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This article discusses the impact of haemophilia symptoms on sexual functioning and health-related quality of life (HRQOL) in men with haemophilia. The study found that pain, the risk of bleeding, and loss of joint movement can restrict sexual activity in men with haemophilia. These restrictions in sexual functioning were associated with lower scores on HRQOL domains such as physical functioning and satisfaction with participation in social roles. The study also highlighted the lack of discussions about sexual functioning between men with haemophilia and healthcare professionals during outpatient visits. The authors emphasize the importance of addressing sexual functioning in clinical care and providing appropriate interventions for men with haemophilia. [Extracted from the article]

Introduction: The Haemophilia Activities List (HAL) and paediatric HAL assess self‐reported limitations in various daily activities. To reduce patient burden, shorter versions of the pedHAL (22 items) and HAL (18 items) have been developed. Aim: This study aimed to determine the agreement between the pedHAL/HALfull and pedHAL/HALshort and construct validity and internal consistency of the pedHAL/HALshort in persons with haemophilia (PWH). Methods: A cross‐sectional secondary analysis of the Hemophilia in the Netherlands‐6 national survey was performed. Adult and paediatric PWH completed the original pedHAL/HALfull, from which pedHAL/HALshort were derived. Score differences between the original and short versions were calculated. Construct validity was studied by testing hypotheses regarding the relationship of the pedHAL/HALshort with the pedHAL/HALfull, Haemophilia & Exercise Project Test‐Questionnaire (HEP‐Test‐Q), Canadian Haemophilia Outcomes‐Kids' Life Assessment Tool (CHO‐KLAT) and RAND 36‐item Health Survey (RAND‐36) (convergent/discriminant validity) as well as its ability to discriminate between subgroups (known‐group validity). Internal consistency was assessed with Cronbach's α. Results: We included 113 children (median 10y [range 4–17], 53% severe haemophilia) and 691 adults (median 51y [range 18–88], 35% severe). Scores of the pedHAL/HALfull and pedHAL/HALshort were similar with high correlations (>0.9). Construct validity was confirmed for the pedHAL/HALshort. The HALshort was able to discriminate between different disease severities and ages. Cronbach's α of the pedHAL/HALshort was 0.95–0.97. Conclusion: This study confirmed the agreement between the pedHAL/HALfull and the pedHAL/HALshort and the construct validity of the pedHAL/HALshort. The next step is to study construct validity of the pedHAL/HALshort when administered as short forms. [ABSTRACT FROM AUTHOR]

Aim: Currently, it is unknown which patient‐reported outcomes are important for patients with autosomal inherited bleeding disorders. Therefore, the purpose of this study is to systematically review the available literature assessing patient‐reported outcomes and their measurement methods in autosomal inherited bleeding disorders. Methods: The Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trails and Google Scholar databases were searched from inception until 14 August 2020. Studies on patient‐reported outcomes in patients with von Willebrand disease, inherited platelet function disorders and coagulation factor deficiencies were included. Results: Twenty‐one articles met the inclusion criteria. Three studies were assessed as having poor quality, and therefore a high risk of bias. Nineteen studies had fair quality rating. Different measurements methods were used, ranging from predefined to self‐developed questionnaires. The majority of included studies focused on von Willebrand disease. Patients with von Willebrand disease reported lower health‐related quality of life compared to the general population. Overall, this trend was especially visible in the following domains: vitality, physical and social functioning and pain. Women with inherited bleeding disorders scored lower on health‐related quality of life compared to men, especially women with heavy menstrual bleeding. Patients with joint bleeds or heavy menstrual bleeding reported an increased level of pain. Conclusion: Patients with autosomal inherited bleeding disorders report lower health related quality of life, especially those with joint bleeds or heavy menstrual bleeding. Numerous measurement methods are used in patients with autosomal inherited bleeding disorders, highlighting the need for studies using established, standardized measurement methods. [ABSTRACT FROM AUTHOR]

