Tests
1st tests to order
prothrombin time (PT)
Test
A measure of the extrinsic pathway of coagulation. Reference range is usually around 12-15 seconds. Can be measured on whole blood, but more usually is measured from blood plasma. Requires liquid citrated tube, which should be well filled. Normally PT is within reference range in VWD.
Result
within reference range in VWD
activated partial thromboplastin time (APTT)
Test
Prolonged only if factor VIII is decreased sufficiently; usually this must be less than approximately 35% of normal. The exact value depends on the individual laboratory.
A normal APTT does not exclude the diagnosis of VWD.
Result
prolonged if factor VIII activity less than approximately 35% of normal
CBC
Test
Used as a baseline screening test and assesses a range of blood parameters. In particular, it assesses platelet number and morphology, which should be normal in most patients with VWD, except in those with type 2B VWD.
Result
results usually normal with VWD, except in type 2B, when the platelet count may be reduced
von Willebrand factor antigen
Test
Borderline values (40% to 60% of normal) are not diagnostic and only marginally indicate the probability of type 1 VWD.[7] Some authorities designate 0.3 to 0.5 international units (IU)/mL as low von Willebrand factor (VWF) rather than VWD.[20]
Repeat testing if result within normal range but diagnosis suspected.
VWF levels are lower in patients with type O blood.
Levels increase with exercise, inflammation, and stress and vary with menstrual cycle.[21]
Result
diagnostic for VWD if <0.30 international units (IU)/mL
von Willebrand factor function assay (ristocetin cofactor and collagen binding assays)
Test
Values decrease in parallel to VWF antigen, except in type 2 disease.
The ristocetin cofactor assay and collagen binding assay both measure function of VWF, and results are normally broadly consistent.
Result
diagnostic for VWD if <0.30 international units (IU)/mL; ratio of von Willebrand factor (VWF) function to VWF antigen <0.6 is consistent with a diagnosis of type 2 VWD
factor VIII activity
Test
Factor VIII activity value is frequently higher than von Willebrand factor (VWF) antigen level in type 1 VWD. In type 2N VWD it is lower than the VWF antigen.
Result
may be decreased but often within normal range
Investigations to avoid
Tests to consider
von Willebrand factor multimer analysis
Test
The test should be ordered if the von Willebrand factor (VWF) analysis is abnormal. VWF multimers are sensitive to conditions where degradation can occur and require technical sophistication. Care must be given to specimen handling and laboratory expertise.
Comparison of VWF ristocetin cofactor activity (VWF:RCo) and VWF collagen binding activity (VWF:CB) can often give useful information on presence of high-molecular-weight multimers.
Result
type 1: all multimers present, decreased in intensity; type 2A, loss of medium- and high-molecular-weight multimers; type 2B, loss of high-molecular-weight multimers; type 2M, normal multimers
platelet aggregometry
Test
Used when ratio of VWF function to VWF antigen is <0.6. Classic platelet aggregometry is not useful except for detecting increased sensitivity to ristocetin for the diagnosis of type 2B VWD.
Result
platelet agglutination to low concentrations of ristocetin (<0.7 mg/mL) is consistent with the diagnosis of type 2B VWD
factor VIII - von Willebrand factor binding assay
Test
Performed in a few reference laboratories only.
Result
decreased binding in type 2N
TFTs
Test
Acquired von Willebrand syndrome has been reported in hypothyroidism.
TSH is increased in primary hypothyroidism; decreased or normal in central hypothyroidism.
Result
may be consistent with hypothyroidism
serum protein electrophoresis
Test
Acquired von Willebrand syndrome may be seen in patients with monoclonal gammopathies. Ordered for patients with history compatible with an acquired bleeding disorder.
Result
may be consistent with monoclonal gammopathy
Emerging tests
mutation analysis
Test
Most available for type 2 VWD. More information for types 1 and 3 becoming available.
If there are existing genetic test results, do not order a duplicate test unless there is uncertainty about the existing result, e.g., the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[17]
Result
mutations consistent with a diagnosis of VWD
PFA-100 and other platelet function analyzers
Test
The PFA-100 has better performance characteristics than the outdated bleeding time, but it and similar testing devices are not thought to be sensitive and specific enough to be widely recommended for the diagnosis of VWD. Its role has not been clearly defined.[15]
Result
abnormal results are device specific
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