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Summary. This paper reports a systematic review of the cost-effectiveness of treatment options in patients with haemophilia A with inhibitors. As very little relevant published evidence was identified, an economic modelling exercise was undertaken to calculate the cost-effectiveness of different strategies in the treatment of high-responding haemophilia A patients with inhibitors. A decision analysis approach was used to model the expected lifetime clinical outcomes and costs of the more common regimens currently used in UK in treating severe haemophiliacs with inhibitors. The model attempts to reflect the outcomes of clinical events, costs and life expectancy for each different treatment regimen for haemophilic boys with inhibitors who are high responders (defined as inhibitor level ≥10 BU) throughout their life. The basic model structure is centred on a Markov decision process, which was used to simulate, at quarter-yearly intervals, the movement through discrete health states and their complications. The model allows a comparison of cost-effectiveness between three immune tolerance induction (ITI) regimens (Bonn, Mälmo and Low-Dose protocols) and against a relevant ‘on-demand’ (OD) regimen. It also shows the cost-effectiveness of different OD regimens using different bypassing agents. The results of the economic modelling indicate that treating haemophilia A patients who have high-responding inhibitors OD with recombinant activated factor VII is cost-effective compared to treatment with activated prothrombin complex concentrates. However, when OD treatment regimens are compared with the three ITI protocols, the Malmö ITI protocol is the preferred treatment strategy, generating more quality adjusted life-years (QALYs) and less cost than either an OD regimen or the Bonn or Low-Dose ITI protocols. [ABSTRACT FROM AUTHOR]

Summary. This paper reports a systematic review of the best available evidence of clinical effectiveness in the treatment of acute bleeding in haemophilia A patients with inhibitors. Because of the lack of randomized controlled trials (RCTs) on this topic, broad inclusion criteria with regard to study design were applied in order to assess the best available evidence for each intervention. Because of the clinical and methodological heterogeneity of the evidence, it was not appropriate to pool data across studies; instead, data were synthesized using tabulation and qualitative narrative assessment. No evidence was found to support the use of high-dose factor VIII (FVIII) in bleeding episodes. However in surgery it was found to be highly successful (100%) for low-titre, low-responding inhibitors although not reliable for high-responding inhibitors. Porcine FVIII (pFVIII) was effective in the control of severe bleeding episodes with high-titre or high-responding inhibitors (100%) and in 60–90% of surgical procedures. Activated prothrombin complex concentrates (APCCs) appear to be more effective than prothrombin complex concentrates (PCCs) in the control of mild to severe bleeding episodes. There was no good evidence for the use of PCCs in surgery. APCCs controlled bleeding in approximately 90% of surgical episodes. Recombinant factor VIIa (rFVIIa) controlled 70–100% of mild to severe bleeding episodes with high-responding inhibitors, and achieved better results when used early. It was effective in 60–100% of surgical episodes. Doses varied from study to study, and side-effects from mild to infrequent but serious adverse events were reported. The quality of the evidence is variable. Limited evidence relating to other treatment options is also included in the review. [ABSTRACT FROM AUTHOR]

Summary. Medical imaging of haemophilic joints is important for detecting abnormalities, grading their severity and selecting the appropriate therapy. The plain-film scoring systems for staging joint disease that were developed prior to the availability of magnetic resonance imaging (MRI) are inadequate for planning modern prevention and treatment. MRI is capable of delineating all of the soft tissue findings long before they are evident on plain radiographs. In this paper, an MRI scoring system is presented along with examples of joint effusion, haemarthrosis, synovial hypertrophy, haemosiderin deposition, erosions, cysts and cartilage loss. MRI is a powerful tool in the diagnosis, staging and treatment of patients with haemophilic joint disease. [ABSTRACT FROM AUTHOR]

Summary. Pain is an important consequence of bleeding episodes in haemophilia. Previous research has included pain frequency and severity among measures of illness-related disability and quality of life in haemophilia, but little systematic evidence exists about analgesic use and pain coping in haemophilia. This paper reports cross-sectional findings from a national survey of patients with severe haemophilia type A and type B. Respondents provided information about pain frequency, pain coping strategies (using the haemophilia-adapted CSQ), use of analgesics and other drugs, and described any concerns they had about their drug use. Participants registered with comprehensive care haemophilia centres did not differ from the rest of the sample on any of the factors recorded. Over one-third of participants expressed concerns about their drug use, the most frequent of which were about dependence on prescribed analgesics. Pain frequency was the most important predictor of analgesic use, but pain coping, and specifically negative thoughts about pain, was associated with concerns about drug use independently of other factors, including analgesic use and pain frequency. Further research will be needed to evaluate possible interventions to promote more effective pain coping in haemophilia, and to examine the possible effects of pain coping on illness outcomes beyond analgesic use, such as well-being and quality of life. [ABSTRACT FROM AUTHOR]

Summary. Haemophilia was recognized early on as an ideal candidate for a gene transfer approach to therapy. In the past decade, gene transfer experimentation in the haemophilias has indeed played an integral role in furthering the science in the global field of gene therapy. However, these expectations have placed haemophilia gene transfer researchers under pressure to succeed in a scientific domain in which successes are infrequent and progress is necessarily slow. These same expectations have also fuelled the perception of gene therapy as the inevitable therapeutic goal for the youngest children with haemophilia. In this paper, we will discuss the ethical implications of this perception in light of anticipated benefits, acceptable risk, perceived consumer need and the unknown cost of this intervention. A framework for the future study and therapeutic implementation of gene transfer technology in this specific population is proposed. Public debate on this issue that includes the voices of the intended beneficiaries, especially the parents of the youngest children with haemophilia and the children themselves, is encouraged. [ABSTRACT FROM AUTHOR]

Presents abstracts of research papers on musculoskeletal issues pertinent to hemophilia. Hemophilic pseudotumor; Total knee replacement in hemophiliacs; Physiotherapy and hemophilia; Orthopedic surgery of hemophilia in the 20th century.

