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Record keeping among individuals who manage haemophilia at home is an essential tool of communication between patient and Haemophilia Treatment Center ( HTC). Complete records help HTCs monitor patients, their use of factor and ensure treatment is optimal. HTCs provide patients with a number of methods to track infusion practices. The study objectives were to: [1] determine the current methods of record keeping; [2] identify previous methods of record keeping; [3] understand the strengths and weaknesses associated with each method; and [4] gather suggestions for improvement. Survey methods were used to address the research objectives. Of the 83 patients in the Hamilton-Niagara region who received the survey distributed through the local HTC, 51 returned surveys were included into the analysis. Descriptive statistics were used. Results indicate individuals with haemophilia record infusion practices using: paper diaries, excel spreadsheets, hand-held PDAs and/or the online EZ-Log Web Client. The most popular method of record keeping was EZ-Log (45.1%) followed by paper diaries (35.2%). Advantages to using paper methods include the visual tracking of information and retaining hardcopies. The disadvantage was the inconvenience of physically submitting the records monthly. Advantages to using the online EZ-Log Web Client included ease of use and improved accuracy. The primary disadvantage was technical errors that were difficult to troubleshoot. Record keeping practices among individuals with haemophilia seem to vary according to personal preference and convenience. Respondents suggested that saving infusion history, incorporating barcode scanners or a copy and paste function could improve electronic methods. [ABSTRACT FROM AUTHOR]

Introduction: People with haemophilia rely on specialists for their care, yet the specific dosing regimens of treatments prescribed by these specialists have not been widely studied. Aim: The objective of this study is to describe trends in clinician prescribing practices for the management of haemophilia in the United States (US). Methods: We administered surveys to members of the Hemostasis and Thrombosis Research Society via paper surveys at its in‐person annual symposia in 1999 and 2015, and an online survey in 2021. The surveys collected information on haemophilia treatments including factor dosing, inhibitor therapy and gene therapy. Results: Clinicians treating haemophilia for more than 50% of their practice time have increased from 37.5% of respondents in 1999 to 46.3% in 2021. Clinicians prescribing factor concentrates at >40 units/kg for routine bleeding events increased from 0% in 1999 to 29.3% in 2021 in haemophilia A (HA) and from 22.5% to 87.8% in haemophilia B (HB). In 2021, the clinicians reported prescribing emicizumab to treat HA patients (>89.5% paediatric, >85.7% adult) with or without inhibitors at least some of the time. Approximately 78.0% of respondents reported that they expected to recommend gene therapy at least some of time. Conclusion: These data indicate changing trends in prescribing practices among US haemophilia specialists during the past 22 years. Preference for high doses of factor (>40 units/kg) has increased during this period. Emicizumab prophylaxis has been prescribed for patients with and without HA inhibitors. Clinicians expect gene therapy to have value for some haemophilia patients. [ABSTRACT FROM AUTHOR]

Introduction: Tailored prophylaxis is the current treatment regimen for patients with severe haemophilia A. Recently, published guidelines describe two possible approaches, based on clinical characteristics or estimation of pharmacokinetic parameters. However, both have strengths and weaknesses, and their characteristics need to be integrated to optimize treatment appropriately. In this paper, we present a model that considers together the characteristics of prophylaxis and the relevance of each. Methods: The age at initiation of prophylaxis, number of bleeding events, treatment regimen, therapeutic adherence, FVIII trough levels, and joint status were analyzed in 59 patients followed at La Paz University Hospital between January 2000 and December 2019. Results: The mean duration of primary prophylaxis of 113.37 ± 57.79 months. Eighty‐three percent (n = 49) had no joint status involvement at the end of follow‐up (HJHS and HEAD‐US = 0). The median ABR was 0.7 (IQR 0.2 –1.0) and 54.2% presented trough levels of FVIII during follow‐up >1 IU/dL. 72,9% engaged in some type of physical activity and overall adherence was over 85% in all patients evaluated. The regression analysis performed, considering all these factors, showed that the initiation of prophylaxis before 21 months of age was the most relevant protective factor against the appearance of joint involvement (OR 88.33 p.031 CI 95% 1.49‐5224.40) Conclusion: Early initiation of prophylaxis was the most relevant factor in the protection of joint status. More comprehensive analysis models adapted to the characteristics of each population, are needed to adequately individualize treatment. [ABSTRACT FROM AUTHOR]

KEY POINTS OF CONSIDERATION: To prepare for the introduction of gene therapies in haemophilia care, healthcare frameworks for evaluation and valuation will need to evolve to address the unique requirements of current and future innovations for treating this rare disease.The papers in this supplement provide an insightful and comprehensive state‐of‐the‐art assessment of these requirements and challenges.In terms of evaluation, the definition of a patient‐defined value framework that captures multi‐dimensional, patient‐centered outcomes is an important first step for determining the full benefit of gene therapy for persons with haemophilia.In terms of valuation and rewards for innovation, health systems will need to develop alternative payment models for risk‐sharing that will allow payers and society to address uncertainties about the ultimate clinical and economic value of these innovations. And health technology assessment authorities will need to exercise greater flexibility in evidence requirements given the unique features of data collection for a potentially curative therapy for a rare disease with long‐term uncertainties about durability of impact.Collaboration among stakeholders will be essential for developing the critical evidence requirements and providing the incentives needed to achieve sustainable budgets and broad access for persons with haemophilia worldwide. [ABSTRACT FROM AUTHOR]

