Von Willebrand Disease Overview

Von Willebrand Disease (VWD)

• VWD is a congenital bleeding disorder, the most common hereditary bleeding disorder affecting both sexes.
• It's characterized by a lifelong tendency towards easy bruising, frequent nosebleeds (epistaxis), and heavy menstrual bleeding (menorrhagia).
• Von Willebrand factor (VWF) acts as a carrier for factor VIII (FVIII) and is crucial for platelet adhesion and aggregation.

VWD Classification

• VWD is classified based on either reduced levels or abnormal function of VWF, stemming from a point mutation or major deletion.
• Quantitative VWD:
  • Type 1: Partial VWF deficiency
  • Type 3: Complete VWF deficiency
• Qualitative VWD:
  • Type 2: Qualitative mutants of VWF (further categorized into subtypes 2A, 2B, 2M, and 2N)

Type 1 VWD

• This is the most common subtype (70-80% of cases).
• Characterized by a partial quantitative decrease in VWF and FVIII.
• Individuals often have mild symptoms.
• Inherited as an autosomal dominant trait.
• Lab findings: A proportional decrease in VWF activity, VWF antigen, and FVIII is observed.

Type 3 VWD

• The most severe form.
• Marked deficiency of both VWF and FVIII in the bloodstream.
• Absence of VWF from platelets and endothelial cells.
• Characterized by severe clinical bleeding.

Type 2 VWD

• Qualitative mutants of VWF.
• Classified further into four subtypes based on functional defects:
  • 2A: Decreased affinity for GP1b
  • 2B: Increased affinity for platelets leading to platelet aggregation
  • 2M: Large multimers with decreased affinity for platelets
  • 2N: Defective factor VIII binding site, decreased affinity for FVIII, but normal in other aspects (often mistaken for hemophilia)

Secondary Classification of Type 2 VWD

• A table classifying type 2 VWD subtypes further based on platelet-associated function, factor VIII binding capacity, and high MW VWF multimers.

Lab Investigations for VWD

• Bleeding time is often prolonged.
• Factor VIII levels are frequently low; if low, a factor VIII/VWF binding assay is performed.
• Activated Partial Thromboplastin Time (APTT) may be prolonged.
• VWF levels are typically low.
• Platelet aggregation with ristocetin (VWF:RCo) and other agents (ADP and thrombin) is often normal.
• Multimer analysis is used for subtype classification.
• Platelet count is usually normal, except in type 2B VWD.

Comparison of VWD with Hemophilia A and B

• Comparison table showing differences in inheritance, main sites of bleeding, platelet count, bleeding time, clotting factors, ristocetin-induced platelet aggregation, and other tests for VWD, Hemophilia A, and Factor IX deficiency.