Presents abstracts of research papers on the use of physiotherapy in managing hemophilia. Orthoses and reduction of gait in hemophilia; Evaluation of outcome of care in patients with hemophilia; Overview of rehabilitation in less economically developed countries.

Presents abstracts of research papers focused on psychological and social issues pertinent to hemophilia. Coping with pain; Treatment strategies for adolescents with hemophilia; Sexuality and hemophilia; Enhancement of sexual communication; Management of stress before it causes bleeding.

Presents abstracts of research papers on FVIII inhibitors. Diagnostic and therapeutic dilemmas involving inhibitors; Orthopedic surgery in hemophilia patients with inhibitors; Pathophysiology of inhibitors to FVIII in patients with hemophilia A; Genetic basis of inhibitor formation; Target episodes for FVIII inhibitors.

Presents abstracts of research papers on treatment modalities for hemophilia. Circumcision in neonates with hemophiliacs; Overview of electrotherapy; Helicobacter pylori infection and gastrointestinal hemorrhage in patients with congenital bleeding disorders.

Presents abstracts of research papers on nursing issues focused on hemophilia. Cultural awareness for nurses involved in hemophilia care; Home treatment health education programs by nursing staff for parents of children with bleeding disorders.

Presents abstracts of research papers concerning education and career development among hemophiliacs. Obesity among hemophiliacs; Pediatric care of the child with hemophilia; Risk and advantages of career development among hemophiliacs; Career advice for people with hemophilia.

Haemophilia is a potentially disabling condition associated with high financial costs, and so the need for robust measures to evaluate outcome of care is essential. This paper is a review of some of the outcome measures commonly used to evaluate treatment in haemophilia and includes quality of life measures, evaluation of the musculoskeletal system and orthopaedic surgical procedures. Quality-of-life questionnaires are discussed with particular reference to the SF36 and AIMS2. Results of published studies to date have demonstrated variable results. Overall, haemophilia appears to reduce quality of life compared to normal population figures. Several factors are perceived to reduce quality of life, and these include being human immunodeficiency virus (HIV) positive, having impairments, and a history of orthopaedic surgery. The evaluation of the musculo-skeletal system is important in order to detect any deterioration over time. Various standardized measurement tools are described. Orthopaedic surgical procedures have also been evaluated in patients with haemophilia. To date, the Hospital for Special Surgery Knee rating scale has been the most commonly used to evaluate the outcome of total knee replacement. The limitations of this system for patients with haemophilia are outlined. Overall, these measures provide useful tools for evaluating outcome, but none have been specifically developed for patients with haemophilia. Further studies would be useful to evaluate these tools and others in more depth. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this paper is to put some of the ethical considerations concerning the genetic aspects of haemophilia not only in the national, but also in the international context, especially from the point of view of human rights. Particular attention is given to the issues pertaining to consent from children, and the respect for their autonomy within family relationships. This will be analysed within the context of genetic screening and testing, as well as codes of practice and guidelines. The specific issues around prenatal diagnosis in general and preimplantation genetic diagnosis (PGD) are also discussed. [ABSTRACT FROM AUTHOR]

Electrotherapy has an established role in the management of a wide range of musculoskeletal and neurological problems. Used in conjunction with other therapeutic interventions, it can make a positive contribution to patient care. The means by which a range of different exogenous energy forms can influence the physiological state of the tissue is well documented. Different therapeutic modalities achieve their effects in different tissues, and the clinical decision-making process should employ the available evidence in order to maximize the potential benefit for each patient. The applied energy essentially acts as a trigger that is responsible for stimulating, enhancing or activating particular physiological events, which in turn are utilized to achieve therapeutic benefit. There appear to be windows of opportunity related to the magnitude of the applied energy, the amplitude of the stimulus and the frequency of application. Tissues appear to vary in their responsiveness to these factors, and thus an appropriate modality applied in an inappropriate manner will fail to achieve the anticipated effect. This paper aims to review the current concepts of electrotherapy intervention, taking into account various theories which support the principles. Application of various energies in this way can result in significant benefit for the patient. [ABSTRACT FROM AUTHOR]

The impact of having a child with an inherited bleeding disorder such as haemophilia can have a far-reaching effect on the individual as well as other close family members. This situation is further complicated in the case of human immunodeficiency (HIV) serodiscordant couples, where the haemophilic man is affected with HIV through infected blood products whilst his partner is seronegative and wanting to have children. It is essential that information on the effects of haemophilia, its inheritance, the possibilities of antenatal diagnosis, the consideration of selective abortion and the new reproductive opportunities available to these couples are made accessible so that an informed decision about proceeding with having a family can be made. Couples may wish to have a family through nonreproductive methods such as fostering or adoption. Alternatively, they may wish to remain childless. In this paper, the terms 'having children' and 'having a family' will refer to conception through biological reproduction. Pre-implantation genetic diagnosis (PGD) offers families at risk of having a child with certain inherited genetic disorders the opportunity to give birth to an unaffected child. It may be considered as an option for couples who would not wish to have prenatal diagnosis leading to possible termination of a pregnancy. Assisted conception techniques, such as 'sperm washing' or the use of 'donor sperm', offer serodiscordant couples affected by HIV a riskreduced or risk-free opportunity, respectively, to have a child without infecting the mother, who could in turn infect the fetus by vertical transmission. This article, in addition to outlining the inheritance of haemophilia and the more common prenatal screening and diagnostic tests, discusses in more detail the latest reproductive opportunities available for families affected by haemophilia and considering having a family. [ABSTRACT FROM AUTHOR]

