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Hemophilia A (HA) and B are inherited bleeding disorders caused by a deficiency of factor VIII or factor IX, respectively. The current standard of care is the administration of recombinant or purified factor. However, this treatment strategy still results in a high economic and personal burden to patients, which is further exacerbated by the development of inhibitors-alloantibodies to factor. The treatment landscape is changing, with nonfactor therapeutics playing an increasing role in what we consider to be the standard of care. Emicizumab, a bispecific antibody that mimics the function of factor VIIIa, is the first such nonfactor therapy to gain US Food and Drug Administration approval and is rapidly changing the paradigm for HA treatment. Other therapies on the horizon seek to target anticoagulant proteins in the coagulation cascade, thus "rebalancing" a hemorrhagic tendency by introducing a thrombotic tendency. This intricate hemostatic balancing act promises great things for patients in need of more treatment options, but are these other therapies going to replace factor therapy? In light of the many challenges facing these therapies, should they be viewed as a replacement of our current standard of care? This review discusses the background, rationale, and potential of nonfactor therapies as well as the anticipated pitfalls and limitations. This is done in the context of a review of our current understanding of the many aspects of the coagulation system., (Copyright © 2021 by The American Society of Hematology.)

The current mainstay of therapy for hemophilia is to replace the deficient clotting factor with the intravenous administration of exogenous clotting factor concentrates. Prophylaxis factor replacement therapy is now considered the standard of care in both pediatric and adult patients with hemophilia with a severe phenotype to protect musculoskeletal health and improve quality of life. Heterogeneity in bleeding presentation among patients with hemophilia due to genetic, environmental, and treatment-related factors has been well described. Accordingly, the World Federation of Hemophilia recommends an individualized prophylaxis regimen that considers the factors mentioned above to meet the clinical needs of the patient, which can vary over time. This review focuses on the practical points of choosing the type of factor concentrate, dose, and interval while evaluating appropriate target trough factor levels and bleeding triggers such as level of physical activity and joint status. We also discuss the use of a pharmacokinetics assessment and its incorporation in the clinic for a tailored approach toward individualized management. Overall, adopting an individualized prophylaxis regimen leads to an optimal utilization of factor concentrates with maximum efficacy and minimum waste., (Copyright © 2021 by The American Society of Hematology.)

Background: Knowledge about sexual health, difficulty with sexual activity and intimacy (sexual difficulty), in people with hemophilia is little understood., Objectives: The objectives were to determine the prevalence of sexual difficulty in people living with hemophilia (PWH) compared to people with no bleeding disorders (PWNoBD), and to determine factors associated with it., Methods: This was an analysis of the PROBE study. We recruited individuals who had hemophilia A or B (PWH) and PWNoBD who were 18 years old or older. We calculated proportions of participants with sexual difficulty and odds ratios (ORs) adjusted for sex and age with 95% confidence intervals., Results: There were 2007 PWH and 1972 PWNoBD. Mean (standard deviation) age was 41 (15) years in PWH and 42 (13) years in PWNoBD. Sexual difficulty was reported in 302 (15.1%) PWH and 79 (4.0%) PWNoBD. The odds of sexual difficulty were significantly higher in PWH (OR 3.82, 95% CI 2.85, 5.11). Among PWH, older age, experiencing acute or chronic pain in the past 12 months, bleeds within the past two weeks, ≥3 spontaneous joint bleeds (past six months), limitation of range of motion of any joints, and any life- or limb-threatening bleeds in the past 12 months were associated with sexual difficulty., Conclusions: Sexual difficulty is more prevalent in people living with hemophilia and associated with markers of disease severity. Sexual health issues should be incorporated in comprehensive hemophilia care, future research, and hemophilia related health policy., (© 2021 John Wiley & Sons Ltd.)

Background: Several studies have reported that haemophilia carriers have a bleeding tendency independent of factor activity. However, investigations have been fraught with methodological concerns. The ATHNdataset houses the largest data set of haemophilia carriers in the world. We undertook an analysis of haemophilia carriers in this data set using methodologies that characterize bleeding symptoms in carriers., Aim: Determine the proportion of haemophilia carriers who have a normal bleeding score (BLS) and factors that affect the BLS., Methods: The ATHNdataset was queried for haemophilia carriers with a documented BLS. Collected data included demographics, ISTH-BAT score, factor activity level, type of haemophilia (A or B), genotype and geographic residence., Results: Nine hundred twenty-two haemophilia carriers in the ATHNdataset reported a BLS. When adjusted for age, 74% reported a normal score. Logistic regression identified age, factor activity level, ethnicity and region of residence as risk factors for an abnormal score., Conclusions: The majority of haemophilia carriers (74%) in the ATHNdataset had a normal BLS, including the majority (59%) with factor activity levels < 40 IU/dl. Conversely, 24% of haemophilia carriers with a factor activity level > 40 IU/dl reported an abnormal BLS. These results are consistent with previous studies of haemophilia carriers. Additional investigation is needed to determine why a majority of haemophilia carriers with low factor activity levels report normal BLSs while a significant minority of haemophilia carriers with normal activity levels report abnormal BLSs., (© 2021 John Wiley & Sons Ltd.)

Introduction: Published guidelines are available to assist in the management of patients with inherited bleeding disorders in the elective surgical setting however good quality outcome data is lacking., Aim: - Evaluate the outcomes of adult patients with inherited bleeding disorders, who received factor replacement for elective surgery in NSW/ACT, Australia. - Assess adherence to relevant guidelines including Haemophilia Treatment Centre (HTC) utilisation and appropriate factor replacement., Method: A retrospective analysis was performed between 2000 and 2018 to describe patient characteristics, surgical details, factor provision and outcomes. Univariate analysis was used to determine variables associated with guideline adherence. Covariates with p < 0.1 were included in the multivariate analysis., Results: A total of 1065 surgeries were performed on 571 patients. Diagnoses included Haemophilia A (43.5%), Haemophilia B (9.7%), von Willebrand disease (VWD) (45.3%) and rare bleeding disorders (RBDs) (1.6%). Bleeding complications were reported in 14 surgeries and 19 patients received factor replacement beyond standard duration of prophylaxis. Approximately 50% of all surgeries were performed in a HTC. Multivariate analysis demonstrated that diagnosis, surgical specialty, sex and year (p < 0.001) were associated with non-compliance with variable pattern within each category. Factor replacement was as expected except for plasma-derived Factor VIII/VWF usage in patients with VWD undergoing major bleeding risk surgery. VWD classification (p < 0.001) was associated with this deviation., Conclusion: Low complication rates demonstrate that elective surgery in Australia is being safely performed in patients with inherited bleeding disorders however non-compliance with published guidelines exists highlighting areas of practice and policy discrepancies that warrant further exploration., (© 2021 John Wiley & Sons Ltd.)

