Coagulation laboratory tests

von Willebrand disease testing

Topic Completed: 1 November 2012

Minor changes: 24 September 2021

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PubMed Search: von Willebrand disease testing

See also: von Willebrand disease

Jeremy C. Parsons, M.D.
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Cite this page: Parsons JC. von Willebrand disease testing. website. Accessed January 17th, 2022.
Definition / general
  • Often need to repeat tests because von Willebrand factor and factor VIII are elevated during acute phase reactions, pregnancy, estrogen use and in newborns - can measure fibrinogen (acute phase reactant) to determine if acute phase condition exists

  • Tests: von Willebrand factor antigen assay, von Willebrand factor activity (ristocetin cofactor activity), factor VIII levels, fibrinogen (or other acute phase reaction marker) or multimer analysis
  • All results normal (considering ABO blood type) - unlikely to have vWD if no acute phase reaction, pregnancy, estrogen use or newborn (Thromb Haemost 1994;71:520)
  • All results normal but elevated fibrinogen / factor VIII - acute phase reaction may mask abnormalities; repeat when fibrinogen and factor VIII levels are normal
  • Reduced antigen, activity and factor VIII - likely type 1 vWD
  • Severely reduced (< 10%) or undetectable antigen, activity and factor VIII - likely type 3 vWD

  • Activity reduced more than antigen and factor VIII - possibly type 2 vWD; perform multimer analysis and low dose ristocetin cofactor
    • Normal multimer analysis - likely type 2M vWD
    • Missing high molecular weight multimers - likely type 2A vWD
    • Missing high and intermediate molecular weight multimers - likely type 2B or platelet type vWD
    • Increased low dose ristocetin aggregation - likely type 2B or platelet type vWD
    • Normal or decreased low dose ristocetin aggregation - not type 2B or platelet type vWD
    • Reduced factor VIII (5 - 40%), normal activity and activity - possibly type 2N vWD or in males, mild hemophilia A; also possibly factor VIII degradation due to processing delay
von Willebrand factor antigen assay
  • Levels can increase 2 - 3x with injury, infection or other acute phase reactant stimulus (30% level at baseline can increase to 90% by the time the patient is tested); can determine presence of acute phase reaction by measuring fibrinogen
  • Reference range is higher in children < 6 months old than adults (abnormal value in 3 month old may be normal for an adult)
  • Minor injuries may produce major bleeds in children, leading to false accusations of child abuse
  • Type O patients have significantly lower vWF antigen levels (75%) compared to type A (106%), type B (117%) and type AB (123%); although bleeding symptoms may depend on vWF antigen levels, regardless of ABO type
  • Used to determine if patient with personal or family history of bleeding has von Willebrand disease; also to assist in determining hemophilia A carrier status in females
  • ELISA assay measures quantity of vWF, not function (Can J Vet Res 2008;72:420)
  • Can also use latex particles coated with anti-vWF antibodies, measure light absorbance; rocket immunoelectrophoresis
von Willebrand factor activity
  • Low dose ristocetin platelet aggregation assay
    • To diagnose type 2B von Willebrand disease
    • Similar to von Willebrand factor activity test, but uses patients platelets and lower dose of ristocetin
    • Platelets from patient are mixed with standard concentrations of ristocetin and patient plasma is added to cause platelet agglutination (measured in aggregometer)
    • Increased aggregation in type 2B vWD in this assay due to GP Ib mutation, which increases affinity for vWF
  • Also called ristocetin cofactor activity
  • Ristocetin is an antibiotic that causes vWF to bind to and activate platelets
  • Test measures function of von Willebrand factor
  • Platelets from healthy individuals are mixed with standard concentrations of ristocetin, and patient plasma is added to cause platelet agglutination (measured in aggregometer), which is proportional to the vWF concentration
  • Used to confirm type 2B von Willebrands disease (increased agglutination due to increased affinity of vWF for GPIb); similar results for platelet type von Willebrands disease (although the defect is in GPIb)
  • Note: aggregation of platelets implies linkage via fibrinogen and GP IIb / IIIa; ristocetin links platelets through vWF and GP Ib; appropriate term is actually agglutination
  • Other functional tests: collagen binding ELISA assay, functional vWF binds to collagen and is detected (Br J Haematol 2002;116:187)
von Willebrand factor multimer analysis
  • To detect type 2 von Willebrand disease
  • Involves separation of multimers by size using agarose gel electrophoresis of patients plasma (Thromb Res 2010;126:543)
  • Then detect multimers using radiolabeled or enzyme linked anti-vWF antibody
  • Normal in von Willebrands disease types 1, 2N or 2M (type 1 has reduced quantity of all sizes but difficult to identify on gel)
  • No / reduced high molecular weight multimers in types 2A and 2B von Willebrands disease
  • No / reduced intermediate molecular weight multiples in type 2A
  • No / marked reduction in all multimers in type 3
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