What is the significance of the Factor VIII (FVIII) to von Willebrand factor antigen (VWF:Ag) ratio?

From the Guidelines

The FVIII to VWF:Ag ratio is a crucial diagnostic tool for differentiating between types of von Willebrand disease (VWD), with a normal ratio being approximately >0.5–0.7, as indicated in the 2008 NHLBI/NIH guidelines 1. The significance of this ratio lies in its ability to distinguish between various subtypes of VWD, including Type 1, Type 2A, Type 2B, Type 2M, and Type 2N, each with distinct laboratory characteristics and clinical implications.

• In Type 1 VWD, both FVIII and VWF:Ag are proportionally reduced, maintaining a normal ratio 1.
• In Type 2N VWD, the ratio is decreased (<0.5–0.7) due to impaired binding of FVIII to VWF, resulting in lower FVIII levels despite relatively normal VWF:Ag levels 1.
• Conversely, in Type 2B, 2A, and 2M VWD, the ratio is often decreased (<0.5–0.7) because functional VWF is reduced while FVIII remains relatively preserved 1. This ratio helps clinicians distinguish between hemophilia A (where only FVIII is low) and various VWD subtypes, guiding appropriate treatment strategies.
• The test should be interpreted alongside other laboratory findings, including VWF activity assays, ristocetin cofactor activity, and collagen binding assays for comprehensive diagnosis 1. It is essential to consider the FVIII to VWF:Ag ratio in the context of other clinical and laboratory findings to ensure accurate diagnosis and effective management of VWD.

From the Research

Significance of the Factor VIII (FVIII) to von Willebrand factor antigen (VWF:Ag) ratio

• The FVIII to VWF:Ag ratio is significant in the diagnosis and characterization of von Willebrand disease (VWD) subtypes 2, 3, 4, 5
• A high VWF:FVIII ratio can prevent FVIII accumulation, which is a clinical concern due to the potential risk of thromboembolism 6
• The VWF:FVIII binding (VWF:FVIIIB) assay and the VWF:FVIIIB/VWF:Ag ratio are used to identify type 2N VWD, which is characterized by an abnormal FVIII binding capacity of VWF 3
• The response of FVIII:C and VWF parameters to desmopressin (DDAVP) can help differentiate between VWD subtypes, with some subtypes showing a good response and others showing a poor or restricted response 2, 4, 5
• The FVIII to VWF:Ag ratio can also be used to monitor the efficacy of treatment with FVIII/VWF concentrates in patients with VWD 5

Diagnostic Utility

• The FVIII to VWF:Ag ratio can help diagnose VWD subtypes, including type 1, type 2A, type 2M, and type 2N 2, 3, 4
• The ratio can also help differentiate between VWD and other bleeding disorders, such as hemophilia 2
• The VWF:FVIIIB/VWF:Ag ratio is a specific diagnostic marker for type 2N VWD 3

Therapeutic Implications

• A high VWF:FVIII ratio can prevent FVIII accumulation and reduce the risk of thromboembolism in patients with VWD 6
• The FVIII to VWF:Ag ratio can be used to monitor the efficacy of treatment with FVIII/VWF concentrates and adjust the dose accordingly 5