IntroductionCare for adolescents with haemophilia is transferred from paediatric to adult care around the age of 18 years. Transition programs help to prepare adolescents for this transfer and... Show moreIntroductionCare for adolescents with haemophilia is transferred from paediatric to adult care around the age of 18 years. Transition programs help to prepare adolescents for this transfer and prevent declining treatment adherence. Evaluating transition readiness may identify areas for improvement. ObjectiveAssess transition readiness among Dutch adolescents and young adults with haemophilia, determine factors associated with transition readiness, and identify areas of improvement in transition programs. MethodsAll Dutch adolescents and young adults aged 12-25 years with haemophilia were invited to participate in a nationwide questionnaire study. Transition readiness was assessed using multiple-choice questions and was defined as being ready or almost ready for transition. Potential factors associated with transition readiness were investigated, including: socio-demographic and disease-related factors, treatment adherence, health-related quality of life, and self-efficacy. ResultsData of 45 adolescents and 84 young adults with haemophilia (47% with severe haemophilia) were analyzed. Transition readiness increased with age, from 39% in 12-14 year-olds to 63% in 15-17 year-olds. Nearly all post-transition young adults (92%, 77/84) reported they were ready for transition. Transition readiness was associated with treatment adherence, as median VERITAS-Pro treatment adherence scores were worse in patients who were not ready (17, IQR 9-29), compared to those ready for transition (11, IQR 9-16). Potential improvements were identified: getting better acquainted with the adult treatment team prior to transition and information on managing healthcare costs. ConclusionsNearly all post-transition young adults reported they were ready for transition. Improvements were identified regarding team acquaintance and preparation for managing healthcare costs. Show less
Background Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and... Show moreBackground Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI ( increment t(inhi-ITI)) is debatable. Objective The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi. Methods Severe (factor VIII activity level <1%) PwHA-HRi on ITI (n = 142) were enrolled in 15 hemophilia treatment centers. PwHA-HRi were treated according to the Brazilian ITI Protocol. ITI outcomes were defined as success (i.e., recovered responsiveness to exogenous FVIII) and failure (i.e., no responsiveness to exogenous FVIII and requirement of bypassing agents to control bleeding). Results Median ages at inhibitor detection and at ITI start were 3.2 years (interquartile range [IQR], 1.6-8.1) and 6.9 years [IQR, 2.6-20.1), respectively. PwHA-HRi were stratified according to increment t(inhi-ITI) quartiles: first (0.0-0.6 year), second (>0.6-1.7 year), third (>1.7-9.2 years), and fourth quartile (>9.2-24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders. Conclusion In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start. Show less
Jardim, L.L.; Santana, M.P.; Chaves, D.G.; Bom, J. van der; Rezende, S.M. 2021
Up to 35% of patients with hemophilia A and 5% with hemophilia B develop neutralizing antibodies which can inhibit the therapeutic activity of factor replacement (inhibitors). Despite the clinical... Show moreUp to 35% of patients with hemophilia A and 5% with hemophilia B develop neutralizing antibodies which can inhibit the therapeutic activity of factor replacement (inhibitors). Despite the clinical relevance of antifactor VIII and IX neutralizing antibodies, there is still a major gap on the knowledge of risk factors for their development. Furthermore, most of the studies on risk factors for inhibitor development come from Caucasian and Afro-American populations. The HEMFIL is a Brazilian prospective cohort study of previously untreated children with hemophilia, which primary aim is to identify new risk factors related to inhibitor development. This manuscript aims at describing the study design and its methodology. After the diagnosis, children are followed up to 75 exposure days or to inhibitor development. Standardized forms and blood samples are collected to describe clinical characteristics and to perform the measurement of immunological and genetic biomarkers at three time points; Inclusion time (T0), at inhibitor development or at 75 exposure days without inhibitors (T1) and after immune tolerance induction for patients in whom it is indicated and performed (T2). Currently, 120 children have been included, of whom, 95 have completed the follow-up. For severe/moderately severe hemophilia A, the cumulative incidence of inhibitors at 75 exposure days was 35% (95% confidence interval, 26-46%). The inclusion of additional patients and a longer follow-up will allow the analysis of risk factors for inhibitor development. Show less
Camelo, R.M.; Caram-Deelder, C.; Duarte, B.P.; Moura, M.C.B. de; Costa, N.C.D.; Costa, I.M.; ... ; Bom, J. van der 2021
Since the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related... Show moreSince the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related diseases such as cardiovascular disease (CVD) have also become more prevalent in PwH. This cross-sectional study aimed to evaluate CVD risk factors and estimate 10-year risk for CVD events among PwH. Male patients >= 30 years were interviewed and examined. Blood tests were performed at the local laboratory. Eighty-two patients were included, of whom 83% had haemophilia A and half had severe disease. Median age at study entry was 43.0 years (interquartile range [IQR], 36.0-51.3). Prevalence of obesity, systemic arterial hypertension (SAH) and diabetes mellitus were 16%, 60% and 16%, respectively. Hypertriglyceridaemia, hypercholesterolaemia and low HDL blood levels were present in 18%, 41% and 30% of patients, respectively. Metabolic syndrome was found in 37%. The Framingham Risk Score showed that 39% of PwH had a high risk of developing cardiovascular events in the following 10 years. We conclude that, in this cohort, PwH have a higher prevalence of SAH when compared with Brazilian men without haemophilia and about two-fifths have a high risk of developing a CVD event in the following 10 years. Show less
McCall, S.J.; Henriquez, D.; Edwards, H.M.; Akker, T. van den; Bloemenkamp, K.W.M.; Bom, J. van der; ... ; Knight, M. 2021
Background This study aimed to compare incidence, management and outcomes of women transfused their blood volume or more within 24 hours during pregnancy or following childbirth.MethodsCombined... Show moreBackground This study aimed to compare incidence, management and outcomes of women transfused their blood volume or more within 24 hours during pregnancy or following childbirth.MethodsCombined analysis of individual patient data, prospectively collected in six international population-based studies (France, United Kingdom, Italy, Australia, the Netherlands and Denmark). Massive transfusion in major obstetric haemorrhage was defined as transfusion of eight or more units of red blood cells within 24 hours in a pregnant or postpartum woman. Causes, management and outcomes of women with massive transfusion were compared across countries using descriptive statistics.FindingsThe incidence of massive transfusion was approximately 21 women per 100,000 maternities for the United Kingdom, Australia and Italy; by contrast Denmark, the Netherlands and France had incidences of 82, 66 and 69 per 100,000 maternities, respectively. There was large variation in obstetric and haematological management across countries. Fibrinogen products were used in 86% of women in Australia, while the Netherlands and Italy reported lower use at 35-37% of women. Tranexamic acid was used in 75% of women in the Netherlands, but in less than half of women in the UK, Australia and Italy. In all countries, women received large quantities of colloid/crystalloid fluids during resuscitation (>3.5 litres). There was large variation in the use of compression sutures, embolisation and hysterectomy across countries. There was no difference in maternal mortality; however, variable proportions of women had cardiac arrests, renal failure and thrombotic events from 0-16%.InterpretationThere was considerable variation in the incidence of massive transfusion associated with major obstetric haemorrhage across six high-income countries. There were also large disparities in both transfusion and obstetric management between these countries. There is a requirement for detailed evaluation of evidence underlying current guidance. Furthermore, cross-country comparison may empower countries to reference their clinical care against that of other countries. Show less
Sanders, Y.; Fijnvandraat, K.; Boender, J.; Mauser-Bunschoten, E.; Bom, J. van der; Meris, J. de; ... ; WiN Study Grp 2015