Introduction: Although sports participation is advocated in people with haemophilia (PWH), detailed data concerning sports participation in Dutch PWH is lacking. Aim: to assess sports participation in Dutch PWH (6‐65 years) compared to the Dutch general population (GP). Methods: Data from a nationwide, cross‐sectional study in PWH were analysed. Sports participation (type, duration, frequency) was assessed by the Modifiable Activities Questionnaire (MAQ), limitations in activities using the (Paediatric) Haemophilia Activities List ((Ped)HAL). Sports in the two highest categories according to the National Hemophilia Foundation classification were considered high‐risk sports. Groups were compared using Chi‐square testing. Results: A total of 524 Adult PWH (median age: 45 (IQR: 30–55); 37% severe) and 126 paediatric PWH (median age: 11 (IQR: 8–14); 52% severe) were included. Sports participation was higher in adults (70%) than the GP (58%) and similar to the GP in children (PWH: 68%, GP: 72%). High‐risk sports participation decreased with age in PWH: from 65% (6‐12 years) to 17% (50‐65 years), which was also observed in the GP. Sports participation in children was independent of severity (non‐severe: 67% vs. severe: 65%; P = 0.97), but not in adults (non‐severe: 75%, severe: 62%; P < 0.01). Non‐severe PWH played more high‐risk sports than severe PWH: children at 65% vs. 48% (P = 0.05), adults at 25% vs. 15% (P = 0.07). Discussion: These results suggest that sports participation in PWH was comparable to the GP. Sports participation was dependent of haemophilia severity in adults. Children were more involved in high‐risk sports than adults. More studies on sports‐related injury‐risk are needed for adequate counselling. [ABSTRACT FROM AUTHOR]

Introduction: Prophylactic replacement therapy (prophylaxis) in patients with haemophilia (PWH) requires lifelong, frequent (self)infusions. Prophylaxis effectiveness depends on adherence, and the drivers of treatment adherence among PWH are unclear. Aim: To quantify prophylaxis adherence and associations between adherence and patients' treatment attitudes and satisfaction in a large cohort of children and adults with haemophilia. Methods: In a nationwide, cross‐sectional, questionnaire‐based study, PWH with complete information currently using prophylaxis were selected. Validated Hemophilia Regimen Treatment Adherence Scale‐Prophylaxis (VERITAS‐Pro; normalised score range: 0–100, optimum 0) measured treatment adherence; the Patient Activation Measure (PAM‐13; total score range 0–100, optimum 100) measured activation of self‐management; Hemophilia Patient Satisfaction Scale (Hemo‐Sat; range 0–100, optimum 0) measured treatment satisfaction. Groups were compared according to age (children: <12 years; adolescents: 12–18 years; adults >18 years) and adherence levels using non‐parametric tests, and correlations were assessed using Spearman's rho. Results: Among 321 participants (median age 33 years, interquartile range [IQR]:15–54 years), adherence was high (median VERITAS‐Pro total score 17, 89% adherent) but worsened with age, with median scores of 5, 14 and 20 in children, adolescents, adults, respectively (p <.001). Attitudes towards treatment (median 66 vs. 68) participants and treatment satisfaction (12 vs. 10) were similar between adherent and non‐adherent patients. The VERITAS‐Pro total score was moderately correlated with PAM‐13 (r =.41) but not with Hemo‐Sat (r = −.11). Discussion: Prophylaxis adherence was high (89%) but decreased significantly with age and was not correlated with treatment attitude or treatment satisfaction. [ABSTRACT FROM AUTHOR]

Background: There is a need to identify patients with haemophilia who have a very low or high risk of developing inhibitors. These patients could be candidates for personalized treatment strategies. Aims: The aim of this study was to externally validate a previously published prediction model for inhibitor development and to develop a new prediction model that incorporates novel predictors. Methods: The population consisted of 251 previously untreated or minimally treated patients with severe haemophilia A enrolled in the SIPPET study. The outcome was inhibitor formation. Model discrimination was measured using the C‐statistic, and model calibration was assessed with a calibration plot. The new model was internally validated using bootstrap resampling. Results: Firstly, the previously published prediction model was validated. It consisted of three variables: family history of inhibitor development, F8 gene mutation and intensity of first treatment with factor VIII (FVIII). The C‐statistic was 0.53 (95% CI: 0.46–0.60), and calibration was limited. Furthermore, a new prediction model was developed that consisted of four predictors: F8 gene mutation, intensity of first treatment with FVIII, the presence of factor VIII non‐neutralizing antibodies before treatment initiation and lastly FVIII product type (recombinant vs. plasma‐derived). The C‐statistic was 0.66 (95 CI: 0.57–0.75), and calibration was moderate. Using a model cut‐off point of 10%, positive‐ and negative predictive values were 0.22 and 0.95, respectively. Conclusion: Performance of all prediction models was limited. However, the new model with all predictors may be useful for identifying a small number of patients with a low risk of inhibitor formation. [ABSTRACT FROM AUTHOR]