The good quality of life now anticipated by individuals with haemophilia A and B can be drastically altered by the unpredictable development of an inhibitor, a polyclonal high-affinity IgG antibody directed against factor VIII or IX. This paper discusses our current state of knowledge about inhibitors within the context of: (1) the extent and nature of the problem, including its incidence and prevalence, diagnostic options, and the characteristics of the individual immunologic response; (2) possible underlying aetiological factors, both inherited and situational; and (3) existing and future therapeutic options for both the interim treatment of haemorrhage and the ultimate restoration of normal clotting factor recovery and survival. Current and future strategies for immune tolerisation are also reviewed. [ABSTRACT FROM AUTHOR]

Haemophilia is a chronic disease, affecting patients and their families. The impact of such a disease upon each family is dependent upon family type and characteristics and adjustment to it varies with time, in concordance with the family's lifecycle. In the National Hemophilia Center in Israel we lead a special support system and conduct group therapy from the very early stage of haemophilia diagnosis throughout the lifetime of patients. The general definitions of a family's lifecycle, the effect of the disease and the required adjustment to it are described in this paper. We refer to special difficulties associated with haemophilia as a chronic, genetic disease and describe ways to cope, discussing the support systems that have been established in our centre. [ABSTRACT FROM AUTHOR]

A broad overview of sexuality issues and needs as they relate to haemophilia are presented. Venturing well beyond 'safer sex', sexuality is defined here to encompass physical, emotional, social, interpersonal, moral, and cultural aspects. From this perspective, sexuality extends beyond behaviour and includes a person's thoughts, feelings, nature, and identity. As a means of experiencing intimacy, sexuality is a significant factor in achieving quality of life with chronic illness. Its impact in haemophilia is influenced by different stages of physical and psychosexual development, misconceptions about sexuality, and unique concerns for this group, including joint disability, human immunodeficiency virus, medication side-effects, and other complications. This paper explores the interconnections of sexuality with haemophilia, with a focus on the roles that haemophilia care providers can play in addressing these issues. A biopsychosocial model of aspects and interrelationships regarding sexuality and haemophilia is proposed for use in understanding individuals and planning care approaches. The PLISSIT model is offered to guide counselling about sexuality on different levels of complexity. Sample strategies for initiating discussion, communicating about sex, and developing goals and interventions are presented. [ABSTRACT FROM AUTHOR]

Examines the epidemiology of hemophilia in Maharashtra, India. Ratio of hemophilia A to B; Longevity of sever hemophiliacs; Diagnosis of hemophilia around 11-15 years of age.

Four years prior to transplantation, a 14-year-old boy with severe haemophilia A and a high-responding factor VIII (FVIII) inhibitor developed an anteroseptal myocardial infarct while receiving high doses of an activated prothrombin complex concentrate (PCC). Cardiac transplantation was required for survival because of the ensuing cardiomyopathy. At surgery, the patient’s inhibitor titre was 1.8 Bethesda units (BU). High-dose bolus therapy, followed by a continuous infusion of FVIII provided excellent operative and initial postoperative haemostasis without additional blood-product support. Once anamnaesis developed on day 6 postoperatively, recombinant factor VIIa (rFVIIa) therapy was initiated. Haemostasis remained excellent, except for the transient increase in chest-tube bleeding that was noted on day 7. ℇ-aminocaproic acid was added and haemostasis was re-established. On day 15, rFVIIa was replaced with alternate day infusions of prothrombin complex concentrates (PCCs). On day 21 following the transplant, the patient was discharged, remaining on daily FVIII immune tolerance and thrice-weekly PCC prophylaxis. He remains well 24 months after transplant with an inhibitor titre of 39 BU. This paper describes the second case of cardiac transplantation complicated by haemophilia and an inhibitor, and discusses preoperative planning and operative and postsurgical haemostasis management. [ABSTRACT FROM AUTHOR]

The PFA-100® (platelet function analyser) is a relatively new tool for the investigation of primary haemostasis. Recent studies have shown its utility in monitoring antiplatelet therapy (including aspirin) and as a screening tool for investigating possible von Willebrand disease (vWD) and various platelet disorders. More recently, the PFA-100® has been shown to be of value in monitoring DDAVP therapy in both vWD and platelet disorders. This paper reviews current findings, details the utility of the PFA-100® for some of these purposes, as well as reviewing analytical variables that may complicate the interpretation of results. The author highlights the benefits, as well as noting the limitations, of its use. Ultimately, the greatest strengths of the PFA-100® are its simplicity in use and excellent sensitivity to particular haemostatic disturbances such as vWD, platelet disorders and platelet-affecting medication. However, because it is thus a ‘global’ test system, this also creates a significant limitation, as the PFA-100® is not specific for, nor predictive of, any particular disorder. However, utilized appropriately, the PFA-100® can be considered a worthwhile addition to any haemostasis laboratory involved in the diagnosis or therapeutic-monitoring of bleeding disorders including vWD and platelet-dysfunctions. This review should be of value to both haemostasis scientists and clinical specialists. [ABSTRACT FROM AUTHOR]

