Expected Drop in von Willebrand Factor Levels in Type 2 von Willebrand Disease with Hemorrhage
In patients with type 2 von Willebrand disease experiencing significant hemorrhage, you should expect a VWF:RCo/VWF:Ag ratio to drop below 0.5-0.7 with loss of high molecular weight multimers, while platelet counts may decrease significantly, particularly in type 2B VWD. 1
Laboratory Parameters in Type 2 von Willebrand Disease
Type 2 von Willebrand disease is characterized by qualitative defects in von Willebrand factor (VWF) that affect its function. During significant hemorrhage, the following changes can be expected:
VWF Activity and Antigen Levels
- VWF:RCo (ristocetin cofactor activity) typically falls below 30 IU/dL
- VWF:Ag (antigen) levels may remain between 30-200 IU/dL
- VWF:RCo/VWF:Ag ratio drops below 0.5-0.7 1
Multimer Analysis
- Loss of high molecular weight (HMW) multimers is characteristic, particularly in:
- Type 2A: Loss of both high and intermediate molecular weight multimers
- Type 2B: Loss of high molecular weight multimers only 1
Platelet Count Changes
- Type 2B specifically may show thrombocytopenia that worsens during hemorrhage
- Platelet counts can drop significantly during bleeding episodes or physiologic stress 2
- This thrombocytopenia is not typically associated with increased platelet consumption or activation 3
Subtype-Specific Considerations
Different subtypes of type 2 VWD show distinct laboratory patterns during hemorrhage:
Type 2A VWD
- Decreased VWF activity (<30 IU/dL)
- Normal or slightly decreased VWF antigen levels
- Loss of both high and intermediate molecular weight multimers
- RIPA (ristocetin-induced platelet aggregation) may be normal at low doses 1
Type 2B VWD
- Enhanced binding of VWF to platelets
- Thrombocytopenia that can worsen during hemorrhage
- Loss of high molecular weight multimers
- Enhanced RIPA at low doses (characteristic finding) 1, 2
Type 2M VWD
- Decreased VWF activity (<30 IU/dL)
- Normal VWF antigen levels
- Normal multimer pattern despite decreased function
- Normal RIPA at low doses 1
Type 2N VWD
- Normal VWF:RCo and VWF:Ag
- Low FVIII:C (resembles mild hemophilia A)
- Normal VWF:RCo/VWF:Ag ratio
- Reduced VWF:FVIII binding 1
Clinical Implications
During significant hemorrhage in type 2 VWD patients:
- A minimum VWF activity level of 50 IU/dL is required for adequate hemostasis
- For severe bleeding, target VWF activity levels should be ≥80 IU/dL 1
- In type 2B VWD, VWF-containing factor concentrates are the treatment of choice 1
- Platelet transfusions may be necessary in addition to VWF concentrates in severe cases 4
Important Caveats
- Standard PT/aPTT screening may not reliably detect VWD, even during active bleeding 1
- Complete diagnostic workup should include VWF antigen, VWF ristocetin cofactor activity, and factor VIII coagulant activity 1
- Repeated testing may be necessary as values can fluctuate during the course of hemorrhage 5
- The platelet-plasma discrepancy in multimer patterns may be observed in some subtypes 6
In summary, monitoring both VWF functional parameters and platelet counts is essential in managing patients with type 2 VWD experiencing significant hemorrhage, with particular attention to the specific subtype and its characteristic laboratory findings.