Von Willebrand’s Disease (VWD)

Learning objectives

von Willebrand Disease is the most common inherited bleeding disorder with a prevalence of approximately 1% in the population
Due to a qualitative or quantitative defect of the von Willebrand factor (vWF)
Three types:
- Type 1 is a quantitative defect
- Type 2 is a qualitative defect
- Type 3 is a very rare but severe form characterized by a mutant inhibitor protein against the vWF (vWF inhibitor)
  - It demonstrates autosomal dominant (e.g. type 1, 2B) & – recessive (e.g. types 2M, 2N, 3) inheritance, with marked phenotypic variations
It may be discovered at any age and in either sex

Is extremely rare but has been documented in clonal hematological, cardiovascular (aortic valve stenosis with higher sheer stresses in the vessels), and immunological (hypothyroidism), and other lymphoproliferative auto-immune diseases
A vWF-inhibitor protein or the adhesion of vWF with malignant cells can occur
It has a marked reduced vWF activity interfering with the production and/or the stability of vWF
Leading to the production of autoantibodies to endogenous vWF which can result in decreased functional high molecular weight vWF multimers
Acquired vWS responds well to vWF-concentrates administration but the effects can be mitigated by these inhibitor proteins since they affect the half-life time of the administered vWF

vWF is a ligand between platelets and subendothelial cells
vWF stabilizes circulating factor VIII hereby preventing its degradation
On average the levels of vWF and FVIII are lower in humans with type O blood and are increased in inflammatory conditions and during pregnancy
Bleeding time and platelet function analysis will be prolonged in relation to the severity of the abnormality
APTT can be prolonged in relation to the remaining quantity of FVIII

Determination of the exact type is of utmost importance for the therapeutical approach

Type 1	Type 2	Type 3
~85% with vWD have this form Decreased quantities of vWF in several degrees Characterized by a mild bleeding tendency but has increased risks peri-operatively Responds well to desmopressin infusion	~ 5% with vWD have this form Subtypes 2A, 2B, 2M, and 2N are described Types 2A and 2B differ in the platelet binding capacity but the amount of high molecular weight multimers circulating in the plasma is decreased in both Type 2A presents with a decreased platelet binding Type 2B presents with an increased platelet agglutination with a concomitant increased risk of thrombosis Type 2B is marked by accompanying thrombocytopenia due to a higher clearance of platelets Subtype 2M has a decreased platelet binding with normal quantities of HMW multimers Subtype 2N is characterized by a flawed ability to stabilize circulating FVIII and results in a factor VIII deficiency	A complete defect in vWF synthesis Plasma factor VIII is decreased despite normal synthesis due to the lack of stabilization by the total absence of vWF