scholarly journals Von Willebrand Factor Levels in The Diagnosis of Von Willebrand Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Mohamad A. Kalot ◽  
Nedaa Husainat ◽  
Abdallah El Alayli ◽  
Omar Abughanimeh ◽  
Osama Diab ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Health Benefit ◽  
Von Willebrand Disease ◽  
Test Accuracy ◽  
Sequence Variants ◽  
Continuous Variables ◽  
Von Willebrand

Von Willebrand Disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding symptoms. Patients with VWD can experience easy bruising, epistaxis, gastrointestinal and oral cavity bleeding, as well as heavy menstrual bleeding and bleeding after dental work, surgical procedures, and childbirth. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cut-off values of VWF:Ag and platelet-dependent VWF activity assays in the diagnosis of VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity and reported patient important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis, including the approach to patients with VWF levels that have normalized with age (6 studies), VWF cut-off levels for the diagnosis of Type 1 VWD (9 studies), and platelet-dependent VWF activity/VWF:Ag ratio cut-off levels for the diagnosis of Type 2 VWD (6 studies). The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD versus simply removing the disease in patients with VWF levels that have normalized with age. For the diagnosis of Type 1 VWD, in patients with VWF:Ag <0.30 IU/mL, VWF sequence variants were detected in 75-82% of patients in 2 studies, and for VWF:Ag between 0.30-0.50 IU/mL, VWF sequence variants were detected in 44-60% of patients in 3 studies. A sensitivity of 0.90 (95% CI: 0.83 to 0.94), and a specificity of 0.91 (95% CI: 0.76 to 0.97) were observed for a platelet-dependent VWF activity /VWF:Ag ratio of <0.7 in detecting type 2 VWD (moderate certainty in the test accuracy results). VWF antigen and platelet-dependent activity are continuous variables with an increase in bleeding risk with decreasing levels. This systematic review shows that using a VWF activity/VWF:Ag ratio of <0.7 versus lower cutoff levels in patients with an abnormal initial VWD screen is more accurate for the diagnosis of type 2 VWD.

scholarly journals Bleeding Assessment Tools in the Diagnosis of von Willebrand Disease: Systematic Review & Meta-Analysis of Test Accuracy

2021 ◽  
Author(s):  
Mohamad A. Kalot ◽  
Nedaa Husainat ◽  
Sammy Tayiem ◽  
Abdallah El Alayli ◽  
Ahmad Bilal Dimassi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Sensitivity And Specificity ◽  
Pediatric Patients ◽  
Screening Tool ◽  
Reference Lists ◽  
Meta Analysis ◽  
Von Willebrand Disease ◽  
Assessment Tools ◽  
Test Accuracy ◽  
Von Willebrand

Background: Von Willebrand Disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. Objective: We systematically reviewed diagnostic test accuracy results of bleeding assessment tools (BATs) to screen patients for VWD. Methods: We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. Results: The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval [CI] 66%-83%) and 54% (29%-77%), respectively. Certainty of evidence varied from moderate to high. Conclusion: This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates will influence patient management.

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.

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

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.

Prevalence and risk factors of fatigue in type 1 and type 2 diabetes: A systematic review and meta‐analysis

2021 ◽  
Author(s):  
Debby Syahru Romadlon ◽  
Faizul Hasan ◽  
Bayu Satria Wiratama ◽  
Hsiao‐Yean Chiu
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Meta Analysis

scholarly journals The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: A systematic review and meta-analysis update

Bone ◽  
2020 ◽  
Vol 137 ◽  
pp. 115457 ◽  
Author(s):  
Tatiane Vilaca ◽  
Marian Schini ◽  
Susan Harnan ◽  
Anthea Sutton ◽  
Edith Poku ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Vertebral Fractures ◽  
Meta Analysis

scholarly journals Incidence and prevalence of hypoglycaemia in type 1 and type 2 diabetes individuals: A systematic review and meta-analysis

2020 ◽  
Vol 170 ◽  
pp. 108522
Author(s):  
Hassan Alwafi ◽  
Alaa A. Alsharif ◽  
Li Wei ◽  
Dean Langan ◽  
Abdallah Y. Naser ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Meta Analysis

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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