Search

The purpose of this paper is to summarize the state of the art in measuring quality of life in haemophila populations. The paper reviews the measures recently included in haemophila trials in the published literature. It also summarizes the development of four new disease-specific measures of health-related quality of life. Two of these were developed for children (the Haemo-QoL and the CHO-KLAT), and two for adults (the Hemofilia-QoL and the Hemolatin-QoL). These new measures show promise for use in clinical trials. Further research is in progress to complete the psychometric testing and cross-cultural validation. [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]

Summary. In some patients with haemophilia A, therapeutically administered factor VIII (FVIII) comes to stimulate the production of antibodies (inhibitors) which react with FVIII to render it ineffective. As a result, FVIII cannot be used prophylactically and patients become liable to recurrent bleeds. There are two elements to the management of patients with inhibitors: the treatment of bleeding episodes, and attempts to abolish inhibitor production through the induction of immune tolerance. This paper reports a systematic review of the best available evidence of clinical effectiveness in relation to immune tolerance induction (ITI) in patients with haemophilia A with inhibitors. Owing to the lack of randomized controlled trials on this topic, broad inclusion criteria with regard to study design were applied in order to assess the best available evidence for each intervention. As a result 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. The International Registry provides the most reliable estimate of the proportion of successful cases of ITI [48.7%, 95% confidence interval (CI) 42.6–52.7%]. The duration of effect is unclear, but relapses appear to be infrequent. The International Registry shows a rate of relapse of 15% at 15 years. The comparative effectiveness of different protocols is uncertain, as no trials have been undertaken which compare them directly. However, the evidence suggests that the Bonn protocol may be more effective than the Malmö or low-dose protocols. There is no good evidence that immunosuppressive drug regimens are effective. [ABSTRACT FROM AUTHOR]

The article presents a an assessment test and an evaluation form for continuing medical education (CME) for medical personnel sponsored by Informedical Communications Inc. TheCME activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accredition Council for Continuing Medical Education (ACCME) by InforMEDical Communications Inc. InforMEDical designates this education activity.

Abdominal surgery became routinely possible over a hundred years ago, after the introduction of general anaesthesia and sterile procedures. Abdominal surgery for haemophiliacs had to wait another 60 or 70 years for adequate control of haemostasis. This paper traces its gradual achievement from the 1920s to the 1970s through a series of reports of appendectomies, gastric and intestinal operations, gall bladder operations and splenectomies in patients with haemophilia of varying degrees of severity. A short-lived flurry of interest in splenectomy as a proposed treatment for haemophilia is also mentioned. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to assess the effectiveness of intra-articular injected rifampicine[sup ®] in haemophilic patients in order to achieve synovectomy by preventing repeated intra-articular bleeding. We have used this technique in haemophilic patients previously and reported our results on 13 cases [1]. Two hundred and fifty milligrams of rifampicine was injected into the elbow and ankle joints and 500 mg was injected into knee joints with 3–10 mL of lidocaine, depending on the joint size. The injections were repeated once a week for 7 weeks. Patients were only covered with antihaemophilic factor on the day of the injection at 30% above their coagulation level. We evaluated the results using two measures: subjective reports from the patient and objective assessment by the examiner. In the subjective reports the patient graded the results from their own perspective from 1 (poor) to 10 (excellent): 1–3, poor; 4–6, fair; 7–8, good; and 9–10, excellent. In the objective reports the grading was: excellent (‘dry joint’, full function, no haemarthrosis, no synovitis); good (clinical improvement, synovitis, reduction of haemarthroses, full function); fair synovitis (reduction of haemarthroses, no change in function); poor synovitis (persistent haemarthroses). This paper reports on the results of 38 patients with 39 joints with more that 3 years follow up, mean 1.8 years. There were 22 knees, nine elbows and eight ankles. Subjectively, there were excellent results in 21 joints (11 knees, six elbows and four ankles) good results in 15 joints (eight knees, three elbows and four ankles), fair results in two knees and a poor result in one knee. Objectively, results obtained were excellent in 20 joints (11 knees, six elbows and three ankles); good in 17 (nine knees, three elbows and five ankles); fair in one knee and poor in one knee. [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]

