Von Willebrand Disease Type 2N Binding (Sendout)

Test Information: This 2N-von Willebrand Disease panel is designed to distinguish type 2N-von Willebrand disease from mild hemophilia A and hemophilia A carriers.

Overview of Type 2N von Willebrand Disease (VWD): Type 2N von Willebrand disease (VWD) is characterized by decreased von Willebrand factor (VWF) affinity for factor VIII. This condition can clinically resemble hemophilia A. Typically, concerning laboratory values for Type 2N VWD include:

• Factor VIII activity < 50%
• Factor VIII activity/VWF antigen ratio < 0.5

These values indicate that the factor VIII is disproportionately lower than VWF. VWF binds to factor VIII in the blood and stabilizes it, preventing its degradation by proteolytic enzymes. Therefore, when both the factor VIII activity and the Factor VIII activity/VWF antigen ratio are disproportionately low, Type 2N VWD or mild hemophilia may be considered.

Diagnostic Flow Chart: An algorithm for the diagnosis of type 2N VWD²

Recommended Testing Steps:

• Begin with Von Willebrand Disease Type 2N DNA (Sendout) to determine the status of relatives.
• If there is a VUS (Variant of Uncertain Significance), or if no variant is found: Perform the Von Willebrand Disease Type 2N Binding assay (this test) to validate or complete the evaluation for Type 2N VWD.
• If Type 2N VWD is not identified, but clinical concern is high: Testing for hemophilia A may be warranted to rule out alternative diagnoses.

Ordering Requirements:

• Orders from Washington Center for Bleeding Disorders (SEAWBD) and FHCC Hematology are pre-approved. Orders from other locations require Laboratory Medicine Resident approval.
• Recommended: Providers should complete the Versiti Hemostasis Requisition Form, including the Patient History section, to ensure proper test interpretation (leave the billing/client information blank for lab staff to complete). Alternatively, relevant clinical information (anticoagulant use, recent lab values, family history, etc.) may be entered in the Epic comment field for inclusion with the order.

Normal Values:

Outside Laboratories: Centrifuge sample, transfer plasma to a separate plastic vial, and freeze at -20°C within four hours of collection.

Stability: Frozen: Required; Ambient: 4 hours; Refrigerated: Unacceptable.

• Critical Frozen: Freeze plasma within 4 hours of collection. If multiple tests are requested, separate aliquots must be submitted. Do not thaw and refreeze.

Unacceptable: Thawed, hemolyzed, or clotted specimens.

Centrifuge sample, transfer plasma to a separate plastic vial, and freeze citrate plasma at -20°C within four hours of collection.

Sendouts:

• Order Versiti Wisconsin Test: 1089
  • Test is listed under the "von Willebrand Disease" section on the Hemostasis Reference Lab requisition.
• Lab staff will complete the Versiti requisition if not completed by the provider.
  • If clinical information (anticoagulant use, relevant lab values, family history, etc.) is included in the LABUND order, print the Epic requisition and include it with the Versiti requisition.
  • Do not send samples with only the Epic requisition; a Versiti requisition is required for testing.
• Ship samples Monday through Thursday via FedEx Priority Overnight with sufficient dry ice to ensure that sample remains frozen throughout transport.

Stability: Frozen: Required; Ambient: 4 hours; Refrigerated: Unacceptable.

• Critical Frozen: Freeze plasma within 4 hours of collection. If multiple tests are requested, separate aliquots must be submitted. Do not thaw and refreeze.

Unacceptable: Thawed, hemolyzed, or clotted specimens.