Chronic disorders such as haemophilia and yon Willebrand disease can rob people of a feeling of control over their lives. Added to this is often a feeling of confusion or intimidation when dealing with the healthcare system. People may begin to feel like victims of their disorders and of the healthcare system. The healthcare system defines people who are in receipt of care as patients. The word patient comes from the Latin word patiens, which means to suffer, endure, allow, permit or undergo. Even the term implies a sense of victimization. People who become partners in their care and view the receipt and delivery of healthcare as a service wherein they are the consumer and the doctor or clinician is the provider, will feel more in control and will likely have better outcomes than people who assume the more traditional role of 'patient'. [ABSTRACT FROM AUTHOR]

Introduction: The experiences of patients with mild‐to‐moderate haemophilia differ from those of patients with severe haemophilia or those without a bleeding disorder and include a challenging diagnosis and variability in bleeding symptoms and treatment needs. In addition, there is a significant lack of data on mild‐to‐moderate haemophilia, and many unmet needs remain to be identified and addressed in this group of patients. Methods: Challenges for these patients, including women with haemophilia, were identified during a roundtable meeting attended by a group of US‐based experts including healthcare professionals (e.g., physicians, nurses, and physical therapists) and patients who live with a bleeding disorder. Results: Identified unmet needs included a lack of proper education on the management of their disorder and prompt treatment of bleeds, absenteeism from school and work, and challenges with personal relationships. Initiatives to assist with alleviating these unmet needs were proposed and include suggestions for healthcare professionals, haemophilia treatment centres (HTCs) and national and local organizations within the bleeding disorders community. These included HTC and community engagement programmes for patients with mild‐to‐moderate haemophilia, revised transition guidelines for these patients as they approach adulthood and revised diagnostic classification of mild and moderate haemophilia. Challenges unique to women with haemophilia and ways to address these issues were also discussed. Conclusion: This paper summarizes the challenges, initiatives and suggestions that were identified by the haemophilia experts during the roundtable meeting. [ABSTRACT FROM AUTHOR]

Introduction: The awareness and knowledge on bleeding disorders is generally poor among the rural population. Accredited Social Health Activists (ASHAs) serve as the facilitators between the rural community and the health care system. Training of ASHAs in screening of rural population for early identification of bleeding disorders can enable prompt referral, timely detection and management of bleeding disorders. Aim: The aim of the study was to evaluate the effectiveness of an ASHA training programme for identification of suspected bleeding disorder cases. Methods: A population‐based, cross‐sectional survey was implemented by 586 Accredited Social Health Activists (ASHAs) in rural Udupi district, who underwent a structured training programme on identification of bleeding disorders. A survey record book with a screening tool on assessment of bleeding symptoms was given to each ASHA. The screening tool consisted of symptoms related to bleeding disorders and family history of bleeding disorders. Using the screening tool, ASHAs carried out a door‐to‐door survey. After screening, those who reported with bleeding symptoms were referred by the ASHAs to the investigator, who conducted further assessment. A detailed bleeding history was documented and bleeding symptom assessment was carried out using bleeding assessment tool (BAT) at the haemophilia treatment centre. Further coagulation assessments were carried out as per the treatment centre protocol. This paper highlights the evaluation of an ASHA training programme on identification of individuals with bleeding symptoms in the rural population. Results: A total of 586 trained ASHAs surveyed a population of 318 214 in rural Udupi district. Out of the 124 cases reported by ASHAs, 29 bleeding disorder cases were identified; haemophilia (A and B) was the most commonly found bleeding disorder 22 (75.8%), followed by von Willebrand disease (vWD) 3 (10.3%) and 4 (13.8%) immune‐mediated thrombocytopenic purpura (ITP), with an overall prevalence of 2.2/10 000 population. Conclusion: Training ASHA health care workers, who are the most important link between the community and health services, resulted in increased awareness among the public for the early detection of bleeding disorders. [ABSTRACT FROM AUTHOR]

Parents of children affected by haemophilia must face, often without prior knowledge, the difficult challenge imposed by such a pathology. To satisfy the need of information, guideline and psychological support for a better quality of life, 30 parents with haemophiliac children have participated in a programme of counselling and psychological support. Such a programme has the aim of guiding the group trough a process of discovery, comparison and personal growth and stimulating adaptive processes of problem–solving and decision–making. The aim of this paper was to verify how the programme influenced coping strategies and other psychological constructs such as depression and anxiety. Subjects of this study were administered the following psychological tests: COPE (coping, orientation to problems experienced), BDI (beck depression inventory), STAI-Y form (state–trait anxiety inventory) at the beginning and at the end of the programme. The results show that by the end of the programme subjects are characterized by a greater use of problem–focused coping strategies, typical of individuals who think that the situation is susceptible to change, and a minor use of emotion–focused coping strategies, related to individuals who regard the situation as immutable. The use of avoidance –focused coping strategies seems to remain at the same level even if it was low. Also the other psychological aspects investigated, namely depression and anxiety, did receive a positive influence. The results show how significant such programme has been for parents. [ABSTRACT FROM AUTHOR]