Aim Poorly conducted economic evaluations have the potential to mislead both clinicians, leading to inappropriate treatment choices, and payers who must decide on the reimbursement of treatment costs. This paper reviews the methods used in economic evaluations in haemophilia and proposes standards for conducting and reporting such evaluations in the future. Methods A systematic review of economic evaluations in haemophilia published since 2008 was conducted. The reporting and methods of the studies were assessed using the recently published Consolidated Health Economic Evaluation Reporting Guidelines ( CHEERS) checklist. The key methodological deficiencies in the studies were recorded. Results Twenty-one studies met the inclusion criteria, classified as follows: prophylaxis vs. treatment on-demand (five studies); use of bypassing therapy (six); immune tolerance induction (four); and other topics (six). In general, the quality of reporting was good. However, it was poorest for the CHEERS item of patient heterogeneity, with most studies lacking discussion of heterogeneity in the patient population. The main recurring methodological deficiencies were the evaluation of single episodes of care rather than entire treatment strategies; inadequate control for confounders when comparing treatment options; the frequent use of expert opinion to determine drug doses and treatment patterns; lack of consideration of patient heterogeneity; failure to identify patient subgroups; and the inadequate exploration of uncertainty in estimates. Conclusions A set of 12 standards for future reporting and conduct of economic evaluations within haemophilia is proposed, with the objective of making such evaluations more relevant and reliable for those making treatment and reimbursement decisions in the future. [ABSTRACT FROM AUTHOR]

Coagulation disorders in patients with venous malformation of the limbs and trunk: a case series of 118 patients. Venous malformations (VM) are congenital slow-flow vascular malformations, with a prevalence of ~1%. Two patients had a mild decrease in factor V (Table 1), which is known to occur in DIC.9 D-dimers were elevated in the majority of patients (48/77) and were the first and only test noted to be abnormal in some patients with developing DIC (Figure 1B, data for VM subgroups in Supplemental Figure S1A). [Extracted from the article]

The genetic variants responsible for haemophilia are extremely diverse with more than 2100 distinct variants identified in haemophilia A and more than 1100 in haemophilia B. Point variants are the most common. We enrolled 24 patients, 16 with haemophilia A and 8 with haemophilia B. Blood spot samples were obtained from scavenged blood collections from each patient during routine clinic visits and applied to filter paper directly from the venipuncture and allowed to dry. Of the 24 individuals enrolled, nine had severe haemophilia A, six had mild haemophilia A, five had severe haemophilia B, one had moderate haemophilia B, and one had mild haemophilia B. A known carrier of haemophilia A and a symptomatic carrier of haemophilia B were also included. [Extracted from the article]

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]

Haemostatic treatment in patients with von Willebrand disease (vWD) in connection with surgery aims at normalizing the haemostatic defect in order to avoid bleeding complications. Factor VIII (FVIII) levels in plasma must be normalized in connection with major surgery, whereas the bleeding time is more important for mucous membrane bleedings. Most patients respond well to treatment with desmopressin which stimulates the endogenous release of FVIII and von Willebrand factor (vWF) and shortens the bleeding time. Non-responders to desmopressin are substituted with a plasma-derived factor concentrate which contains vWF and FVIII. This paper includes a summary of retrospective data from the last 10 years on haemostatic treatment in connection with surgery from four haemophilia centres in Sweden and Denmark on 40 invasive procedures in 27 vWD patients and on one normal delivery. If a FVIII-containing concentrate is given prior to surgery a dose of 30–40 IU VIII:C kg-1 will normalize FVIII levels in most severe cases. If a pure vWF concentrate is used, a dose of 40–50 IU RCoF kg-1 will normalize RCoF in most cases, but FVIII levels will not be normalized until after about 12 h or later. Repeated doses of FVIII-vWF concentrate may lead to very high levels of FVIII in plasma because of the combined effect of the exogenous FVIII-substitution and the endogenous FVIII-release induces by the infused vWF. Dosage should be adjusted according to FVIII levels in plasma. [ABSTRACT FROM AUTHOR]

The haemorrhagic diathesis in von Willebrand disease (vWD) is caused by a quantitative deficiency or a qualitative defect in the von Willebrand factor (vWF) in plasma and/or platelets causing insufficient primary haemostasis. Since vWF binds and protects factor VIII (FVIII) towards random proteolysis, coagulation may also be impaired in patients with a low plasma level of vWF, and in instances where vWF displays insufficient binding capacity to FVIII. The entity of vWD displays a vast heterogeneity. Apart from rarely occurring acquired cases, vWD is an inherited disorder of autosomal linkage. The major clinical hallmark in vWD is an increased tendency to mucocutaneous bleeding that rarely reach life-threatening proportions, unless vWF is severely reduced or completely absent. Increased bleeding may also occur in sites such as muscles and joints when the level of FVIII is particularly low. Significant progress has recently been achieved through extensive molecular genetic exploration of various forms of vWD. In order to guide treatment and to form a platform for genetic investigation, however, accuracy in diagnosis and phenotypic characterization is important. By means of various laboratory methods, major subclasses of vWD can be differentiated, as presented in another article of this series. Whereas most of the cases of vWD can quite easily be diagnosed and classified using today’s diagnostic methods, the most frequently occurring bleeding disorder of all, vWd type 1 of mild degree, continues to challenge clinicians and diagnostic laboratories. The aim of this paper is to review the laboratory methods most commonly used in diagnostic investigation of the patient suspected of vWD. [ABSTRACT FROM AUTHOR]

The authors reflect on the "Haemophilia" journal, a scientific journal for the haemophilia community. They highlight the contributing effort of editor Christine Lee, noted to be the first professor of haemophilia in Great Britain. They mention that the journal was the official publication of the World Federation of Haemophilia (WFH) as well as the journal of the European Haemophilia and Allied Disorders organisation (EAHAD).

