ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease

Abstract

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.

Conflict of interest statement

Conflict-of-interest disclosure: Authors were members of the diagnosis guideline panel or members of the systematic review team or both, with the addition of V.H.F. who chaired the management panel. All completed disclosure-of-interest forms, which were reviewed by ASH and are available as supplemental Files 2 and 3.

© 2021 by The American Society of Hematology.

Figures

Figure 1.

An overall algorithm addressing the diagnosis of VWD. The numbers in the yellow circles correspond to guideline questions. VWF levels refer to VWF antigen (VWF:Ag) and/or platelet-dependent VWF activity. The algorithm says VWF level 30 to 50 for simplicity; this refers to VWF levels of 0.30 to 0.50 IU/mL, with the caveat that the lower limit of the normal range as determined by the local laboratory should be used if it is <0.50 IU/mL. *Men and children, referred to a hematologist and/or first-degree relative affected with VWD. BS, bleeding score; CBC, complete blood count; DDAVP, desmopressin; FVIII, factor FVIII; FVIII:C, FVIII coagulant activity; PT, prothrombin time; PTT, partial thromboplastin time; r/o, rule out; TT, thrombin time; VWF:CB/Ag, ratio of VWF collagen binding to antigen; VWF:FVIIIB, VWF FVIII binding.

Figure 2.

An algorithm for the diagnosis of type 2B VWD. GPIb, glycoprotein Ib; RIPA, ristocetin-induced platelet agglutination.

Figure 3.

An algorithm for the diagnosis of type 2N VWD.