Sialylation on O-linked glycans protects von Willebrand factor from macrophage galactose lectin mediated clearance.

Terminal sialylation determines plasma VWF half-life. A role for macrophage galactose lectin (MGL) in regulating hyposialylated VWF clearance has recently been proposed. In this study, we show that MGL influences physiological plasma VWF clearance. MGL inhibition was associated with a significantly extended mean residence time and 3-fold increase in endogenous plasma VWF:Ag levels (p

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

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