The safety and efficacy of treatment options for patients with haemophilia have significantly improved over the last two decades, particularly with greater utilization of prophylactic approaches. Consequently, it is becoming increasingly difficult to differentiate the treatment benefits of available choices based on standard endpoints such as annualized bleeding rates and joint health scores. Patient-reported outcomes ( PROs) have shown limited ability to discriminate between treatment outcomes, in part because of their comprehensive nature; i.e. differences in specific outcomes meaningful to individual patients are masked by a global scoring system based on a fixed set of items, many of which may be unimportant for any given patient. There is a clear need for new outcome measures. Initiatives to develop patient-centric outcomes that capture clinically meaningful change are ongoing. One such approach, goal attainment scaling ( GAS), allows patients, in collaboration with a trained clinician, to select goals from a medical condition-specific menu of options and subsequently facilitates quantitative assessment of goal realization. Thus, it is fully personalized and sensitive to small, often idiosyncratic, treatment benefits, such as improvements in functional capacity. In this paper, we present the underlying rationale for GAS and one other novel approach to PRO personalization, and discuss their potential to augment current outcome measures by reliably detecting and quantifying treatment effects in individuals with haemophilia on prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction Musculoskeletal impact of haemophilia justifies physiotherapy throughout life. Recently the Dutch Health Care Institute constrained their 'list of chronic conditions', and withdrew financial coverage of physiotherapy for elderly persons with haemophilia ( PWH). This decision was based on lack of scientific evidence and not being in accordance with 'state of science and practice'. Methods In general, evidence regarding physiotherapy is limited, and especially in rare diseases like haemophilia. 'Evidence based medicine' classifies and recommends evidence based on meta-analyses, systematic reviews and randomized controlled trials, but also means integrating evidence with individual clinical expertise. For the evaluation of physiotherapy - usually individualized treatment - case studies, observational studies and Case Based Reasoning may be more beneficial. Results Overall annual treatment costs for haemophilia care in the Netherlands are estimated over 100 million Euros, of which 95% is covered by clotting factor concentrates. The cost for physiotherapy assessments in all seven Dutch HTCs (seven centres for adult PWH and seven centres for children) is limited at approximately 500 000 Euros annually. Costs of the actual physiotherapy sessions, carried out in our Dutch first-line care system, will also not exceed 500 000 Euros. Thus, implementation of physiotherapy in haemophilia care the Netherlands in a most optimal way would cost less than 1% of the total budget. Aim The present paper describes the role of physiotherapy in haemophilia care including available evidence and providing suggestions regarding generation of evidence. Establishing the effectiveness and cost-effectiveness of physiotherapy in haemophilia care is a major topic for the next decennium. [ABSTRACT FROM AUTHOR]

Introduction The bleeding propensity in von Willebrand disease ( VWD) is usually moderate or mild and patients with VWD do not need continuous treatment, but do require extra increased haemostatic cover when undergoing dental or surgical procedures. Desmopressin can be effective in certain patient groups and this has been considered in a previous publication. Aim This paper now seeks to evaluate current knowledge and practice in the use of factor concentrate in the management of VWD patients undergoing invasive procedures. Methods A literature search was performed on the use of factor concentrates to cover invasive procedures and a survey of current practice in a number of specialist haematology centres across Europe represented by the European Haemophilia Strategy Board was conducted. Results Our review of the literature and the results of the survey showed considerable heterogeneity in treatment regimens, and a lack of consistency in reporting of the variables that determine factor concentrate dosing and monitoring. Conclusion By analysing the literature, examining guidelines and using consensus deliberation, this survey allowed the group to develop recommendations for management of VWD patients undergoing invasive procedures. [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 Looking into the future is difficult and sometimes hazardous. A reliable look into haemophilia treatment in 2030 should be based on history and contemporary progress as well as dilemmas. Today, the issue of inhibitors overshadows the entire haemophilia community together with lack of treatment for large parts of the world's persons with haemophilia. Aims The aim of this paper was to provide a perspective on haemophilia treatment in 2030 and its provenance. Methods Literature review on history, treatment of haemophilia today as well as of emerging therapies give a base for the author's opinion on haemophilia treatment in 2030. Results Development of haemophilia treatment has virtually exploded during the last decade and a number of new clotting factor concentrates and alternative approaches are in the pipeline. Conclusion The collection of treatment resources that we can see on the horizon gives hope that each person with haemophilia will get the care needed in 2030. The products used will be directed by individual needs and tailored to regional and local situations. [ABSTRACT FROM AUTHOR]

