From the Guidelines
In von Willebrand disease (vWD), several laboratory tests would be abnormal, including decreased von Willebrand factor (vWF) antigen levels, reduced vWF activity (ristocetin cofactor activity), and sometimes a prolonged activated partial thromboplastin time (aPTT), as well as abnormal vWF multimer analysis and platelet function tests, such as the platelet function analyzer (PFA-100) and ristocetin-induced platelet aggregation (RIPA) 1.
Key Abnormalities
- Decreased vWF antigen levels
- Reduced vWF activity (ristocetin cofactor activity)
- Prolonged activated partial thromboplastin time (aPTT)
- Abnormal vWF multimer analysis
- Prolonged platelet function analyzer (PFA-100) closure times
- Abnormal ristocetin-induced platelet aggregation (RIPA)
Test Interpretation
The specific pattern of test abnormalities helps distinguish between the different subtypes of vWD (types 1, 2A, 2B, 2M, 2N, and 3), which is important for appropriate management 1.
Laboratory Evaluation
Initial laboratory evaluation for vWD should include measurements of blood plasma VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII) 1.
Specialized Testing
Multimer analysis, collagen binding, RIPA platelet binding, FVIII binding, platelet VWF studies, and DNA sequencing of the VWF gene may be performed in selected cases to further characterize the subtype of vWD and guide management 1.
From the Research
Abnormal Tests in von Willebrand Disease
The following tests may be abnormal in von Willebrand disease:
- Bleeding time: abnormal in 43% of patients 2
- Activated partial thromboplastin time (aPTT): abnormal in 25% of patients 2, and has an excellent diagnostic sensitivity and a satisfactory specificity for identifying isolated von Willebrand factor deficiencies 3
- von Willebrand factor (vWF) activity: abnormal in 79% of patients 2, and is superior to vWF antigen or factor VIII:c in establishing the diagnosis of vWD 2
- vWF antigen: abnormal in 58% of patients 2
- Factor VIII:c: abnormal in 33% of patients 2
- Multimeric analysis of vWF: necessary for diagnosis and classification of vWD, especially in patients with variant forms of the disease 4, 5
- Ristocetin cofactor activity assay: used to confirm the diagnosis of vWD 5
- Platelet count: may be normal or abnormal, but is often included in the initial screening for vWD 4, 2
Diagnostic Approach
The diagnostic approach to von Willebrand disease involves a combination of tests, including:
- Initial screening: bleeding time, aPTT, platelet count, vWF antigen, and vWF activity 4, 2
- Confirmatory tests: vWF:ristocetin cofactor activity assay, vWF:collagen-binding test, ristocetin-induced platelet agglutination, and factor VIII:coagulant activity 5
- Further subtyping: multimeric analysis, vWF:factor VIII binding, and platelet vWF 5, 6