Eleven haemophilia treatment centres in the United States collaborated in the Hemophilia Behavioural Intervention Evaluation Projects (HBIEP) to develop theory-based interventions to reduce the risk of HIV transmission from seropositive adolescents and young adults with haemophilia. While the Transtheoretical Model of Behaviour Change and the Theory of Reasoned Action provided the theoretical underpinnings, the exact form in which these theories would be applied depended on developmental research. This paper presents the various phases of the process to develop the theory based interventions: literature review, qualitative interviews, quantitative surveys, a provider survey, a materials review, and the actual planning. All or portions of this process could be applied to the development of interventions for many behaviour-change projects. A description of the HBIEP interventions is also provided. [ABSTRACT FROM AUTHOR]

In severely affected haemophilic patients arthropathy is a common problem which can lead to considerable pain and functional deficit. Surgical management, including total joint arthroplasty, can be undertaken if conservative management fails. A search of the literature showed that a number of studies describing the use of total knee arthroplasty (TKA) and total hip arthroplasty (THA) in haemophilia have been published, whereas shoulder, elbow and ankle arthroplasties are confined to case reports. This paper reviews the functional outcome of arthroplasty in the different joints, the postoperative and long-term complications, and the impact of HIV. Although complications are commonly described and the surgery is technically demanding, the results suggest that arthroplasty, particularly of the hip and knee, can be a valuable option in the management of severe haemophilic arthropathy. [ABSTRACT FROM AUTHOR]

This paper provides an outline of the results obtained in a cross-sectional study conducted primarily with the aim of ascertaining orthopaedic complications in a group of young severe A and B haemophiliacs, the effects which these complications have on the medical resources used with these patients, and the impact of severe haemophilia on their quality of life. Its secondary aim was to link their current orthopaedic status to the type of treatment they had received prior to the study. Eleven Spanish hospitals took part in this study, monitoring 70 severe haemophiliacs (FVIII:C <2%) without inhibitors who had a mean age of 21.6 years and a median age of 22. Retrospective data collected from birth to the conclusion of the study were used and, for certain variables, data from the last 12 months. The type of treatment given had been on-demand treatment, together with prophylaxis of variable time periods, which in 32 cases (45.7%) were prolonged (>6 months). In 40 cases (57.1%)the patients underwent one or more periods of prophylaxis. Thirty-three patients (47.8%) had over 1000 days of administration of factors VIII and IX. The analysis of the total study group reveal an average of 348 bleeding episodes per patient. The findings of this study revealed that 84.3% of these patients suffer from articular complaints on the Gilbert scale, and 85.7% on the Pettersson scale. In addition, pain was reported in 16.1% of the joints, the most frequently affected being the ankle joints. Twenty-six patients (37%) had undergone orthopaedic surgery from the time of birth to the conclusion of the study. The quality of life of the severe haemophiliacs reviewed seems to have been affected. During the last 12 months, there were 216 outpatient haematological visits and 176 orthopaedic-rehabilitation visits, as well as 12 radiological explorations and two hospitalizations. During these 12 months, medical expenditure totalled $55 473 per patient per year, the most important item... [ABSTRACT FROM AUTHOR]

This document provides concise summaries of several research studies on bleeding disorders, specifically focusing on hemophilia and other coagulation disorders. The studies explore various topics such as treatment options, joint health, mental health outcomes, surgical interventions, and the impact on sexuality and reproductive choices. The findings suggest that personalized therapeutic strategies, extended half-life clotting factors, and psychosocial support can have positive effects on patient outcomes. However, further research is needed to confirm these findings and improve diagnostics and management in these disorders. The document emphasizes the importance of coordinated care, patient empowerment, and addressing the physical, emotional, and financial aspects of these conditions. [Extracted from the article]

This document provides summaries of several studies related to physiotherapy interventions for people with hemophilia. The studies cover topics such as the development of exercise programs, the use of technology to improve balance and reaction time, the role of allied health professions, the effects of blended physiotherapy interventions on joint health, the utilization of primary care physiotherapy, and the measurement properties of physical function outcome measures. These studies collectively emphasize the significance of physiotherapy interventions in enhancing physical function and quality of life for individuals with hemophilia. [Extracted from the article]

This document contains speaker abstracts from a conference on haemophilia, covering a range of topics related to the condition. The abstracts provide insights into treatment choices, artificial intelligence development, non-factor therapies, and the psychological impact of living with haemophilia. The document emphasizes the need for further research, improved care, and comprehensive support for individuals with haemophilia. Presentations at the conference discussed topics such as diagnosis and management, the use of emicizumab, difficulties in recognizing bleeds, nursing challenges, gene therapy, and returning to sports after joint bleeding or injury. [Extracted from the article]

This article explores the treatment of acquired hemophilia A (AHA), a condition where individuals without hemophilia develop factor VIII inhibitors. AHA can lead to severe bleeding and is often linked to other medical conditions. The study examines the effectiveness of a plasma-derived factor VIIa and X mixture called Byclot in patients with AHA using a global coagulation assay. The results indicate that Byclot, along with other bypassing agents, showed positive clinical responses in all patients. However, more research is necessary to determine the safety and efficacy of Byclot in treating AHA. The study also analyzed the coagulation potential of pd-FVIIa/FX and rFVIIa in patients with AHA, finding that both treatments improved coagulant potential in whole-blood samples. The study did not find evidence of increased thrombotic risk associated with pd-FVIIa/FX treatment, but it had limitations such as a small sample size and selection bias. Further large-scale clinical studies are needed to evaluate the coagulation potential of pd-FVIIa/FX in patients with AHA. [Extracted from the article]

