The history of von Willebrand disease

Nilsson, Inga Marie

doi:10.1046/j.1365-2516.1999.0050s2007.x

Cited by 8 publications

(7 citation statements)

References 16 publications

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“…We will only briefly mention the pathophysiological and molecular basis of vWF and vWD, thus limiting the discussion to those aspects relevant to our scope. For a more comprehensive understanding, the reader is invited to refer to several updated reviews [1–10].…”

Section: Introductionmentioning

confidence: 99%

von Willebrand disease: still an intriguing disorder in the era of molecular medicine

Rodeghiero

2002

Haemophilia

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von Willebrand disease (vWD) is a single-locus disorder resulting from a deficiency of von Willebrand factor (vWF): a multimeric multifunctional protein involved in platelet adhesion and platelet-to-platelet cohesion in high shear stress vessels, and in protecting from proteolysis and directing circulating factor VIII (FVIII) to the site of injury. vWD is the most frequent bleeding disorder, with an estimated prevalence in the general population of 1%. Almost all these cases are represented by a partial quantitative deficiency of von Willebrand factor (vWF) (type 1 vWD). Type 1 is transmitted as an autosomal dominant trait with an extremely variable penetrance and expressivity. A consensus figure for the prevalence of cases with significant bleeding symptoms, requiring some form of treatment, is approximately 100 cases million-1. Among these cases, more than 70-80% are represented by type 1 and respond to deamino-D-arginine vasopressin (DDAVP; desmopressin) administration. The remaining cases are represented by type 2 vWD (qualitative), some of which require substitutive treatment. Only 3-5 cases million-1 result from a total deficiency of vWF in plasma and platelets because of the recessive inheritance of two defective alleles. These cases may have severe bleeding episodes and may require frequent substitutive treatment. The molecular basis of type 2 (missense mutation in the functional domains of the vWF subunit) and type 3 (nonsense or large deletions) is quite well understood. On the contrary the molecular basis for most type 1 cases remains largely unknown, and many genetic factors (e.g. ABO blood group) and environmental or circumstantial factors (e.g. age, stress, drugs, pregnancy, and inflammation) are superimposed on to the genetic background determined by the vWF gene to produce a continuous spectrum from normality to mild type 1 cases. It is extremely difficult to make a clear distinction between mild type 1 cases and normal people because of the wide 'normal' range of laboratory measurements (e.g. length of bleeding time, and levels of vWF and FVIII) and of bleeding symptoms. Molecular testing is useless in this situation, and only good history-taking and repeated laboratory testing of vWF-related measurements in the propositus and his/her family members can help in clinical diagnosis, albeit imprecisely. This difficult task is the main focus of this review which is aimed at alerting the physician toward a balanced approach that should take into consideration both the risk of over- and under-diagnosis of this frequent disorder and the unavoidable production of a number of false positive and false negative cases.

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Section: Introductionmentioning

confidence: 99%

von Willebrand disease: still an intriguing disorder in the era of molecular medicine

Rodeghiero

2002

Haemophilia

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“…Another milestone in the history of VWD was the isolation and characterization of VWF in the 1970s, when it was immunologically distinguished from coagulation factor VIII. 2 Another subsequent big milestone was the isolation of VWFspecific clones from human endothelial cell complementary DNA (cDNA) libraries, as reported by four separate groups in 1985. [3][4][5][6][7] This paved the way for new insights into understanding the molecular basis of VWD and the role of VWF in health and disease.…”

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confidence: 99%

Genetic Background of von Willebrand Disease: History, Current State, and Future Perspectives

Žolková

Sokol

Šimurda

et al. 2019

Semin Thromb Hemost

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Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the physiology of VWF as well as its pathophysiology in the context of von Willebrand disease (VWD). Molecular testing in VWD patients has shown high variability in the overall genetic background of this condition. Almost 600 mutations and many disease-causing mechanisms have been described in the 35 years since the VWF gene was identified. Genetic testing in VWD patients is now available in many centers as a part of the VWD diagnostic algorithm. Molecular mechanisms leading to types 2 and 3 VWD are well characterized; thus, information from genetic analysis in these VWD types may be beneficial for their correct classification. However, the molecular basis of type 1 VWD is still not fully elucidated and most likely represents a multifactorial disorder reflecting a combined impact of environmental and genetic factors within and outside of VWF. Regarding sequencing methods, the previous gold-standard Sanger sequencing is gradually being replaced with next-generation sequencing methods that are more cost- and time-effective. Instead of gene-by-gene approaches, gene panels of genes for coagulation factors and related proteins have recently become a center of attention in patients with inherited bleeding disorders, especially because a high proportion of VWD patients, mainly those with low VWF plasma levels (type 1), appear to be free of mutations in VWF. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) are accessible in a very limited number of laboratories. Results from these studies have presented several genes other than VWF or ABO possibly affecting VWF levels, and such findings will need further validation studies.

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“…The history of von Willebrand disease (VWD) has been the subject of a review. 1 In this review, I discuss the progress and the current problems of VWD diagnosis, 80 years after the original description by Erik von Willebrand.…”

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confidence: 99%

Diagnosis of Inherited von Willebrand Disease: A Clinical Perspective

Federici

2006

Semin Thromb Hemost

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The history of von Willebrand disease

Cited by 8 publications

References 16 publications

von Willebrand disease: still an intriguing disorder in the era of molecular medicine

von Willebrand disease: still an intriguing disorder in the era of molecular medicine

Genetic Background of von Willebrand Disease: History, Current State, and Future Perspectives

Diagnosis of Inherited von Willebrand Disease: A Clinical Perspective

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