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Jeroen C. J. Eikenboom - One of the best experts on this subject based on the ideXlab platform.
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Von Willebrand Disease in the Netherlands: the WiN study
Nederlands Tijdschrift voor Geneeskunde, 2020Co-Authors: Y.v. Sanders, Karina Meijer, Jeroen C. J. Eikenboom, C. J. Fijnvandraat, B.a.p. Laros, Marjon H. Cnossen, Eveline P. Mauser-bunschoten, Frank W.g. LeebeekAbstract:Von Willebrand Disease is the most common inherited bleeding disorder and is characterised by mucocutaneous bleeding. Von Willebrand Disease is caused by reduced levels or reduced function of Von Willebrand factor. Depending on the cause, Von Willebrand Disease is distinguished into various types with their own characteristics and treatment options. The frequency and severity of bleeding in patients with Von Willebrand Disease is strongly determined by Von Willebrand factor levels, factor VIII levels and the type of Von Willebrand Disease. Eighty-five percent of all adult females with Von Willebrand Disease reports menorrhagia. A high percentage have postpartum excessive blood loss (37% of all deliveries). The quality of life is reduced in patients with Von Willebrand Disease. Patients with Von Willebrand Disease have a reduced risk of arterial thrombosis such as a myocardial or cerebral infarction.
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developments in the diagnostic procedures for Von Willebrand Disease
Journal of Thrombosis and Haemostasis, 2016Co-Authors: A De Jong, Jeroen C. J. EikenboomAbstract:Summary Von Willebrand Disease (VWD) is the most common inherited bleeding disorder but its diagnosis can be challenging due to the heterogeneity of the Disease. VWD is mainly associated with mild mucocutaneous bleeding, although there are more severe phenotypes with bleeding from the gastrointestinal tract or even the joints. Also, surgical interventions and trauma may lead to critical bleeding events. These bleeding episodes are all related to quantitative or qualitative defects of Von Willebrand factor (VWF), a multimeric glycoprotein produced by endothelial cells and megakaryocytes, which mediates platelet adhesion and aggregation and binds factor VIII (FVIII) in the circulation. This review describes the diagnostic procedures required for correct diagnosis. Accurate diagnosis and classification is required for proper treatment and counseling. Assessment of bleeding starts with the medical history. After a positive bleeding or family history, subsequent laboratory investigations will start with a panel of standard screening tests for hemostatic defects. Patients suspected of having VWD will be tested for plasma VWF antigen levels, the ability of VWF to bind platelets and FVIII activity. When VWD is confirmed, a set of subtyping tests can classify the patients as VWD types 1, 2 (A, B, M or N) or 3. The performance of some additional assays and analyses, such as VWF propeptide measurement or genetic analysis, may help in identifying the pathological mechanism behind certain defects or can guide in the choice of treatment.
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Von Willebrand Disease and aging an evolving phenotype
Journal of Thrombosis and Haemostasis, 2014Co-Authors: Y.v. Sanders, Karina Meijer, Jeroen C. J. Eikenboom, Marjon H. Cnossen, M A Giezenaar, B Larosvan A P Gorkom, M R Nijziel, P F Ypma, Karin Fijnvandraat, E P MauserbunschotenAbstract:BACKGROUND: Because the number of elderly Von Willebrand Disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. OBJECTIVES: To assess age-related changes in Von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related differences in bleeding phenotype between elderly VWD patients and those <65 years. We also studied co-morbidity in elderly patients. PATIENTS/METHODS: We included VWD patients with VWF levels ≤ 30 U dL(-1) in the nationwide cross-sectional 'Willebrand in the Netherlands' (WiN-) study. Patients reported bleeding episodes and treatment of VWD in the year preceding inclusion and during life. This was compared between VWD patients older (n = 71) and younger (16-64 years, n = 593) than 65 years. In elderly patients, age-related changes in VWF and FVIII levels were studied longitudinally by including all historically measured levels. All medical records were examined for co-morbidity. RESULTS: In elderly type 1 patients, a decade age increase was associated with a 3.5 U dL(-1) (95% CI, -0.6 to 7.6) VWF:Ag increase and 7.1 U dL(-1) (95% CI, 0.7 to 13.4) FVIII:C increase. This increase was not observed in elderly type 2 patients. Elderly type 2 patients reported significantly more bleeding symptoms in the year preceding inclusion than younger patients (16/27, 59% vs. 87/221, 39%; P = 0.048), which was not observed in type 1 VWD. CONCLUSIONS: Von Willebrand factor parameters and bleeding phenotype evolve with increasing age in VWD. VWF and FVIII levels increase with age in type 1 patients with no mitigation in bleeding phenotype. In type 2 patients VWF parameters do not increase with age and in these patients aging is accompanied by increased bleeding.
