Von Willebrand
Disease

Not an actual patient.

Von Willebrand Disease (VWD), an inherited disorder characterized by a quantitative deficiency or qualitative defect of von Willebrand Factor (VWF), is the most prevalent inherited bleeding disorder.1,2,3

VWD presents with a broad range of bleeding phenotypes, and this contributes to difficulty in diagnosis and potential delays of 15 years or more from the onset of bleeding symptoms to receiving diagnosis and treatment.3,4

Von Willebrand illustration

Epidemiology

There are an estimated 23 to 110 cases of VWD per million people.5 Population-based estimates are higher, ranging from 0.6-1.3% of people.

There are 3 types of VWD.2,6 Type 1 VWD, which accounts for ~75% of cases, is characterized by a reduced amount of VWF and with mild or moderate bleeding episodes.

Type 2 VWD, which accounts for ~25% of cases, is characterized by qualitative defects of VWF that impair its function.2,6 This is associated with bleeding episodes that can range from mild to severe.

Type 3 VWD accounts for <5% of cases, and is characterized by a near complete quantitative deficiency of VWF in plasma and with severe bleeding episodes.2,6

Diagnosis

The 2021 guideline recommendations from the American Society of Hematology (ASH), International Society on Thrombosis and Haemostasis (ISTH), National Hemophilia Foundation (NHF), and World Federation of Hemophilia (WFH) has outlined the criteria for confirmatory diagnosis and differential diagnosis of VWD subtypes.4

For individuals with low probability of VWD, such as those seen in primary care, a validated bleeding assessment tool (BAT) is recommended as an initial screening to see who needs specific blood tests.4 For those with intermediate risk (those who have been referred to a hematologist because of bleeding history) and for those with high risk (those with an affected first-degree relative), specific blood testing for VWD is recommended:

  • VWF:Ag
  • platelet-dependent VWF activity (e.g., VWF:GPIbM)
  • FVIII:C

Specific blood tests, followed by additional testing if necessary, can rule out VWD or confirm the diagnosis and subtype of VWD.4

Pathophysiology

Von Willebrand Factor (VWF) mediates platelet adhesion and stabilizes FVIII.1,7

In primary hemostasis, VWF mediates platelet adhesion to damaged vascular subendothelium by binding to exposed collagen and platelet receptors such as GPIbα and αIIbβ.1,7

In secondary hemostasis, VWF stabilizes FVIII in circulation by the formation of non-covalently bound VWF:FVIII complexes, thus preventing the rapid clearance of FVIII and increasing the half-life of FVIII.1,7

The quantitative or qualitative defects in VWF that are seen in VWD can lead to an inability to form platelet plugs (primary hemostasis) and to protect FVIII from proteolytic degradation (secondary reduction in FVIII levels), therefore leading to symptoms of bleeding.1,8

Navigating VWD

VWD can manifest in a diverse range of bleeding symptoms:5,8,9,10

  • Heavy menstrual bleeding, defined as abnormal menstrual blood loss of
    >80 mL and characterized by:
    • Blood clots >1 inch in diameter
    • Changing a sanitary pad or tampon more frequently than hourly
    • Anemia
  • Spontaneous gastrointestinal bleeding requiring medical attention, or resulting in acute or chronic anemia
  • Epistaxis: ≥2 episodes without a history of trauma not stopped by short compression of <10 min, or ≥1 episode requiring blood transfusion, or bleeding after dental procedures including tooth extraction, or oral surgery such as tonsillectomy and adenoidectomy
  • Joint bleeds, which may lead to structural joint damage:
    • Synovial iron deposition and inflammatory cell proliferation provoke degeneration of joint surfaces and eventual loss of normal function

Following diagnosis of VWD and its type, the guidelines outline best practices for a variety of VWD manifestations.11 This may range from prophylaxis for patients with a history of severe bleeds, on-demand treatment recommendations for other patients, and perioperative precautions for all patients.

  1. Mannucci PM. N Engl J Med. 2004;351(7):683-694.
  2. Fogarty H, Doherty D, O’Donnell JS. Br J Haematol. 2020;191(3):329-339.
  3. Sharma R and Flood VH. Blood. 2017;130(22):2386-2391.
  4. James PD, Connell NT, Ameer B, et al. Blood Adv. 2021;5(1):280-300.
  5. National Heart, Lung, and Blood Institute website. http://www.nhlbi.nih.gov/guidelines/vwd/vwd.pdf. Accessed October 24, 2022.
  6. James PD and Goodeve AC. Genet Med. 2011;13(5):365-376.
  7. Reininger AJ. Haemophilia. 2008;14(Suppl 5):11-26.
  8. Nichols WL, Hultin MB, James AH, et al. Haemophilia. 2008;14(2):171-232.
  9. Branchford BR and Di Paola J. Hematology ASH Educ Program. 2012;2012:161-167.
  10. van Galen KP, Sanders YV, Vojinovic U, et al. Haemophilia. 2015;21(3):e185-e192.
  11. Connell NT, Flood VH, Brignardello-Petersen R, et al. Blood Adv. 2021;5(1):301-325.

Upcoming & Past Conferences in Hematology

  • Upcoming

  • Past

American Society of Hematology (ASH), 2024

December 7 - 10, 2024 | Link to Event

The premier global congress from the world's largest professional society serving both clinicians and scientists working in malignant and classical hematology.

Hemostasis and Thrombosis Research Society (HTRS), 2025

March 13 - 15, 2025 | Link to Event

Scientific meeting open to all medical, research, and allied health professionals interested in disorders of hemostasis and thrombosis.

