Clinical phenotype and pathophysiological mechanisms underlying qualitative low VWF.

von Willebrand factor antigen levels are associated with burden of rare nonsynonymous variants in the VWF gene

Reduced von Willebrand factor survival in type Vicenza von Willebrand disease

"Outgrowing" the Laboratory Diagnosis of Type 1 Von Willebrand's Disease: A Two Decade Study

Impact of Blood Group O and Von Willebrand Factor on Bleeding Severity in Patients with Von Willebrand Disease and Bleeding Disorder of Unknown Cause

All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with increased triplet structure of each visuable band (not present in types 2M and 2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. VWD 2B differs from 2A by normal VWF in platelets, and increased ristocetine-induced platelet aggregation (RIPA). RIPA, which very likely reflects the VWF content of platelets, is normal in mild, decreased in moderate, and absent in severe type 2A VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically featured by low VWF:RCo and RIPA with the relative lack of high large VWF multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern with a lack of high molecular weight multimers, the presence of one single-banded multimers instead of triplets caused by homozygosity or double hereozygosity for a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is rare and characterized by the lack of high molecular weight multimers and the presence of a characteristic intervening subband between individual oligimers due to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large VWF multimers are missing and the pattern of the individual multimers shows only one clearly identifiable band, and there is no intervening band and no marked increase in the smallest oligomer. 2E appears to be less well defined, is usually autosomal dominant, and accounts for about one third of patients with 2A in a large cohort of VWD patients.

Von Willebrand Factor Collagen Binding Provides a Sensitive Screen for Identification of Type 2A and 2B Von Willebrand Disease

The Von Willebrand Disease Aging and Bleeding Correlation (VWD ABC) Study

Low VWF:RCo In Subjects with VWF Polymorphisms D1472H and P1467S Due to Decreased Binding of Ristocetin to the VWF A1 Domain

Platelet Function Analyzer-100 Shows Poor Predictive Value for Children with Low VWF and Mild Platelet Function Defects

The present study aimed to evaluate the parent-child relationship in differentiating between unaffected healthy individuals and those with von Willebrand disease (VWD). This study was performed on 15 children between the ages of 5 and 15 years and parents with personal and familial evidence of bleeding. Diagnosis of VWD as considered 'low von Willebrand factor (VWF) level or mild type 1 VWD' in the following children: those with low VWF levels (VWF:RCo and VWF:Ag between 30 and 50 U/dl), at least one bleeding symptom and a family member with at least one bleeding symptom. Laboratory values in the parents of families 1-7 were VWF:Ag 65-90, VWF:RCo 54-87, and FVIII:C 74-110, versus VWF:Ag 33-47, VWF:RCo 30-42, and FVIII:C 36-67 in their children. The normal laboratory values in the parents of families 1-7 suggested that their children would probably have low VWF levels. Our findings are that VWF levels are increasing with age. Laboratory values in the parents of families 8-15 were VWF:Ag 30-59, VWF:RCo 32-55, and FVIII:C 44-66, versus VWF:Ag 32-48, VWF:RCo 30-54, and FVIII:C 38-55 in their children. The laboratory values in the children from families 8-15 were close to the minimum range of normal or below normal, which suggested that it was possible that the parents and children in families 8-15 could be diagnosed as having mild type 1 VWD. The present study's findings show that comparison of the VWF levels in parents and their children may be helpful in differentiating children with low VWF levels and mild type 1 VWD from children that only have low VWF levels.

ADAMTS13 regulation of VWF multimer distribution in severe COVID‐19

Altered Von Willebrand Factor Subunit Proteolysis and Multimer Processing Associated with the Cys1599(2362)Phe Mutation in the B2 Domain.

Spectrum of Type 2 Von Willebrand Disease in the Zimmerman Program

We have purified factor VIII/von Willebrand factor complex from rabbit plasma and prepared a specific guinea-pig antiserum to the von Willebrand factor antigen. It was used for electroimmunodiffusion to determine von Willebrand factor level in rabbit plasma and for crossed immunoelectrophoresis to study its electrophoretic behavior. Rabbit von Willebrand factor had properties similar to human von Willebrand factor with respect to molecular weight, size heterogeneity, mobility and pattern in electroimmunodiffusion and crossed immunoelectrophoresis, and content in plasma. Plasma von Willebrand factor antigen levels in rabbits ranged between 46 and 147% of the standard plasma. Responses of plasma von Willebrand factor antigen and factor VIII to various bioactive agents were investigated with rabbits. When a small dose of adrenalin, a large dose of noradrenalin, and endotoxin were injected, plasma von Willebrand factor antigen level and ratio of von Willebrand factor antigen to factor VIII activity were elevated in different fashions during 6 hours after administration. The findings could deliver some information about the mechanism of changes in plasma von Willebrand factor observed in human diseases.

Genetic Determinants of Plasma Von Willebrand Factor Antigen Levels: A Target Gene SNP and Haplotype Analysis of the ARIC Cohort