In the Dutch haemophilia population, the distribution of patients with severe haemophilia is approximately 50%.1 This could lead to selection bias, as more adherent and more active patients are likely more prone to complete these questionnaires. A total of 267 participants with haemophilia A or haemophilia B who used prophylaxis completed both questionnaires and were included in the analyses. Keywords: adherence; compliance; Haemophilia; physical activity; sport EN adherence compliance Haemophilia physical activity sport e402 e405 4 06/14/21 20210501 NES 210501 Patients with severe haemophilia (PWH) lack clotting factor VIII or factor IX activity (<1 IU/dl) and are at risk of spontaneous bleeds in joints, soft tissue and muscles.1 In the Netherlands, regular replacement therapy (prophylaxis) to prevent bleeding and subsequent joint damage is a standard treatment.1 This replacement therapy consists of intravenously self-administered clotting factor concentrate 2-3 times/week, usually started before the age of 3 years.1 In young children, parents generally perform these injections. [Extracted from the article]

Introduction: Brazil has the fourth largest world population of patients with haemophilia. However, mortality rates in this population are unknown. Aim: To analyse mortality and its causes in Brazilian patients with haemophilia from 2000 to 2014. Methods: The number of deceased patients with haemophilia and causes of death were obtained from the Brazilian National Mortality Information System (SIM), according to the 10th International Classification of Diseases (ICD‐10). Standardized mortality ratios (SMR) were calculated to estimate the rate of overall death of patients with haemophilia relative to that of the Brazilian general male population. Results: A total of 784 deaths were identified in the period of 15 years. Mortality of patients with haemophilia was 13% higher when compared with the general male population (SMR 1.13, 95% CI: 1.01‐1.16). Haemorrhage was the main cause of death (n = 254; 32.4%) of which 137 (54%) was intracranial haemorrhage. The total number of deaths due to HIV decreased over the years, and an increase in deaths due to cancer and cardiovascular disease was observed. A total of 129 deaths (16.5%) were related to hepatitis infection, of whom, 109 (86.5%) patients also presented with cirrhosis and hepatocellular carcinoma or other liver diseases. Conclusion: Mortality rate of Brazilian patients with haemophilia decreased over the evaluated period. Intracranial haemorrhage is still an important cause of death in these patients, which requires major effort for prevention. Death due to age‐related cardiovascular disease and cancer has increased over the years, following the same tendency observed in developed countries. [ABSTRACT FROM AUTHOR]

Introduction: Accurate assessment of joint health in persons with haemophilia is crucial. Several haemophilia‐specific measurement tools are available, but an overview of the measurement properties is lacking. Aim: To provide an overview of the measurement properties of haemophilia‐specific measurement tools to assess clinical joint health. Methods: MEDLINE and EMBASE were searched for reports on reliability, validity or responsiveness of the World Federation of Haemophilia Orthopedic Joint Score (WFH), Colorado Physical Examination Score (CPE), joint examination score by Petrini (PJS) and Hemophilia Joint Health Score (HJHS). Methodological quality of the studies was assessed using an adapted COSMIN checklist. Results: The search yielded 2905 unique hits, and 98 papers were included. The methodological quality of the included studies was limited. The HJHS was studied most extensively, which yielded limited evidence for good internal consistency and structural validity, moderate evidence for hypothesis testing in adults and conflicting evidence for hypothesis testing in children. Reliability, measurement error and responsiveness were rated unknown due to low COSMIN scores. For the CPE and PJS, we found limited to moderate evidence for good responsiveness and conflicting evidence for hypothesis testing. Conclusion: Only patchy evidence is available on the quality of measurement properties of all haemophilia‐specific joint health scores. Although significant gaps in the evidence for all instruments remain, measurement properties of the HJHS were most extensively studied and show no drawbacks for use in clinical practice. This review forms the basis for further research aimed at the assessment of measurement properties of measurement tools to assess joint health. [ABSTRACT FROM AUTHOR]