Background: The hallmark of severe hemophilia (A or B) is recurrent bleeding into joints and soft tissues with progressive joint damage, despite on-demand treatment. Prophylaxis has long been used, but not universally adopted, because of medical, psychosocial, and cost controversies., Objectives: To determine the effectiveness of clotting factor concentrate prophylaxis in managing previously-treated individuals with hemophilia A or B., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. In addition, we searched MEDLINE and Embase and online trial registries. Most recent search of Group's Coagulopathies Trials Register: 24 February 2021., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs evaluating people with hemophilia A or hemophilia B, who were previously treated with clotting factor concentrates to manage their hemophilia., Data Collection and Analysis: Two authors independently reviewed trials for eligibility, assessed risk of bias and extracted data. The authors used the GRADE criteria to assess the certainty of the evidence., Main Results: Ten trials (including 608 participants) were eligible for inclusion. Eight of the trials (477 participants) had arms comparing two or more prophylactic regimens to one another and four of the trials (n = 258) compared prophylaxis to on-demand treatment (two trials had multiple arms and were included in both comparisons). Comparison of two or more prophylactic regimens For trials comparing one prophylaxis regimen to another, given the heterogeneity of the data, none of the data were pooled for this comparison. Considering the individual trials, three trials reported the primary outcome of joint bleeding, and none showed a dfference between dosing regimens (low-certainty evidence). For the secondary outcome of total bleeding events, prophylaxis with a twice-weekly regimen of FIX likely results in reduced total bleeds compared to a once-a-week regimen of the same dose, mean difference (MD) 11.2 (5.81 to 16.59) (one trial, 10 participants, low-certainty evidence). Transient low-titer anti-FVIII inhibitors were reported in one of the trials. Blood-transmitted infections were not identified. Other adverse events reported include hypersensitivity, oedema, and weight gain. These were, however, rare and unrelated to study drugs (very low-certainty evidence). Comparison of prophylactic and on-demand regimens Four of the trials (258 participants) had arms that compared prophylaxis to on-demand treatment. Prophylaxis may result in a large decrease in the number of joint bleeds compared to on-demand treatment, MD -30.34 (95% CI -46.95 to -13.73) (two trials, 164 participants, low-certainty evidence). One of these trials (84 participants) also reported the long-term effects of prophylaxis versus on-demand therapy showing improved joint function, quality of life, and pain; but no differences between groups in joint structure when assessed by magnetic resonance imaging (MRI). In one trial (84 participants) validated measures for joint health and pain assessment showed that prophylaxis likely improves joint health compared to an on-demand regimen with an estimated change difference of 0.94 points (95% CI 0.23 to 1.65) and improves total pain scores, MD -17.20 (95% CI -27.48 to -6.92 (moderate-certainty evidence). Two trials (131 participants) reported that prophylaxis likely results in a slight increase in adverse events, risk ratio 1.71 (1.24 to 2.37) (moderate-certainty evidence). No inhibitor development and blood-transmitted infections were identified. Overall, the certainty of the body of evidence was judged to be low because of different types of bias that could have altered the effect.   AUTHORS' CONCLUSIONS: There is evidence from RCTs that prophylaxis, as compared to on-demand treatment, may reduce bleeding frequency in previously-treated people with hemophilia. Prophylaxis may also improve joint function, pain and quality of life, even though this does not translate into a detectable improvement of articular damage when assessed by MRI.  When comparing two different prophylaxis regimens, no significant differences in terms of protection from bleeding were found. Dose optimization could, however, result in improved efficacy. Given the heterogeneity of the data, pooled estimates were not obtained for most comparisons.  Well-designed RCTs and prospective observational controlled studies with standardised definitions and measurements are needed to establish the optimal and most cost-effective treatment regimens., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Nonacog alfa (recombinant factor IX [FIX]) is approved in China for the control and prevention of bleeding events in patients with hemophilia B. This was the first study to assess prophylaxis and on-demand therapy with recombinant FIX replacement in a real-world setting in China. This study aimed to evaluate the safety and efficacy of nonacog alfa in Chinese patients with hemophilia B., Methods: In this open-label, multicenter study (clinicaltrials.gov identifier NCT02336178), patients received on-demand or prophylactic treatment with intravenous nonacog alfa for approximately 6 months or 50 exposure days, whichever occurred first. The primary safety outcome was medically important events (i.e., development of FIX inhibitors, allergic reactions, and thrombotic events). Key secondary efficacy outcomes included the annualized bleeding rate for on-demand treatment and prophylaxis, response to on-demand treatment, the number of infusions per bleeding event, and the number of breakthrough bleeding events within 48 hours of prophylaxis., Results: Seventy male patients (mean [standard deviation] age 7.8 [7.2] years) were enrolled (on-demand, n = 37; prophylaxis, n = 57 [24 patients were included in both groups]). Thirty-eight (54%) patients had up to 50 FIX exposure days before the study. The only medically important event was a transient low-titer FIX inhibitor (incidence 1.4%, 95% confidence interval, 0-7.7). The mean annualized bleeding rate was 26.3 for on-demand treatment and 6.5 for prophylaxis. A mean (standard deviation) of 1.5 (1.7) nonacog alfa infusions were given per bleeding episode; 78.8% of episodes resolved with 1 infusion. Response was "excellent" or "good" for 88% of the on-demand infusions. Twenty-three bleeding events (n = 11 patients) occurred within 48 hours of 2032 prophylaxis doses (1.13%)., Conclusion: In the real-world setting, nonacog alfa is safe and effective for on-demand treatment and for prophylaxis for patients with hemophilia B in China., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Data on outcome in persons with haemophilia B (PwHB) are limited and mainly extrapolated from studies of haemophilia A (HA)., Aim: To characterize treatment outcomes in persons with severe HB in the Nordic region, with a focus on joint health, compared with matched controls with HA., Methods: PwHB attending haemophilia centres in Denmark, Finland, Norway and Sweden were enrolled and matched with controls with HA. Joint assessment using Haemophilia Joint Health Score (HJHS) and ultrasound according to Haemophilia Early Arthropathy Detection protocol (HEAD-US) was conducted. Adherence was evaluated using the Validated Haemophilia Regimen Treatment Adherence Scale (VERITAS)., Results: Seventy-nine males with HB, with median age of 30 years (range 1-75), were enrolled. Eleven patients (14%) had a history of or current inhibitor. Twenty-nine PwHB (37%) reported joint bleeds during the prior year, and 35% had previously undergone joint surgery. Ninety-five per cent were on prophylaxis, and 70% used recombinant concentrates, with a median factor consumption of 3,900 IU/kg/year for standard half-life products. Only two patients had a VERITAS score corresponding to 'non-adherence'. Joint health, assessed with HJHS, showed a significant lower score among PwHB compared with HA controls, explained by a difference in the 18-49 age group, without observed differences in older or younger subgroups. The HEAD-US scores were overall low., Conclusion: The Nordic cohort of PwHB is well treated by prophylaxis, but the goal of zero bleeds for all is not reached. Our findings suggest that patients with severe HB suffer from a milder arthropathy than patients with severe HA., (© 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Urolithiasis may be more prevalent in patients with hemophilia (PWH) than in age-matched non-hemophilic males. We conducted a cross-sectional evaluation of 92 adult PWH at University Hospital Center Zagreb. The primary objective was to investigate the frequency of urolithiasis in adult PWH, and the secondary objective was to determine associated risk factors. Urolithiasis was diagnosed by ultrasound and other patient- and hemophilia-related parameters were recorded. The prevalence of urolithiasis was significantly higher among PWH than the reported prevalence in the general Croatian population (10.9% vs 5.9%; P = 0.042). Similarly, the incidence of urolithiasis during the course of the disease was significantly higher than the estimated cumulative lifetime incidence of urolithiasis in the Croatian population (25% vs 12%; P = 0.001). Multivariate analysis showed that arterial hypertension, the presence of inhibitors, hypercalciuria and hyperbilirubinemia were independent predictors of current urolithiasis (P < 0.05), and that hematuria (P = 0.051) and prior urinary infections (P = 0.059) were also relevant factors.Urolithiasis is a significant burden in adult PWH. Identifying associated risk factors might help in establishing strategies for earlier recognition and more successful prevention and treatment of urolithiasis.

