Von Willebrand disease: Clinical conundrums

Leebeek, Frank W.G.; Susen, Sophie

doi:10.1111/hae.13508

Cited by 12 publications

(14 citation statements)

References 62 publications

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“…Excessive mucocutaneous bleeding is the primary symptom but this ranges from mild to severe; patients completely lacking VWF experience moderate to severe bleeding symptoms including epistaxis, menorrhagia, postoperative bleeding and haemarthrosis that also may be present in cases with partial VWF function (e.g. type 2N VWD) 1‐6 . Based on ISTH recommendations, 1,2 the diagnosis of VWD involves an algorithm that includes biochemical screening tests (e.g.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of von Willebrand disease in Western Mexico

et al. 2020

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Introduction Von Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of 0.1%, characterised by quantitative or functional deficiency of von Willebrand factor (VWF). VWD diagnosis is based on symptomology, biochemical and genetic tests, but limited laboratory resources and VWD heterogeneity still generate an important subdiagnosis gap worldwide and in our country. Aim To identify the type and subtype of VWD in a cohort of patients with a history of excessive bleeding in Western Mexico. Methods This prospective cohort study from 2012 to 2019 included patients with mucocutaneous bleeding or abnormal laboratory tests. A standardised questionnaire and confirmatory tests were applied: FVIII:C, VWF activity, VWF antigen, and VWF multimeric analysis. Results Of the 297 patients recruited, 207 (69.7%) were excluded because their values exceeded 50% in VWF activity and VWF antigen. Of those 90 remaining, 54 (18.2%) had low VWF, and only 36 patients (12.1%) were diagnosed with VWD. Among them, 17 (47.2%) had quantitative deficiencies, of whom 14 were assigned as type 1 and 3 as type 3.The remaining 19 cases were diagnosed as type 2 (52.8%): type 2A and 2B were the most frequent with 6 and 7 cases respectively; 4 cases were possible type 2M and two suggestive of 2N, however, this was not confirmed. Conclusion This study highlights the challenges of VWD diagnosis using a comprehensive panel of diagnostic tests which should extend to supplemental tests of VWF:CB, VWF:FVIIIB, and sequencing the VWD gene to confirm the results from the panel assays.

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Section: Introductionmentioning

confidence: 99%

Diagnosis of von Willebrand disease in Western Mexico

et al. 2020

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“…10 These advances have led to an increasingly complicated decision-making process, reflected by the complex impact that hemostatic imbalance can have on the complement system, immunity, and inflammation and, therefore, the management of hemostatic disorders. 11,12 This situation is compounded, in some instances, where access to even basic laboratory testing and medications is limited, 13 as are opportunities to access the latest scientific knowledge, tests, devices, or medications, compromising provision of optimal clinical care. 14 Given this rapidly evolving context, educational activities are needed to ensure optimal knowledge dissemination to T&H professionals.…”

Section: Introductionmentioning

confidence: 99%

Needs and challenges among physicians and researchers in thrombosis and hemostasis: Results from an international study

Murray

McLintock

Lazure

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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BackgroundSpecialty societies, such as the International Society on Thrombosis and Haemostasis (ISTH), are a key source of support for clinical and scientific communities, through the provision of educational activities, tools, and resources to support evidence‐based care and high‐quality, relevant basic science and clinical research.ObjectiveThe aim of this study was to identify areas where the thrombosis and hemostasis (T&H) community is facing challenges and could benefit from the support of ISTH.MethodsA 3‐phase, mixed‐methods study consisting of semistructured individual interviews (phase 1), an online survey (phase 2), and discussion groups (phase 3) was conducted on the challenges experienced by the T&H community. Participants included physicians, clinical and basic science researchers, residents, fellows, students, and industry representatives. Qualitative data were analyzed using thematic analysis. Quantitative data were analyzed using frequency tables and chi‐squares.ResultsThe study included 468 participants in interviews (n = 45), surveys (n = 404), and discussion groups (n = 19). Nine themes emerged that describe areas where the T&H community may benefit from additional support. Three areas were related to diagnosis and testing: thrombosis risk assessment, genetic testing, and diagnosis of von Willebrand disease (VWD). Another 3 were related to treatment decision making: use of anticoagulants with certain patients, preventive treatments in bleeding disorders, and VWD treatment. The remaining 3 were related to research: collaboration with/among researchers, collaboration between teams to collect data from human subjects, and promotion of basic science research.ConclusionsThis study provides a comprehensive picture of priorities within the T&H community, which should inform the ISTH in its future interventions, including educational offerings and networking opportunities.

