Von Willebrand
Disease

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.