scholarly journals Management of von Willebrand disease with a factor VIII‐poor von Willebrand factor concentrate: Results from a prospective observational post‐marketing study

2020 ◽  
Vol 18 (8) ◽  
pp. 1922-1933 ◽  
Author(s):  
Jenny Goudemand ◽  
Françoise Bridey ◽  
Ségolène Claeyssens ◽  
Nathalie Itzhar‐Baïkian ◽  
Annie Harroche ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Post Marketing ◽  
Factor Concentrate ◽  
Von Willebrand ◽  
Willebrand Factor

Use of von Willebrand Factor Concentrate in Inherited von Willebrand Disease: How Often Is It Useful to Add Factor VIII?

2020 ◽  
Vol 34 (2) ◽  
pp. 128-129
Author(s):  
Nicolas Drillaud ◽  
Laurent Ardillon ◽  
Catherine Ternisien ◽  
Jean Baptiste Valentin ◽  
Marc Fouassier ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Factor Concentrate ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Successful management of multiple pregnancies in a family with varying severity of Von Willebrand disease

2018 ◽  
Vol 11 (4) ◽  
pp. 192-194
Author(s):  
Patrick Harrington ◽  
Pippa Kyle ◽  
Jacky Cutler ◽  
Bella Madan
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
The Other ◽  
Severe Phenotype ◽  
Mild Phenotype ◽  
History Of ◽  
Specialist Treatment ◽  
Factor Concentrate ◽  
Von Willebrand ◽  
Willebrand Factor

We present the obstetric history of a family of three sisters with Von Willebrand disease, managed in our centre over the course of nine successful pregnancies. The abnormalities result from inheritance of an exon 50 skipping mutation in the Von Willebrand factor gene, resulting from consanguinity. Two of the sisters were identified as having a severe phenotype with a Von Willebrand factor level of less than 5 IU/dl, with the other having a mild phenotype. Of the sisters with a severe phenotype, one had a number of prenatal complications and required early onset prophylaxis with Von Willebrand factor concentrate, whilst the other had a less complicated clinical course, only requiring Von Willebrand factor concentrate to cover labour. The sister with mild Von Willebrand disease had a rise in Von Willebrand factor levels during pregnancy and required no specialist treatment. The report highlights the markedly different clinical courses that can occur in patients with Von Willebrand disease and the different approaches to management.

The D′ domain of von Willebrand factor requires the presence of the D3 domain for optimal factor VIII binding

2018 ◽  
Vol 475 (17) ◽  
pp. 2819-2830 ◽  
Author(s):  
Małgorzata A. Przeradzka ◽  
Henriet Meems ◽  
Carmen van der Zwaan ◽  
Eduard H.T.M. Ebberink ◽  
Maartje van den Biggelaar ◽  
...  
Keyword(s):  
Factor Viii ◽  
Binding Affinity ◽  
Von Willebrand Factor ◽  
Conformational Changes ◽  
Effective Interaction ◽  
Von Willebrand Disease ◽  
Binding Assays ◽  
Surface Plasmon Resonance Analysis ◽  
Von Willebrand ◽  
Willebrand Factor

The D′–D3 fragment of von Willebrand factor (VWF) can be divided into TIL′-E′-VWD3-C8_3-TIL3-E3 subdomains of which TIL′-E′-VWD3 comprises the main factor VIII (FVIII)-binding region. Yet, von Willebrand disease (VWD) Type 2 Normandy (2N) mutations, associated with impaired FVIII interaction, have been identified in C8_3-TIL3-E3. We now assessed the role of the VWF (sub)domains for FVIII binding using isolated D′, D3 and monomeric C-terminal subdomain truncation variants of D′–D3. Competitive binding assays and surface plasmon resonance analysis revealed that D′ requires the presence of D3 for effective interaction with FVIII. The isolated D3 domain, however, did not show any FVIII binding. Results indicated that the E3 subdomain is dispensable for FVIII binding. Subsequent deletion of the other subdomains from D3 resulted in a progressive decrease in FVIII-binding affinity. Chemical footprinting mass spectrometry suggested increased conformational changes at the N-terminal side of D3 upon subsequent subdomain deletions at the C-terminal side of the D3. A D′–D3 variant with a VWD type 2N mutation in VWD3 (D879N) or C8_3 (C1060R) also revealed conformational changes in D3, which were proportional to a decrease in FVIII-binding affinity. A D′–D3 variant with a putative VWD type 2N mutation in the E3 subdomain (C1225G) showed, however, normal binding. This implies that the designation VWD type 2N is incorrect for this variant. Results together imply that a structurally intact D3 in D′–D3 is indispensable for effective interaction between D′ and FVIII explaining why specific mutations in D3 can impair FVIII binding.

Sign in / Sign up

Export Citation Format

Share Document