von Willebrand’s disease (vWD)

(NEJM 2016;375:2067)

• von Willebrand’s factor (vWF) function = platelet glue & plasma carrier of factor VIII

• vWD most common inherited bleeding disorder; ~85% (type 1) have partial quantitative vWF defic., ~15% (type 2) qualitative defic., <1% (type 3) total/near-total absence of vWF

• Acquired vWD: a/w many disorders (malig, MPN w/ ↑ plt count; autoimmune; hypo-thyroidism; drugs) and caused by different mechanisms (anti-vWF Abs, ↑ clearance, ↓ synthesis); Heyde’s syndrome = vWF destruction by severe AS, a/w GI AVMs/bleed

• Diagnosis: ↓ vWF:

  • Ag,
  • ↓ vWF activity (measured by ristocetin cofactor assay),
  • ↓ factor VIII,
  • ± ↑ PTT,
  • ± ↓ platelets;
  • confirm with vWF multimer analysis

• Clinical condition, factor VIII levels and ristocetin cofactor assay useful to guide Rx decision

• Rx: desmopressin (dDAVP, IV/IN; tachyphylaxis) → ↑ endothelial cell release of vWF;

  • efficacy depends on type (avoid in type 2), ∴ ✓ response before use w/ bleeding or procedures;
  • vWF replacement: cryo, vWF-rich factor VIII concentrates, recomb. vWF