Von Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 or 3) or qualitative (type 2A/2B/2M/2N) defects of circulating von Willebrand factor (VWF). Circulating VWF levels... Show moreVon Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 or 3) or qualitative (type 2A/2B/2M/2N) defects of circulating von Willebrand factor (VWF). Circulating VWF levels not always fully explain bleeding phenotypes, suggesting a role for alternative factors, like platelets. Here, we investigated platelet factor 4 (PF4) in a large cohort of patients with VWD. PF4 levels were lower in type 2B and current bleeding phenotype was significantly associated with higher PF4 levels, particularly in type 1 VWD. Based on our findings we speculate that platelet degranulation and cargo release may play a role across VWD subtypes. Show less
Introduction The negative impact of haemophilia on social participation is well established in previous studies, however, the impact of Von Willebrand disease (VWD) on social participation has not... Show moreIntroduction The negative impact of haemophilia on social participation is well established in previous studies, however, the impact of Von Willebrand disease (VWD) on social participation has not been studied. Aim To compare the social participation of a large cohort of VWD patients in the Netherlands with the general Dutch population. In addition, to identify factors associated with social participation in VWD. Methods Patients participating in the "Willebrand in the Netherlands" study completed an extensive questionnaire on educational level, absenteeism from school or work, and occupational disabilities. Results Seven-hundred and eighty-eight VWD patients were included (mean age 38.9 years, 59.5% females), of whom 136 children < 16 years. Adult patients with type 3 VWD more often had a low educational level (52.9%) compared to type 1 (40.2%), type 2 VWD (36.8%) and the general population (36.4%) (p = .005). Moreover, in patients aged >= 16 years the days lost from school and/or work in the year prior to study inclusion differed significantly between the VWD types (p = .011). Using negative binomial regression analysis, the occurrence of bleeding episodes requiring treatment in the year preceding study inclusion was significantly associated with the number of days lost from school and/or work among patients aged >= 16 years. Multivariable logistic regression analysis showed that a higher total bleeding score, older age and presence of at least one comorbidity were significantly associated with occupational disability in patients aged >= 16 years. Conclusion Our study shows that social participation was lower in type 3 VWD and VWD patients with a more severe bleeding phenotype. Show less
Atiq, F.; Saes, J.L.; Punt, M.C.; Galen, K.P.M. van; Schutgens, R.E.G.; Meijer, K.; ... ; TiN Study Grp 2021
Background: In recent years, more awareness is raised about sex-specific dilemmas in inherited bleeding disorders. However, no large studies have been performed to assess differences in diagnosis,... Show moreBackground: In recent years, more awareness is raised about sex-specific dilemmas in inherited bleeding disorders. However, no large studies have been performed to assess differences in diagnosis, bleeding phenotype and management of men and women with bleeding disorders. Therefore, we investigated sex differences in a large cohort of well-defined patients with autosomal inherited bleeding disorders (von Willebrand disease (VWD), rare bleeding disorders (RBDs) and congenital platelet defects (CPDs)).Methods: We included patients from three nationwide cross-sectional studies on VWD, RBDs and CPDs in the Netherlands, respectively the WiN, RBiN and TiN study. In all studies a bleeding score (BS) was obtained, and patients filled in an extensive questionnaire on the management and burden of their disorder.Findings: We included 1092 patients (834 VWD; 196 RBD; 62 CPD), of whom 665 (60.9%) were women. Women were more often referred because of a bleeding diathesis than men (47.9% vs 36.6%, p = 0.002). Age of first bleeding was similar between men and women, respectively 8.9 +/- 13.6 (mean +/- sd) years and 10.6 +/- 11.3 years (p = 0.075). However, the diagnostic delay, which was defined as time from first bleeding to diagnosis, was longer in women (11.6 +/- 16.4 years) than men (7.7 +/- 16.6 years, p = 0.002). Similar results were found when patients referred for bleeding were analyzed separately. Of women aging 12 years or older, 469 (77.1%) had received treatment because of sex-specific bleeding.Interpretation: Women with autosomal inherited bleeding disorders are more often referred for bleeding, have a longer diagnostic delay, and often require treatment because of sex-specific bleeding. (C) 2021 The Authors. Published by Elsevier Ltd. Show less
