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Y V Sanders,
J Eikenboom, E M de Wee,
J G van der Bom,
M H Cnossen,
M E L Degenaar-Dujardin,
K Fijnvandraat,
P W Kamphuisen,
B A P Laros- van Gorkom,
K Meijer,
E P Mauser-Bunschoten,
F W G Leebeek
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ABSTRACT: BACKGROUND: High von Willebrand factor (VWF) levels are an established risk factor for arterial thrombosis, including coronary heart disease and ischemic stroke. It has been hypothesized that von Willebrand disease (VWD) patients are protected against arterial thrombosis; however, this has never been confirmed in clinical studies. OBJECTIVES: to investigate the prevalence of arterial thrombosis in VWD patients relative to the general population. PATIENTS/METHODS: We included 635 adult patients with VWF levels ≤30U/dL, aged 16-85, from the nation-wide cross-sectional "Willebrand in the Netherlands" (WiN)study and compared the prevalence of arterial thrombosis with two reference populations from the general Dutch population adjusted for age and sex as standardized morbidity ratios (SMRs). RESULTS: Twenty-nine arterial thrombotic events occurred in twenty-one patients (3.3%). Five patients suffered an acute myocardial infarction and three an ischemic stroke. Unstable angina pectoris was recorded twelve times, transient ischemic attack nine. The prevalence of all arterial thrombotic events combined (acute myocardial infarction, ischemic stroke and coronary heart disease) was 39% and 63% lower than in the two reference populations. The prevalence of cardiovascular disease in VWD was lower than in the general population, SMR 0.60 (95%CI:0.32-0.98) for coronary heart disease and SMR 0.40 (95%CI:0.13-0.83) for acute myocardial infarction. For ischemic stroke the prevalence was 35-67% lower compared to two reference populations, SMR 0.65 (95%CI:0.12-1.59) and 0.33 (95%CI:0.06-0.80), respectively. CONCLUSIONS: This is the first study showing that VWD patients have a reduced prevalence of arterial thrombosis and provides important insights into the role of VWF in the pathogenesis of arterial thrombosis. © 2013 International Society on Thrombosis and Haemostasis.
Journal of Thrombosis and Haemostasis 03/2013; · 5.73 Impact Factor
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E M De Wee,
Y V Sanders,
E P Mauser-Bunschoten,
J G van der Bom,
M E L Degenaar-Dujardin,
J Eikenboom,
A De Goede-Bolder,
B A P Laros-van Gorkom,
K Meijer,
K Hamulyák,
M R Nijziel,
K Fijnvandraat,
F W G Leebeek
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ABSTRACT: We performed a nation-wide cross-sectional study to evaluate determinants of bleeding symptoms in a large unselected cohort of adults with von Willebrand disease (VWD). VWD patients were included (n=664), based on lowest historically measured VWF:Ag and VWF:Act levels ≤30 U/dl. Menorrhagia (85%), cutaneous bleeding (77%), bleeding from minor wounds (77%) and oral-cavity bleeding (62%) occurred most frequently. Higher age was associated with a higher bleeding score (BS), determined according to Tosetto, in females. A 10 year increase in age was associated with 0.8 point (95% confidence interval [CI] 0.4-1.1) higher BS. Females had higher BS than males (median 12 vs. 10, p=0.012). BS differed significantly between VWD type 1, 2 and 3: median 9 (-2-31), 13 (-1-33) and 19.5 (1-35), respectively (p<0.001). BS was strongly associated with VWF and FVIII levels: individuals with VWF:Ag levels ≤10 IU/dl, VWF:Act ≤10 IU/dl and FVIII:C ≤10 IU/dl had, respectively, 5.3 point (95%CI 3.2-7.3), 4.3 point (95%CI 2.9-5.8) and 9.6 point (95%CI 6.5-12.7) higher BS, than those with levels >30 IU/dl. In type 3 patients 1 IU/dl FVIII:C decrease was associated with 0.6 point (95% CI 0.1-1.1) BS increase (p=0.021). In conclusion, in VWD patients the bleeding phenotype is strongly associated with type of VWD and VWF and FVIII levels.
Thrombosis and Haemostasis 08/2012; 108(4):683-692. · 5.04 Impact Factor
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ABSTRACT: Home treatment of haemophilia is currently the standard of care for patients with severe haemophilia. Home treatment increases the responsibility of the patients for their own treatment and care. Therefore, it is of utmost importance to attain a high level of knowledge and practical skills. The aim of our study was to investigate whether or not an educational e-learning program improves knowledge and skills of adult patients with haemophilia on home treatment. Participants treated at the Haemophilia Treatment Center of the Erasmus University Medical Centre completed a questionnaire to test their knowledge of haemophilia, treatment of bleedings and of complications of treatment and were observed during the intravenous injection of clotting factor concentrate, using a standardized scoring list. Afterwards they were randomized to follow an e-learning program or no intervention (control group). After 1 month they completed the same questionnaire again and practical skills were scored once more. At baseline, haemophilia patients (n = 30) scored 24 of 48 questions in the questionnaire correctly. Seventy-five per cent of the items on the practical skills scoring list were performed correctly. One month later, the e-learning group (n = 16; 36; 18-45) showed a higher level of theoretical knowledge compared to the control group (n = 14; 26; 19-32; P < 0.001). Also practical skills were significantly better in the group that followed the e-learning program compared to the control group (respectively P = 0.002). Self-efficacy of 90% vs. 80% the patients with haemophilia was high in all patients. Our study shows that in haemophilia patients with haemophilia, who are on home treatment, knowledge of haemophilia treatment and complications as well as practical skills can be improved by an educational e-learning program.
