von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease

Sanders, Yvonne V.; Groeneveld, Dafna; Meijer, Karina; Fijnvandraat, Karin; Cnossen, Marjon H.; Bom, Johanna G. van der; Coppens, Michiel; Meris, Joke de; Gorkom, Britta A P Laros-van; Mauser‐Bunschoten, Eveline P.; Leebeek, Frank W.G.; Eikenboom, Jeroen

doi:10.1182/blood-2014-09-603241

Cited by 67 publications

(124 citation statements)

References 32 publications

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“…In some patients with very low VWF levels (,5 IU/dL), detectable or even normal levels of VWFpp may be measured. 94,101 These moderate or normal VWFpp levels in patients with severely reduced VWF levels indicate reduced VWF survival, as found in type 1C VWD. In type 3 VWD, VWF is not stored in endothelial cell WPB or platelet a-granules, whereas type 1C patients are expected to have normal WPB and a-granule stores of VWF and may have a milder bleeding phenotype.…”

Section: Vwdmentioning

confidence: 98%

“…The parallel assay of VWF and VWFpp can identify a reduced survival of VWF as is found in acquired, type 1C, type 2B, and some type 2A VWD patients. [88][89][90][91][92][93][94][95][96][97][98] Type 1C VWD patients are characterized by markedly reduced plasma survival of VWF, with half-life of VWF as short as 1.0 hour, in contrast to the 8 to 12 hour half-life in healthy individuals and other type 1 patients ( Figure 4A). 89,99 By definition, there is 1 unit each of VWF and VWFpp in 1 mL of plasma in healthy individuals with a VWFpp/VWF:Ag ratio at steady-state of ;1.0.…”

Section: Vwdmentioning

confidence: 99%

“…by guest www.bloodjournal.org From underlying a patient's VWD phenotype. 94 Perhaps the most striking use for the VWFpp assay is in identifying true type 3 VWD patients. In some patients with very low VWF levels (,5 IU/dL), detectable or even normal levels of VWFpp may be measured.…”

Section: Vwdmentioning

confidence: 99%

“…In type 3 VWD, VWF is not stored in endothelial cell WPB or platelet a-granules, whereas type 1C patients are expected to have normal WPB and a-granule stores of VWF and may have a milder bleeding phenotype. 94 The identification of patients with reduced VWF survival impacts treatment options. DDAVP is the most common treatment of type 1 VWD, releasing VWF from WPBs to increase plasma VWF levels.…”

Section: Vwdmentioning

confidence: 99%

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von Willebrand factor propeptide: biology and clinical utility

Haberichter

2015

Blood

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von Willebrand factor (VWF) is a large multimeric glycoprotein that mediates the attachment of platelets to damaged endothelium and also serves as the carrier protein for coagulation factor VIII (FVIII), protecting it from proteolytic degradation. Quantitative or qualitative defects in VWF result in von Willebrand disease (VWD), a common inherited bleeding disorder. VWF is synthesized with a very large propeptide (VWFpp) that is critical for intracellular processing of VWF. VWFpp actively participates in the process of VWF multimerization and is essential for trafficking of VWF to the regulated storage pathway. Mutations identified within VWFpp in VWD patients are associated with altered VWF structure and function. The assay of plasma VWFpp has clinical utility in assessing acute and chronic vascular perturbation associated with diseases such as thrombotic thrombocytopenic purpura, sepsis, and diabetes among others. VWFpp assay also has clear utility in the diagnosis of VWD subtypes, particularly in discriminating true type 3 subjects from type 1C (reduced plasma survival of VWF), which is clinically important and has implications for therapeutic treatment.