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principles of care for the diagnosis and treatment of Von Willebrand Disease
Haematologica, 2013Co-Authors: Giancarlo Castaman, Anne C Goodeve, Jeroen C. J. EikenboomAbstract:Von Willebrand Disease is a common autosomal inherited bleeding disorder caused by quantitative or qualitative defects of Von Willebrand factor, a multi-adhesive protein that binds platelets to exposed subendothelium and carries factor VIII in circulation. As a result of Von Willebrand factor deficiency or abnormality, levels of factor VIII, the protein deficient in hemophilia A, may be variably reduced. Clinical manifestations are mainly represented by mucous membrane and of soft tissue bleeding. Their severity is variable depending on the degree of Von Willebrand factor and factor VIII reduction. While a clear-cut diagnosis is easy in severe Von Willebrand factor reductions, the advantage of pursuing a definite diagnosis in mild or dubious cases should be weighed against the risk of over-medicalization. The aim of treatment is to correct the dual defect of hemostasis caused by the abnormal/reduced Von Willebrand factor and the concomitant deficiency of factor VIII. Desmopressin is the treatment of choice for type 1 Von Willebrand Disease patients with factor VIII and Von Willebrand factor levels of 10 U/dL or over who have proved responsive to a test-infusion with the compound. Von Willebrand factor/factor VIII concentrates are needed when desmopressin is ineffective (mainly type 2 and 3 Von Willebrand Disease).
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reduced prevalence of arterial thrombosis in Von Willebrand Disease
Journal of Thrombosis and Haemostasis, 2013Co-Authors: Y.v. Sanders, Karina Meijer, Jeroen C. J. Eikenboom, Marjon H. Cnossen, B Larosvan A P Gorkom, Karin Fijnvandraat, E P Mauserbunschoten, M E L Degenaardujardin, P W Kamphuisen, Frank W.g. LeebeekAbstract: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 ≤ 30 U dL-1, aged 16-85 years, from the nationwide 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 21 patients (3.3%). Five patients suffered an acute myocardial infarction and three an ischemic stroke. Unstable angina pectoris was recorded 12 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 with 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.
Evan J Sadler - One of the best experts on this subject based on the ideXlab platform.
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clinical and laboratory diagnosis of Von Willebrand Disease a synopsis of the 2008 nhlbi nih guidelines
American Journal of Hematology, 2009Co-Authors: William L. Nichols, Mae B. Hultin, Thomas L Ortel, Barbara P. Yawn, Margaret E. Rick, Andra H. James, Robert R Montgomery, Evan J Sadler, Marilyn J MancojohnsonAbstract:Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand Disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired Von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/ vwd). Am. J. Hematol. 84:366-370, 2009. (C) 2009 Wiley-Liss, Inc.
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new concepts in Von Willebrand Disease
Annual Review of Medicine, 2005Co-Authors: Evan J SadlerAbstract:Von Willebrand factor (VWF) behaves as an extracellular adapter molecule, linking platelets to the extracellular matrix at sites of vascular injury. These interactions are crucial for hemostasis. Too little platelet adhesion causes bleeding that is typical of Von Willebrand Disease, whereas too much platelet adhesion may cause thrombotic thrombocytopenic purpura. Mutations in VWF or platelet glycoprotein Ib can either reduce or increase the affinity of platelet binding. Paradoxically, affinity changes in either direction cause bleeding. Crystallographic studies now suggest molecular explanations for all of these phenotypes. Clinical investigations of Von Willebrand Disease type 1 are defining the relationship between plasma VWF level and the risk of bleeding or thrombosis. Emerging data suggest that VWF level is a useful biomarker for the risk of either bleeding or thrombosis and could be incorporated into a comprehensive approach to treat or prevent these adverse events.
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Von Willebrand Disease type 1 a diagnosis in search of a Disease
Blood, 2003Co-Authors: Evan J SadlerAbstract:Von Willebrand Disease (VWD) type 1 is reported to be common but frequently is difficult to diagnose. Many people have nonspecific mild bleeding symptoms, Von Willebrand factor (VWF) levels display low heritability, and low VWF levels (15% to 50% of normal) are weak risk factors for bleeding. Therefore, bleeding and low VWF levels often associate by chance. Even with stringent diagnostic criteria based on a triad of bleeding symptoms, a low VWF level, and a positive family history, the prevalence of “false-positive” VWD type 1 is comparable to the published prevalence of the Disease. Consequently, many patients diagnosed with VWD type 1 do not have a specific hemorrhagic Disease at all, which limits the utility of the diagnosis. This unfortunate reality is a consequence of trying to force patients into binary categories of “Diseased” or “healthy” that are incompatible with the continuous biologic context in which VWF functions. The problem may be avoided by substituting an empirical epidemiologic approach like that applied to other modest risk factors for Disease such as elevated cholesterol and high blood pressure. Such a risk management strategy could be generalized to include other hemorrhagic and thrombotic risk factors.