Academy of Managed Care Pharmacy (AMPC), 2025

March 30 - April 3, 2025 | Link to Event

Annual event with more than 2,500 members and non-members of the AMCP to engage on the latest innovations and most intentional networking in managed care pharmacy.

International Society on Thrombosis and Haemostasis (ISTH), 2025

June 21 - 25, 2025 | Link to Event

Global congress featuring the world’s leading experts on thrombosis, hemostasis and vascular biology presenting the most recent advances, the latest science, and the newest clinical applications designed to improve patient care.

American Thrombosis and Hemostasis Network Data Summit (ATHN Data Summit), 2024

October 22 - 23, 2024

Annual meeting discussing important research areas of hemophilia, health equity, thrombosis, Von Willebrand disease, rare blood disorders, and data management.

Academy of Managed Care Pharmacy Nexus (AMCP Nexus), 2024

October 14 - 17, 2024

Annual event with more than 2,500 members and non-members of the AMCP to engage on the latest innovations and most intentional networking in managed care pharmacy.

Bleeding Disorders Conference (BDC), 2024

September 12 - 14, 2024

The National Bleeding Disorders Foundation (formally NHF)’s Annual Bleeding Disorders Conference brings the bleeding disorders community together for educational sessions, networking opportunities, and exhibits.

International Society on Thrombosis and Haemostasis (ISTH), 2024

June 22 - 26, 2024

Global congress featuring the world’s leading experts on thrombosis, hemostasis and vascular biology presenting the most recent advances, the latest science, and the newest clinical applications designed to improve patient care.

  • Global Prevalence of Anticoagulant Reversal for Major Bleeding and Urgent Surgery in Patients with Atrial Fibrillation and Venous Thromboembolism: A Systematic Review of Data from 38 Countries

Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] & Advate® [Antihemophilic Factor (Recombinant)] & "other FVIII replacement therapies"

  • Physical Activity Engagement and Health-Related Quality Of Life in Patients with Hemophilia A Receiving Either Octocog Alfa Or Rurioctocog Alfa Pegol Versus Other FVIII Replacement Therapies
  • Clinical Outcomes in Patients with Hemophilia A Receiving Octocog Alfa or Rurioctocog Alfa Pegol Versus Other FVIII Replacement Therapies: Insights From The Ahead, CHESS II, and CHESS PAEDS Studies
  • The Impact of Recombinant Factor VIII Products on Inhibitor Development in Previously Untreated and Previously Treated Children with Hemophilia A: A Systematic Review

Ceprotin® [Protein C Concentrate (Human)]

  • High-Concentration Protein C Concentrate: In Vitro and In Vivo Feasibility Studies
  • Pharmacokinetics of Protein C in Neonates with Severe Congenital Protein C Deficiency
  • Pharmacokinetics of Protein C Concentrate After Intravenous and Subcutaneous Administration in Göttingen Minipigs

Obizur® [Antihemophilic Factor (Recombinant), Porcine Sequence]

  • Evaluation of Factor VIII Population Pharmacokinetics and Exposure-Response to Support Dosing of Recombinant Porcine Factor VIII in Patients with Acquired Hemophilia A

TAK-330 (4-factor prothrombin complex concentrate [4F-PCC])

  • A Phase 3 Trial of TAK-330 (4-Factor Prothrombin Complex Concentrate [4F-PCC]) vs Standard-Of-Care 4F-PCCs for FXa Inhibitor-Induced Anticoagulation Reversal Before Urgent Surgery/Invasive Procedure

Prothromplex® (Human Prothrombin Complex)

  • Safety Assessment of Prothromplex®, a 4-Factor Prothrombin Complex Concentrate, Focused on Heparin-Related Adverse Events

Professional Society for Health Economics and Outcomes Research (ISPOR), 2024

May 5 - 8, 2024

Leading global conference discussing how to establish, incentivize, and share value sustainable for health systems, patients, and technology developers.

Thrombosis and Hemostasis Societies of North America (THSNA), 2024

April 4 - 6, 2024

A summit of 10 of the leading non-profit organizations in hemostasis and thrombosis, providing expertise and insight on improving patient care.

American Society of Hematology (ASH), 2023

December 9 - 12, 2023

The premier global congress from the world's largest professional society serving both clinicians and scientists working in malignant and classical hematology.

Adynovate® [Antihemophilic Factor (Recombinant), PEGylated] & Advate® [Antihemophilic Factor (Recombinant)]

  • Clinical Outcomes of Noninhibitor Patients with Hemophilia A Switching from Prophylaxis with Factor VIII to Emicizumab: a Meta-analysis of Real-world Evidence Studies
  • Identifying Ideal Individuals for PK-guided Dosing: Recreational Risks and Elevated Breakthrough Bleeding

Vonvendi® [von Willebrand factor (recombinant)]

  • Real-world Use of Recombinant Von Willebrand Factor in People with Clinically Severe Congenital Von Willebrand Disease: Interim Analysis of ATHN 9, A Natural History Study for People with Severe VWD

Videos

 

Watch videos focused on von Willebrand disease (VWD).

The Role of von Willebrand Factor in Hemostasis

Learn about von Willebrand's dual role in hemostasis, along with its process of storage, secretion and cleavage in this animated video.

Additional Resources

 

Find materials to help foster a deeper understanding of von Willebrand disease (VWD).

von Willebrand Disease Milestones

A timeline of milestones from disease discovery in 1926 to current guidelines and management approaches.

Medication Resources

Vonvendi®

[von Willebrand factor (Recombinant)]