Introduction: In patients with haemophilia, repeated bleeding in large joints leads to chronic haemophilic arthropathy, a rare disease that can be managed surgically with ankle arthrodesis or with total ankle replacement (TAR). TAR has been reported to provide good surgical results in the medium/long‐term and allow preservation of joint mobility but the medical therapeutic management of the patients has not been described. Aim: To describe the medical therapeutic management of TAR. Methods: All patients with haemophilia A/B, with haemophilic ankle arthropathy, and who underwent TAR between April 2006 and October 2019 were retrospectively included. Factor consumption, perioperative and early complications, volume of blood lost, and orthopaedic data were collected. Results: A total of 25 patients underwent 29 TAR (mean age was 44.7 years [range: 26–65]). In the 17 patients with HA without history of anti‐FVIII inhibitor, the mean ± SD consumption the day of surgery was 116 ± 16 UI/kg when clotting factors were administered by continuous infusion, 106 ± 13 UI/kg when SHL factors were administered by bolus infusion, and 75 ± 22 UI/kg when EHL factors were administered by bolus infusion. During hospitalisation, the mean factor cost was €38,073 (83.7% of the total cost of surgery). Mean blood loss was significantly lower in patients treated with tranexamic acid (164 mL, range: 40–300) than in those not (300 mL, range: 70–800; p =.01). Six patients had haematoma. The 10‐year survival free of any prosthesis removal/arthrodesis was estimated to be 92.2% (95% CI [83; 100]). Conclusion: The medical therapeutic management of TAR is complex, carried out by a multidisciplinary team but effective in avoiding the occurrence of complications. [ABSTRACT FROM AUTHOR]

Introduction: The impact of moderate haemophilia on health‐related quality of life (HRQoL) and physical activity (PA) is not well known. In previous studies, persons with factor VIII/factor IX activity (FVIII/FIX:C) below 3 IU/dL were associated with a more severe bleeding phenotype than predicted. Aim: To explore HRQoL and PA in patients with moderate haemophilia A (MHA) and B (MHB). Methods: A cross‐sectional, multicentre study covering patients with MHA and MHB in Sweden, Finland, and Norway. HRQoL was assessed with the EuroQoL 5‐Dimensions (EQ‐5D) form and PA with the International Physical Activity Questionnaire among participants aged ≥15 years. Results: We report on 104 patients aged 15–84 years from the MoHem study. Overall, EQ‐5D utility was.85 (median) (Q1–Q3 0.73–1.0) with corresponding visual analogue scale (VAS) 80 (70–90), which were similar regardless of treatment modality, FVIII/FIX:C, and MHA or MHB. Pain and mobility were most frequently affected dimensions. Utility (r = ‐.54), VAS (r = ‐.42), and PA (r = ‐.32) correlated negatively with arthropathy (HJHS). Only patients aged 41–50 years displayed lower utility (p =.02) and VAS (p <.01) than the Norwegian population norm. Patients on prophylaxis aged 35–54 years reported higher PA than those treated on‐demand (p =.01). Conclusion: Haemophilic arthropathy had negative impact on HRQoL and PA in Nordic patients with moderate haemophilia. Middle‐aged patients captured lower utility and VAS than observed in the general population. Tailored prophylaxis and improved joint health may influence positively on HRQoL and PA also in moderate haemophilia. [ABSTRACT FROM AUTHOR]

Introduction: Patient‐reported outcomes (PROs) in people living with haemophilia A (PLWHA) are often under‐reported. Investigating PROs from a single study with a diverse population of PLWHA is valuable, irrespective of FVIII product or regimen. Aim: To report available data from the Expanding Communications on Haemophilia A Outcomes (ECHO) registry investigating the associations of patient, treatment and disease characteristics with PROs and clinical outcomes in PLWHA. Methods: ECHO (NCT02396862), a prospective, multinational, observational registry, enrolled participants aged ≥16 years with moderate or severe haemophilia A using any product or treatment regimen. Data collection, including a variety of PRO questionnaires, was planned at baseline and annually for ≥2 years. Associations between PRO scores and patient, treatment and disease characteristics were determined by statistical analyses. Results: ECHO was terminated early owing to logistical constraints. Baseline data were available from 269 PLWHA from Europe, the United States and Japan. Most participants received prophylactic treatment (76.2%), with those using extended‐half‐life products (10.0%) reporting higher treatment satisfaction. Older age and body weight >30 kg/m2 (>BMI) were associated with poorer joint health. Older age was associated with poorer physical functioning and work productivity. Health‐related quality of life and pain interference also deteriorated with age and >BMI; >BMI also increased pain severity scores. Conclusion: ECHO captured a variety of disease characteristics, treatment patterns, PROs and clinical outcomes obtained in real‐world practice with ≤1 year's follow‐up. Older age, poorer joint health and >BMI adversely affected multiple aspects of participant well‐being. [ABSTRACT FROM AUTHOR]

This article discusses the transfer of data from the Thai haemophilia treatment center registry to the Annual Global Survey (AGS) of the World Federation of Hemophilia (WFH). The data collection aims to improve care for patients with hereditary bleeding disorders by identifying available treatment resources, evaluating their effectiveness, and advocating for better care. The Thai Society of Haematology (TSH) initiated the Haemostasis Registry, which includes the Hereditary Bleeding Disorders Registry (HBDR) and Thrombosis. The data from the HBDR is transferred to the World Bleeding Disorders Registry (WBDR) and the AGS of the WFH. This data transfer reduces redundancy and improves the reliability, accuracy, cost-effectiveness, and efficiency of data collection. The article highlights the importance of the AGS in collecting data on patients with hereditary bleeding disorders and the treatments used worldwide. The data collected through the AGS is used for resource planning, advocacy, research, and development activities to improve the management of patients with these disorders. The authors emphasize the need for collaboration between clinicians and information technology personnel to ensure accurate data input and output. The dataset of the World Bleeding Disorders Registry and the questionnaire of the AGS are recommended as useful templates for data collection and reporting. The study was conducted ethically and the data is available upon request. [Extracted from the article]