Introduction: Our purpose was to determine the bleeding risk of obligate and potential carriers, highlight the prophylactic applications before interventions for families and physicians., Method: Forty-six sisters who had at least one family member with hemophilia A or B were included. Laboratory parameters were tested.Bleeding tendency interrogated by a detailed questionnaire.The results were compared with 43 healthy female controls., Results: Mean factor activity levels were significantly lower in sisters than control subjects (p = 0,004). Bleeding score was higher in sisters than controls (p = 0.001). Prolonged bleeding after minor injury was significantly higher in the sisters than control subjects (p = 0.008). Requiring further treatment due to prolonged bleeding after tooth extraction was significantly higher in sisters (p = 0.001). Sisters had postpartum hemorrhage lasting longer than 6 weeks than controls (p = 0.025). Menstrual period lasted longer in the sisters than controls (p < 0.001). Spontaneous epistaxis, oral and gingival bleeding were more frequently observed in sisters whose factor activity levels were 60 % or below (p = 0.014 and p = 0.047, respectively). There was no statistically significant difference between the severity of hemophilia in the affected family member and the factor levels in the sisters (p = 0.398).Spontaneous epistaxis has found to be significantly associated with the hemophilia severity in the family (p = 0.004)., Conclusion: Clotting factor levels were found to be lower in the sisters and associated with spontaneous epistaxis, oral and gingival bleeding.Also, regardless of clotting factor levels, sisters significantly experienced more bleeding problems.Our study demonstrated the importance of taking precautions for prolonged bleeding in cases where medical interventions are inevitable in these patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In a pivotal, multicenter, open-label study, 25 patients aged 12-54 years with moderately severe/severe hemophilia B received on-demand nonacog alfa (6 months; dose at investigator's discretion) followed by once-weekly prophylaxis with nonacog alfa 100 IU/kg (12 months). During prophylaxis, patients had a median spontaneous annualized bleeding rate (sABR) of 1.0 and significant reductions in ABR (P < 0.0001). This post hoc analysis examined the time of onset of spontaneous bleeding events (sBEs) and spontaneous target joint bleeding events (sTJBEs). The postdosing day (D) of onset of sBEs observed during prophylaxis and steady-state FIX activity data (FIX:C) between 144 and 196 h postdose were collected at weeks 26 and 78. Twelve patients (48%) had no sBEs; the remaining 13 (52%) had the following onset of sBEs: less than 1 D (0%), 1 to less than 2D (5%), 2 to less than 3 D (22%), 3 to less than 4 D (9%), 4 to less than 5D (22%), 5 to less than 6D (23%), 6 to less than 7D (11%), and at least 7D (8%). Reductions in sBEs and sTJBEs during on-demand versus prophylaxis treatment were experienced by all 13 patients. Target joint sABR during prophylaxis was 0 for 5/13 patients. ABR reduction ranged from 66.1% (27.2→9.2) to 97.8% (46.2→1.0); sTJBE reductions ranged from 6.2% (2.1→2.0) to 100% (from 40.1, 19.1, 3.9, 9.0, 6.1--0). During prophylaxis, 47% (8/17) of trough FIX activity samples were more than 2%. In sBE patients, ABR and number of TJBEs were reduced with once-weekly nonacog alfa. When sBEs occurred, they followed no apparent pattern for day of occurrence. Clinicaltrials.gov identifier: NCT01335061., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The paediatric Haemophilia Activities List (pedHAL) was developed to measure activities and participation in children and youth with haemophilia. Results from international studies provide an opportunity to determine which items are universally important., Aim: The aim of this study was to determine which items of the pedHAL are redundant to construct a shorter version of the pedHAL., Methods: This study is a cross-sectional multicentre secondary analysis on pooled data of published studies using the pedHAL (7 domains, 53 items, optimum score: 100) in children with haemophilia A/B aged 4-18 years. To identify redundant items, the following aspects were evaluated: floor and ceiling effects, proportions of missing and 'not applicable' responses, inter-item correlations, component loadings in an exploratory factor analysis, internal consistency and item-total correlations., Results: Data on 315 patients with haemophilia from 6 studies were evaluated. Median age was 12.2 years) (range 4.0-18.0), 87.3% had severe haemophilia and 80.3% received prophylaxis. Median (IQR) pedHAL sum score was 96.7 (88.0-100). After a stepwise procedure, 31 items were removed, resulting in a pedHAL short of 22 items, representing all original 7 domains. Most remaining items belonged to the domains 'sitting/kneeling/standing' and 'functions of the legs'. The pedHAL short sum score was similar to the original pedHAL sum score, with small differences in 5 domains., Conclusion: This clinimetric study resulted in >50% reduction of the length of the pedHAL. The 22-item pedHAL short reduces patient burden and is expected to capture the information on activities and participation. The pedHAL short needs validation in other populations., (© 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Introduction : People with hemophilia (PWH) may require some surgical procedures (orthopedic surgery, cardiac surgery, neurosurgery, et cetera) throughout their lives. Areas covered : Articles on surgery and hemophilia published during the year 2020 were analyzed. The principal inclusion factor was a focal point on surgery in hemophilia. Articles that did not concentrate on this subject were not included. Expert opinion : Turoctocog alfa pegol appears to be efficacious for perioperative hemostatic treatment of all kind of surgical operations (minor and major) in PWH A. Long-acting recombinant coagulation factor IX (FIX) albumin fusion protein ( rIX-FP ) seems to facilitate perioperative management in PWH B. In people suffering from von Willebrand disease (VWD), the utilization of concentrates of von Willebrand factor (VWF) is commonly used for the decrease of exaggerated bleeding during surgical operations. On-demand management with 30-60 IU/kg may keep hemostasis under control during all kind of surgical operations. Factor concentrates with extended half-life (EHL) are a good option to standard half-life (SHL) products in PWH undergoing surgery, permitting diminished number of infusions and inferior consuming, particularly for EHL factor IX (FIX). Supplementary factor VIII (FVIII) and/or bypassing management have demonstrated to be secure and efficacious in association with emicizumab for major surgical procedures.