Haemophilia 03/2012; 18(5):693-8. · 2.60 Impact Factor
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Journal of Thrombosis and Haemostasis 12/2011; 9(12):2509-11. · 5.73 Impact Factor
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E M De Wee,
H M Knol,
E P Mauser-Bunschoten,
J G van der Bom,
J C J Eikenboom,
K Fijnvandraat,
A De Goede-Bolder,
B Laros-van Gorkom,
P F Ypma,
S Zweegman,
K Meijer,
F W G Leebeek
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ABSTRACT: A nation-wide cross-sectional study was initiated to assess gynaecological and obstetrical symptoms in an unselected cohort of women with moderate and severe von Willebrand disease (VWD) in the Netherlands. A total of 423 women aged ≥16 years were included. Bleeding severity was measured using the Tosetto Bleeding Score (BS). Menorrhagia, defined as occurrence of ≥2 menorrhagia symptoms, was reported by 81%. Of all VWD women, 78% received any kind of treatment for menorrhagia and 20% underwent a hysterectomy predominantly because of severe menstrual bleeding. Over half of the women reported more blood loss than can be expected with a normal delivery. In 52% of reported pregnancy losses curettage was needed because of bleeding. Mean number of live births was 1.9, which is comparable with the general Dutch population. In conclusion, women with moderate or severe VWD frequently have menorrhagia in need of treatment, and 20% of the VWD women underwent a hysterectomy. Bleeding complications occurred in over 50% of the women after childbirth or pregnancy loss. Progeny seems not to be affected in women with moderate or severe VWD.
Thrombosis and Haemostasis 09/2011; 106(5):885-92. · 5.04 Impact Factor
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E M De Wee,
K Klaij,
H C J Eikenboom,
J G Van Der Bom,
K Fijnvandraat,
B A P Laros-Van Gorkom,
E P Mauser-Bunschoten,
K Meijer,
G Goverde,
P W G Van Der Linden,
D C Rijken,
F W G Leebeek
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ABSTRACT: Patients with von Willebrand disease (VWD), the most common inherited bleeding disorder, display large variation in bleeding tendency, which is not completely related to VWF levels. The cause of variability in clinical expression is largely unknown. The effect of plasma fibrinolytic capacity on bleeding tendency in VWD patients has not been investigated. We hypothesized that enhanced fibrinolysis may result in a more severe bleeding phenotype. Therefore, we measured the fibrinolytic potential in patients with moderate or severe VWD to investigate the contribution of fibrinolysis to the bleeding tendency. Fibrinolytic potential was measured as plasma clot lysis time (CLT) with and without addition of potato carboxypeptidase inhibitor (PCI) in 638 patients with moderate or severe VWD who participated in a nationwide multicentre cross-sectional study. Bleeding severity was measured using the Bleeding Score (BS).The CLTs were significantly longer, indicative of hypofibrinolysis, in men compared to women with VWD [106.2 (IQR 95.7-118.1) vs. 101.9 (IQR 92.8-114.0) min]. The CLTs prolonged with increasing age. No association was found between VWF or FVIII levels and CLT, or between VWF or FVIII levels and CLT(+PCI) . No association was observed for BS in a model with 10log-transformed CLT, adjusted for age, gender, VWF:Act and FVIII [b = 6.5 (95%CI -0.3 to 13.4)]. Our study showed that the plasma fibrinolytic potential does not influence bleeding tendency in VWD patients and therefore does not explain the variability in bleeding phenotype in VWD.
Haemophilia 09/2011; 18(3):444-51. · 2.60 Impact Factor
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E M de Wee,
K Fijnvandraat,
A de Goede-Bolder,
E P Mauser-Bunschoten,
J C J Eikenboom,
P P Brons,
F J Smiers,
R Tamminga,
R Oostenbrink,
H Raat,
J G van der Bom,
F W G Leebeek
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ABSTRACT: 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.
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.
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.
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.
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.
Journal of Thrombosis and Haemostasis 12/2010; 9(3):502-9. · 5.73 Impact Factor
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E M de Wee,
E P Mauser-Bunschoten,
J G Van Der Bom,
M E L Degenaar-Dujardin,
H C J Eikenboom,
K Fijnvandraat,
A de Goede-Bolder,
B A P Laros-van Gorkom,
K Meijer,
H Raat,
F W G Leebeek
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ABSTRACT: von Willebrand Disease (VWD) is the most frequent inherited bleeding disorder. It is unknown how this disorder affects quality of life.
This nationwide multicenter cross-sectional study determined health-related quality of life (HR-QoL) in adult patients with moderate or severe VWD, and assessed whether bleeding severity and type of VWD are associated with HR-QoL.
HR-QoL was assessed using the Short Form (SF)-36, and bleeding severity was measured using the Bleeding Score (BS).
Five hundred and nine patients participated; 192 males and 317 females, median age and range 45 (16-87) and 47 (16-84) years, respectively. Compared with the general population, HR-QoL in VWD patients was lower in the vitality domain (61 vs. 66 P < 0.001 for females, 67 vs. 72 P < 0.001 for males). Patients with the most severe bleeding phenotype (highest quartile BS, BS > 17) had a lower HR-QoL in eight domains than patients with a less severe bleeding type (lowest quartile BS, BS < 7) in the univariate analysis. After adjustment for age, gender, co-morbidity and employment/educational status, a more severe bleeding phenotype was associated with lower scores on the domains of physical functioning, role limitations due to physical functioning, bodily pain, general health, social functioning and physical component summary.
HR-QoL is lower in VWD patients compared with the general population. HR-QoL is strongly associated with bleeding phenotype.
Journal of Thrombosis and Haemostasis 03/2010; 8(7):1492-9. · 5.73 Impact Factor
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Haemophilia 08/2008; 14(5):1133-4. · 2.60 Impact Factor
