall medical care standard of the whole hospital. It is also important to emphasize the need for selfreliance, employing simple yet effective methodology, equipment and mechanical facilities. The effective coordination of World Federation of Hemophilia assistance and the host country's committed action will ensure success in the emerging trend of better haemophilia care in developing countries.