Table 1.

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