Background Integrated care models have been adopted for individuals with chronic conditions and for persons with rare diseases, such as haemophilia. Objective To summarize the evidence from reviews for the effects of integrated multidisciplinary care for chronic conditions in adults and to provide an example of using this evidence to make recommendations for haemophilia care. Search methods We searched MEDLINE, EMBASE, CINAHL and Cochrane Database of Systematic Reviews up to January 2016, and reviewed reference lists of retrieved papers. Selection criteria Systematic reviews of at least one randomized study, on adults with non-communicable chronic conditions. Data collection and analysis Two investigators independently assessed eligibility and extracted data. Quality of reviews was assessed using ROBIS, and the evidence assessed using GRADE. Results We included seven reviews reporting on three chronic conditions. We found low to high quality evidence. Integrated care results in a reduction in mortality; likely a reduction in emergency visits and an improvement in function; little to no difference in quality of life, but shorter hospital stays; and may result in little to no difference in missed days of school or work. No studies reported educational attainment, or patient adherence and knowledge. When used for haemophilia, judgment about the indirectness of the evidence was driven by disease, intervention or outcome characteristics. Conclusion This overview provides the most up to date evidence on integrated multidisciplinary care for chronic conditions in adults, and an example of how it can be used for guidelines in rare diseases. [ABSTRACT FROM AUTHOR]

Over the past 20 years, there have been many advances in haemophilia treatment that have allowed patients to take greater control of their disease. However, the development of factor VIII ( FVIII) inhibitors is the greatest complication of the disease and a challenge in the treatment of haemophilia making management of bleeding episodes difficult and surgical procedures very challenging. A meeting to discuss the unmet needs of haemophilia patients with inhibitors was held in Paris on 20 November 2014. Topics discussed were genetic and non-genetic risk factors for the development of inhibitors, immunological aspects of inhibitor development, FVIII products and inhibitor development, generation and functional properties of engineered antigen-specific T regulatory cells, suppression of immune responses to FVIII, prophylaxis in haemophilia patients with inhibitors, epitope mapping of FVIII inhibitors, current controversies in immune tolerance induction therapy, surgery in haemophilia patients with inhibitors and future perspectives for the treatment of haemophilia patients with inhibitors. A summary of the key points discussed is presented in this paper. [ABSTRACT FROM AUTHOR]

Introduction Desamino D-arginine vasopressin ( DDAVP or desmopressin) is a useful and effective haemostatic treatment for patients with von Willebrand Disease ( VWD). However, there are still issues regarding in which subtypes of VWD DDAVP is appropriate and little consensus on its use in different surgical settings. We also lack information concerning the appropriate laboratory parameters that should be monitored. Aim The European Haemophilia Therapy Strategy Board ( EHTSB) wished to investigate published information and clinical use of DDAVP in VWD patients. Methods We conducted a literature survey on management of VWD during surgical interventions and undertook a survey of specialist haematologist centres across Europe to assess current management of VWD patients. Results DDAVP is ineffective in type 3 VWD and its use in type 2B remains controversial due to the possibility of thrombocytopenia. It can, however, be used effectively to cover minor surgery and dental procedures in most other VWD patients. For major surgery there is wider use of factor concentrate in preference to DDAVP depending on the subtype of VWD. We give consensus recommendations on the use of DDAVP for surgical interventions in VWD including laboratory parameters that denote an adequate response and contraindications to its use. Conclusions DDAVP can be recommended to cover invasive procedure in selected patients with VWD, however, we need more information and systematic recording of adverse events associated with DDAVP use in VWD. A companion paper will be published covering the use of factor concentrates in VWD patients. [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]

Introduction In haemophiliacs, recurrent hemarthrosis and chronic synovitis lead to chronic arthropathy. Synovectomy is indicated when medical treatment fails. Few studies report the results of open synovectomy of the ankle in haemophiliacs with a small number of procedures and also a limited follow-up. Aim The aim of this paper is to report the long-term results of open surgical synovectomy of the tibio-talar joint. Methods Thirty-two open synovectomies were performed in 21 young haemophiliacs in the same haemophilia center using an antero-lateral and postero-medial approaches. The median follow-up was 15.4 years. Clinical (Petrini scores) and radiological evaluations (Pettersson scores) were made preoperatively and at each multidisciplinary follow-up visit. Wilcoxon and Spearman's tests were used for the statistical analysis. Results Preoperative median Petrini score was 6 (range 3-12), and improved at 2 and 5 years follow-up ( P = 0.0003 and P = 0.0001 respectively). At 10 and 15 years follow-ups, median score remained below preoperative score (median 3.5, range 0-11). Ten ankles had a follow-up of more than 20 years. Preoperative median Petterson score presented a slight but continuous worsening in the first 2 and 5 years of follow-ups ( P = 0.02, P = 0.003), but not correlation between clinical and radiological results was observed. Conclusion Our long-term results support that clinical scores are improved even if radiological scores progress. Open synovectomy retards the progression of the arthropathy, but not stops it. Bleeding and pain are controlled and even if recurrence of bleedings is frequent, it is less severe, less painful and requiring less factors replacement. [ABSTRACT FROM AUTHOR]