Summary. This paper emphasizes the importance of distinguishing between the prevalence, incidence and cumulative incidence of inhibitors in haemophilia A. Incidence and cumulative incidence data will include patients with transient inhibitors or whose inhibitors have been eliminated by treatment. As these will not be included in prevalence data, prevalence studies will tend to give rise to lower figures than incidence studies. As a result, the most accurate estimates of the true risk of inhibitor development comes from prospective studies of newly diagnosed haemophiliacs who are tested regularly for the presence of inhibitors. This paper reports a systematic review of the best available evidence relating to the epidemiology of inhibitors in haemophilia A. Cohort studies, registry data reporting incidence or prevalence of inhibitors in patients with haemophilia A, and prospective studies of factor VIII (FVIII) in the treatment of previously untreated patients which reported the development of inhibitors as an outcome, were included in the review. The overall prevalence of inhibitors in unselected haemophiliac populations was found to be 5–7%. The cumulative risk of inhibitor development varied (0–39%). Incidence and prevalence were substantially higher in patients with severe haemophilia. Studies of patients using a single plasma-derived FVIII (pdFVIII) preparation reported lower inhibitor incidence than those using multiple pdFVIII preparations or single recombinant FVIII preparations. Incidence data should be used to estimate the likely demand for treatments aimed at eliminating inhibitors, whereas the best estimates of the overall burden to the National Health Service (NHS) of treating bleeding episodes in patients with continuing inhibitors will come from prevalence studies. [ABSTRACT FROM AUTHOR]

Introduction Haemtrack is an electronic home treatment diary for patients with inherited bleeding disorders, introduced in 2008. It aimed to improve the timeliness and completeness of patient-reported treatment records, to facilitate analysis of treatment and outcome trends. The system is easy to use, responsive and accessible. Methods The software uses Microsoft technologies with a SQL Server database and an ASP.net website front-end, running on personal computers, android and I-phones. Haemtrack interfaces with the UK Haemophilia Centre Information System and the National Haemophilia Database ( NHD). Data are validated locally by Haemophilia Centres and centrally by NHD. Data collected include as follows: treatment brand, dose and batch number, time/date of bleed onset and drug administration, reasons for treatment (prophylaxis, bleed, follow-up), bleed site, severity, pain-score and outcome. Results Haemtrack was used by 90% of haemophilia treatment centres ( HTCs) in 2015, registering 2683 patients using home therapy of whom 1923 used Haemtrack, entering >17 000 treatments per month. This included 68% of all UK patients with severe haemophilia A. Reporting compliance varied and 55% of patients reported ≥75% of potential usage. Centres had a median 78% compliance overall. A strategy for progressively improving compliance is in place. Age distribution and treatment intensity were similar in Haemtrack users/non-users with severe haemophilia treated prophylactically. Conclusion The Haemtrack system is a valuable tool that may improve treatment compliance and optimize treatment regimen. Analysis of national treatment trends and large-scale longitudinal, within-patient analysis of changes in regimen and/or product will provide valuable insights that will guide future clinical practice. [ABSTRACT FROM AUTHOR]

Background The evaluation of health related quality of life (HRQOL) is essential for a full assessment of the influence of an illness on patients' lives. The aim of this paper is to critically appraise and compare the measurement properties of HRQOL questionnaires studied in haemophilia. Methods Bibliographic databases (Embase, Medline, Cinahl and PsycInfo) were searched for articles evaluating measurement properties of HRQOL questionnaires in haemophilia. Articles were excluded that did not report HRQOL measurement properties, or when <50% of the study population had haemophilia. The methodological quality of the selected studies was evaluated using the COSMIN checklist. The measurement properties of the HRQL questionnaires were rated as 'positive', 'indeterminate' or 'negative', accompanied by levels of evidence. Results The search resulted in 1597 unique hits, of which 22 studies were included. These articles evaluated three questionnaires for children (CHO-KLAT, Haemo-QoL and one unnamed measure) and five for adults (Hemofilia-QoL, Haemophilia Well-Being Index, HAEMO-QoL-A, Haem-A-QoL, and SF-36). The CHO-KLAT was the paediatric measure that showed the strongest measurement properties in high-quality studies. The Haemophilia Well-Being Index and HAEMO-QoL-A performed best among the adult measures. None of the studies reported measurement error and responsiveness. Conclusion Our findings suggest that there is no need for new disease-specific HRQOL questionnaires for haemophilia, but rather that additional research is necessary to document the measurement properties of the currently available questionnaires, specifically focusing on the structural validity, measurement error and responsiveness of these questionnaires. [ABSTRACT FROM AUTHOR]

Haemophilia patients with inhibitors are treated for acute bleeding with prothrombin complex concentrates (PCCs) or activated prothrombin complex concentrates (aPCCs). Despite this therapy, patients with high-level inhibitors are at increased risk of developing devastating joint disease. This paper examines available information that supports the study of PCCs and/or aPCCs as prophylactic therapy for haemophilia patients with inhibitors. This strategy would require that PCCs or aPCCs be administered repetitively in a dose that is sufficient to prevent haemarthrosis without causing thrombogenic events, or causing anamnestic response in inhibitor titre. PCC doses ranging from 30 to 50 U kg-1 every other day for up to 8 months have resulted in subjective improvement both in bleeding associated with target joints and in the management of chronic joint inflammation. aPCC doses as low as 50–100 U kg-1 every other day have been useful in postsurgical prophylaxis. The risk of developing a myocardial infarction or clinically relevant disseminated intravascular coagulation is linked to total dosages of either PCCs or aPCCs greater than 200 U kg-1 day-1. It is uncertain what anamnestic response would result from prophylaxis, but with typical therapy the aPCCs cause such a response in only a small percentage of patients. Based on these findings, a clinical trial of these products used in doses of 50–100 U kg-1 every other day would appear to be warranted in patients who have permanent inhibitors and frequent joint bleeding. [ABSTRACT FROM AUTHOR]

