What factor is associated with Von Willebrand disease?

Von Willebrand Factor and Von Willebrand Disease

Von Willebrand disease is associated with deficiency or dysfunction of von Willebrand factor (VWF), which plays crucial roles in primary hemostasis through platelet adhesion and in secondary hemostasis as a carrier protein for Factor VIII. 1

Understanding Von Willebrand Factor (VWF)

Von Willebrand factor is a multimeric plasma protein that has two essential hemostatic functions:

• Mediates the initial adhesion of platelets at sites of vascular injury
• Binds and stabilizes coagulation factor VIII (FVIII) in the blood

When VWF is deficient or dysfunctional, it leads to Von Willebrand disease (VWD), the most common inherited bleeding disorder, affecting up to 1% of the general population 1.

Classification of Von Willebrand Disease

VWD is classified into three main types based on the nature of the VWF defect:

1. Type 1 VWD (~75% of cases)

   • Partial quantitative VWF deficiency
   • VWF:Ag and VWF:RCo levels typically <30 IU/dL
   • FVIII levels may be reduced or normal
   • VWF:RCo/VWF:Ag ratio >0.5-0.7 2

2. Type 2 VWD

   • Qualitative defects in VWF
   • Four subtypes: 2A, 2B, 2M, and 2N
   • VWF:RCo typically <30 IU/dL
   • VWF:Ag may range from <30-200 IU/dL
   • VWF:RCo/VWF:Ag ratio typically <0.5-0.7 (except Type 2N) 2

3. Type 3 VWD (~1 in 1,000)

   • Virtually complete deficiency of VWF
   • VWF:Ag and VWF:RCo levels <3 IU/dL
   • FVIII levels severely reduced (<10 IU/dL) 2

Laboratory Diagnosis

Diagnosis of VWD requires specific laboratory tests:

• VWF antigen (VWF:Ag) - measures the amount of VWF protein
• VWF ristocetin cofactor activity (VWF:RCo) - measures VWF function
• Factor VIII coagulation activity (FVIII) - often reduced due to decreased VWF carrier function
• VWF:RCo/VWF:Ag ratio - helps distinguish between quantitative and qualitative defects

Normal ranges for these tests are:

• VWF:Ag: 50-200 IU/dL
• VWF:RCo: 50-200 IU/dL
• FVIII: 50-200 IU/dL
• VWF:RCo/VWF:Ag ratio: >0.5-0.7 2

Clinical Manifestations

The clinical presentation of VWD typically includes:

• Mucocutaneous bleeding (epistaxis, gingival bleeding)
• Easy bruising
• Prolonged bleeding from minor wounds
• Menorrhagia or postpartum bleeding in women
• Bleeding after surgical procedures
• Gastrointestinal bleeding (in severe cases)

The severity of symptoms correlates with the degree of VWF and FVIII reduction 3.

Treatment Approaches

Treatment depends on the type and severity of VWD:

1. Desmopressin (DDAVP)

   • First-line therapy for Type 1 VWD with FVIII levels >5%
   • Stimulates release of endogenous VWF from endothelial cells
   • Not effective for Type 3 VWD and variable efficacy in Type 2 4, 5

2. VWF/FVIII Concentrates

   • Indicated for Type 2 and Type 3 VWD
   • Used when desmopressin is ineffective or contraindicated
   • Essential for major surgical procedures 6

3. Antifibrinolytic Agents

   • Adjunctive therapy for mucosal bleeding
   • Can be used alone for minor bleeding or in combination with other treatments 5

Special Considerations

• Pregnancy: Women with VWD may experience improvement in VWF and FVIII levels during pregnancy, but remain at risk for postpartum hemorrhage. Close monitoring and prophylaxis are recommended for at least 2 weeks after delivery 7.

• Surgery: Prophylaxis before surgical procedures requires consideration of the VWD type, procedure type, and bleeding risk. VWF/FVIII levels should be maintained above 50 IU/dL for minor procedures and above 100 IU/dL for major surgeries 6.

• Acquired VWD: Can occur in conditions like aortic stenosis or with mechanical circulatory support devices due to shear forces affecting VWF multimers 1.

Understanding the role of VWF in hemostasis is crucial for proper diagnosis and management of patients with VWD, one of the most common inherited bleeding disorders.