Unfortunately, about 30% of patients do not achieve complete remission, including those who die of the condition, and relapse occurs in 20% of those who do remit.6 In many patients, rpFVIII is not neutralized by human FVIII inhibitors. To the Editor, We wish to present the case of a patient with acquired haemophilia A who needed ocular surgery to prevent vision loss. In our patient, we aimed to achieve FVIII:C >= 80 U/dl because invasive procedures in patients with acquired haemophilia A can cause life-threatening bleeding. [Extracted from the article]

Introduction: HaemoassistTM 2 is an electronic system designed for people with bleeding disorders and their physicians to record prophylactic infusions and treatment of bleeds. It aims to improve adherence by permitting reminders and accuracy of documentation by facilitating real‐time reporting. Aim: To assess documentation quality and adherence to prophylactic regimens in patients with haemophilia A, haemophilia B or von Willebrand disease who are using HaemoassistTM 2. Methods: Ten centres enrolled consecutive patients, who had been using HaemoassistTM 2 for ≥ 3 months (Cohort 1, 'quality of documentation'). Of these, patients who had a specified prophylactic regimen in HaemoassistTM 2 for ≥ 3 months were eligible for inclusion in Cohort 2 ('adherence to prophylaxis'). Results: Cohort 1 comprised 796 patients (71% with severe haemophilia A; median 20.5 months of HaemoassistTM 2 use). The most common method of documentation for patients was using the mobile app; the median time between infusion and documentation was 4 hours using the app, compared with 85 hours using a web portal on a stationery device. The median total annualised number of infusions was consistent in the first and last 3 months of documentation (128; IQR: 70‐184 and 120; IQR 64‐176, respectively). Cohort 2 comprised 202 patients (79% severe haemophilia A; median of 13 months on prophylactic regimen in HaemoassistTM 2). The rate of adherence to prophylaxis was 83%; median deviation between planned and actual infusion time was ± 2 hours. Conclusion: HaemoassistTM 2 was used consistently over prolonged periods of time and allowed for precise analysis of adherence to prophylaxis. [ABSTRACT FROM AUTHOR]

Dear Editor, Present-day care treatment for patients with severe haemophilia A (HA) consists of factor VIII (FVIII) replacement as prophylaxis or on demand in case of bleeding. Reconsidering the results of the NHA, treatment with rFVIIa in this patient would have led to a more pronounced thrombin generation in the acute setting of haemorrhage, thereby providing probably better haemostasis. In the pivotal report of this new agent, TGA is used to monitor the pharmacodynamic effect of this drug.5 In this patient, FVIII replacement therapy was given for breakthrough bleeding by the emergency physician as this was mentioned in his treatment plan. 2014; 20 (1):e 7 - 14. 10 Dargaud Y, Lienhart A, Janbain M, Le Quellec S, Enjolras N, Negrier C. Use of thrombin generation assay to personalize treatment of breakthrough bleeds in a patient with hemophilia and inhibitors receiving prophylaxis with emicizumab. [Extracted from the article]

Introduction: Estimates of the size and characteristics of the US haemophilia population are needed for healthcare planning and resource needs assessment. A network of comprehensive haemophilia treatment centres (HTCs) located throughout the United States receives federal support for diagnosis and management of haemophilia and other rare bleeding disorders. Aim: Estimate the incidence and prevalence of haemophilia among US males using the HTC network. Methods: During the period 2012‐2018, de‐identified surveillance data were collected on all males who visited an HTC that included year of birth, gender, race, Hispanic ethnicity, residence zip code, haemophilia type and severity. Data from all patients were used to calculate period prevalence by haemophilia type, severity and state of residence. Data from a subset of patients born 1995‐2014 were used to estimate incidence rates over the 20‐year period. Results: During the period, 21 748 males with haemophilia visited the HTCs resulting in an age‐adjusted prevalence of 15.7 cases per 100 000 males (12 for haemophilia A and 3.7 for haemophilia B). Prevalence was higher among whites (15.1) than blacks (12.4) or Hispanics of either race (12.4). State‐specific prevalence varied from 1.6 to 23.3 cases per 100 000. Based on 9587 males born during the index period, the average haemophilia incidence was 1 case per 4334 live male births. Conclusion: Based on these data, we estimate that there are between 29 761 and 32 985 males with haemophilia living in the United States today, the majority of whom receive comprehensive care in specialized clinical centres. [ABSTRACT FROM AUTHOR]

