von Willebrand disease (VWD): evidence‐based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA)¹

Abstract

Summary. von Willebrand disease (VWD) is a commonly encountered inherited bleeding disorder affecting both males and females, causing mucous membrane and skin bleeding symptoms, and bleeding with surgical or other haemostatic challenges. VWD may be disproportionately symptomatic in women of child‐bearing age. It may also occur less frequently as an acquired disorder (acquired von Willebrand syndrome). VWD is caused by deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates platelet haemostatic function and stabilizes blood coagulation factor VIII. The pathophysiology, classification, diagnosis and management of VWD are relatively complex, but understanding them is important for proper diagnosis and management of patients with VWD. These evidence‐based guidelines for diagnosis and management of VWD from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel (USA) review relevant publications, summarize current understanding of VWD pathophysiology and classification, and present consensus diagnostic and management recommendations based on analysis of the literature and expert opinion. They also suggest an approach for clinical and laboratory evaluation of individuals with bleeding symptoms, history of bleeding or conditions associated with increased bleeding risk. This document summarizes needs for further research in VWF, VWD and bleeding disorders, including clinical research to obtain more objective information about bleeding symptoms, advancements in diagnostic and therapeutic tools, and enhancement in the education and training of clinicians and scientists in bleeding and thrombotic disorders. The NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd) has a more detailed document, a synopsis of these recommendations, and patient education information.

Current issues in diagnosis and treatment of von Willebrand disease

“…Others consider any detectable VWF to represent type 1 VWD, albeit a more severe phenotype, and reserve the label of type 3 VWD for those with completely undetectable VWF levels 2, 7. The distinction is relevant to the inheritance, as type 1 is considered to be autosomal dominant and type 3 autosomal recessive, but not to treatment, as any patient with VWF levels <10 IU/dL will likely require treatment with a VWF concentrate.…”

“…These patients will have a decreased VWF:Ag, a low VWF:GPIbM/VWF:Ag ratio, a low VWF:CB/VWF:Ag ratio, and an absence of HMWM. Platelet binding (VWF:PB) and low‐dose ristocetin‐induced platelet aggregation (LD‐RIPA) on these patients would be absent 7. Genetic testing may reveal a known type 2A variant and help solidify the diagnosis.…”

“…The former NHLBI consensus guideline statement used a cut‐off of 30 IU/dL to declare the presence of VWD 7. UK guidelines have also adopted this cutoff 24.…”

Preoperative screening for bleeding disorders: A comprehensive laboratory assessment of clinical practice

“…As it was not designed to relate hemostatic traits and the bleeding questionnaire to the outcome bleeding, the perioperative significance of (mild) hemostatic abnormalities and the diagnostic value of a positive bleeding questionnaire regarding the identification of patients who bleed during surgery remain unknown. However, to optimize perioperative preventive measures, establishing a diagnosis of a hemostatic deficiency is preferred over recognizing a patient as having a “positive bleeding history,” as measures to prevent bleeding differ per disorder 35, 36, 37. Other limitations concern the study design that led to an imbalance between the two patient groups and the relative low number of hemostatic abnormalities that was found.…”

Von Willebrand factor multimer quantitation for assessment of cardiac lesion severity and bleeding risk

“…After written informed consent was obtained the patients provided research blood samples. Patients were asked to complete a bleeding questionnaire (Appendix) modified from the consensus conference on the assessment of von Willebrand disease as previously described 2, 10. For patients with positive bleeding questionnaire responses, further chart review and patient history acquisition were performed to identify clinically significant bleeding, and to determine whether Heyde syndrome (transfusion‐dependent anemia resulting from GI bleeding and endoscopically documented angiodysplasia) was present.…”