Current treatments in the field of haemophilia are changing the phenotype of many patients with severe haemophilia to that of mild haemophilia. Despite this improvement, those with mild-to-moderate haemophilia A and haemophilia B continue to experience unmet needs. Whereas some patients with mild-to-moderate haemophilia experience similar complications to those of patients with severe haemophilia, they possess several unique attributes. These include a challenging diagnosis and variability in bleeding symptoms and treatment needs. In addition, haemophilia is an under-recognized condition in women even though many women with mild-to-moderate haemophilia experience the same symptoms and complications as men with haemophilia. These women also have their own unique challenges with this disease. This supplement highlights many of the unmet needs in men and women with mild-to-moderate haemophilia. The conclusions of each of these papers reinforce the need for additional research and resources for this patient population., (© 2021 John Wiley & Sons Ltd.)

Introduction: Epidemiologic studies suggest that joint bleeding occurs in patients with mild-to-moderate haemophilia, including women and girls. However, most previous studies on the impacts of haemophilia focus on men with severe disease., Aim: To identify unmet needs in men and women with mild-to-moderate haemophilia., Methods: The Pain, Functional Impairment, and Quality of Life (P-FiQ) study assessed the impact of pain on functional impairment and health-related quality of life in men with haemophilia A or B of any severity. The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) study evaluated the psychosocial needs of adults and children with haemophilia B of any severity, including women and girls. Both studies employed patient-reported outcome measures., Results: In the P-FiQ study, 16% (62/381) of participants had mild and 13% (50/381) had moderate haemophilia. In the B-HERO-S study, 29% (86/299) of adult participants were female, 25% (74/299) had mild haemophilia, and 63% (189/299) had moderate haemophilia. In addition, 63% (46/74) of patients with mild and 86% (162/189) of patients with moderate haemophilia routinely infused factor products to prevent bleeding. Patients reported difficulty gaining access to factor products (54%; 142/263) and a haemophilia treatment centre (17%; 44/263). During the P-FiQ study, 78% (48/62) of patients with mild and 87% (44/50) with moderate haemophilia described problems with pain on the Brief Pain Inventory. Patients also reported issues with anxiety, depression and relationships., Conclusions: Mild-to-moderate haemophilia has physical and psychosocial impacts on patients. We offer some solutions to help alleviate these impacts and resolve unmet needs., (© 2021 John Wiley & Sons Ltd.)

Background: The risk of developing cancer increases with age and also adverse environmental conditions. The same holds true in the aging people with hemophilia (PwH). Furthermore, cancer is an important challenge for physicians working in multidisciplinary hemophilia care centers., Aim: Here, the authors report 7 hemophiliacs with malignancies diagnosed and managed at our center., Study Design: Hemophilia A and B were included., Method: Patients with mild, moderate, or severe hemophilia A or B, who were followed-up in our center between January 1999 and December 2018 were included in the study. A total of 470 PwH (391 Hemophilia A and 79 Hemophilia B) were followed in this time period., Results: With a minimum 1 and maximum 20 years (median: 11.5 y) of the following time, 7 of 470 (1.48%) PwH were diagnosed with cancer. The diagnosed cancer types were acute lymphoblastic leukemia, acute myeloid leukemia, thyroid cancer, rectum cancer, malign melanoma, basal cell carcinoma, and gastric cancer. All patients except patients with leukemia had major surgical intervention and the hemostasis control was provided on the basis of institutional protocols. At the end of the study, all of the patients were alive besides the patient with acute myeloid leukemia., Conclusions: Nowadays, the management of PwH has improved immensely and the life span has progressively become similar to healthy male individuals. For accurate improvement and standardizing care, prospective data collection on the epidemiology of cancer in PwH is an important tool.

Management of haemophilia carrier women during labour and postpartum is yet to be standardized. Pregnancy was accompanied by a marked rise in factor VIII levels compared with only a small rise in factor IX levels. After delivery, a carrier's factor level drops down to prepregnancy levels, which increases the chance of postpartum haemorrhage. Availability of management guideline and care provided in a multidisciplinary approach can help to minimize bleeding complications in carriers of haemophilia and their newborns., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

: The objectives of this study were firstly to determine the prevalence of overweight/obesity in adult persons with hemophilia in Utah, and to explore the association between age, disease severity and race with body mass index (BMI), and secondly to provide recent data on the prevalence of overweight/obesity in the hemophilia population via a review of the literature. We conducted a retrospective cross section study of adult persons with hemophilia who were seen at a Utah hemophilia treatment center from 1 January 2017 to 31 December 2019. The electronic database PubMed was searched for studies with observation periods from 1 January 2012 to 31 December 2019. The age-adjusted prevalence for overweight/obesity in the adult Utah hemophilia population was higher than the overall Utah population and the general US population. After adjusting for race and age, mild hemophilia was associated with a 7.7% higher BMI (95% confidence interval, 0.023-15.98%, P < 0.05). Review of the literature demonstrated high levels of overweight/obesity in hemophilia communities globally with considerable heterogeneity between studies. Despite increasing awareness, prevalence of overweight/obesity in the hemophilia population remains high in comparison with the general population. There is a critical need to address this issue acutely at hemophilia treatment centers due to the considerable burden of obesity.