The paper describes the experience of the Genetic Diagnostic Laboratory in prenatal testing for haemophilia A, an X-linked recessive disease caused by mutations in the F8 gene. Knowledge of a familial mutation prior to pregnancy can benefit prenatal diagnosis and decrease wait time for molecular testing during pregnancy. This is a retrospective review of a series of pregnant women who pursued F8 gene testing from December 1997 through May 2012, highlighting three cases, which demonstrate the technical complexities of analysis and the implications of not knowing carrier status prior to pregnancy. Mutations of the F8 gene were detected in affected males, obligate female carriers and suspected female carriers by DNA sequencing, inverse-PCR, qRT-PCR, Southern blot and exonic dosage analysis. The same methods were used to analyse prenatal samples from obligate or suspected female carriers upon request. Maternal cell contamination studies were performed for all prenatal samples analysed. Ninety-nine women pursued F8 testing during pregnancy, either for carrier status alone or carrier status and prenatal diagnosis. Ninety-one women (91%) requested carrier testing because they did not know their F8 mutation carrier status prior to pregnancy. Eight women requested prenatal diagnosis only, and only 4 of these were aware of their mutation status. Thirty-seven individuals were found to be mutation carriers. Forty-two prenatal samples were received for prenatal diagnosis. In total 21 foetuses were identified as mutation carriers. Mutation detection was complex and increased the turnaround time in some cases. Only four of 99 women who submitted samples for F8 testing were aware of their F8 mutation status prior to pregnancy. Knowledge of F8 mutation status prior to pregnancy allows for efficient prenatal diagnosis, when desired. Thus, preconception genetic counselling is required to inform patients of the available options and the complex and timeconsuming nature of F8 testing. [ABSTRACT FROM AUTHOR]

The article profiles Finnish internist Erik Adolf von Willebrand whose focus of interest was the properties of blood and its coagulation. He was born in Vaasa, Finland in 1870. He excelled in chemistry, botany and zoology while attending Vaasa Lyceum. He published papers on metabolism and therapies for diabetes, obesity and gout. Early observations in von Willebrand disease are also discussed.

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

Long-term adherence to prophylactic therapy is the key to successful prevention of bleeds in severe haemophilia. The present study aims to provide a systematic review of the literature on the determinants of adherence to prophylaxis in haemophilia. A literature search in the largest medical databases in Oct 2011 yielded 880 articles, which were reduced to 72 by further selection on title. Twenty-eight articles were excluded due to inclusion criteria. Full paper evaluation of 44 articles yielded five relevant articles that were critically appraised using the STrengthening the Reporting of OBservational studies in Epidemiology ( STROBE) statement and items extracted from the critical appraisal criteria for cohort studies (Dutch Cochrane Centre). After critical appraisal, 2/5 studies were considered as the best evidence available. The results of these two studies were further used in the synthesis for description of the determinants of adherence. This concerned a total of 245 subjects in all age groups. Data were collected using questionnaires and interviews. Motivators for a high adherence were as follows: experience of symptoms, a positive belief of necessity of treatment and a good relationship with the health care provider. Important barriers were defined as: infrequent or absence of symptoms and increasing age. Two high-quality studies were identified. Reported determinants of adherence to prophylaxis were age, symptoms, beliefs, and the relation with the health care provider. This information may provide a first step towards a strategy to promote adherence in haemophilia, with an important focus on age-specific interventions and patient education. [ABSTRACT FROM AUTHOR]

Introduction: Turoctocog alfa is a recombinant, B domain‐truncated factor VIII (FVIII) approved for patients with haemophilia A. Aim: To evaluate the safety and efficacy of turoctocog alfa in previously untreated patients (PUPs) with severe haemophilia A. Methods: Guardian 4 was a multicentre, multinational, non‐randomized, open‐label phase 3 trial comprising a main and extension phase. The former concluded once ≥ 50 patients had received treatment for ≥ 50 exposure days (EDs) or developed inhibitors. Patients received turoctocog alfa intravenously for prevention and treatment of bleeds. The primary endpoint was the incidence rate of FVIII inhibitors (≥0.6 Bethesda Units) reported during the first 50 EDs. Results: Of the 58 patients who completed the main phase, 25 (43.1%) patients developed inhibitors (detected within 6‐24 [mean: 14.2] EDs from treatment start). High‐risk mutations were identified in 60% of patients who developed inhibitors in the main phase and were a significant predictor of inhibitor development (P =.003). Of the 21 patients who started immune tolerance induction therapy, 85.7% completed treatment with a negative inhibitor test (note that data on the last 3 patients completing ITI are based on information collated from sites prior to the final database lock). Haemostatic response (including missing values as failure) was rated as 'excellent' or 'good' for 86.1% of bleeds occurring during prophylaxis. The estimated mean annualized bleeding rate for patients on prophylaxis was 4.26 bleeds/patient/year (95% CI: 3.34 − 5.44). Conclusions: Turoctocog alfa was effective at preventing and stopping bleeds and was well tolerated. Inhibitor development was within the expected range for this PUP population. [ABSTRACT FROM AUTHOR]

