From the Guidelines
To screen for von Willebrand disease, I recommend ordering initial hemostasis tests, including a complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (PTT), followed by VWD assays, including measurements of VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII), as suggested by the 2008 NHLBI/NIH guidelines 1. When evaluating a patient for von Willebrand disease, it is essential to consider their clinical presentation, including mucocutaneous bleeding history.
- The initial laboratory evaluation should include the initial hemostasis tests, which are grade C recommendations, to rule out other potential causes of bleeding, such as coagulation factor deficiency or thrombocytopenia.
- If the clinical evaluation suggests a high likelihood of von Willebrand disease, the initial VWD assays, which are grade B recommendations, should be ordered, including VWF:Ag, VWF:RCo, and FVIII.
- The results of these tests may establish the diagnosis and suggest the type and severity of von Willebrand disease, and if abnormal, may warrant further specialized testing, such as VWF multimer analysis. Key considerations when interpreting test results include:
- The ratio of VWF:RCo to VWF:Ag, which should be above 0.5-0.7 to rule out von Willebrand disease.
- The presence of abnormally low test results, which may indicate the need for reflexive testing or evaluation of another plasma sample. It is crucial to note that VWF multimer analysis is not recommended for initial VWD screening and should only be performed if initial VWD testing identifies an abnormal result or clinical information suggests a high likelihood of abnormal VWF multimer analysis, as stated in the guidelines 1.
From the Research
Screening for von Willebrand Disease
To screen for von Willebrand disease, the following tests are recommended:
- Determinations of prothrombin time, partial thromboplastin time, platelet count, and bleeding time 2
- vWF activity (ristocetin cofactor activity) and vWF factor antigen tests 2, 3, 4
- Factor VIII procoagulant (VIII:c) test 2
- Multimer analysis to contribute to diagnosis and classification 5
- Platelet binding assay to differentiate between qualitative and quantitative defects 4
Diagnostic Criteria
The diagnosis of von Willebrand disease requires:
- A personal and family history of bleeding symptoms 2, 3, 6
- A documented abnormality of vWF activity or vWF antigen 2, 6
- von Willebrand factor levels of 30 IU per dL or lower for a definite diagnosis of inherited von Willebrand disease 6
Laboratory Tests
Laboratory tests used to assess VWF levels and functions include:
- vWF antigen test 2, 3, 4
- vWF activity (ristocetin cofactor activity) test 2, 3, 4
- Factor VIII procoagulant (VIII:c) test 2
- Multimer analysis 5
- Platelet binding assay 4
- Ristocetin-induced platelet agglutination (RIPA) test 5
- von Willebrand factor:collagen-binding test (CB) 5
- von Willebrand factor:factor VIII binding test 5