VWD classification and pathogenetic mechanisms
| VWD subtype . | Pathogenetic mechanisms . |
|---|---|
| Type 1 VWD | • ∼65% of index cases have candidate VWF mutations |
| • ∼70% of VWF variants are missense substitutions influencing VWF trafficking, storage, secretion, and clearance | |
| • Additional transcription and splicing VWF mutations | |
| Type 2A VWD | • Missense variants in D1/D2/D′D3 assemblies, A2 and CTCK domains |
| • Interference with HMW multimer formation, storage, and secretion | |
| • Enhanced ADAMTS13 proteolysis | |
| Type 2B VWD | • Missense variants in A1 domain |
| • Enhanced binding to GPIbα | |
| Type 2M VWD | • Missense variants in A1 and A3 domains |
| • Reduced binding to GPIbα (A1 domain) or collagen (A3 domain) | |
| Type 2N VWD | • Missense variants in D′D3 assembly |
| • Reduced FVIII binding | |
| Type 3 VWD | • VWF mutations found in 85%-90% of index cases |
| • VWF deletions, nonsense, splice site, and missense mutations |
| VWD subtype . | Pathogenetic mechanisms . |
|---|---|
| Type 1 VWD | • ∼65% of index cases have candidate VWF mutations |
| • ∼70% of VWF variants are missense substitutions influencing VWF trafficking, storage, secretion, and clearance | |
| • Additional transcription and splicing VWF mutations | |
| Type 2A VWD | • Missense variants in D1/D2/D′D3 assemblies, A2 and CTCK domains |
| • Interference with HMW multimer formation, storage, and secretion | |
| • Enhanced ADAMTS13 proteolysis | |
| Type 2B VWD | • Missense variants in A1 domain |
| • Enhanced binding to GPIbα | |
| Type 2M VWD | • Missense variants in A1 and A3 domains |
| • Reduced binding to GPIbα (A1 domain) or collagen (A3 domain) | |
| Type 2N VWD | • Missense variants in D′D3 assembly |
| • Reduced FVIII binding | |
| Type 3 VWD | • VWF mutations found in 85%-90% of index cases |
| • VWF deletions, nonsense, splice site, and missense mutations |