von Willebrand's disease ( VWD) is probably the most common bleeding disorder, with some studies indicating that up to 1% of the population may have the condition. Over recent years interest in VWD has fallen compared to that of haemophilia, partly the result of focus on blood-borne diseases such as HIV and hepatitis. Now the time has come to revisit VWD, and in view of this some 60 international physicians with clinical and scientific interest in VWD met over 4 days in 2010 in the Åland islands to discuss state-of-the-art issues in the disease. The Åland islands are where Erik von Willebrand had first observed a bleeding disorder in a number of members of a family from Föglö, and 2010 was also the 140th anniversary of his birth. This report summarizes the main papers presented at the symposium; topics ranged from genetics and biochemistry through to classification of VWD, pharmacokinetics and laboratory assays used in the diagnosis of the disease, inhibitors, treatment guidelines in different age groups including the elderly who often have comorbid conditions that present challenges, and prophylaxis. Other topics included managing surgeries in patients with VWD and the role of FVIII in VWF replacement, a controversial subject. [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]

. Progress in the evidence-based care of haemophilia A and B worldwide has been historically challenged by the dearth of evaluable outcome data, including but not limited to the safety and effectiveness of therapeutic interventions. These challenges are partially rooted in the inherent difficulty of conducting prospective clinical trials and observational studies with statistically meaningful endpoints in a rare disease such as haemophilia. Despite the logistical barriers, the need for outcome data has never been more critical than in this time of expansive therapeutic advance tempered by the shrinking economic capacity to fund the rapidly increasing cost of treatment. Given that systematic analyses of published literature have been largely unsuccessful in compensating for the lack of rigorous and purposeful data collection, new approaches to clinical study design and statistical modelling are urgently needed. However, even as these are considered, the lack of broadly accepted and well-defined clinical outcome endpoints poses an additional barrier to progress. The three presentations encompassed by this paper highlight the timely need for quality data from the perspectives of the clinicians, regulatory agencies and health care funders, and describe the ongoing coordinated efforts by the international haemophilia community to further understand and dismantle the barriers to harmonized and standardized data collection on a global scale using well-defined clinical outcome endpoints. [ABSTRACT FROM AUTHOR]

. For 50 years, the World Federation of Hemophilia (WFH) has been working globally to close the gap in care and to achieve Treatment for All patients, men and women, with haemophilia and other inherited bleeding disorders, regardless of where they might live. The WFH estimates that more than one in 1000 men and women has a bleeding disorder equating to 6,900,000 worldwide. To close the gap in care between developed and developing nations a continued focus on the successful strategies deployed heretofore will be required. However, in response to the rapid advances in treatment and emerging therapeutic advances on the horizon it will also require fresh approaches and renewed strategic thinking. It is difficult to predict what each therapeutic advance on the horizon will mean for the future, but there is no doubt that we are in a golden age of research and development, which has the prospect of revolutionizing treatment once again. An improved understanding of 'optimal' treatment is fundamental to the continued evolution of global care. The challenges of answering government and payer demands for evidence-based medicine, and cost justification for the introduction and enhancement of treatment, are ever-present and growing. To sustain and improve care it is critical to build the body of outcome data for individual patients, within haemophilia treatment centers (HTCs), nationally, regionally and globally. Emerging therapeutic advances (longer half-life therapies and gene transfer) should not be justified or brought to market based only on the notion that they will be economically more affordable, although that may be the case, but rather more importantly that they will be therapeutically more advantageous. Improvements in treatment adherence, reductions in bleeding frequency (including microhemorrhages), better management of trough levels, and improved health outcomes (including quality of life) should be the foremost considerations. As part of a new WFH strategic plan (2012-2014) the WFH has identified several key initiatives for particular emphasis - continuation of the Global Alliance for Progress (GAP) program, a new initiative to address underserved countries and regions (The Cornerstone Initiative), enhancing health outcomes research and analysis, and a new research mentorship program. Despite our progress to date in closing the global gap in care, our work is not complete. Too many patients remain undiagnosed and too few receive adequate treatment. This paper will also discuss historical, present and future challenges and opportunities to close the gap in care and achieve Treatment for All. [ABSTRACT FROM AUTHOR]