It is known that hemophilia carries have a higher incidence of abnormal bleeding in wounds, dental extractions, surgeries, epistaxis, but how does this symptomatology affect her in her daily life? In her family environment and works? This supplement outlines the importance of patient associations and the resources available to help women with bleeding disorders., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

A 57-year-old man with mild haemophilia B was admitted for coronary artery bypass graft surgery. His factor IX (FIX) activity was 15% on admission. Our goal was to maintain his FIX activity at 80%-100% for post-op days (PODs) 0-3, and at 60%-80% for PODs 4-14. Preoperatively, the patient was given recombinant FIX (rFIX) bolus using the formula:Dosage needed=%(desired FIX level-current level of FIX)×weight (kg)×1.3.This increased his activity to 100%. One IU of rFIX increased FIX activity by 0.8%; the half-life of rFIX is 18-24 hours. The rFIX infusion was started intraoperatively and continued after surgery to maintain target FIX activity. He was discharged on POD 9 on rFIX bolus dosing of 5000 IU every 12 hours for an additional 5 days. Using continuous factor infusion, we managed to decrease the amount rFIX used by >60% while maintaining steady state FIX activity level., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The risk of chronic haemophilic arthropathy (CHA) is related to severity. Evidence suggests that primary prophylaxis (PPr) could reduce CHA incidence and its impact on quality of life., Aim: To evaluate the association between PPr and CHA in Colombian males with haemophilia B (HB) during 2015 to 2019., Methods: A panel-time analysis was performed with data provided by the National Health System to update a nationwide open cohort of people with congenital coagulopathies. The association was evaluated in a logistic random-effect regression model (LRERM), adjusted by age at diagnosis, prophylaxis dose and frequency, severity, haemarthrosis and high-titre inhibitors., Results: During 2015-2019, a total of 362 men with HB and treated with either, primary, secondary or tertiary prophylaxis were identified. At baseline, CHA prevalence in the cohort was 36.84% (n = 133), median age was 19.0 years (IQR: 10.0-27.0), and median age at diagnosis was 1.0 year (IQR: 0.0-4.0). PPr was prescribed in 37.85% (n = 137), and median dose (IU/Kg/dose) was almost the same for primary vs. secondary/tertiary prophylaxis. Patients in PPr had a lower frequency of severe HB, CHA, haemarthrosis, infectious complications and high-titre inhibitors than those in secondary or tertiary prophylaxis (STPr). In the LRERM, PPr was associated with a significant reduction of 89.70% in the odds of CHA (aOR = 0.103, IC 95%: 0.040, 0.270; P < .001), compared with STPr., Conclusions: PPr decreased the odds of CHA by 89.70% in males with HB in Colombia. Our findings are consistent with previous studies and support the strategy to prescribe PPr to our patients., (© 2020 John Wiley & Sons Ltd.)

The authors describe the first case of simultaneous liver and kidney transplantation (SLK) in a human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patient with severe hemophilia in Japan, and it could be second case in the world. The patient was a 61-year-old Japanese man with HCV cirrhosis complicated with HIV coinfection through contaminated blood product for hemophilia B at age 1 year. The patient's liver disease was classified as Child-Pugh C, Model for End-Stage Liver Disease score 38. He had been on hemodialysis for 6 years, but HIV RNA and HCV RNA had been undetectable after appropriate antiviral therapies. In September 2019, the patient underwent successful deceased donor (DD) SLK. The donor was a man in his 60s deceased due to cerebral hemorrhage. Regular DD liver transplantation was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 566 min, and the graft liver weighed 1154 g. The graft kidney was transplanted extraperitoneally in the right iliac fossa. The administration of clotting factor IX was discontinued on day 3. The immunosuppressive regimen was based on intravenous induction with 2 mg/kg of basiliximab and 1 g methylprednisolone and subsequent oral administration of mycophenolate mofetil and prednisolone, followed by low-dose tacrolimus after 1 week for kidney-sparing purpose. Steroid therapy was gradually discontinued at 3 months after SLK. The same pretransplantation antiretroviral therapy (ART; tenofovir and dolutegravir) was introduced after 3 days when the CD4 cell count was more than 300/μL and HIV RNA was within an undetectable range. The postoperative course was uneventful without infectious complication, and the patient was transferred to a referral hospital on day 90 and discharged home on day 111. Strategic surgical planning and meticulous pre- and post-transplant management of ART and clotting factors could lead to the success of SLK., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Extended half-life of factor IX (FIX) demonstrated clinical benefit and lower treatment burden than standard half-life FIX products in clinical trials. We analysed the impact in efficacy, pharmacokinetics (PKs) and costs of the switch from nonacog alfa (rFIX) to albutrepenonacog alfa (rFIX-FP) in the first patient with haemophilia B (HB) treated in Spain outside clinical trials. A 7-year-old boy presented with HB with poor venous access and repetition infections using rFIX, which was switched to rFIX-FP. Prophylaxis was adjusted by PKs using WAPPS-Hemo tailoring from 100 IU/kg/week of rFIX to 80 IU/kg/3 weeks of rFIX-FP. Comparing 6 months before, rFIX-FP reduced 68.5% FIX consumption/kg and 58.3% infusion frequency, but total costs/weight showed a slight increase. Ratio of half-life between rFIX and rFIX-FP was 3.4-3.7. This case report revealed that switch to rFIX-FP decreased frequency and FIX consumption, without adverse events and bleeds., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Dr. Tagliaferri reports personal fees from Bayer, Novo Nordisk, and Roche, outside the submitted work. Dr. Coppola reports personal fees from Bayer, Novo Nordisk, and Werfen, outside the submitted work. Dr. Quintavalle reports personal fees from Bayer, outside the submitted work.

