Faculty Opinions recommendation of VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease.

2014 ◽  
Author(s):  
Alberto Tosetto
Keyword(s):  
Von Willebrand Disease ◽  
Von Willebrand

scholarly journals Identification and characterization of a novel P2Y12 variant in a patient diagnosed with type 1 von Willebrand disease in the European MCMDM-1VWD study

Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 4110-4113 ◽  
Author(s):  
Martina E. Daly ◽  
Ban B. Dawood ◽  
William A. Lester ◽  
Ian R. Peake ◽  
Francesco Rodeghiero ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Surface Expression ◽  
Von Willebrand Disease ◽  
Heterozygous Mutation ◽  
Bleeding Tendency ◽  
Locus Heterogeneity ◽  
Reversible Aggregation ◽  
Von Willebrand

Abstract We investigated whether defects in the P2Y12 ADP receptor gene (P2RY12) contribute to the bleeding tendency in 92 index cases enrolled in the European MCMDM-1VWD study. A heterozygous mutation, predicting a lysine to glutamate (K174E) substitution in P2Y12, was identified in one case with mild type 1 von Willebrand disease (VWD) and a VWF defect. Platelets from the index case and relatives carrying the K174E defect changed shape in response to ADP, but showed reduced and reversible aggregation in response to 10 μM ADP, unlike the maximal, sustained aggregation observed in controls. The reduced response was associated with an approximate 50% reduction in binding of [3H]2MeS-ADP to P2Y12, whereas binding to the P2Y1 receptor was normal. A hemagglutinin-tagged K174E P2Y12 variant showed surface expression in CHO cells, markedly reduced binding to [3H]2MeS-ADP, and minimal ADP-mediated inhibition of forskolin-induced adenylyl cyclase activity. Our results provide further evidence for locus heterogeneity in type 1 VWD.

scholarly journals VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease

Blood ◽  
2013 ◽  
Vol 121 (12) ◽  
pp. 2336-2339 ◽  
Author(s):  
Jeroen Eikenboom ◽  
Augusto B. Federici ◽  
Richard J. Dirven ◽  
Giancarlo Castaman ◽  
Francesco Rodeghiero ◽  
...  
Keyword(s):  
Von Willebrand Disease ◽  
Pathophysiological Mechanisms ◽  
Key Points ◽  
Von Willebrand

Key Points VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios define the pathophysiological mechanisms that play a role in VWD and various VWF mutations. A high VWFpp/VWF:Ag ratio indicates increased clearance of VWF and a high FVIII:C/VWF:Ag ratio decreased synthesis of VWF.

Characterization of Partial Gene Deletions in Type III von Willebrand Disease with Alloantibody Inhibitors

1994 ◽  
Vol 72 (02) ◽  
pp. 180-185 ◽  
Author(s):  
David J Mancuso ◽  
Elodee A Tuley ◽  
Ricardo Castillo ◽  
Norma de Bosch ◽  
Pler M Mannucci ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Pcr Analysis ◽  
Gene Deletions ◽  
Factor Gene ◽  
Type Iii ◽  
Large Deletions ◽  
Von Willebrand ◽  
Willebrand Factor

Summaryvon Willebrand factor gene deletions were characterized in four patients with severe type III von Willebrand disease and alloantibodies to von Willebrand factor. A PCR-based strategy was used to characterize the boundaries of the deletions. Identical 30 kb von Willebrand factor gene deletions which include exons 33 through 38 were identified in two siblings of one family by this method. A small 5 base pair insertion (CCTGG) was sequenced at the deletion breakpoint. PCR analysis was used to detect the deletion in three generations of the family, including two family members who are heterozygous for the deletion. In a second family, two type III vWD patients, who are distant cousins, share an -56 kb deletion of exons 22 through 43. The identification and characterization of large vWF gene deletions in these type III vWD patients provides further support for the association between large deletions in both von Willebrand factor alleles and the development of inhibitory alloantibodies.

Characterisation of Type 2N von Willebrand Disease Using Phenotypic and Molecular Techniques

1996 ◽  
Vol 75 (06) ◽  
pp. 959-964 ◽  
Author(s):  
I M Nesbitt ◽  
A C Goodeve ◽  
A M Guilliatt ◽  
M Makris ◽  
F E Preston ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Von Willebrand Disease ◽  
Molecular Techniques ◽  
Haemophilia A ◽  
Binding Region ◽  
Gene Encoding ◽  
Covalently Linked ◽  
Von Willebrand ◽  
Willebrand Factor

Summaryvon Willebrand factor (vWF) is a multimeric glycoprotein found in plasma non covalently linked to factor VIII (FVIII). Type 2N von Willebrand disease (vWD) is caused by a mutation in the vWF gene that results in vWF with a normal multimeric pattern, but with reduced binding to FVIII.We have utilised methods for the phenotypic and genotypic detection of type 2N vWD. The binding of FVIII to vWF in 69 patients, 36 with type 1 vWD, 32 with mild haemophilia A and one possible haemophilia A carrier with low FVIII levels was studied. Of these, six were found to have reduced binding (five type 1 vWD, one possible haemophilia A carrier), DNA was extracted from these patients and exons 18-23 of the vWF gene encoding the FVIII binding region of vWF were analysed. After direct sequencing and chemical cleavage mismatch detection, a Thr28Met mutation was detected in two unrelated individuals, one of whom appears to be a compound heterozygote for the mutation and a null allele. No mutations were found in the region of the vWF gene encoding the FVIII binding region of vWF in the other four patients

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

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