Persons with haemophilia, living with their condition from infancy, require attention from a biopsychosocial approach, in which both the biological and the biographical dimension are addressed. These patients and their environment may benefit greatly from having professionals to help them manage, pre-emptively if possible, to adapt to the disease, cope with the experience of suffering and overcome the difficulties caused by chronicity. The ultimate goal of the interventions was to achieve the best quality of life possible with tailored objectives throughout the patient's life, including disease control, addressing the particular difficulties, and achieving optimal empowerment. This article aims to describe the role of Health Psychology and its professionals in supporting the young patient with haemophilia and provide a brief guide that might be useful for health professionals involved in his care. From the psychological perspective, this paper focuses on communication of diagnosis, the role and support of the family, issues during infancy, childhood and adolescence and how the healthcare team can address them to provide successful support. [ABSTRACT FROM AUTHOR]

Introduction The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence. Aims We report the data available in the literature on FVII prophylaxis and our personal experience regarding three patients affected by severe FVII deficiency. Methods Specific papers on long-term prophylaxis in severe FVII deficiency were identified using the database, PUBMED. Results The most frequent indications for long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding (9%). Patients were treated with various dosages and frequency. Prophylactic treatment with 10-30U/kg (pd FVII) or 20-30mcg/kg ( rFVIIa) twice or three times/weeks was described to be effective. Conclusions In the literature and in our experience, prophylaxis can be considered in patients with severe FVII deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pd FVII) or 20-30 microg/kg ( rFVIIa) twice or three times/week is usually administrated, but dose and frequency can be tailored based on the clinical follow-up of the patients. Since hemarthrosis is a frequent manifestation, a suggestion to improve the outcomes of patients with severe FVII deficiency is to monitor joint condition in order to identify early arthropathy that could be another indication to start secondary prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction Haemophilia is a rare genetic haemorrhagic disease characterized by partial or complete deficiency of coagulation factor VIII, for haemophilia A, or IX, for haemophilia B. As in any other medical research domain, the field of haemophilia research is increasingly concerned with finding factors associated with binary or continuous outcomes through multivariable models. Traditional models include multiple logistic regressions, for binary outcomes, and multiple linear regressions for continuous outcomes. Yet these regression models are at times difficult to implement, especially for non-statisticians, and can be difficult to interpret. Aims The present paper sought to didactically explain how, why, and when to use classification and regression tree (CART) analysis for haemophilia research. Materials & methods The CART method is non-parametric and non-linear, based on the repeated partitioning of a sample into subgroups based on a certain criterion. Breiman developed this method in 1984. Classification trees (CTs) are used to analyse categorical outcomes and regression trees (RTs) to analyse continuous ones. Results The CART methodology has become increasingly popular in the medical field, yet only a few examples of studies using this methodology specifically in haemophilia have to date been published. Two examples using CART analysis and previously published in this field are didactically explained in details. Conclusion There is increasing interest in using CART analysis in the health domain, primarily due to its ease of implementation, use, and interpretation, thus facilitating medical decision-making. This method should be promoted for analysing continuous or categorical outcomes in haemophilia, when applicable. [ABSTRACT FROM AUTHOR]

Introduction Continuous infusion ( CI) of clotting factors has facilitated surgical procedures and intensive replacement therapy in haemophilia patients. This procedure could, however, be further optimized by using a short-term central venous catheter ( CVCs) instead of via peripheral venous access. Aim In this paper, we present our results on using a short-term CVC in haemophilia patients during major surgical operations. Methods In total, 40 patients with haemophilia A or B (37 and 3, respectively), aged 21-81 years, underwent 67 surgeries with 65 CVCs. Patients requiring intensive treatment lasting over 5 days had the indications for CVC placement. The catheters were placed by experienced anaesthesiologists in the operating theatre under general anaesthesia and following activated partial thromboplastin time correction. Results No interruption of CI was observed and only one catheter had to be removed prematurely due to a suspected infection. There were no signs found for prosthesis or wound infection, nor was there any thrombosis documented. Conclusion Our study produced encouraging results regarding the use of short-term CVCs in haemophilia patients. Even though our patient sample was small, the data corroborates short-term CVCs to be safe and convenient for factor concentrate delivery in CI during major surgical operations. [ABSTRACT FROM AUTHOR]

. Projects are underway in many developing countries to try to improve the provision of treatment and access to care for people with haemophilia (PWH), as long-term prophylactic treatment, which improves quality of life for PWH, is still restricted to developed countries. In most developing countries, therapy is limited to on-demand treatment or even no replacement treatment at all. Combined with limited healthcare resources, this lack of treatment can lead to a vicious circle of lack of care, disability, unemployment and lack of access to health insurance for haemophilia patients. In China, the establishment of the Haemophilia Treatment Centre Collaborative Network of China (HTCCNC), in conjunction with the World Federation of Hemophilia, has improved haemophilia care and the identification of PWH. In Brazil, on-demand treatment has improved the health of PWH but does not prevent musculoskeletal (MSK) complications, the major cause of deterioration in quality of life for PWH. The Novo Nordisk Haemophilia Foundation BR2 project was therefore designed to improve quality of life of PWH through improvements in their physical, mental and social wellbeing. This paper will briefly review these projects and describe the current status of haemophilia care in these countries. While there is still a long way to go before optimal care becomes a reality for all PWH in developing countries, significant progress has been made, and knowledge of the impact and outcomes of these projects can inform best practice worldwide. [ABSTRACT FROM AUTHOR]

