A need to increase von Willebrand disease awareness: vwdtest.com – A global initiative to help address this gap

Corrales-Medina, Fernando F.; Federici, Augusto B.; Srivastava, Alok; Dougall, Alison; Millar, Carolyn M.; Roberts, Jonathan C.; Jaffray, Julie; Berntorp, Erik

doi:10.1016/j.blre.2022.101018

Cited by 7 publications

(7 citation statements)

References 76 publications

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“…The high VWD prevalence established in this large-scale genetic database indicates that the genetic predisposition to develop VWD due to VWF variants is likely to be more common than hitherto reported and also highlights that many patients carrying these variants are still undiagnosed. Available data suggests that despite the fact that VWD is common, it is paradoxically underdiagnosed owing to several factors, including complex diagnosis, inaccurate distinction between normal or abnormal bleeding symptoms, relatively mild clinical severity as well as lack of disease awareness among non-specialist healthcare providers [23,24]. We identi ed 287 novel and potentially pathogenic and 218 previously reported VWF variants in the gnomAD population, in which among a total of 282,912 alleles 31,785 carried VWF pathogenic variants.…”

Section: Discussionmentioning

confidence: 99%

Population-based prevalence and mutational landscape of von Willebrand disease using large-scale genetic databases

Peyvandi

Seidizadeh

Cairo³

et al. 2023

Preprint

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Von Willebrand disease (VWD) is a common bleeding disorder caused by mutations in the von Willebrand factor gene (VWF). The true global prevalence of VWD has not been accurately established. We estimated the worldwide and within-population prevalence of inherited VWD by analyzing exome and genome data of 141,456 individuals gathered by the genome Aggregation Database (gnomAD). We also extended our data deepening by mining the main databases containing VWF variants i.e., the Leiden Open Variation Database (LOVD) and the Human Gene Mutation Database (HGMD) with the goal to explore the global mutational spectrum of VWD. A total of 4,313 VWF variants were identified in the gnomAD population, of which 505 were predicted to be pathogenic or already reported to be associated with VWD. Among the 282,912 alleles analyzed, 31,785 were affected by the aforementioned variants. The global prevalence of dominant VWD in 1000 individuals was established to be 74 for type 1, 3 for 2A, 3 for 2B and 6 for 2M. The global prevalences for recessive VWD forms (type 2N and type 3) were 0.03 and 3 in 1000 individuals, respectively. This comprehensive analysis provided a global mutational landscape of VWF by means of 927 already reported variants in the HGMD and LOVD datasets and 287 novel pathogenic variants identified in the gnomAD. Our results reveal that there is a considerably higher than expected prevalence of putative disease alleles and variants associated with VWD and suggest that a large number of VWD patients are undiagnosed.

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Section: Discussionmentioning

confidence: 99%

Population-based prevalence and mutational landscape of von Willebrand disease using large-scale genetic databases

Peyvandi

Seidizadeh

Cairo³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…These data provide a hint that VWD is likely to be grossly underdiagnosed worldwide, which could contribute to undertreatment, significant (avoidable) morbidity, and health care system burden. Available data suggests that despite the fact that VWD is common, it is paradoxically underdiagnosed owing to several factors, including complex diagnosis, inaccurate distinction between normal or abnormal bleeding symptoms, relatively mild clinical severity as well as lack of disease awareness among non-specialist healthcare providers 23 , 24 . We identified 287 novel and potentially pathogenic and 218 previously reported VWF variants in the gnomAD population, in which among a total of 282,912 alleles 31,785 carried VWF pathogenic variants.…”

Section: Discussionmentioning

confidence: 99%

Population-based prevalence and mutational landscape of von Willebrand disease using large-scale genetic databases

Seidizadeh,

Cairo,

Baronciani

et al. 2023

npj Genom. Med.

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Von Willebrand disease (VWD) is a common bleeding disorder caused by mutations in the von Willebrand factor gene (VWF). The true global prevalence of VWD has not been accurately established. We estimated the worldwide and within-population prevalence of inherited VWD by analyzing exome and genome data of 141,456 individuals gathered by the genome Aggregation Database (gnomAD). We also extended our data deepening by mining the main databases containing VWF variants i.e., the Leiden Open Variation Database (LOVD) and the Human Gene Mutation Database (HGMD) with the goal to explore the global mutational spectrum of VWD. A total of 4,313 VWF variants were identified in the gnomAD population, of which 505 were predicted to be pathogenic or already reported to be associated with VWD. Among the 282,912 alleles analyzed, 31,785 were affected by the aforementioned variants. The global prevalence of dominant VWD in 1000 individuals was established to be 74 for type 1, 3 for 2A, 3 for 2B and 6 for 2M. The global prevalences for recessive VWD forms (type 2N and type 3) were 0.31 and 0.7 in 1000 individuals, respectively. This comprehensive analysis provided a global mutational landscape of VWF by means of 927 already reported variants in the HGMD and LOVD datasets and 287 novel pathogenic variants identified in the gnomAD. Our results reveal that there is a considerably higher than expected prevalence of putative disease alleles and variants associated with VWD and suggest that a large number of VWD patients are undiagnosed.

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“…These features are similar to those observed in type 2 VWD ( 3 ). Clinically, VWD is an inherited bleeding disorder and is divided into three types, i.e., types 1, 2, and 3 ( 59 , 60 ). Approximately 70%–80% of the patients express type 1 VWD, which is characterized by a quantitative deficiency of VWF.…”

Section: Diagnosis Of Avws Under Ecmo Supportmentioning

confidence: 99%

Shear-induced acquired von Willebrand syndrome: an accomplice of bleeding events in adults on extracorporeal membrane oxygenation support

Wang

Chen

et al. 2023

Front. Cardiovasc. Med.

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Extracorporeal membrane oxygenation (ECMO) is an increasingly acceptable life-saving mechanical assistance system that provides cardiac and/or respiratory support for several reversible or treatable diseases. Despite important advances in technology and clinical management, bleeding remains a significant and common complication associated with increased morbidity and mortality. Some studies suggest that acquired von Willebrand syndrome (AVWS) is one of the etiologies of bleeding. It is caused by shear-induced deficiency of von Willebrand factor (VWF). VWF is an important glycoprotein for hemostasis that acts as a linker at sites of vascular injury for platelet adhesion and aggregation under high shear stress. AVWS can usually be diagnosed within 24 h after initiation of ECMO and is always reversible after explantation. Nonetheless, the main mechanism for the defect in the VWF multimers under ECMO support and the association between AVWS and bleeding complications remains unknown. In this review, we specifically discuss the loss of VWF caused by shear induction in the context of ECMO support as well as the current diagnostic and management strategies for AVWS.

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A need to increase von Willebrand disease awareness: vwdtest.com – A global initiative to help address this gap

Cited by 7 publications

References 76 publications

Population-based prevalence and mutational landscape of von Willebrand disease using large-scale genetic databases

Population-based prevalence and mutational landscape of von Willebrand disease using large-scale genetic databases

Population-based prevalence and mutational landscape of von Willebrand disease using large-scale genetic databases

Shear-induced acquired von Willebrand syndrome: an accomplice of bleeding events in adults on extracorporeal membrane oxygenation support

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