F Hill - One of the best experts on this subject based on the ideXlab platform.
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distinguishing between type 2b and pseudo Von Willebrand Disease and its clinical importance
British Journal of Haematology, 2006Co-Authors: Mohammad S Enayat, Andrea M Guilliatt, William Lester, Jonathan T Wilde, M D Williams, F HillAbstract:SummaryPseudo-Von Willebrand Disease (p-VWD) and type 2B Von WillebrandDisease (VWD) have similar phenotypic parameters and clinical symptoms,but different aetiologies. Fourteen individuals from five families with ahistorical diagnosis of type 2B VWD but with no mutation in the VonWillebrand factor gene were re-investigated for the possibility of p-VWD,using platelet aggregation in the presence of cryoprecipitate. p-VWD wasconfirmed by targeted DNA sequencing of the glycoprotein Iba gene,identifying a heterozygous Glycine 233 Valine substitution. This studysuggests that p-VWD may be under diagnosed, and that platelet aggregationin the presence of cryoprecipitate is useful in differentiating this disorderfrom type 2B VWD.Keywords: pseudo-Von Willebrand Disease, type 2B Von Willebrand Disease,platelet aggregation with cryoprecipitate, mutation, GPIba gene. short report a 2006 The Authorsdoi:10.1111/j.1365-2141.2006.06078.x Journal Compilation a 2006 Blackwell Publishing Ltd, British Journal of Haematology, 133, 664–666
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the diagnosis of Von Willebrand Disease a guideline from the uk haemophilia centre doctors organization
Haemophilia, 2004Co-Authors: Michael Laffan, F Hill, I R Peake, Simon A Brown, Peter Collins, A M Cumming, David Keeling, K J PasiAbstract:Summary. Von Willebrand Disease (VWD) is the commonest inherited bleeding disorder. However, despite an increasing understanding of the pathophysiology of VWD, the diagnosis of VWD is frequently difficult because of uncertainty regarding the relationship between laboratory assays and function in vivo. The objective of this guideline is to provide contemporary advice on a rational approach to the diagnosis of VWD. This is the second edition of this UK Haemophilia Centre Doctors’ Organisation (UKHCDO) guideline and supersedes the previous edition which was published in 1997.
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management of Von Willebrand Disease a guideline from the uk haemophilia centre doctors organization
Haemophilia, 2004Co-Authors: K J Pasi, F Hill, Michael Laffan, Simon A Brown, Peter Collins, A M Cumming, David Keeling, G Dolan, I R PeakeAbstract:Von Willebrand Disease (VWD) is the commonest inherited bleeding disorder. The aim of therapy for VWD is to correct the two defects of haemostasis in this disorder, impaired primary haemostasis because of defective platelet adhesion and aggregation and impaired coagulation as a result of low levels of factor VIII. The objective of this guideline is to inform individuals making choices about the treatment and management of VWD including the use of therapeutic products. This is the second edition of this UK Haemophilia Centre Doctors' Organization (UKHCDO) guideline and supersedes the previous edition which was published in 1994.
Michael Laffan - One of the best experts on this subject based on the ideXlab platform.
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cellular and molecular basis of Von Willebrand Disease studies on blood outgrowth endothelial cells
Blood, 2013Co-Authors: Richard D Starke, Michael Laffan, Koralia E Paschalaki, C Dyer, Kimberly J Harrisonlavoie, J Cutler, Thomas A J Mckinnon, Carolyn M Millar, Daniel F Cutler, Anna M RandiAbstract:Von Willebrand Disease (VWD) is a heterogeneous bleeding disorder caused by decrease or dysfunction of Von Willebrand factor (VWF). A wide range of mutations in the VWF gene have been characterized; however, their cellular consequences are still poorly understood. Here we have used a recently developed approach to study the molecular and cellular basis of VWD. We isolated blood outgrowth endothelial cells (BOECs) from peripheral blood of 4 type 1 VWD and 4 type 2 VWD patients and 9 healthy controls. We confirmed the endothelial lineage of BOECs, then measured VWF messenger RNA (mRNA) and protein levels (before and after stimulation) and VWF multimers. Decreased mRNA levels were predictive of plasma VWF levels in type 1 VWD, confirming a defect in VWF synthesis. However, BOECs from this group of patients also showed defects in processing, storage, and/or secretion of VWF. Levels of VWF mRNA and protein were normal in BOECs from 3 type 2 VWD patients, supporting the dysfunctional VWF model. However, 1 type 2M patient showed decreased VWF synthesis and storage, indicating a complex cellular defect. These results demonstrate for the first time that isolation of endothelial cells from VWD patients provides novel insight into cellular mechanisms of the Disease.