Introduction: Hereditary factor X (FX) deficiency (HFXD) is an autosomal recessive rare bleeding disorder that leads to defects in the FX protein. Depending on the degree of deficiency, patients may be at risk of life‐threatening bleeding episodes. Historical treatments for FX deficiency include prothrombin complex concentrates, which can increase the risk of thrombosis, and fresh frozen plasma, which can cause volume overload and transfusion reactions. Plasma‐derived FX (pdFX), a single‐factor, high‐purity, high‐potency human FX treatment, was approved in 2015 in the United States and in 2016 in Europe for on‐demand treatment and prophylaxis of bleeding episodes and perioperative management of patients with HFXD. Methods: Five studies that examined the use of pdFX in patients with mild (plasma FX activity [FX:C] ≥5 IU/dL), moderate (FX:C ≥1 and <5 IU/dL), or severe (FX:C < 1 IU/dL) HFXD were reviewed: TEN01, TEN02 and TEN03 were prospective, open‐label, multicentre, nonrandomised studies, and TEN05 and TEN06 were multicentre retrospective studies. Results: When used as an on‐demand treatment, pdFX was judged by investigators to be successful in treating 41/42 (97.6%), 2/3 (66.6%) and 79/79 (100%) bleeds in TEN01, TEN02 and TEN05, respectively. When used prophylactically, pdFX was judged 'excellent' for the prevention of bleeds in nine (100%) and eight (100%) patients in TEN02 and TEN05, respectively. Perioperative treatment and pharmacokinetics were also assessed. pdFX was safe and well tolerated. Conclusions: Together, these studies support the use of pdFX for on‐demand treatment of bleeding, routine prophylaxis, and perioperative management of bleeding in patients with HFXD. [ABSTRACT FROM AUTHOR]

Introduction: Patients with hemophilia A treated with coagulation Factor VIII (FVIII) products are at risk for developing anti‐FVIII antibodies. The ABIRISK Consortium aimed to provide knowledge on the formation and detection of anti‐drug antibodies against biopharmaceutical products, including FVIII. Accordingly, standardized and validated assays for the detection of binding (total) and neutralizing antibodies are needed. Aim: Two‐center validation of an ELISA for the detection of total FVIII‐binding IgG‐antibodies and Nijmegen‐Bethesda assays for the quantification of FVIII‐neutralizing antibodies according to consensus validation guidelines. Methods: Validation of assays at both sites was done according to published recommendations and included preanalytics, the determination of key assay parameters, including cut‐points, assay sensitivity, precision, and FVIII interference. Results: The validated assays reproducibly detected FVIII‐binding and ‐neutralizing antibodies with comparable performance in both laboratories. Floating screening cut‐points were established for both assays. Determined mass‐based sensitivity of both assays (all values ≤66 ng/mL) complied with the minimum sensitivity for the detection of anti‐drug antibodies as recommended by the FDA (<100 ng/mL). Intra‐ and inter‐assay coefficients of variation did not exceed 25%. Assay validation further revealed that pre‐analytical heat treatment led to potentially false‐positive ELISA results, while up to 0.15 IU/mL, residual FVIII showed no significant impact. Overall, good agreement of results was found for patient samples analyzed at both study sites. Conclusion: Comprehensive validation of different anti‐FVIII‐antibody assays in two laboratories gave novel insights into the impact of pre‐analytical sample treatment as well as the comparability of test results generated by the use of methodically different assays. [ABSTRACT FROM AUTHOR]

This paper considers the literature relating to the course of hepatitis C infection and its implications for those with haemophilia. It goes on to discuss a model that assessed the economic aspects of treating hepatitis C cases with interferon-α, discusses recent changes in recommended treatment of hepatitis C and critically reviews the model and its application to patients with haemophilia. [ABSTRACT FROM AUTHOR]

Acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with clinical and laboratory features closely resembling hereditary von Willebrand disease (vWD), arising in previously haemostatically normal individuals. We present a retrospective review of 10 cases with AvWS diagnosed over 17 years. The severity of the bleeding tendency varied from mild to severe forms. Multimers electrophoresis showed that 8/10 patients had a normal pattern similar to type 1 vWD, 1/10 had a type 2A vWD pattern (with absence of high and intermediate molecular weight multimers) and 1/10 had a type 3 vWD pattern. An inhibitor screen was performed in 6/10 patients and autoantibodies against von Willebrand factor were found in only two cases. The underlying cause/associated conditions were identified in 8/10 patients. Treatment of the bleeding diathesis was successfully achieved with desmopressin or clotting factor concentrates. Resolution of underlying hypothyroidism (in two cases) and multiple myeloma (in one case) led to normalization of the coagulation parameters. The report on this cohort of 10 patients with AvWS illustrates the complexity of AvWS and its multifactorial aetiology. A brief review of the recent literature on AvWS is also presented, with emphasis on the current opinions in pathogenesis and treatment. Acquired von Willebrand syndrome (AvWS) is an acquired bleeding disorder, characterized by a phenotype similar to the inherited von Willebrand disease (vWD), with a prolonged bleeding time and low plasma levels of factor VIII – von Willebrand factor (vWF) measurements. It occurs in patients with no family history of vWD, who present with recent onset of bleeding symptoms. AvWS appears to be associated mainly with lymphoproliferative disorders, immunological conditions and neoplasia. AvWS is a rare condition and it is difficult to conduct prospective studies, therefore it is important to document the experience with such cases. The aim of this paper is first, to report 10 cases of AvWS identified at our Haemophilia Centre during the past 17 years. Second, to present a brief review of the recent literature on AvWS – outlining the salient features, associated disorders, mechanisms of acquisition and the available options of treatment. [ABSTRACT FROM AUTHOR]

