von Willebrand Factor: Form for Function

Yee, Andrew; Kretz, Colin A.

doi:10.1055/s-0033-1363155

Cited by 41 publications

(21 citation statements)

References 139 publications

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“…The signal peptide (pre) is disconnected, pro-dimers are formed in the endoplasmic reticulum through disulfide bonds between C-terminal cysteine 1908-2050-residues, which undergo glycosylation and sulfonation in subsequent stages of biosynthesis. Pro-dimers are trafficked into Golgi apparatus where multimerization continues with the formation of interchain disulfide bonds between cysteine residues within the N-terminal D3 domain of pro-VWF [37][38][39]. D1, D2 domains of VWFpp and D 'and D3 domains of N-terminal of the VWF mono-mer are involved in the multimerization process [40][41][42][43][44][45].…”

Section: Von Willebrand Factor Propetidementioning

confidence: 99%

Von Willebrand factor propeptide (VWFpp) — potential biomarker in inherited von Willebrand disease and acquired von Willebrand syndrome

Bykowska

Ceglarek²,

Gwozdowska³

et al. 2019

Journal of Transfusion Medicine

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Von Willebrand factor propeptide (VWFpp) is a fragment of a new synthesized VWF molecule that plays an important part in the biosynthesis of this protein. After completion of multimerisation of von Willebrand factor (VWF) dimers in the Golgi apparatus, as result of furin proteolysis VWFpp is truncated/disconnected from the mature VWF molecule to form a non-covalent complex with VWF. The VWFpp-VWF complex is stored in endothelial and platelet storage granules and released into the bloodstream where it dissociates into VWFpp and VWF. Plasma VWFpp level and ratio of plasma VWF propeptide (VWFpp) to VWF antigen (VWF:Ag) i.e VWFpp /VWF:Ag ratio are important biomarkers of VWF synthesis/release/clearance. These biomarkers have distinct therapeutic utility as they help to identify patients with von Willebrand disease (VWD) in whom DDAVP (desmopressin 1-desamino-8-D-arginine vasopressin) is ineffective due to rapid VWF clearance. They also have significant diagnostic value because they help to differentiate between congenital VWD subtypes as well as between congenital VWD and acquired von Willebrand Syndrome (AVWS). The purpose of the study was to determine the VWFpp level and the VWFpp/VWF: Ag ratio in patients with VWD and AVWS and to assess the significance of these biomarkers for diagnosis and management of congenital and acquired von Willebrand disease. Our study involved 120 VWD patients; 21 with AVWS and 111 healthy controls. Study results confirm that VWFpp level and the VWFpp/VWF: Ag ratio have significant value for discrimination between severe type 1 VWD and type 3 VWD as well as between acquired and congenital VWD which has serious implications for therapy. The biomarkers are also useful for identification of patients in whom DDAVP treatment may prove ineffective. In type 1 VWD (< 30 IU/ml) the VWFpp/VWF: Ag ratio was elevated in 57% of patients while in the group of patients with threshold VWF values ('Low VWF', 30-50 IU/dL) the ratio was within normal, which may be suggestive of other underlying causes of VWF deficiency. Assays in patients with non-neutralizing anti-VWF antibodies (AVWS) have shown that the VWFpp/VWF: Ag ratio www.jtm.viamedica.pl Ksenia Bykowska et al., Von Willebrand factor propeptide (VWFpp) can have significant impact on monitoring therapy and assessment of remission in patients with anti VWF antibodies.

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Section: Von Willebrand Factor Propetidementioning

confidence: 99%

Von Willebrand factor propeptide (VWFpp) — potential biomarker in inherited von Willebrand disease and acquired von Willebrand syndrome

Bykowska

Ceglarek²,

Gwozdowska³

et al. 2019

Journal of Transfusion Medicine

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“…VWD is caused by a deficiency and/or abnormality of von Willebrand factor (VWF), a large multimeric adhesive plasma glycoprotein, that plays an essential role in both primary and secondary hemostasis [5]. …”

Section: Von Willebrand Diseasementioning

confidence: 99%

Diagnosis and Treatment of von Willebrand Disease and Rare Bleeding Disorders

Castaman

Linari

2017

JCM

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Along with haemophilia A and B, von Willebrand disease (VWD) and rare bleeding disorders (RBDs) cover all inherited bleeding disorders of coagulation. Bleeding tendency, which can range from extremely severe to mild, is the common symptom. VWD, due to a deficiency and/or abnormality of von Willebrand factor (VWF), represents the most frequent bleeding disorder, mostly inherited as an autosomal dominant trait. The diagnosis may be difficult, based on a bleeding history and different diagnostic assays, which evaluate the pleiotropic functions of VWF. Different treatment options are available for optimal management of bleeding and their prevention, and long-term outcomes are generally good. RBDs are autosomal recessive disorders caused by a deficiency of any other clotting factor, apart from factor XII, and cover roughly 5% of all bleeding disorders. The prevalence of the severe forms can range from 1 case in 500,000 up to 1 in 2–3 million, according to the defect. Diagnosis is based on bleeding history, coagulation screening tests and specific factor assays. A crucial problem in RBDs diagnosis is represented by the non-linear relationship between clinical bleeding severity and residual clotting levels; genetic diagnosis may help in understanding the phenotype. Replacement therapies are differently available for patients with RBDs, allowing the successful treatment of the vast majority of bleeding symptoms.

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“…Von Willebrand factor (vWF), a large multimeric plasma glycoprotein, is well known for its role in hemostasis, where it binds to platelets and to the constituents of the sub-endothelial connective tissue [ 6 , 7 ]. Following synthesis, vWF is transported to storage organelles in both megakaryocytes/platelets (α-granules) and endothelial cells (Weibel-Palade bodies) [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Kinetics of plasma von Willebrand factor in acute myocardial infarction patients: a meta-analysis

et al. 2017

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Previous studies have shown a variation in plasma level of von Willebrand factor (vWF) in acute myocardial infarction (AMI) patients but with contentious results. In this study, we performed a meta-analysis to evaluate the kinetics of plasma vWF after AMI. A total of 11 qualified studies were obtained through systematical search in PubMed, Web of science, Cochrane Library database and CNKI, followed by search of reference lists, involving 519 AMI patients and 466 non-AMI controls. The standard mean difference (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects model. Results indicated that the plasma vWF was significantly increased in the first several hours after onset of AMI (SMD = 1.94, 95% CI = 1.39–2.48, P < 0.001) and stayed at high level until 24 h (SMD = 1.17, 95% CI = 0.45–1.89, P = 0.001). Elevated level of vWF appeared to persist for one week and reduced to normal until the fourteenth day after AMI (SMD = 0.44, 95% CI = −0.14–1.02, P = 0.14). Subgroup analysis revealed that the high level of vWF lasted just for 1 day in patients with a symptom duration ≤ 6 h before admission. For patients with a symptom duration > 6 h, elevated vWF was found in all 7 days except day 1. Our findings determined the kinetics of plasma vWF after AMI, and might provide a new insight in monitoring AMI progression.

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von Willebrand Factor: Form for Function

Cited by 41 publications

References 139 publications

Von Willebrand factor propeptide (VWFpp) — potential biomarker in inherited von Willebrand disease and acquired von Willebrand syndrome

Von Willebrand factor propeptide (VWFpp) — potential biomarker in inherited von Willebrand disease and acquired von Willebrand syndrome

Diagnosis and Treatment of von Willebrand Disease and Rare Bleeding Disorders

Kinetics of plasma von Willebrand factor in acute myocardial infarction patients: a meta-analysis

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