Von Willebrand factor levels in the diagnosis of von Willebrand disease: a systematic review and meta-analysis.
journal contributionposted on 2021-11-01, 16:58 authored by Mohamad A Kalot, Nedaa Husainat, Abdallah El Alayli, Omar Abughanimeh, Osama Diab, Sammy Tayiem, Bader Madoukh, Ahmad Bilal Dimassi, Aref Qureini, Barbara Ameer, Jeroen CJ Eikenboom, Nicolas Giraud, Claire McLintock, Simon McRae, Robert R Montgomery, James O'DonnellJames O'Donnell, Nikole Scappe, Robert F Sidonio, Romina Brignardello-Petersen, Veronica H Flood, Nathan T Connell, Paula D James, Reem A Mustafa
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.
CommentsThis research was originally published in Blood Advances. Mohamad A. Kalot, Nedaa Husainat, Abdallah El Alayli, Omar Abughanimeh, Osama Diab, Sammy Tayiem, Bader Madoukh, Ahmad Bilal Dimassi, Aref Qureini, Barbara Ameer, Jeroen C.J. Eikenboom, Nicolas Giraud, Claire McLintock, Simon McRae, Robert R. Montgomery, James O'Donnell, Nikole Scappe, Robert F Sidonio, Romina Brignardello-Petersen, Veronica H Flood, Nathan T. Connell, Paula D. James, Reem A. Mustafa; Von Willebrand Factor Levels in The Diagnosis of Von Willebrand Disease: A Systematic Review and Meta-Analysis. Blood Adv 2021; bloodadvances.2021005430. © the American Society of Hematology.
Published CitationKalot MA et al. Von Willebrand factor levels in the diagnosis of von Willebrand disease: a systematic review and meta-analysis. Blood Adv. 2021:bloodadvances.2021005430.
Publication Date5 Oct 2021
- Irish Centre for Vascular Biology
- School of Pharmacy and Biomolecular Sciences
- Vascular Biology
PublisherAmerican Society of Hematology
- Published Version (Version of Record)