From the Guidelines
A von Willebrand disease (vWD) workup should include initial hemostasis tests such as a complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (PTT), followed by initial VWD assays including von Willebrand factor antigen (VWF:Ag), von Willebrand factor activity (VWF:RCo), and factor VIII activity, as recommended by the 2008 NHLBI/NIH guidelines 1.
Initial Evaluation
The initial evaluation should start with a detailed bleeding history assessment using a standardized bleeding questionnaire, as well as a physical examination to identify any signs of bleeding disorders.
- A strong bleeding history should prompt consideration of performing initial VWD assays, including VWF:Ag, VWF:RCo, and factor VIII activity.
- Initial hemostasis tests, such as CBC, PT, and PTT, should be ordered to rule out other causes of bleeding, such as thrombocytopenia or coagulation factor deficiencies.
Laboratory Assessment
The laboratory assessment algorithm for VWD or other bleeding disorders is outlined in Figure 2 of the 2008 NHLBI/NIH guidelines 1.
- If the initial clinical evaluation suggests a bleeding disorder, the initial hemostasis tests should be ordered, followed by or along with the initial VWD assays.
- Referral to a hemostasis specialist is appropriate for help in interpretation, repeated testing, and specialized VWD studies.
- The ratio of VWF:RCo to VWF:Ag should be calculated, and if abnormally low, selected specialized VWD assays, such as multimer analysis, should be considered.
Specialized Testing
Multimer analysis is not recommended for initial VWD screening, but should be performed if initial VWD testing identifies an abnormal result or clinical information suggests a high likelihood of abnormal VWF multimer analysis 1.
- Other specialized VWD studies, such as collagen binding, RIPA platelet binding, FVIII binding, platelet VWF studies, and DNA sequencing of the VWF gene, may be indicated in certain cases.
Coordination of Care
Testing should be coordinated with a hematologist, and samples should be properly collected in citrated tubes and processed within 2-4 hours to prevent degradation of VWF.
- This comprehensive approach helps determine the type and severity of vWD, which guides treatment decisions, including the potential use of desmopressin (DDAVP), tranexamic acid, or VWF concentrate replacement therapy based on the specific subtype and clinical scenario.
From the Research
Von Willebrand Disease Diagnosis
The diagnosis of von Willebrand disease (VWD) involves a combination of clinical evaluation, personal and family history, and laboratory testing 2, 3. The laboratory testing typically includes:
- Initial plasma testing of factor VIII coagulant, von Willebrand factor (VWF) protein ('antigen'), and VWF function 2
- VWF antigen testing to assess VWF levels 4
- VWF activity assays, such as ristocetin cofactor (VWF:RCo) assay, collagen binding, and VWF activity assays 2
- Multimer analysis to differentiate between type 1, type 2, and type 3 VWD 5, 6
Laboratory Testing
The laboratory testing for VWD can be divided into several steps:
- Screening procedures: bleeding time, filter tests, platelet counts, activated partial thromboplastin time (aPTT) 6
- Confirmatory tests: VWF:antigen, VWF:ristocetin cofactor activity assay, VWF:collagen-binding test, ristocetin-induced platelet agglutination, and factor VIII:coagulant activity 6
- Tests for final classification: multimeric analysis, VWF:factor VIII binding, and platelet VWF 6
Multimer Analysis
Multimer analysis is a critical part of the laboratory testing for VWD, as it helps to differentiate between type 1, type 2, and type 3 VWD 5, 6. The multimer distribution patterns can also help to understand the underlying molecular mechanism of VWF synthesis, multimerization, and clearance defects in VWD 5. The analysis can be performed using manual or semi-automated electrophoresis and immunoblotting 5.