Von Willebrand disease laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Prince Tano Djan, BSc, MBChB [3] Nazia Fuad M.D.

Overview

The diagnosis of von Willebrand disease (vWD) begins with a relevant personal or family history of mucocutaneous bleeding. When vWD is suspected, several levels of testing are needed in order to make diagnosis. Initial tests involve measurement of vWF antigen (VWF:Ag) level, Factor VIII activity (FVIII:C) and vWF–ristocetin cofactor activity [VWF:RCo]. When the results of all first-level tests are normal, vWD is ruled out; because of biologic variability, however, the tests should be repeated if values are at the low end of the normal range or if vWD is strongly suspected. Persons with a bleeding tendency who have vWF levels between 30 and 50 IU per deciliter are classified as having “low vWF” or “possible type 1 disease” but are not classified as having definitive vWD. When von Willebrand factor antigen is undetectable (or the level is <5 IU per deciliter, according to the latest disease classification), type 3 von Willebrand disease is diagnosed. If these first-level tests reveal definitive abnormalities, a diagnosis of vWD can be made; if the results are not conclusive, second-level tests are required. Second level testing involves repeating the initial tests and then measurement of vWF multimer distribution using gel electrophoresis and ristocetin-induced platelet aggregation (RIPA). Other tests performed in any patient with bleeding problems include: complete blood count (especially platelet counts), APTT (activated partial thromboplastin time), prothrombin time, thrombin time, fibrinogen level, testing for factor IX if hemophilia B is suspected and other coagulation factor assays may be performed depending on the results of a coagulation screen. Patients with von Willebrand disease will typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time.

Laboratory Findings

The diagnosis of von Willebrand disease (VWD) begins with a relevant personal or family history of mucocutaneous bleeding. When VWD is suspected, several levels of testing are needed in order to make diagnosis as shown below:

Screening tests

Screening testing include the following 3 tests:

• vWF antigen (vWF:Ag) level
  • Normal values are between 50 and 200 IU/dL
  • Levels below 50 are considered to be low
• Factor VIII activity (FVIII:C)
  • Type 1&2 has somewhat lower levels of FVIII
  • Type 3 has markedly reduced levels of FVIII
• vWF–ristocetin cofactor activity [VWF:RCo] as a measure of platelet-binding activity of vWF
  • The normal range of VWF:RCo is 50 to 200 IU/dL

Type	vWF antigen level
low vWD or possible Type 1	30-50 IU
1	<30 IU
2	Ratio of von Willebrand factor–ristocetin cofactor activity to von Willebrand factor antigen ≤0.6
3	< 5 IU

• When the results of the screening tests are normal, the tests should be repeated, if values are at the low end of the normal range or if VWD is strongly suspected.
• If the screening tests reveal definitive abnormalities, a diagnosis of VWD can be made.

• A proportional decrease in von Willebrand factor antigen and von Willebrand factor–ristocetin cofactor activity fits the diagnosis of type 1 von Willebrand’s disease.

Confirmatory tests

These tests are required to determine the phenotypic characteristics that define types 2A, 2B, and 2M:

• VWF multimer distribution using gel electrophoresis
• Ristocetin-induced platelet aggregation (RIPA)

• A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used.
• Type 2B can be distinguished by enhanced ristocetin-induced platelet aggregation in the presence of low-dose ristocetin.
• Type 2N can only be diagnosed by performing a "factor VIII binding" assay.

Other tests

Other tests performed in any patient with bleeding problems are:

• complete blood count shows normal platelets except in
• APTT (activated partial thromboplastin time) may be normal or prolonged
• prothrombin time is normal
• thrombin time
• fibrinogen level.
• Testing for factor IX may also be performed if hemophilia B is suspected.

Other coagulation factor assays may be performed depending on the results of a coagulation screen.

• Patients with Von Willebrand disease will typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time.