Introduction: Haemophilia (H) is frequently associated with a multifactorial reduction in bone mineral density (BDM), but little is known about possible differences between HA and HB according to their severity., Aim: To evaluate the association between low bone mineral density (BMD), 25-hydroxyvitamin D [25(OH)D] concentrations and bone turnover markers in patients with HA and HB younger or older than 50 years., Methods: In 78 patients <50 years and 33 patients >50 years with severe (S) or moderate (M) HA and HB, BMD was measured by dual-energy X-ray absorptiometry at femoral neck (FN) and lumbar spine and then correlated to annual bleeding rate (ABR), World Federation of Haemophilia orthopaedic joint scale (WFH score), 25(OH)D concentrations, parathyroid hormone (PTH), amino-terminal telopeptide of type 1 collagen (NTx), urinary pyridinolines, osteocalcin and bone-specific alkaline phosphatase., Results: Overall, a high prevalence of hypovitaminosis D was diagnosed. In patients <50 years, low FN-BMD was significantly more frequent in HA than in HB, while PTH, pyridinolines, ABR and WFH score were associated with H type and severity. In patients >50 years, similarly low FN-BMD was observed in HA and HB, while ABR and WFH score were associated with H type and severity, being milder in HB., Conclusions: Low bone mass is a frequent comorbidity in haemophilic patients of all ages, apart from those with MHB. Clinical and laboratory assessments confirm a higher bone impairment and faster bone resorption in HA compared with HB. Looking at H type and severity, MHB seems to have a normal bone metabolism and a less severe disease., (© 2020 John Wiley & Sons Ltd.)

Background: Total ankle arthroplasty (TAA) can result in excellent outcomes in patients with end-stage arthritis, but most patients with end-stage hemophilic ankle arthropathy (ESHAA) still undergo ankle arthrodesis (AA). The purpose of this study was to analyze clinical and radiological results of TAA and AA for ESHAA., Methods: A total of 29 cases (16 TAAs and 13 AAs) of painful ESHAA were included. For clinical outcome evaluation, visual analog scale (VAS) for pain, Foot Function Index (FFI), and range of motion (ROM) were analyzed. Postoperative clinical and radiological complications were also analyzed. The mean duration of follow-up was 6.8 ± 3.0 years. The mean age was 44.1 ± 9.9 years., Results: The VAS for pain was significantly improved from 5.5 ± 2.3 to 0.9 ± 1.2 ( P < .001). The FFI scale was significantly improved from 61.6% ± 15.5% to 16.6% ± 15.4% ( P < .001). In FFI disability and activity subscales, the TAA group exhibited meaningful outcomes relative to those of the AA group ( P = .012 and .036, respectively). The total ROM in the TAA group changed from 30.8 ± 12.6 degrees to 37.3 ± 12.8 degrees at final follow-up ( P = .090). Three cases of osteolysis and 1 case of heterotopic ossification were noted in the TAA group. No cases of nonunion were noted in the AA group. Progressive arthrosis of adjacent joints after AA was observed in 1 case., Conclusion: Both TAA and AA in ESHAA exhibited significant improvement in pain based on VAS and FFI scales. Compared to AA, TAA resulted in superior outcomes in FFI disability and activity subscales, suggesting that TAA may be considered as a surgical option alongside AA for ESHAA., Level of Evidence: Level III, retrospective comparative study.

Introduction: Iliopsoas muscle hemorrhage in patients with hemophilia is a serious complication with relevant related morbidity., Areas Covered: A Cochrane Library and PubMed (MEDLINE) search of studies related to iliopsoas hematomas in hemophilia was analyzed. Pain in the hip joint area and femoral nerve involvement in people with hemophilia should alert physicians to the likelihood of a hemorrhage of the iliopsoas muscle. Clinically, reduced hip range of motion and deficient motor and sensory function of the femoral nerve can be found. Imaging studies, such as ultrasonography (US), CT scan, and MRI will confirm the diagnosis. The first-line therapy for iliopsoas hematoma must be conservative (hematological treatment using high-dose replacement therapy until full resorption monitored by means of imaging studies). Related femoral nerve involvement typically resolves with conservative treatment (rehabilitation). Pelvic hemophilic pseudotumors can occur in patients with hemophilia due to recurrent iliopsoas muscle bleeding, often related to late diagnosis and poor hemostasis., Expert Opinion: Long-term clotting factor replacement is the pillar of the management of iliopsoas hematomas. Percutaneous US-guided aspiration of blood can be performed in hematomas of large size. However, the rate of failed aspirations and hematoma repetition is substantial (13%).

Hemophilia A (HA) and B (HB) are X-linked bleeding disorders caused by mutations in the F8 or F9 gene that result in the absence, or reduced activity, of the corresponding clotting factor. The severity of bleeding and related complications is proportional to the amount of residual circulating functional factor. The development of a safe and effective hemophilia treatment lasted several decades and has been mainly based on clotting factor replacement. Advances in the engineering and manufacturing of clotting concentrates have led to the widespread availability of extended half-life products that reduced the number of intravenous infusions needed to achieve adequate trough levels. The recent development of new nonfactor replacement treatments and biotechnology techniques has offered therapeutic alternatives for hemophilia patients with and without inhibitors. These are characterized by an easier route of administration, low immunogenicity, and, regarding gene therapy and cell-based treatments, potential long-term protection from bleeding after a single treatment course. In this review, we analyze recent progresses in the management of hemophilia and discuss opportunities and challenges., Competing Interests: Dr. Matino reports personal fees from Sanofi, grants and personal fees from Sobi, personal fees from UBS, grants and personal fees from Pfizer, personal fees from NovoNordisk, personal fees from BIOVIIIX, outside the submitted work., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Adherence to prophylaxis regimens is essential for bleed prevention in haemophilia but remains a challenge due to the need for frequent infusions., Aim: To evaluate patient adherence to prophylaxis regimens with a long-acting recombinant factor IX (rIX-FP; IDELVION ® ) in clinical studies and real-world practice., Methods: In two phase 3 clinical studies, patients with haemophilia B (FIX ≤2%) recorded their dose, dosing frequency and rIX-FP consumption in an e-diary. Adherence to prescribed prophylaxis regimens was assessed in all patients and to prescribed dose in patients ≥12 years only. Additionally, adherence to rIX-FP prophylaxis regimens in real-world practice was captured., Results: In clinical studies, 94.9% (n = 56/59) of patients ≥12 years and 100% (n = 27) of paediatric patients received ≥80% of the expected number of infusions for their assigned prophylaxis schedule. Overall, mean adherence rate was 95.5% across all prophylaxis regimens in patients ≥12 years and 97.9% with a 7-day regimen in paediatric patients. In patients ≥12 years, 85.7% (n = 54/63) were dose adherent, defined as receiving within 10% of their prescribed dose ≥80% of the time. In real-world practice, adherence was observed in 100% (n = 14 and n = 15, respectively) of patients in two haemophilia treatment centres and 57.1% (n = 4/7) of patients in a third centre; non-adherence (n = 3/7) was linked to insurance-related and parental issues., Conclusion: In clinical studies, patients with haemophilia B had high adherence rates to rIX-FP prophylaxis regimens with a variety of dosing intervals, enabling them to achieve very low bleeding rates. High adherence may also be achievable in real-world practice., (© 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Introduction: Sports participation in children with hemophilia is generally considered to be associated with increased injury risk, which is generally considered highest in severe hemophilia., Aim: To assess sports participation according to age and severity in children with hemophilia and its association with sports injuries., Methods: In a retrospective single-center study, sports participation, injuries, and bleeding data from three consecutive annual clinic visits were collected for young patients with hemophilia (PWH, aged 6-18). Sports in categories 2.5 and 3 of 3 according to the National Hemophilia Foundation classification were considered high-risk. Groups were compared using chi-square testing., Results: 105 PWH (median age: 13(IQR 10-14); 53% severe; bleeding rate: 1/y) were identified; three were unable to perform sports and were excluded. The majority of PWH (77%) played sports weekly, of which 80% high-risk sports. Sports participation (median 3.0x/wk), and the proportion of injured PWH was similar in severe (42%) and non-severe (33%) PWH. Sports injuries were rare (65% no injuries in 3 years, median 0/y (IQR 0-1)). Annually, PWH did not report more injuries (15%) than age-matched boys (28%). Sports injuries were not associated with frequency and type of sports., Discussion: This retrospective study showed high sports participation (including high-risk sports) and low injury rates. Sports participation was similar across severities and injury rates were not higher than among the general population. Injuries were not associated with frequency or type of sports. A prospective study with objective assessment of sports participation and injuries is warranted to confirm these findings and avoid recall bias., (© 2020 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: None declared.

