Recessive von Willebrand Disease Type 2 Normandy: Variable Expression of Mild Hemophilia and VWD Type 1

2009 ◽  
Vol 121 (2-3) ◽  
pp. 119-127 ◽  
Author(s):  
Jan Jacques Michiels ◽  
Alain Gadisseur ◽  
Inge Vangenegten ◽  
Wilfried Schroyens ◽  
Zwi Berneman
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Variable Expression ◽  
Von Willebrand

Desmopressin parenteral bei VWD 1, VWD 2A und Thrombozytopathie

2011 ◽  
Vol 31 (S 01) ◽  
pp. S29-S33 ◽  
Author(s):  
H. Pollmann ◽  
B. Siegmund
Keyword(s):  
Side Effects ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Occlusion Time ◽  
Almost All ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

SummaryDesmopressin (DDAVP, Minirin® parenteral), which induces the release of von-Willebrand factor from endogenous stores, is indicated in von Willebrand disease type 1 (VWD 1). In the present study effectiveness of DDAVP was tested and side effects were recorded in patients with VWD 1, von Willebrand disease type 2 (VWD 2) or thrombocytopathy (TCP). Patients, methods Subjects were analysed prior to and after Minirin parenteral infusion (0.4 μg/kg body weight (b.w.) over 60 minutes) for partial thromboplastin time (PTT, seconds), ADP/epinephrine triggered plateletfunction analyzer (PFA-100) occlusion time (seconds), factor VIII activity (FVIII, %), VWF as ristocetin cofactor activity (VWF:RCo, %) and VWF antigen (VWF:Ag, %). Side effects of DDAVP during operative interventions were recorded per questionnaires by the patients. Results The mean ± standard deviation dose (n = 165 patients) of Minirin parenteral administered was 0.37 ± 0.02 μg/kg b.w., most often upcoming dental operations (57%) necessitated testing. Coagulation parameters of patients with VWD 1 or TCP normalised in almost all patients, but only in approximately 50% of patients with VWD 2 respectively. Appraisal of effectiveness of Minirin parenteral as good was 96% in case of VWD 1 and 95 % in case of TCP. During minor surgeries (n = 23) in 91% of the patients no complications and in 2 patients (9%) postoperative haemorrhages without need for further interventions occurred, but 83% of the patients reported adverse reactions in the questionnaires, although Minirin parenteral was well tolerated by all patients during DDAVP efficacy tests. Conclusion Desmopressin is well tolerated and affective in patients with VWD 1 and thrombocytopathy.

Response to DDAVP in children with von Willebrand disease type 2

2009 ◽  
Vol 29 (02) ◽  
pp. 143-148 ◽  
Author(s):  
U. Budde ◽  
K. Beutel ◽  
W.-A. Hassenpflug ◽  
H. Hauch ◽  
T. Obser ◽  
...  
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Molecular Defect ◽  
Variable Response ◽  
Functional Parameters ◽  
Functional Defect ◽  
Biologic Response ◽  
High Level ◽  
Von Willebrand

SummaryWe have prospectively evaluated the biologic response to desmopressin (DDAVP) in 28 children with type 2 von Willebrand disease (VWD) in correlation with the phenotype and the molecular defect of VWF. The diagnosis of VWD type 2 was mainly based on VWF functional parameters and/or an aberrant VWF multimer pattern. Seventeen different mutations were identified (6 of them novel). No response with respect to the functional parameters VWF:RCo and/or VWF:CB was seen in patients with severe abnormality of the VWF multimer pattern. One patient with VWD type 2A phenotype IIC Miami did not respond with respect to VWF:CB, but showed a good response of VWF:Ag and FVIII:C as expected. Interestingly he showed a persistently high level of VWF:Ag and FVIII:C up to 4 hours after DDAVP infusion. Patients with minor alterations of multimer structure and particular mutations responded well to DDAVP, whereas patients with normal multimer structure but a defect in platelet dependent functional parameters did not respond with VWF:RCo. Conclusion: Children with VWD type 2 show a variable response to desmopressin depending on the mutation that correlates with the functional defect and the presence or absence as well as the half-life of large VWF multimers. Our data emphasize the usefulness of DDAVP testing even in patients with VWD type 2, possibly with the exception of VWD type 2B.

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.

Identification of Type 2 von Willebrand Disease in Previously Diagnosed Type 1 Patients: a Reappraisal Using Phenotypes, Genotypes and Molecular Modelling

2000 ◽  
Vol 84 (12) ◽  
pp. 998-1004 ◽  
Author(s):  
Ioana Nitu-Whalley ◽  
Anne Riddell ◽  
K. Pasi ◽  
Dale Owens ◽  
M. Enayat ◽  
...  
Keyword(s):  
Molecular Modelling ◽  
Correct Diagnosis ◽  
Von Willebrand Disease ◽  
Single Amino Acid ◽  
Elisa Assay ◽  
Modelling Analysis ◽  
A1 Domain ◽  
Von Willebrand