Background: Inhibitor development in previously untreated patients (PUPs) with severe haemophilia A is a multifactorial event. It is unknown whether paediatric vaccinations given in close proximity to factor VIII (FVIII) are associated with inhibitor development. Objective: To assess whether paediatric vaccinations in close proximity to FVIII within the first 75 exposure days (EDs) are associated with inhibitor development in PUPs with severe haemophilia A. Methods: We included 375 PUPs with severe haemophilia A (<0.01 IU/mL) from the PedNet Registry who had received vaccinations between the first and 75th ED or inhibitor development. Inhibitor risk was compared between patients who did and who did not receive vaccinations within 24, 72 or 120 hours of FVIII infusion. Unadjusted and adjusted hazard ratios were calculated for any or repeated vaccinations in close proximity to FVIII, using Cox regression. Results: Inhibitor development occurred in 77 of 375 patients (20.5%). Overall inhibitor development appeared similar or lower in patients receiving vaccinations in close proximity to FVIII as compared to patients receiving vaccinations without FVIII: for 24 hours, this was 19.2% and 21.4% (P = .186), for 72 hours, 16.4% and 27.3% (P = .023) and for 120 hours, 18.3% and 25.0% (P = .085), respectively. Conclusion: We found no association between vaccinations given in close proximity to FVIII exposure within the first 75 EDs and inhibitor development. Our data do not support avoiding administration of FVIII at time of routine vaccinations. [ABSTRACT FROM AUTHOR]

Introduction: Monitoring clinical outcome in persons with haemophilia (PWH) is essential in order to provide optimal treatment for individual patients and compare effectiveness of treatment strategies. Experience with measurement of activities and participation in haemophilia is limited and consensus on preferred tools is lacking. Aim: The aim of this study was to give a comprehensive overview of the measurement properties of a selection of commonly used tools developed to assess activities and participation in PWH. Methods: Electronic databases were searched for articles that reported on reliability, validity or responsiveness of predetermined measurement tools (5 self‐reported and 4 performance based measurement tools). Methodological quality of the studies was assessed according to the COSMIN checklist. Best evidence synthesis was used to summarize evidence on the measurement properties. Results: The search resulted in 3453 unique hits. Forty‐two articles were included. The self‐reported Haemophilia Acitivity List (HAL), Pediatric HAL (PedHAL) and the performance based Functional Independence Score in Haemophilia (FISH) were studied most extensively. Methodological quality of the studies was limited. Measurement error, cross‐cultural validity and responsiveness have been insufficiently evaluated. Conclusion: Albeit based on limited evidence, the measurement properties of the PedHAL, HAL and FISH are currently considered most satisfactory. Further research needs to focus on measurement error, responsiveness, interpretability and cross‐cultural validity of the self‐reported tools and validity of performance based tools which are able to assess limitations in sports and leisure activities. [ABSTRACT FROM AUTHOR]

A letter to the editor regarding second-generation recombinant factor VIII and inhibitor risk is presented.

Different regimens are used to achieve immune tolerance in patients with severe haemophilia A and inhibitory allo-antibodies against factor VIII (FVIII). In this study, results of 26 years of low dose immune tolerance induction are evaluated. We evaluated 21 patients, who were treated with regular infusions of low dose FVIII (25–50 IU kg−1 every other day or three times a week) to obtain immune tolerance. Several risk factors for success rate and time to success were analysed. In 18 of 21 patients (86%) immune tolerance induction (ITI) was successful. The median of the maximum inhibitor titre before start of ITI was 4.5 BU mL−1. Success rate was associated with both a pre-ITI titre and a maximum titre during ITI below 40 BU mL−1 ( P = 0.003). The time to success was significantly shorter if the maximum inhibitor level during ITI was below 40 BU mL−1 ( P = 0.040). In low titre inhibitors (<5 BU mL−1) this effect was even stronger ( P = 0.033). Low dose immune tolerance induction therapy was successful in severe haemophilia A patients with a pre-ITI titre below 40 BU mL−1. The time to success is predicted by a maximum ITI titre below 40 BU mL−1, and is even shorter in low titre inhibitors (<5 BU mL−1). We suggest that all patients with severe haemophilia A and a pre-ITI inhibitor titre below 5 BU mL−1, should be treated with low dose immune tolerance induction therapy. Patients with a maximum titre below 40 BU mL−1 may also strongly benefit from the beneficial effects of low dose immune tolerance induction therapy. [ABSTRACT FROM AUTHOR]