. The National Pain Study was a prospective, computer-based, descriptive survey of the pain experience of persons with a bleeding disorder conducted in the United States over a 28 month period from 2007 to 2009. The aim of this study was to (i) determine the language used by patients to describe and differentiate acute and persistent pain, (ii) describe pharmacological and non-pharmacological strategies utilized to control pain, (iii) assess the perceived effectiveness of current pain management on quality of life and, (iv) to determine who provides pain management to this population. One thousand, one hundred and four surveys were received. Only the responses of the 764 respondents who reported having hemophilia A or B were evaluated for this paper. Thirty nine percent of participants reported their pain was not well treated. The average acute pain score associated with a bleed reported was 5.97/10 while the average persistent pain score reported was 4.22/10. The most frequently reported word descriptors for acute pain were: throbbing, aching, sharp, tender and miserable. The most frequently reported word descriptors for persistent pain were aching, nagging, tiring, sharp, and tender. The most frequently reported pain strategies for acute and persistent pain included factor, rest, ice, elevation, and compression. Alcohol and illicit drugs were reportedly used to manage both acute pain as well as persistent pain. Primarily, short-acting opioids and acetaminophen were reported to treat both acute and persistent pain. Hematologists and primary care providers provide the majority of pain management for persons with hemophilia (PWH). Quality of life (QOL) scores were lowest in the domains of pain, energy/fatigue and physical problems indicating disruption of QOL. This substantiates under-recognition and under-treatment of pain in the hemophilia population when combined with the 39% of respondents who felt their pain was not well treated and literature in the general pain population of wide spread under-treatment of pain. Recommendations: The NPS is an initial step in recognizing the prevalence and description of pain in PWH. HTC providers should educate themselves in pain management techniques to better serve this population. Further research is necessary to develop specific pain management guidelines for the bleeding disorders population that include multimodal holistic treatment plans. [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]

Patient-reported outcome (PRO) measures have been used to assess quality of life and health state preferences from the patient’s perspective. However, they have not been fully utilized in haemophilia clinical practice and research. A series of meetings were convened to review and document the state of the art in PROs relevant to haemophilia. Experts developed a process for selection of measures and identified published measures of health-related quality of life (HRQoL) relevant to patients with haemophilia. These were synthesized and reviewed. Patient preference measures were also identified and reviewed. Although the majority of measures were developed for and validated in adults, several measures were identified for use in paediatric populations. This paper recommends an approach to the selection of PROs for application in haemophilia clinical research and practice and identifies several potential measures relevant for application in haemophilia clinical research and practice. [ABSTRACT FROM AUTHOR]

Patients with haemophilia complicated by inhibitors have a significant burden of joint disease, which is associated with a negative impact on their quality of life. Successful elective orthopaedic surgery can result in decreased bleed frequency into a new joint, less time spent in hospital, increased mobility and improved well being. This paper describes a new protocol for use of recombinant activated factor VII (rFVIIa) in elective orthopaedic surgery, based on a review of published data as well as the personal experience of a group of expert physicians. The protocol offers guidance on the planning of the surgery and preoperative testing as well as the bolus schedule for rFVIIa and advice on the concomitant use of antifibrinolytic agents and fibrin sealants. A total of 10 operations involving 13 procedures in eight patients in five comprehensive care centres have been undertaken until now using the protocol, which employs an initial bolus dose of rFVIIa in the range of 120–180 μg kg−1 to cover surgery. The clinical experience reported here encompasses all cases of elective orthopaedic surgery using rFVIIa as initial treatment carried out in the UK and Republic of Ireland over the last 2 years. In all cases, there was good control of haemostasis during surgery and the final outcome was rated as ‘excellent’ or ‘extremely satisfactory’ by the reporting clinicians. Although the initial cost of product to cover surgery such as arthroplasty is high, it needs to be borne in mind that this may be offset in subsequent years by savings resulting from avoidance of bleeding episodes in the affected joint. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about hemophiliacs.

The development of an inhibitor against factor VIII (FVIII) is a serious complication in children with haemophilia A. Immune tolerance induction (ITI) therapy is generally considered to be the best approach to eradicate the inhibitor. In this paper, the low-dose (≤50 IU kg−1 twice or three times weekly with plasma-derived factor concentrates) ITI regimen used in Turkey is discussed. This regimen was given to 21 haemophilia A patients with high titer inhibitors. The median age at the beginning of ITI was 9 years and exposure days were 25. The median pre-ITI historical peak inhibitor titer, and inhibitor titer when ITI started were 80 BU (range 6.0–517), 19.2 BU (range 3.6–515), respectively. Complete immune tolerance was defined as the time at which at least two negative inhibitor assays was obtained with no anamnestic response. Our two cases were not reached in follow-up period. Immune tolerance could be achieved in 5 of 19 (26.3%) patients within a median time of 6 months. Partial tolerance was obtained in 7 patients while treatment failed in spite of significant decreased inhibitor levels in the other patients. A relapse developed in one immune-tolerized patient, one year later. The level of inhibitor titer at the beginning of ITI (≤10 BU), the pre-ITI historical peak inhibitor titer (<50 BU), and the time between the first diagnosis inhibitor to starting ITI (<12 months) were main factors in the success (complete or partial tolerance) of ITI. In conclusion, the outcome of low-dose ITI protocol was not satisfactory in this retrospective study. [ABSTRACT FROM AUTHOR]