Bleeding disorders in women are an underestimated problem that deserves increased attention. About 9%–14% of females have menorrhagia and, amongst them, there is a significant over-representation of von Willebrand disease (VWD), with a prevalence of 13% in this group as compared with about 1% in the general population. The bleeding disorder has not been diagnosed in most of these women and they may therefore be withheld from treatment with desmopressin, which is effective in most cases of VWD and also in platelet dysfunctions and mild factor VIII deficiency. This paper is a review of the haemostatic use of desmopressin with special reference to women’s bleeding disorders, the mechanisms of action, modes of administration, clinical indications, dosage recommendations, and hospital or home treatment. Desmopressin stimulates endogenous release of FVIII and von Willebrand factor (VWF), it increases platelet adhesiveness and shortens bleeding time. It can be given as intravenous or subcutaneous injection, but the intranasal spray is probably the most practical mode of administration for females with bleeding disorders as it is simple to administer and suitable for home treatment. The spray has been used successfully in connection with menorrhagia and other bleeding symptoms. [ABSTRACT FROM AUTHOR]

The experience with extensor supracondylar femoral osteotomy as treatment for the flexed haemophilic knee is presented with the description of 19 patients treated during a 30-year period (1968–98).The average age of the patients was 16 (8–35 years), and the average age follow-up was 13 years (3–30 years). Six patients had flexion fixed deformity while the rest presented 40° average range of motion (10–75°). In 13 patients a single osteotomy without internal fixation was performed, in one an osteosynthesis with a condylar plate and in five stabilization was achieved by means of Blount staples. Previous surgery was performed in two patients with patello-femoral ankylosis. The osteotomy site was consolidated in every patient and the deformity was corrected. Two bleeding complications were observed: one haemarthrosis and one psoas haematoma. Flexion relapsed in one patient who underwent another procedure after 12 years. One patient presented with a peroneal nerve paralysis; another one a genu recurvartum; which required flexor osteotomy. The extensor supracondylar femoral osteotomy is a procedure that aligns the limb with scarce modification of articular mobility. [ABSTRACT FROM AUTHOR]

Although haemophilia is a relatively rare hereditary disease, and is curable by blood products, the psychological and social problems of haemophilic patients and of their families are always serious. Anxiety for the risks of bleedings and the fear for infections transmitted by blood products cause stress and difficulty in coping with the situation. The aim of this paper is to assess resources, stress, and coping in parents with a haemophilic child. In order to measure the dimensions related to family stress and resources, social desirability, tendency to depression, and anxiety, the subjects were administered the short-form of the Questionnaire on Resources and Stress by Friedrich et al . revised by Saviolo & Cristante, along with the Social Desirability Scale, the Beck Depression Inventory, and the Ipat Anxiety Scale. The subjects of this study were 20 couples who were the parents of haemophilic sons. We analysed how the parents perceived the behavioural characteristics of their child, the differences between mothers and fathers in the questionnaire scores, and the correlation among the considered dimensions. The results show that the parents paid great attention to the problems of their sons, but mothers were more depressed and anxious about the disease of their child. [ABSTRACT FROM AUTHOR]

The monocyte–macrophage system is known to play a central role in HIV infection, and expression of CD4 on the surface of monocytes/macrophages is important, since this molecule is a key factor for the entrance of HIV into susceptible cells. In this paper we evaluated the expression of CD4 in monocytes of haemophiliac patients (He) who had been infected with HIV (HIV+ He) through transfusion of contaminated plasma concentrates. Thirty seropositive patients (HIV+ He), 10 seronegative He patients (HIV- He) and 20 voluntary normal blood donors were studied. Phenotypic evaluation of monocytes was performed by flow cytometry of peripheral blood stained with anti-CD45, -CD3, -CD4 and -CD14 monoclonal antibodies. The percentage of CD4 monocytes was increased in all HIV+ patient groups, but it was highest in those belonging to Groups III and IV A of the CDC classification. Furthermore, the median of fluorescence intensity of CD4+ monocytes from individual patients was shifted to the right, indicating expression of increased numbers of CD4 molecules on the cell membrane of monocytes. This could in turn favour HIV infection and viral persistence, facilitating in vivo dissemination of the virus. [ABSTRACT FROM AUTHOR]

Summary. This paper reviews personal experience in the treatment of recurrent haemarthrosis and chronic synovitis by non-surgical means. Experience with synoviorthesis with rifampicine and radioactive colloids is analyzed, and a multiple chromosomal study to demonstrate safety of radioactive injections is described. The results obtained are so very satisfactory as to recommend non-aggressive synoviorthesis as the treatment of choice to prevent recurrence of bleeding. Long experience in the treatment of chronic arthropathy with intrarticular corticosteroids and hyaluronic acid has shown very promising results. [ABSTRACT FROM AUTHOR]

Summary. Rifampicin synoviorthesis has been empirically used for the treatment of haemophilic synovitis for some time. This paper reports on the experience of three Latin American centers with this treatment and compares it with radioactive synoviorthesis results. Chemical synoviorthesis with rifampicin is best indicated in younger patients (<15 years) and small joint (ankles and elbows). [ABSTRACT FROM AUTHOR]