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“…Bleeding disorder associated with VWF is known as von Willebrand disease (VWD) and has been the leading influence in identification, characterization, and determination of function for VWF molecule. VWD, which has been the subject of many excellent reviews periodically, can be broadly classified into categories that represent qualitative (type II) or quantitative (type I and III) deficiencies of VWF . In either case, VWF deficiency is the culprit leading to prolonged bleeding phenotype, some forms of which are reminiscent of hemophilia that arise as a result of coagulation factor VIII deficiency .…”

Section: Introductionmentioning

confidence: 99%

“…The two major functions of VWF have been long established as: (a) mediator of platelet adhesion and aggregate formation at the site of vascular injury, leading to formation of platelet plugs to seal the damaged vessel wall and (b) functioning as carrier for factor VIII, thus prolonging its half‐life in circulation . Although severe deficiencies of VWF clearly correlated to significant bleeding disorders, milder deficiencies were also identified that manifested only as a result of hemostatic challenges, such as surgeries, or menorrhagia . Wide variation in VWF levels among healthy population hinders diagnosis of mild VWD, but also made it difficult to appreciate potential pathological consequences of high levels of VWF .…”

Section: Introductionmentioning

confidence: 99%

“…Collectively, this information reveals that VWF participates in development, progression, and/or complication of diseases beyond von Willebrand disease. Biosynthesis, structure, hemostatic function, and dysfunction of VWF leading to a spectrum of VWD have been the subjects of many excellent and regularly updated reviews . In this review, which by no means is exhaustive, we aimed to highlight recent evidence demonstrating participation of VWF in various diseases beyond VWD.…”

Section: Introductionmentioning

confidence: 99%

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Von Willebrand factor contribution to pathophysiology outside of von Willebrand disease

2018

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VWF is a large multimeric glycoprotein that was identified through its association with an inherited bleeding disorder first described by physician, Erik von Willebrand in 1926. 1 Bleeding disorder associated with VWF is known as von Willebrand disease (VWD) and has been the leading influence in identification, characterization, and determination of function for VWF molecule. VWD, which has been the subject of many excellent reviews periodically, can be broadly classified into categories that represent qualitative (type II) or quantitative (type I and III) deficiencies of VWF. [2][3][4][5] In either case, VWF deficiency is the culprit leading to prolonged bleeding phenotype, some forms of which are reminiscent of hemophilia that arise as a result of coagulation factor VIII deficiency. 6,7 The phenotypic consequences of VWF deficiency were instrumental in early studies that established the major role of VWF in hemostasis. 8 The two major functions of VWF have been long established as: (a) mediator of platelet adhesion and aggregate formation at the site of vascular injury, leading to formation of platelet plugs to seal the damaged vessel wall and (b) functioning as carrier for factor VIII, thus prolonging its half-life in circulation. 8-10 Although severe deficiencies of VWF clearly correlated to significant bleeding disorders, milder deficiencies were also identified that manifested only as a result of hemostatic challenges, such as surgeries, or menorrhagia. 3,11,12 Wide variation in VWF levels among healthy population hinders diagnosis of mild VWD, but also made it difficult to appreciate potential pathological consequences of high levels of VWF. [13][14][15][16] Nevertheless, based on structural and functional characteristics of the VWF, a potential role for VWF in diseases associated with increased thrombogenicity was not unexpected. Several clinical studies had reported a correlation between elevated levels of VWF and prothrombotic diseases specifically in high-risk populations, including heart disease and stroke; however, direct evidence beyond associations was lacking. [17][18][19][20][21] Discovery of VWF cleaving enzyme, ADAMTS13, and demonstration of its dysfunction in TTP provided clear evidence that excessive VWF levels contribute to undesired thrombogenicity. [22][23][24] Physiological balance of VWF levels is highly regulated through its expression, storage and release in one hand, and clearance on the other hand. 25,26 If this balance is disturbed in favor of sustained increased levels of VWF, as in TTP, it leads to significant undesired thrombogenicity. 27 The potential for VWF association with increased thrombogenicity is clearly consistent with its role as a mediator of platelet aggregate formation, which is the first and central step in thrombus formation. 28 However, based on highly adhesive properties of VWF, its participation in other pathophysiological conditions, specifically those that involve cell adhesion to the vascular wall, has been considered.These include processes that participate...

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Von Willebrand disease: Clinical conundrums

Cited by 12 publications

References 62 publications

Diagnosis of von Willebrand disease in Western Mexico

Diagnosis of von Willebrand disease in Western Mexico

Needs and challenges among physicians and researchers in thrombosis and hemostasis: Results from an international study

Von Willebrand factor contribution to pathophysiology outside of von Willebrand disease

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