In this paper, the most recent developments on arthropathy and inhibitors in haemophilia are reviewed. Firstly, early long-term prophylaxis is strongly recommended in children with severe haemophilia. Secondly, in joint bleeds not responding to substitution of factor VIII to normal factor VIII levels angiographic embolization might be considered as a promising therapeutic option. Thirdly, recent data indicate disruption of normal development for adolescents with inhibitors. Fourthly, some case reports indicate the benefit of secondary prophylaxis with recombinant factor VIIa (rFVIIa) or factor eight inhibitor bypassing activity (FEIBA) in patients with severe haemophilia A and inhibitors. Finally, surgical procedures in haemophilia patients with factor inhibitors can be accomplished safely and effectively with FEIBA and/or rFVIIa, although the risk of complications is higher than in haemophilia patients without inhibitors. [ABSTRACT FROM AUTHOR]

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 μg kg−1 per week to 220 μg 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. [ABSTRACT FROM AUTHOR]

Radiological imaging of joints in children with haemophilia is important to detect abnormalities, grade their severity and monitor the effects of treatment. Scoring systems for staging haemophilic arthropathy have been developed based on plain film or magnetic resonance imaging (MRI) findings. Radiographs alone may be inadequate for evaluating joint disease in children with haemophilia on prophylaxis while MRI may be difficult to access and require the child to be sedated. Sonography can be a useful complementary modality in the evaluation of haemophilic arthropathy that is readily available and does not require the child to be sedated. In this paper, we briefly review the current imaging scales available for the assessment of haemophilic arthropathy and present a systematic protocol for sonographic assessment of the knee and ankle in haemophilic children along with examples of findings in joint effusion/hemarthrosis, synovial hypertrophy and cartilage loss. Also, we correlate the ultrasound findings with the corresponding MRI images demonstrating the anatomic planes used for imaging acquisition. Sonography is a promising technique for the assessment of soft tissue changes which are the earliest findings in haemophilic arthropathy. Further investigation is required for evaluation of osteochondral changes given limitations of sonography in this regard and in minimizing operator dependency, especially if applied in multicentric clinical trials. [ABSTRACT FROM AUTHOR]

This paper reports the findings of a global survey of practice patterns for the management of patients with haemophilia A. A total of 147 haemophilia treatment centres worldwide responded to the questionnaire, supplying data for 16 115 patients with haemophilia A. From these responses, 38% (range: 25–48%) of patients were under 18 years old. Almost half (47%) of patients were reported to have mild or moderate haemophilia A, 48% had severe haemophilia A (no inhibitor) and 5% were inhibitor patients. Less than half of patients with severe haemophilia A received prophylactic therapy (37%, excluding inhibitor patients) and 54% received on-demand treatment; the remaining 9% were inhibitor patients. Primary prophylaxis rates for severe haemophilia ranged from 73% in Sweden to 17% in the USA. Most respondents (80%) ranked infrequent bleeds as one of the top five reasons for not administering prophylactic treatment, followed by venous access (60%) and cost (45%). Of patients with severe haemophilia (non-inhibitor), 32% on primary prophylaxis and 27% on secondary prophylaxis had indwelling catheters. Risk of infection and the patient's inability to maintain the line were the key concerns cited by nurses relating to venous access. The mean ratio of nurses to patients with haemophilia A was 1:69 and nurses felt that they were either fully (26%) or mostly (45%) autonomous in assessment and treatment decisions. Results from this current survey suggest that worldwide research should be continued so as to improve outcomes through the identification of optimal treatment protocols for the management of haemophilia A. [ABSTRACT FROM AUTHOR]

Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life-long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement. [ABSTRACT FROM AUTHOR]

The objective of the present paper was to provide an estimate of the benefits of on-demand and prophylaxis treatment strategies for severe haemophilia in monetary terms. Using the contingent-valuation method, which simulates a missing market by asking people about their willingness to pay (WTP), we asked a representative sample (n = 609) of the Swedish population if they would be willing to pay a specific amount (bid) so that patients with severe haemophilia could receive on-demand treatment and another bid for prophylactic treatment. Different respondents were offered different bids and the bid vector ranged from 71 Euro cents to EUR 130. The order of the bid questions was randomized so that half of the respondents were asked first about their WTP for on-demand treatment, and then about their WTP for prophylaxis, while the order was reversed for the other half of the respondents. The mean estimated WTP (year 2002) was EUR 39 (95% CI 31–47) for on-demand and EUR 65 (95% CI 55–73) for prophylaxis. Our sensitivity analysis showed that the ranking of the two treatment alternatives was robust in that the WTP was greater for prophylaxis in all possible subsets. The point estimates of WTP varied somewhat in subsets defined by individual characteristics, but confidence intervals always overlapped that of the main results. The WTP for on-demand and prophylaxis exceeded the calculated cost of treatment per taxpayer of providing on-demand and prophylactic treatment, respectively, based on our previous results []. [ABSTRACT FROM AUTHOR]

