International Society of Thrombosis and Haemostasis classification of von Willebrand disease
| Type Subtype | VWD type 1 | VWD type 2 | VWD type 3 | ||||
|---|---|---|---|---|---|---|---|
| Classic | 1C | 2A | 2B | 2M | 2N | ||
| Frequency | Common (70% of cases) | Uncommon (25% of cases) | Rare (5% of cases) | ||||
| Pathophysiology | Mutations result in partial quantitative deficiency of functionally normal VWF | Qualitative defects in VWF | Almost complete quantitative deficiency of VWF | ||||
| Specific mechanism | Decreased synthesis of VWF due to various genetic mutations | Increased clearance of available VWF in circulation | Mutations result in fewer glycoprotein Ib binding sites and less effective platelet clot formation | Mutations increase affinity of glycoprotein Ib binding site and clearance of high-molecular-weight multimers | Mutations decrease affinity of glycoprotein Ib site or decrease VWF-collagen interaction | Mutation in factor VIII binding site decreases affinity of VWF for factor VIII | |
| Inheritance | Autosomal dominant | Autosomal dominant | Autosomal dominant | Autosomal dominant | Autosomal dominant | Autosomal recessive | Autosomal recessive |
| Clinical phenotype | Mild to moderate mucocutaneous bleeding | Mild to moderate mucocutaneous bleeding | Moderate to severe mucocutaneous bleeding | Moderate to severe mucocutaneous bleeding | Severe mucocutaneous bleeding | Hemophilialike bleeding | Severe mucocutaneous and hemophilia-like bleeding |
| Response to desmopressin | Very effective in treating minor bleeding episodes | Used to diagnose type 1C (> 30% decrease in VWF 4 hours after infusion) Ineffective in treatment of type 1C VWD | May respond to desmopressin Recommend challenge before therapeutic administration | Desmopressin usually contraindicated due to thrombocytopenia | May respond to desmopressin Recommend challenge before therapeutic administration | May respond to depression Recommend challenge before therapeutic administration | Recommend avoiding desmopressin |
VWD = von Willebrand disease; VWF = von Willebrand factor
Data adapted from reference 13.