. Current treatment for haemophilia provides excellent efficacy and safety albeit with a number of unresolved issues. The development of inhibitors following treatment with factor VIII (FVIII) is the most challenging complication of haemophilia and bears the highest economic burden for a chronic disease. Moreover, prophylactic therapy for haemophilia requires repeated infusions of FVIII, frequently as often as two or three times weekly, which can impact greatly on patients' daily lives. As considerable scope remains for further advancements in the management of this condition, the primary focus of this paper relates to issues regarding current treatment and strategies in place to resolve the various issues. For countries approaching access to replacement therapy, it is important to know whether or not plasma-derived and recombinant products are associated with different risks of inhibitor development in previously untreated patients with severe haemophilia. The ongoing international SIPPET study is expected to provide an answer to this clinical dilemma. Methods under investigation to prolong the half-life of factor concentrates offer new hope to reduce the burden of prophylaxis for patients with haemophilia, with early results suggesting greater benefits with FIX. [ABSTRACT FROM AUTHOR]

. Development of factor VIII (FVIII) inhibitors is the most severe and challenging complication of haemophilia A treatment and represents the highest economic burden for a chronic disease. Therefore, major research efforts are ongoing to optimize the therapeutic approaches able to minimize this complication. FVIII inhibitors have variable immuno-reactivity against different FVIII concentrates and generally have a lower reactivity against von Willebrand factor (VWF)-containing FVIII concentrates than plasma-derived FVIII (pdFVIII) or recombinant FVIII (rFVIII) that are devoid of VWF, in particular when the inhibitors are directed against the light chain of FVIII. This paper provides an overview of several in vitro and in vivo studies that compared three clinically available clinical FVIII products (Kogenate®, Bayer AG, Leverkusen, Germany; Advate®, Baxter Healthcare, Zurich, Switzerland; and Fanhdi®, Grifols S.A., Barcelona, Spain) in order to evaluate the functional actvity of the FVIII fractions in rFVIII that cannot bind VWF; explore the use of the thrombin generation assay (TGA) as a potential tool for optimizing the choice of FVIII concentrate for use in haemophilia A patients with inhibitors; compare the kinetics of the interactions between anti-FVIII antibodies and FVIII both in the presence/absence of VWF, using surface plasmon resonance. [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]

Summary. Factor V (FV) deficiency is a rare coagulation disorder, characterized by a bleeding phenotype varying from mild to severe. To date, 115 mutations have been described along the gene encoding for FV ( F5) but only few of them have been functionally characterized. Aim of this study was the identification and the molecular characterization of genetic defects underlying severe FV deficiency in a 7-month-old Turkish patient. Mutation detection was performed by sequencing the whole F5 coding region, exon-intron boundaries and about 300 bp of the promoter region. Functional analysis of the identified missense mutation was conducted by transient expression of wild-type and mutant FV recombinant molecules in COS-1 cells. Two novel mutations: a missense (Pro132Arg) and a 1-bp deletion (Ile1890TyrfsX19) were identified in the F5 gene. While the frameshift mutation is responsible for the introduction of a premature stop codon, likely triggering F5 mRNA to nonsense-mediated mRNA degradation, the demonstration of the pathogenic role of the Pro132Arg mutation required an experimental validation. Expression experiments showed that the missense mutation causes a significant reduction in FV secretion and in the specific activity of the residual secreted molecule (77% and 78% decrease, respectively). This paper reports the identification of two novel mutations responsible for FV deficiency, thus widening the mutational spectrum of the F5 gene. The Pro132Arg mutation adds to the only other two functionally characterized missense defects in the FV A1 domain. [ABSTRACT FROM AUTHOR]

Summary. The topic of this monograph is liver cancer associated with chronic HCV infection. We start with some background information on chronic HCV infection and its long-term sequelae, one of which is liver cancer. The rest of the article is concerned with liver cancer or hepatocellular carcinoma (HCC). Epidemiology, risk factors, treatment and outcomes are discussed. We focus on those aspects that are of specific interest in people with haemophilia: studies performed in haemophilia populations, the use of invasive diagnostic and therapeutic tools and the outcome of liver transplantation. Throughout the paper, recommendations are given on surveillance for and diagnosis of HCC and on the practical aspects of invasive procedures. These recommendations are based on professional guidelines, other published evidence and the authors' experience. In general, diagnostic and therapeutic options are the same in persons with and without haemophilia. [ABSTRACT FROM AUTHOR]

The article presents a study which reported eight unrelated patients from Pakistan suffering from congenital factor V (FV) deficiency. Topics discussed include the severity of bleeding symptoms of the patients, the lack of correlation found between the clinical expression of the disease and genetic defects, and implication of the paradox between the expected pathogenicity of frameshift mutations and the relatively mild clinical phenotype of the patients.