Quality of life (QoL) is a recent focus of research in haemophilia. It can be defined − in analogy to the World Health Organization (WHO) definition of health − as patient-perceived wellbeing and function in terms of physical, emotional, mental, social and behavioural life domains. The paper describes conceptual, methodological and practical foundations of QoL research in adults and children at an international level. It then proceeds to review the QoL literature in the field of haemophilia. With regard to assessment of QoL in haemophilia patients, both generic and very recently targeted instruments have been applied. Recent publications have focused on describing QoL in adults, showing specific impairments in terms of physical function (arthropathy) and mental wellbeing (HIV infection) as well as focusing on the cost–benefit (QoL) ratio of haemophilia care. In paediatric haemophilia, research has suggested the beneficial QoL outcomes with prophylaxis and stressed the role of the family for patients' wellbeing and function. QoL research is a relevant area for haemophilia research which should be pursued further. [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]

The interest in economic evaluation of alternative strategies for haemophilia treatment has increased through the years. Few studies have actually been undertaken, however, and most of them have been simple cost-minimization or cost-effectiveness analyses. From the perspective of the binational project ‘Treatment strategies for severe haemophilia − prophylaxis vs. on-demand’, the present paper discusses the pros and cons of different methods for economic evaluation and their data requirements. Severe haemophilia is a rare disease that requires lifelong treatment. In addition, treatment has both short- and long-term effects which are likely to differ between strategies. Accordingly, regardless of the chosen evaluation method, data requirements are non-trivial. Hence, the various problems connected to the generation of data, as well as how they may be addressed, are also discussed. [ABSTRACT FROM AUTHOR]

Prophylaxis is an expensive form of management in haemophilia but has demonstrated many advantages with respect to decreasing joint bleeds and potentially preventing joint damage. The valuation of prophylaxis and how the costs and benefits of this intervention compare with other interventions in the management of haemophiliacs can be evaluated through cost–utility analysis (CUA). CUA is an economic method of analysis where the benefits of a healthcare intervention are expressed as an overall utility or preference, usually in the form of quality-adjusted life years (QALYs). This is a composite measure, which takes into consideration both an individual's lifespan and quality of life (QoL). The most difficult aspect of performing a CUA is the measurement of health-related QoL (HRQoL). Much work is ongoing into evaluating HRQoL in haemophiliacs. This paper addresses some of the ways in which this can be achieved and some of the problems with evaluating HRQoL. Ultimately CUA may provide a tool to allow societies to decide if prophylaxis is worth the cost and how the costs and benefits of prophylaxis compare to other healthcare interventions for other disease entities. [ABSTRACT FROM AUTHOR]

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 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.

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 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]

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 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: 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]

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]

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]

Introduction: Emicizumab is used as hemostatic prophylaxis for patients with hemophilia A (PwHA), irrespective of the presence of inhibitors. Although bacterial infection can lead to a procoagulant state, there is limited information on coagulation and fibrinolysis potentials in emicizumab‐treated PwHA and on the use of anticoagulants in such cases. Aim: We examined whether anticoagulants affect the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab. Methods: Plasma from PwHA was in vitro supplemented with emicizumab (50 μg/mL; emi‐plasma) and anticoagulants (recombinant thrombomodulin (rTM), nafamostat mesylate (NM), unfractionated heparin (UFH), or low‐molecular‐weight heparin (LMH)). PwHA plasma spiked with rFVIII (1 IU/mL) was used as a reference (ref‐plasma). The coagulation and fibrinolysis potentials in plasma was measured by thrombin and plasmin generation assay (T/P‐GA) and clot‐fibrinolysis waveform analysis (CFWA). Results: In T/P‐GA and CFWA, coagulation potentials (maximum coagulation velocity; |min1|, and peak thrombin; Th‐Peak) in plasma rose with increasing concentrations of emicizumab and rFVIII, but fibrinolytic potentials (peak plasmin; Plm‐Peak, and maximum fibrinolytic velocity; |FL‐min1|) remained unchanged. Adding rTM, NM, and UFH to emi‐plasma suppressed coagulation and fibrinolysis potentials, similar to ref‐plasma. Regarding the heparin, UFH and LMH inhibited the improved coagulation in emi‐plasma. UFH inhibited fibrinolysis as well, but LMH did not. Conclusions: Anticoagulants could exhibit the inhibitory effects on the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab, similar to those in normal plasma. [ABSTRACT FROM AUTHOR]

Introduction: Joint health is one of the most important factors contributing to a healthy life in patients with haemophilia. Recent study revealed that starting early prophylaxis was not enough to prevent joint disease in most paediatric patients with haemophilia. Aim: In this study, we aimed to determine the age‐specific incidence of acute joint disease during childhood at single haemophilia treatment centre (HTC). Method: The joint health in 48 patients was evaluated based on consecutive US testing for 5 years at annual multidisciplinary comprehensive care. Results: During the study period, 23 patients (47.9%) had no joint disease since the initial examination, whereas 13 patients (27.0%) showed development from negative to positive findings. The incidence of joint disease increased with age: 0% in preschool, 5.3% in elementary school, 14.3% in junior high school and 35% beyond high school age. Among the 13 patients who developed joint disease, two experienced acquired synovitis that resolved during the follow‐up period. Statistical analysis revealed that the patients who routinely underwent follow‐up by the HTC exhibited a significantly lower incidence of joint disease than did those followed up at other institutions (p <.001). Conclusion: These results indicated that close check‐up, including routine joint examination using US as well as frequent assessment of pharmacokinetic profile at the HTC, might play an important role in avoiding joint disease among paediatric patients with haemophilia. [ABSTRACT FROM AUTHOR]