Introduction: Despite the well-documented benefits of prophylaxis, treatment burden is still a barrier to adherence in patients with haemophilia. An extended half-life fusion protein linking recombinant FIX (rFIX) with human albumin (rIX-FP) has been developed for the treatment of patients with haemophilia B and is indicated for dosing up to every 14 days. This analysis evaluated real-world outcomes in patients switching to rIX-FP from the previous FIX product in Italy, Belgium and the UK., Methods: Anonymised chart data were collected from the pre-existing medical records of patients with haemophilia B between May and September 2018. Patients were included in the analysis if they had been treated with rIX-FP for ≥ 8 weeks. Data were compared between rIX-FP and the patient's prior FIX product., Results: Twenty-three HTCs from Italy (n = 13), Belgium (n = 3) and the UK (n = 7) provided data for 84 male patients, 92.8% of which had severe haemophilia B. The majority of patients were previously on prophylactic regimens with their prior FIX product (Italy, 44/49; Belgium, 7/10; UK, 22/25). The switch to prophylaxis with rIX-FP led to reductions in mean annualised bleeding rate of 94.3% in Italy, 93.9% in Belgium and 67.7% in the UK compared with prior FIX prophylaxis. Overall, 41% of patients experienced zero spontaneous bleeds prior to switching, compared with 88% following the switch to rIX-FP. The majority of patients had a reduction in dosing frequency following the switch, with 98.6% of patients dosing once weekly or less frequently compared with 9.6% of patients dosing at this frequency with their prior FIX. Mean weekly FIX consumption was reduced compared with prior FIX prophylaxis., Conclusion: This retrospective review of real-world evidence demonstrated that switching to rIX-FP from prior FIX was associated with improved haemostatic efficacy and reduced factor consumption in patients with haemophilia B from Italy, Belgium and the UK.

Background: The life expectancy of hemophiliacs is similar to that of the general population. As a result, the prevalence of age-related cardiovascular diseases has increased. We present our experience with hemophilia patients who underwent cardiac surgery in our Medical Center between 2004 and 2019., Methods: All hemophilia patients who underwent cardiac surgery were identified, and their peri-operative data evaluated retrospectively., Results: Ten patients were identified: six with hemophilia-A, one with hemophilia-B, and three with hemophilia-C (factor XI deficiency). Cardiac procedures included ten coronary artery bypass grafts and one aortic valve replacement. Hemophilia-A and B patients were treated with factor substitution, whereas patients with factor XI deficiency were treated with fresh frozen plasma. One patient died, and one patient suffered from non-active gastrointestinal bleeding., Conclusions: While major cardiac surgery can be performed safely on patients with hemophilia, a multidisciplinary team approach and strict postoperative monitoring are essential in order to achieve optimal results.

