What is the replacement dose for von Willebrand factor (VWF)?

From the Guidelines

The recommended replacement dose for von Willebrand factor (VWF) in patients with acquired von Willebrand syndrome (AVWS) during extracorporeal membrane oxygenation (ECMO) support is 40 IU/kg once, as demonstrated by a significant increase in VWF:Ag and VWF:RCo levels and resolution of bleeding in 10 adult ECMO patients with AVWS-related bleeding 1.

Key Considerations

• The dose of 40 IU/kg once has been shown to increase VWF function in adult ECMO patients, but may also be associated with increased thrombotic risk 1.
• The clinical implications of AVWS on bleeding and its potential treatments are still unclear, and larger studies are needed to determine VWF concentrate's safety, efficacy, and optimal dosing in adult ECMO patients 1.
• Products like Humate-P contain both VWF and Factor VIII, and dosing is individualized based on the patient's baseline VWF levels, weight, and clinical response.

Clinical Context

• AVWS is a common but underrecognized disorder in pediatric ECMO patients, and the clinical implications of this disorder on bleeding and its potential treatments are still unclear 1.
• In vitro studies have shown that recombinant VWF (rVWF) is more effective than plasma-derived VWF (pdVWF) in correcting a pathologic PFA closure time in blood samples from patients with ECMO-induced AVWS 1.
• Higher doses of VWF were needed to normalize PFA closure time in blood samples of patients with ECMO-induced AVWS compared with hereditary VWD 1.

Treatment Approach

• Treatment should continue until bleeding stops or wound healing is complete, typically 1-7 days for minor events and 7-14 days for major surgeries.
• VWF replacement works by correcting the primary hemostatic defect in VWD, allowing proper platelet adhesion to damaged blood vessels and stabilizing Factor VIII in circulation, which is essential for effective clotting.
• Dosing is individualized based on the patient's baseline VWF levels, weight, and clinical response, and products like Humate-P, Wilate, and Alphanate contain both VWF and Factor VIII, while newer products like Vonvendi contain only VWF.

From the Research

VWF Replacement Dose

• The replacement dose of VWF is individualized based on the type of von Willebrand disease (VWD), history and risk of bleeding, and risk of thrombosis 2.
• The goal of treatment for VWD is to reverse the double hemostatic defect resulting from the abnormal or reduced expression of VWF and the concomitant factor VIII (FVIII) deficiency, and treatment consists of managing any bleeds and both short-term prophylaxis and long-term prophylaxis 3.
• VWF/FVIII concentrates are the treatment of choice for types of VWD other than type 1, and products containing only VWF have become available and marketed more recently 3, 4.
• The clinical use of VWF-only products is particularly attractive in the setting of surgery and long-term prophylaxis, such as the prevention of recurrent gastrointestinal bleeding in cases of angiodysplasia 3.
• Recombinant VWF (vonicog alfa, Vonvendi) was approved by the U.S. Food and Drug Administration (FDA) in December 2015 and may have an important role in the management of VWD, but more studies are needed, especially in special populations such as surgical patients, patients with major gastrointestinal bleeding from arteriovenous malformations, and pregnant women and children 5.

Factors Affecting Replacement Dose

• The type of VWD, with different types requiring different treatment approaches 2, 3.
• The history and risk of bleeding, with patients at higher risk requiring more aggressive treatment 2.
• The risk of thrombosis, with patients at higher risk requiring careful monitoring and adjustment of treatment 2.
• The use of desmopressin, which is suitable for most patients with type 1 VWD but not for other types of VWD 3.