How is von Willebrand disease diagnosed?

First-line laboratory tests

Test

APPT(1)
Activated partial thromboplastin time

Mixing test(2)

PT
Prothrombin time

TT
Thrombin time

Fibrinogen

BT(3)
Bleeding time

Platelet count(4)

Result

prolonged

corrected

unaffected

unaffected

unaffected

prolonged

unaffected

 

 

(1) APPT: "inconsistent" prolongation of APPT occurs; lengthening depends on levels of factor VIII present and on the sensitivity to factor VIII of the reagent being used.
(2) Mixing test: Prolongation of APPT is corrected by mixing the patient's plasma in equal parts with a pool of normal plasma.
(3) BT: bleeding time (Ivy method) is only increased in around 50% of cases; it is never increased in type 2N von Willebrand disease; in vitro tests to reproduce bleeding time can provide diagnosis (except in type 2N von Willebrand disease).
(4) Platelet count: this parameter is normal in most forms of von Willebrand disease. The platelet count may be depressed in some patients with type 2B von Willebrand disease, in whom fluctuating thrombocytopenia of varying severity may be seen.

Specialist tests

WVF ristocetin cofactor activity

  • Assay of von Willebrand factor ristocetin cofactor activity measures ristocetin-induced binding of von Willebrand factor to platelet glycoprotein GPIb. This activity is increased in all types of von Willebrand disease except type 2N.

Von Willebrand factor antigen

  • Assay of von Willebrand factor antigen allows differential diagnosis between quantitative deficits, in which it is decreased, and qualitative deficits, in which it is normal and in which the ratio VWF:RCo / VWF Ag is < 0.7.
    As a general rule, von Willebrand factor levels vary according to blood group and are lower in people with blood type O than in non-O subjects.

Binding to factor VIII

  • Assay of factor VIII (FVIII:C) generally reveals a decrease, although it is still higher than the level of von Willebrand factor, except in type 2N von Willebrand disease.
    Determination of the binding capacity of factor VIII for von Willebrand factor allows differential diagnosis with regard to haemophilia A.

Collagen binding assay

  • Assay of collagen binding of von Willebrand factor (VWF:CB) can be used to detect abnormalities in VWF multimerisation.

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