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Section: Vwdmentioning

confidence: 98%

Section: Vwdmentioning

confidence: 99%

Section: Vwdmentioning

confidence: 99%

Section: Vwdmentioning

confidence: 99%

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von Willebrand factor propeptide: biology and clinical utility

Haberichter

2015

Blood

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“…Statistical analysis showed a significant upregulation of von Willebrand factor (vWF), which is a multimeric adhesive glycoprotein encoded as both an antihaemophilic factor carrier and a platelet-vessel wall mediator involved in the blood coagulation cascade22 in ASS HCC, which notably had downregulated expression in the ASMq treatment group ( P < 0.05). Its plasma level increases in neoplastic diseases and arises from adverse changes in the endothelium.…”

Section: Discussionmentioning

confidence: 99%

Differential integrative omic analysis for mechanism insights and biomarker discovery of abnormal Savda syndrome and its unique Munziq prescription

Guo

Iskandar

Abudula

et al. 2016

Sci Rep

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Research has shown that many cancers have acommon pathophysiological origin and often present with similar symptoms. In terms of Traditional Uighur Medicine (TUM) Hilit (body fluid) theory, abnormal Savda syndrome (ASS) formed by abnormal Hilit is the common phenotype of complex diseases and in particular tumours. Abnormal Savda Munziq (ASMq), one representative of TUM, has been effective in the treatment of cancer since ancient times. Despite the physiopathology of ASS, the relationship between causative factors and the molecular mechanism of ASMq are not fully understood. The current study expanded upon earlier work by integrating traditional diagnostic approaches with others utilizing systems biology technology for the analysis of proteomic (iTRAQ) and metabolomic (1H-NMR) profiles of Uighur Medicine target organ lesion (liver) tumours. The candidate proteins were analyzed by enrichment analysis of the biological process and biomarker filters. Subsequently, 3Omics web-based tools were used to determine the relationships between proteins and appropriate metabolites. ELISA assay and IHC methods were used to verify the proteomic result; the protein von Willebrand factor (vWF) may be the “therapeutic window” of ASMq and biomarkers of ASS. This study is likely to be of great significance for the standardization and modernization of TUM.

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ADAMTS‐13 and bleeding phenotype in von Willebrand disease

Boender

Nederlof

Meijer

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Background The bleeding phenotype of von Willebrand disease (VWD) varies highly between patients and can only partly be explained by von Willebrand factor (VWF) parameters. By cleaving large VWF multimers into smaller, less active multimers, ADAMTS‐13 is an important regulator of VWF activity. However, it is unknown what the role of ADAMTS‐13 is in individuals with VWD. Objectives We therefore studied how ADAMTS‐13 activity is associated with the laboratory and bleeding phenotype in individuals with VWD. Methods We measured ADAMTS‐13 activity using the fluorescence resonance energy transfer substrate VWF 73 assay in 638 individuals with VWD in the nationwide cross‐sectional Willebrand in the Netherlands study and in 36 healthy controls. The bleeding phenotype was assessed using the Tosetto bleeding score. Results ADAMTS‐13 activity was similar in individuals with VWD (109% ± 20.6%) and controls (110% ± 19.7%). ADAMTS‐13 activity was higher in individuals with VWD with type 3 than those with type 1 (mean difference, 11.8%; 95% confidence interval [CI], 2.9%‐20.8%) or type 2 (mean difference, 16.1%; 95% CI, 7.1%‐25.1%). ADAMTS‐13 activity was not associated with the Tosetto bleeding score (0.1 Tosetto bleeding score increase per 10% ADAMTS‐13 increase, 95% CI, −0.2 to 0.3). Furthermore, ADAMTS‐13 activity did not differ between individuals with and without a bleeding event during the year preceding blood sampling (mean difference, 1.4%; 95% CI, −2.1% to 4.9%). Conclusion ADAMTS‐13 activity was highest in individuals with type 3 VWD, but it had only minor associations with VWF parameters. ADAMTS‐13 activity does not influence the bleeding phenotype in individuals with VWD.

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von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease

Abstract: Key Points VWFpp discriminates between type 3 VWD patients and severe type 1 VWD patients with very low VWF levels. The pathophysiological mechanisms of all types of VWD can be defined by the combined ratios of VWFpp/VWF:Ag and FVIII:C/VWF:Ag.

Cited by 67 publications

References 32 publications

von Willebrand factor propeptide: biology and clinical utility

von Willebrand factor propeptide: biology and clinical utility

Differential integrative omic analysis for mechanism insights and biomarker discovery of abnormal Savda syndrome and its unique Munziq prescription

ADAMTS‐13 and bleeding phenotype in von Willebrand disease

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