4 research outputs found
ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease
Background: von Willebrand disease (VWD) is the most common inherited bleeding disorder known in humans. Accurate and timely diagnosis presents numerous challenges.Objective: These evidence-based guidelines of the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and other health care professionals in their decisions about VWD diagnosis.Methods: ASH, ISTH, NHF, and WFH established a multidisciplinary guideline panel that included 4 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Outcomes and Implementation Research Unit at the University of Kansas Medical Center (KUMC) supported the guideline-development process, including performing or updating systematic evidence reviews up to 8 January 2020. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subsequently subject to public comment.Results: The panel agreed on 11 recommendations.Conclusions: Key recommendations of these guidelines include the role of bleeding-assessment tools in the assessment of patients suspected of VWD, diagnostic assays and laboratory cutoffs for type 1 and type 2 VWD, how to approach a type 1 VWD patient with normalized levels over time, and the role of genetic testing vs phenotypic assays for types 2B and 2N. Future critical research priorities are also identified.</p
Bleeding assessment tools in the diagnosis of von Willebrand disease: systematic review & meta-analysis of test accuracy.
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</p
Laboratory assays of VWF activity and use of desmopressin trials in the diagnosis of VWD: a systematic review and meta-analysis.
Von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of any VWF activity assay in the diagnosis and classification of patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. The review included 77 studies that evaluated the use of newer tests of VWF platelet binding activity (VWF:GPIbR , VWF:GPIbM) and VWF:RCo for the diagnosis of VWD (13 studies), VWF propeptide to VWF:Ag ratio and desmopressin trial for the diagnosis of type 1C VWD (5 studies), VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD (11 studies), genetic testing and ristocetin-induced platelet aggregation to diagnose type 2B VWD (14 studies), genetic testing and FVIII:VWF binding to diagnose type 2N VWD (17 studies). Based on available diagnostic test accuracy, there appears to be comparable test accuracy results between newer tests of platelet binding activity of VWF function and VWF:RCo. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with VWD suspected of type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD
von Willebrand disease: proposing definitions for future research
von Willebrand disease (VWD) is a common bleeding disorder, which affects 1 in 100 individuals based
on laboratory testing and at least 1 in 1000 individuals based on presence of abnormal bleeding
symptoms.1,2 VWD was first described almost 100 years ago, and since the initial report, major
advances in both diagnostic testing and treatment options have improved outcomes for patients living
with VWD; however, many patients still experience significant complications and barriers to treatment.
An underlying problem is the lack of consistent unified definitions.
In recent work developing evidence-based guidelines for VWD,3,4 it was noted that studies on VWD
often used varying definitions. For example, studies of von Willebrand factor (VWF) concentrates did not
have consistent definitions for major bleeding, studies on VWF prophylaxis did not use consistent
definitions of what constituted a prophylaxis regimen, and studies on desmopressin did not use
consistent definitions of desmopressin responsiveness. In addition, common bleeding conditions,
such as heavy menstrual bleeding (HMB) and postpartum hemorrhage are variably defined. Such
inconsistencies in describing study regimens and endpoints hinder the ability to compare study
outcomes and to advance treatment of patients with VWD.
We propose definitions for future use in VWD research to facilitate comparison of treatment options.
These definitions are based on the most common usage in the literature and endeavor to encompass the
most common situations in VWD. The proposed definitions were derived from existing literature and
discussed at the first in-person meetings of the guideline panels. Group members made amendments,
and the consensus document was circulated to the group. All authors approved the final document