Background: The bleeding phenotype of von Willebrand disease (VWD) varies highly between patients and can only partly be explained by von Willebrand factor (VWF) parameters. By cleaving large VWF... Show moreBackground: The bleeding phenotype of von Willebrand disease (VWD) varies highly between patients and can only partly be explained by von Willebrand factor (VWF) parameters. By cleaving large VWF multimers into smaller, less active multimers, ADAMTS-13 is an important regulator of VWF activity. However, it is unknown what the role of ADAMTS-13 is in individuals with VWD.Objectives: We therefore studied how ADAMTS-13 activity is associated with the laboratory and bleeding phenotype in individuals with VWD.Methods: We measured ADAMTS-13 activity using the fluorescence resonance energy transfer substrate VWF 73 assay in 638 individuals with VWD in the nationwide cross-sectional Willebrand in the Netherlands study and in 36 healthy controls. The bleeding phenotype was assessed using the Tosetto bleeding score.Results: ADAMTS-13 activity was similar in individuals with VWD (109% +/- 20.6%) and controls (110% +/- 19.7%). ADAMTS-13 activity was higher in individuals with VWD with type 3 than those with type 1 (mean difference, 11.8%; 95% confidence interval [CI], 2.9%-20.8%) or type 2 (mean difference, 16.1%; 95% CI, 7.1%-25.1%). ADAMTS-13 activity was not associated with the Tosetto bleeding score (0.1 Tosetto bleeding score increase per 10% ADAMTS-13 increase, 95% CI, -0.2 to 0.3). Furthermore, ADAMTS-13 activity did not differ between individuals with and without a bleeding event during the year preceding blood sampling (mean difference, 1.4%; 95% CI, -2.1% to 4.9%).Conclusion: ADAMTS-13 activity was highest in individuals with type 3 VWD, but it had only minor associations with VWF parameters. ADAMTS-13 activity does not influence the bleeding phenotype in individuals with VWD. Show less
Atiq, F.; Mauser-Bunschoten, E.P.; Eikenboom, J.; Galen, K.P.M. van; Meijer, K.; Meris, J. de; ... ; WiN Study Grp 2019
Background: Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder. Whether VWD is associated with health-related quality of life (HR-QoL) in children is unknown. Objectives:... Show moreBackground: Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder. Whether VWD is associated with health-related quality of life (HR-QoL) in children is unknown. Objectives: This nationwide cross-sectional study measured HR-QoL in children with moderate or severe VWD. Our primary aim was to compare HR-QoL of VWD patients with that of reference populations. Additionally, we studied the impact of bleeding phenotype and VWD type on HR-QoL. Methods: HR-QoL was assessed with the Infant/Toddler QoL Questionnaire (0-5 years) and Child Health Questionnaire (6-15 years), and compared with reference population scores. Multivariate analysis was used to evaluate the influence of type of VWD and bleeding phenotype on HR-QoL scores. Results: Preschool children (0-5 years, n = 46) with VWD had lower HR-QoL scores for general health perceptions and parental time than reference populations. School children (6-15 years, n = 87) with VWD had lower scores for physical functioning, role functioning - emotional/behavioral, general health perceptions, and physical summary. Type of VWD was associated with HR-QoL in school children for bodily pain, general health perceptions, parental emotion, family activities, and physical summary. Scores of children with type 3 VWD were, on average, 15 points lower than those of the reference population on the above-mentioned scales. A more severe bleeding phenotype was associated with a lower score on 11/15 physical, emotional and social scales. Conclusion: HR-QoL is lower in VWD children than in reference populations, in particular in school children. The negative impact of VWD is sensitive to type of VWD and bleeding phenotype; as well as physical scales, emotional and social scales are affected. Show less