SummaryIn order to investigate the possibility that qualitative type 2 defects in von Willebrand factor (VWF) occurred in patients previously diagnosed with quantitative type 1 von Willebrand disease (VWD), the phenotypes and genotypes were reanalysed in 30 patients who exhibited discrepant VWF activity/VWF:Ag ratios of less than 0.7. The capacity of VWF to bind to glycoprotein Ib (GpIb) was reassessed using the ristocetin co-factor activity (VWF:RiCo) assay compared to an in-house and a commercial ELISA assay (based on a mAb directed against the GpIb binding site on VWF). This was supplemented by multimeric analysis and the amplification and sequencing of a 936 bp fragment of exon 28 of the VWF gene with the aim of identifying mutations in the A1 domain. On reappraisal, using the VWF:RiCo assay all patients demonstrated a disproportionately reduced VWF:RiCo/VWF:Ag ratio, indicative of a qualitative defect, while abnormal ratios were detected in only seven kindreds using the in-house ELISA assay and in only one kindred with the commercial ELISA assay. Eight single amino acid substitutions were found in nine kindreds, four of which were novel candidate VWF mutations and four previously described in association with type 2 VWD. In agreement with the phenotype, the novel VWF mutations were located in the VWF-A1 crystal structure at positions that corresponded to potential type 2M defects. This study underlines the difficulties of correct diagnosis of the subtype of VWD and emphasises the importance of using sensitive phenotypic assays, the relevance of the VWF:RiCo/ VWF:Ag ratio, multimeric analysis and molecular modelling analysis.

Expression of angiogenic factors in the uteroplacental unit is altered at time of placentation in a porcine model of von Willebrand disease type 1

2019 ◽  
Vol 19 (4) ◽  
pp. 412-420
Author(s):  
Hanna Allerkamp ◽  
Stefanie Lehner ◽  
Mahnaz Ekhlasi-Hundrieser ◽  
Carsten Detering ◽  
Mario von Depka Prondzinski ◽  
...  
Keyword(s):  
Porcine Model ◽  
Disease Type ◽  
Angiogenic Factors ◽  
Von Willebrand Disease ◽  
Von Willebrand

Von Willebrand disease type 1 in a porcine model influences expression of integrin αVβ3, members of the VEGF/VEGFR-2 system and ANG/TIE ratios at the time of placentation

Placenta ◽  
2019 ◽  
Vol 83 ◽  
pp. e18
Author(s):  
Hanna Allerkamp ◽  
Stefanie Lehner ◽  
Carsten Detering ◽  
Mahnaz Ekhlasi-Hundrieser ◽  
Mario von Depka Prondzinski ◽  
...  
Keyword(s):  
Porcine Model ◽  
Integrin Αvβ3 ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Von Willebrand

Managing Patients with von Willebrand Disease Type 1, 2 and 3 with Desmopressin and von Willebrand Factor-Factor VIII Concentrate in Surgical Settings

2009 ◽  
Vol 121 (2-3) ◽  
pp. 167-176 ◽  
Author(s):  
Jan Jacques Michiels ◽  
Huub H.D.M. van Vliet ◽  
Zwi Berneman ◽  
Wilfried Schroyens ◽  
Alain Gadisseur
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Von Willebrand ◽  
Willebrand Factor

Limitations of Current Plasma VonWillebrand Factor (VWF) Activity Tests: A Comprehensive Comparison of Five VWF Activity Assays.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3376-3376
Author(s):  
Dong Chen ◽  
Rajiv Pruthi ◽  
William L. Nichols ◽  
John A. Heit
Keyword(s):  
Activity Ratio ◽  
Light Transmission ◽  
Von Willebrand Disease ◽  
Assay Method ◽  
Type I ◽  
Platelet Activity ◽  
Platelet Aggregometry ◽  
Von Willebrand

Abstract Accurate measurement of plasma von Willebrand factor (VWF) activity is essential for the laboratory diagnosis and treatment monitoring of von Willebrand disease (VWD). Currently available VWF activity assays include VWF ristocetin cofactor activity by manual light transmission platelet aggregometry (VWF:RCo–Agg) or flow cytometry (VWF:RCo–FL), collagen I and III binding activity (VWF:Co–I and –III) (Technozym), and platelet activity by latex agglutination (VWF:Lx) (Instrumental Laboratory). In this study we evaluated and compared the accuracy and precision of these 5 assay methods. Plasma samples from 11 normal donors and 41 patients categorized as type 1 (n=20) or type 2 (n=21) VWD based on clinical evaluation, fVIII:C activity, VWF:RCo–Agg, VWF antigen (VWF:Ag) level and plasma VWF multimer analysis by agarose gel electrophoresis were assayed for VWF activity by VWF:RCo–FL, VWF:Co–I, VWF:Co–III and VWF:Lx methods. The VWF:Ag/VWF activity ratio by VWF activity assay method was calculated for each sample. For normal donors and type I VWD patients, VWF:RCo–FL and VWF:Lx correlated well with VWF:RCo–Agg (R2=0.87, and 0.97, respectively), while VWF:Co–I and –III were lower compared to VWF:RCo-Agg. For type 2 VWD patients, different VWF:Ag/VWF activity ratio cutoffs (range 0.3–0.7) were used (Figure). Both VWF:RCo–Agg and –FL were sensitive (95%) and specific (97%) for type 2 VWD while the VWF:Lx was slightly less sensitive (81%) but was very specific (100%). VWF:Co–I and –III were the least sensitive (<90%) and specific (<90%); both methods had high false positive and negative rates for type 2 VWD. In Summary, for normals and type 1 VWD patients, VWF:RCo–FL and VWF:Lx correlate well with VWF:RCo–Agg and have similar sensitivities and specificities for type 2 VWD. VWF:Co–I and –III are unreliable for assessing plasma VWF activity.

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