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the diagnosis of Von Willebrand Disease a guideline from the uk haemophilia centre doctors organization
Haemophilia, 2004Co-Authors: Michael Laffan, F Hill, I R Peake, Simon A Brown, Peter Collins, A M Cumming, David Keeling, K J PasiAbstract:Summary. Von Willebrand Disease (VWD) is the commonest inherited bleeding disorder. However, despite an increasing understanding of the pathophysiology of VWD, the diagnosis of VWD is frequently difficult because of uncertainty regarding the relationship between laboratory assays and function in vivo. The objective of this guideline is to provide contemporary advice on a rational approach to the diagnosis of VWD. This is the second edition of this UK Haemophilia Centre Doctors’ Organisation (UKHCDO) guideline and supersedes the previous edition which was published in 1997.
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management of Von Willebrand Disease a guideline from the uk haemophilia centre doctors organization
Haemophilia, 2004Co-Authors: K J Pasi, F Hill, Michael Laffan, Simon A Brown, Peter Collins, A M Cumming, David Keeling, G Dolan, I R PeakeAbstract:Von Willebrand Disease (VWD) is the commonest inherited bleeding disorder. The aim of therapy for VWD is to correct the two defects of haemostasis in this disorder, impaired primary haemostasis because of defective platelet adhesion and aggregation and impaired coagulation as a result of low levels of factor VIII. The objective of this guideline is to inform individuals making choices about the treatment and management of VWD including the use of therapeutic products. This is the second edition of this UK Haemophilia Centre Doctors' Organization (UKHCDO) guideline and supersedes the previous edition which was published in 1994.
I R Peake - One of the best experts on this subject based on the ideXlab platform.
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management of Von Willebrand Disease a guideline from the uk haemophilia centre doctors organization
Haemophilia, 2004Co-Authors: K J Pasi, F Hill, Michael Laffan, Simon A Brown, Peter Collins, A M Cumming, David Keeling, G Dolan, I R PeakeAbstract:Von Willebrand Disease (VWD) is the commonest inherited bleeding disorder. The aim of therapy for VWD is to correct the two defects of haemostasis in this disorder, impaired primary haemostasis because of defective platelet adhesion and aggregation and impaired coagulation as a result of low levels of factor VIII. The objective of this guideline is to inform individuals making choices about the treatment and management of VWD including the use of therapeutic products. This is the second edition of this UK Haemophilia Centre Doctors' Organization (UKHCDO) guideline and supersedes the previous edition which was published in 1994.
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the diagnosis of Von Willebrand Disease a guideline from the uk haemophilia centre doctors organization
Haemophilia, 2004Co-Authors: Michael Laffan, F Hill, I R Peake, Simon A Brown, Peter Collins, A M Cumming, David Keeling, K J PasiAbstract:Summary. Von Willebrand Disease (VWD) is the commonest inherited bleeding disorder. However, despite an increasing understanding of the pathophysiology of VWD, the diagnosis of VWD is frequently difficult because of uncertainty regarding the relationship between laboratory assays and function in vivo. The objective of this guideline is to provide contemporary advice on a rational approach to the diagnosis of VWD. This is the second edition of this UK Haemophilia Centre Doctors’ Organisation (UKHCDO) guideline and supersedes the previous edition which was published in 1997.
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impact diagnosis and treatment of Von Willebrand Disease
Thrombosis and Haemostasis, 2000Co-Authors: J E Sadler, Erik Berntorp, Pier Mannuccio Mannucci, D Ginsburg, D. Meyer, Nikolay P Bochkov, V Boulyjenkov, I R Peake, Francesco Rodeghiero, Alok SrivastavaAbstract:Von Willebrand Disease (VWD) is one of the most common inherited bleeding Diseases. Based on a conservative estimate of prevalence (at least 100 per million persons) (1-7) and a population of 5.8 billion, there are at least 580,000 persons with symptomatic VWD worldwide who could benefit from appropriate diagnosis followed by replacement or pharmacological therapy. Approximately 80% of these persons live in the developing world. Because severe menorrhagia is common in VWD, the Disease tends to cause greater morbidity in women of childbearing age. Consequently, VWD impairs the health of a critical segment of the population during a time of life when the demands of work and family are the greatest.