Introduction:  A phase 3b extension study evaluated the long-term safety and efficacy of a recombinant fusion protein-linking coagulation factor IX (FIX) with albumin (rIX-FP) for the routine prophylaxis and on-demand treatment of bleeding in pediatric hemophilia B patients., Methods:  Previously treated patients aged <12 years with moderate to severe hemophilia B enrolled in a 3-year extension study following a phase 3 pivotal study in which they received weekly rIX-FP prophylaxis. In the extension study, they could maintain or extend their prophylaxis interval to every 10 or 14 days if they were well controlled on the 7-day regimen., Results:  Compared with their initial regimen, by the end of the study, dosing intervals were the same, extended, and shortened in 16, 4, and 4 patients, respectively. Very low annualized spontaneous bleeding rates (AsBRs) were observed; median AsBR was 0.0 for the 7- and 10-day regimens, and 1.1 for the 14-day regimen. The 7- and 14-day regimens were comparable in preventing spontaneous bleeds; mean (95% confidence interval) difference in AsBR of -1.2 (-2.6 to 0.3) bleeding episodes/year/subject. Overall, 96% of bleeding episodes were successfully treated with one or two injections of rIX-FP. Patients on a 14-day regimen maintained a mean steady-state trough FIX level of >7.2 IU/dL. No patient developed an inhibitor., Conclusion:  This extension study demonstrated the long-term safety and efficacy of weekly rIX-FP in pediatric patients. Additionally, it showed that adequate bleed protection can be achieved with 10- or 14-day rIX-FP regimens in selected pediatric patients while maintaining safety., Competing Interests: G.K.: Research grant support from Alnylam, BPL, Bayer, Baxalta, CSL Behring, Opko biologics, Pfizer, Shire; consultant for Alnylam, Bayer, Opko biologics, Pfizer, Shire, Roche; honoraria/speakers bureau for Bayer, CSL, Pfizer, Roche. H.C.: Research support from CSL Behring, LFB, Novo Nordisk, Octapharma, Shire/Takeda, SOBI; honoraria from Bayer, LFB, Octapharma, Pfizer, Roche, SOBI; travel support from Bayer, LFB, Octapharma, Pfizer, Roche, Sobi; C.M.: Research support from Bayer, Biotest, CSL Behring, Shire/Takeda; honoraria from Bayer, Biotest, CSL Behring, Novo Nordisk, Pfizer, Roche, Takeda; travel support from Biotest, Bayer, CSL Behring, Novo Nordisk. S.H.: received honoraria for speaking from Bayer Healthcare, Baxalta Innovation, Biotest, CSL Behring, Novartis Pharma, Novo Nordisk, Octapharma, Pfizer; research grants from Bayer Healthcare, Baxalta, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer; T.L.: Research grant support and honoraria from Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, SOBI; honoraria from Uniqure; Y.L. and W.S. are employees of CSL Behring; E.S.: Research grant support from CSL Behring; honoraria for speaking and/or for consulting from Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, Shire/Takeda, SOBI, Spark, Uniqure., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Hemophilia is a rare bleeding disorder caused by a deficiency of the plasma coagulation factors VIII and IX (hemophilia A [HA] and hemophilia B [HB], respectively). Replacement therapy with clotting factor concentrates is the mainstay of treatment. Unlike in patients with HB, anaphylaxis in patients with HA is extremely rare., Methods: A retrospective study of prospectively collected data on patients with hemophilia who experienced anaphylaxis was conducted in our center. Demographic and clinical data were collected, and laboratory workups that included thrombin generation were conducted., Results: Our first patient underwent successful immune tolerance induction (ITI) following the administration of rituximab. The second patient was transitioned to emicizumab. The third patient receives recombinant activated VIIa (rFVIIa) on demand. Thrombin generation was performed following current medical management protocols for supporting hemostasis., Discussion: Our case series illustrates the difficulty in managing patients with anaphylaxis to replacement therapy. In the era of novel therapies, such as emicizumab, the management of HA patients who experience anaphylaxis to replacement therapy is becoming easier and may obviate the need for ITI. Current treatment strategies for HB patients with such anaphylaxis, however, are limited to rFVIIa, and it continues to pose a challenge., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ankles and knees are commonly affected in people with hemophilia and thus are targets for prevention or rehabilitation. However, to our knowledge, no studies have evaluated muscle activity and safety during exercises targeting the lower limbs in people with hemophilia; this lack of information hinders clinical decision-making., Objective: The aim of this study was to compare the tolerability of, safety of, and muscle activity levels obtained with external resistance (elastic or machine)-based and non-external resistance-based lower limb exercises in people with hemophilia., Design: This was a cross-sectional study., Methods: Eleven people who had severe hemophilia and were undergoing prophylactic treatment participated. In a single experimental session, participants performed knee extension and ankle plantar flexion during 3 exercise conditions in random order: elastic band-based resistance (elastic resistance), machine-based resistance (machine resistance), and no external resistance. Exercise intensities for the 2 external resistance-based conditions were matched for perceived exertion. Muscle activity was determined using surface electromyography (EMG) for the rectus femoris, biceps femoris, gastrocnemius lateralis, and tibialis anterior muscles. Participants were asked to rate exercise tolerability according to a scale ranging from "very well tolerated" to "not tolerated" and to report possible adverse effects 24 and 48 hours after the session., Results: No adverse effects were reported, and exercise tolerability was generally high. In the knee extension exercise, the rectus femoris normalized EMG values during the elastic resistance and machine resistance conditions were similar; 29% to 30% higher activity was obtained during these conditions than during the non-external resistance condition. In the ankle plantar flexion exercise, the gastrocnemius lateralis normalized EMG value was 34% higher during the machine resistance condition than without external resistance, and the normalized EMG values during the elastic resistance and other conditions were similar., Limitations: The small sample size and single training session were the primary limitations of this study., Conclusions: Exercises performed both with elastic bands and with machines at moderate intensity are safe, feasible, and efficient in people with severe hemophilia, providing comparable activity levels in the agonist muscles., (© 2019 American Physical Therapy Association.)

Introduction: The research was conducted at a UK teaching hospital and Haemophilia Comprehensive Care Centre (CCC) as part of a research programme investigating physiotherapy for acute bleed management., Aim: The aim of the study was to understand the perspectives of people with haemophilia (PWH) on validated outcome measures (OM) and whether these measures capture changes relevant to them whilst recovering from an acute bleed episode., Methods: Any person with haemophilia registered to the CCC who reported an acute bleed within the past 2 years was invited to participate. Semi-structured interviews or workshops (activity-focused discussions with small groups) were conducted with PWH who had received physiotherapy treatment in the previous two years. These were used to explore opinions of PWH of commonly used outcome measures., Results: Eight male PWH participated, mean age 61 years, ranging between 39 and 71. Seven participants had severe haemophilia A and 1 had von Willebrands. Participants described numerical rating scales of pain as abstract and expressed a preference for verbal or visual descriptors. In relation to function, the men generally found haemophilia-specific OM to be more relevant. The EuroQol 5-Dimension 5-Level (EQ5D-5L) and Haemophilia and Exercise Project Test Questionnaire (HEP-Test-Q) were considered as good measures due to brevity and ability to capture relevant changes promptly., Conclusion: Participants in this study reported a preference for short OMs that allow them to reference their ability during the acute bleed episode in comparison with their normal function., (© 2019 John Wiley & Sons Ltd.)

Introduction: Distress related to disease burden has been defined and described among people with chronic diseases including diabetes and cancer. In these populations, disease-specific distress is associated with health outcomes. Haemophilia-related distress is less understood., Aim: To identify qualitative features of haemophilia-related distress among affected adults to ultimately inform the creation of a measurement tool., Methods: Adults with haemophilia A or B associated with a large haemophilia treatment centre in the south-eastern U.S. were recruited to participate in this qualitative study. Fifteen participants completed semi-structured telephone interviews. Interviews lasted 1-2 hours and explored experiences of distress related to various aspects of haemophilia. Interviews were audio taped, transcribed and coded using NVIVO, software for organizing, managing and analysing qualitative data. Coding was deductive and inductive, and the analysis was thematic., Results: Haemophilia-related distress was broadly related to feelings of isolation and vulnerability which incorporated health system factors, physical functioning, caretaker roles and psychological considerations. Specific features associated with haemophilia-related distress included lack of trust in the knowledge of haemophilia and care provided by staff in community healthcare settings, concerns about the future such as health insurance access and ageing/disability, long-standing feelings of being different from others and feeling like an outsider, treatment burdens and fear of acute bleeds. Protective factors included supportive relationships with family, friends and haemophilia care teams through which participants received practical and emotional support., Conclusion: Features of haemophilia-related distress were identified. Results will facilitate distress measurement and intervention efforts to reduce distress in adults with haemophilia., (© 2019 John Wiley & Sons Ltd.)