Introduction: Treatment adherence is critical to minimize bleeding episodes in persons with haemophilia. Suboptimal adherence increases risk of adverse medical outcomes and negatively impacts quality of life. Assessment of treatment adherence is therefore an integral component of intervention to mitigate the adverse impacts of haemophilia. Aim: To develop and validate a multifactorial, patient (self or caregiver) report adherence measure for emicizumab treatment and report the first patient‐report data on adherence to specific components of emicizumab treatment (dosing, timing, injection, planning and bleeds). Methods: An IRB approved multi‐site prospective study enrolled 83 participants with factor VIII deficiency being treated with emicizumab. Participants completed the 25‐item VERITAS NexGen (self‐report from 50 adults age 18+ years; caregiver‐report from 33 parents of children aged 6 months to 17 years) as well as a global adherence rating (GAR) scale. Providers of participants also completed a GAR scale. Results: Most VERITAS‐NexGen subscales had good‐to‐excellent internal consistency reliability, test‐retest reliability, and validity. VERITASNexGen scores revealed globally strong patient‐reported adherence; however timing and bleed management were reported as greater challenges to adherence compared to dosing and injections. Adults struggled more with timing and planning of injections than caregivers. Conclusion: The VERITASNexGen is the first validated multifactorial patient‐report measure of adherence designed specifically for emicizumab treatment. Results suggest excellent adherence, with only 4%–13% of participants reporting suboptimal adherence to different components of the treatment regimen. Used in conjunction with other adherence measures, VERITAS‐NexGen meets a crucial need for monitoring and understanding patient adherence to emicizumab in clinical and research settings. [ABSTRACT FROM AUTHOR]

Introduction The sensory strategies of postural control in adult haemophilic arthropathy patients are still poorly understood. Aim To determine sensorial posture-control strategies through postural sway frequency analysis when in a bipedal quiet stance with and without visual stimulus deprivation in healthy subjects and patients with haemophilic arthropathy. Secondarily, to determine the irregularity of postural balance control through sample entropy (SampEn). Methods A triaxial accelerometer attached at the L3 level determined the displacement and acceleration of the centre of mass (DCoM and ACoM, respectively) under open- and closed-eyes conditions. Sensorial strategies were studied by spectral analysis of the DCoM signal, divided into low, medium and high frequencies for visual/vestibular, cerebellum and somatosensory strategies respectively. DCoM irregularity was also analysed by SampEn. Results Fifteen young, healthy subjects and fifteen young, haemophilia patients were included. The mediolateal DCoM and anteroposterior ACoM differed between groups. During the open-eyes condition, haemophiliacs presented limited high and medium frequencies, and more low frequency bands as compared to non-haemophiliacs ( P<.05). In the closed-eyes condition, haemophiliacs had a minor percentage of high frequencies but an elevated percentage of low frequencies as compared to non-haemophiliacs ( P<.05). Non-haemophiliacs had higher SampEn than haemophiliacs in the mediolateral axis with open- and closed-eyes ( P<.05 and <.001, respectively). Conclusions The presented results indicate that patients with haemophilic arthropathy, as compared to healthy subjects, have less postural control irregularity and poor somatosensory system contributions that are compensated by more vestibular inputs. [ABSTRACT FROM AUTHOR]

Introduction Health-related quality of life ( HRQoL) is reduced among persons with haemophilia. Little is known about how HRQoL varies with complications of haemophilia such as inhibitors and joint disease. Estimates of preference-based HRQoL measures are needed to model the cost-effectiveness of prevention strategies. Aim We examined the characteristics of a national sample of persons with severe haemophilia A for associations with two preference-based measures of HRQoL. Methods We analysed utility weights converted from EuroQol 5 Dimensions ( EQ-5D) and the Short Form 6 Dimensions ( SF-6D) scores from 1859 males aged ≥14 years with severe haemophilia A treated at 135 US haemophilia treatment centres in 2005-2011. Bivariate and regression analyses examined age-group-specific associations of HRQoL with inhibitor status, overweight/obesity, number of bleeds, viral infections, indicators of liver and joint disease, and severe bleeding at the time of the first HRQoL measurement. Results Overall mean HRQoL utility weight values were 0.71 using the SF-6D and 0.78 using the EQ-5D. All studied patient characteristics except for overweight/obesity were significantly associated with HRQoL in bivariate analyses. In a multivariate analysis, only joint disease was significantly associated with utility weights from both HRQoL measures and across all age groups. After adjustment for joint disease and other variables, the presence of an inhibitor was not significantly associated with HRQoL scores from either of the standardized assessment tools. Conclusion Clinically significant complications of haemophilia, especially joint disease, are strongly associated with HRQoL and should be accounted for in studies of preference-based health utilities for people with haemophilia. [ABSTRACT FROM AUTHOR]