In an era of increasing constraints in health care expenditure, it has become necessary for the practising physician to utilise resources economically. Due to expenditure ceilings in many countries, the rational allocation of health care resources has become a central goal in health policy. Medical economics is the discipline which covers the issues of economic evaluation, policy and decision analysis and outcomes research. This paper discusses tee fundamentals of this new type of research, highlighting the importance of such results in formulating health policy. Undoubtedly, medical economics will play a similar role as evidence-based medicine and clinical epidemiology in the continuous education within the medical community. This holds specially tree for costly indications such as haemophilia and other coagulation disorders. [ABSTRACT FROM AUTHOR]

Summary. The overall purpose of the “Decade Plan” published in 1992 was to do everything possible to make effective treatment available to people with haemophilia throughout the world. In 1990 it was estimated that there were 350,000 individuals with haemophilia worldwide, with 80% or 280,000 without treatment. By the year 2020 this may have reached the figure 440,000, or the population of Jerusalem. Earlier this century Carroll Birch reported a series of 113 patients where 82 died before their 15th year, and only six survived beyond 40. Thus as Jones has pointed out for the developing world this is a paediatric problem for the WFH to face now. The examples described in this paper illustrating the WFH programmes and the committment of many people from the 88 member organisations worldwide as well as the doctors and scientists shows what can be done through cooperation. There is no doubt that these achievements are capitalising from the unique quality of WFH from the beginning, that is a membership which includes both those with haemophilia and their families, and those with an interest in treating haemophilia. [ABSTRACT FROM AUTHOR]

The present paper describes various kinds of surgery carried out with great success in 16 cases which included both severe and moderate Haemophilia patients with modest amounts of factor concentrates and antifibrinolytic drugs. This is very important in developing countries where factor concentrates are not easily available. In one patient Haemophilia was diagnosed only after surgery. None of the patients had inhibitor pre- or post-operatively. One patient who was HIV positive underwent orchidectomy successfully with only 6000 IU of factor VIII concentrate. [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]

Background: Hereditary thrombotic thrombocytopenia purpura (hTTP) is an ultra‐rare disorder resulting from an inherited deficiency of ADAMTS13, a von Willebrand factor (VWF)‐cleaving metalloprotease. The plasma‐derived factor VIII/VWF Koate (FVIII/VWFKoate) has been shown to contain ADAMTS13, allowing for its use to treat hTTP at home by the patient/caregiver. Aim: Based on prior demonstration of safe and effective use of FVIII/VWFKoate in eight patients with hTTP, we conducted a retrospective study to gather additional data regarding the use of FVIII/VWFKoate for hTTP. Methods: This was a multicentre, retrospective, noninterventional chart review of patients who had received FVIII/VWFKoate for the management of hTTP. Data collected included demographics, medical history, relevant family history, past use and tolerability of fresh frozen plasma, and details regarding FVIII/VWFKoate therapy. Results: The cohort included 11 patients (seven males, four females) with hTTP, ranging in age at study entry from 2 to 28 years. The average duration of FVIII/VWFKoate therapy was 4.8 years (range, 0.5–6.5 years). Among nine patients using FVIII/VWFKoate as prophylaxis, the normalized annual rate of breakthrough TTP episodes ranged from 0.2 to 1.1 episodes/year. All nine patients who received FVIII/VWFKoate prophylaxis had thrombocytopenia recorded at baseline, while eight (88.9%) did not have thrombocytopenia after using FVIII/VWFKoate. There was one AE (unspecified) attributed to FVIII/VWFKoate. Conclusion: These data suggest that FVIII/VWFKoate is a safe and well‐tolerated source of the missing ADAMTS13 enzyme in patients with hTTP, producing a marked reduction in thrombocytopenia prevalence, low frequency of TTP episodes, and with the added benefit of self‐ or caregiver‐administration. [ABSTRACT FROM AUTHOR]

Introduction: Factor X deficiency is a rare inherited bleeding disorder. To date, 181 variants are reported in the recently updated F10‐gene variant database. Aim: This study aimed to describe new F10 variants. Method: The F10 gene was analysed in 16 consecutive families with FX deficiency by a targeted high‐throughput sequencing approach, including F10, F9, F8 genes, and 78 genes dedicated to haematological malignancies. Results: We identified 19 variants (17 missense, one nonsense and one frameshift) and two copy number variations. Two patients presenting a combined FVII‐FX deficiency showed a loss of one F10 gene copy (del13q34) associated with a missense variant on the remaining allele, leading to a FX:C significantly lower than the FVII:C level and explaining their unusual bleeding history. We reported five novel variants. Three missense variants (p.Glu22Val affecting the signal peptide cleavage site, p.Cys342Tyr removing the disulphide bond between the FX heavy and light chains, and p.Val385Met located in FX peptidase S1 domain) were detected at compound heterozygosis status in three patients with severe bleeding symptoms and FX:C level below 10 IU/dL. Two truncating variants p.Tyr279* and p.Thr434Aspfs*13 leading to an altered FX protein were found at heterozygous state in two patients with mild bleeding history. Conclusion: This study showed the feasibility and the interest of high‐throughput sequencing approach for rare bleeding disorders, enabling the report of F10 gene screening in a 3‐weeks delay, suitable for clinical use. The description of five new variants may contribute to a better understanding of the phenotype‐genotype correlation in FX deficiency. [ABSTRACT FROM AUTHOR]