Which tests may be ordered to characterize type 2 von Willebrand disease?

Which tests may be ordered to characterize type 2 von Willebrand disease?

• A. Platelet count and function tests
• B. PT and INR
• C. Multimer analysis by electrophoresis, ristocetin-induced platelet aggregation, vWF propeptide, vWF-collagen binding assay
• D. D-dimer and fibrinogen

Answer: (C)

The key concept is distinguishing qualitative defects of von Willebrand factor that define type 2 VWD from simple quantity loss. To characterize type 2, you need tests that assess the structure and function of vWF, not just how much is present. Multimer analysis by electrophoresis reveals the size distribution of vWF multimers. In many type 2 variants, there is loss or reduction of the high-molecular-weight multimers, which are most effective at supporting platelet adhesion. This pattern helps identify the specific subtype within type 2. Ristocetin-induced platelet aggregation measures how well vWF can bridge platelets via the GPIb receptor in the presence of ristocetin. Abnormal aggregation patterns indicate a functional defect in vWF, as seen in type 2 VWD, and can help differentiate some subtypes. The vWF propeptide level and the ratio of vWF propeptide to vWF antigen provide insight into whether the problem is decreased production/secretion or increased clearance of vWF, which has implications for distinguishing subtype mechanisms within type 2. The vWF–collagen binding assay assesses how well vWF binds to collagen, a function impaired in several type 2 variants. Together, these tests give a comprehensive picture of both the structural and functional abnormalities characteristic of type 2 VWD. Tests like platelet count and function tests, PT/INR, and D-dimer/fibrinogen assess general hemostasis or other pathways and do not characterize the qualitative defects of vWF that define type 2 VWD.

The key concept is distinguishing qualitative defects of von Willebrand factor that define type 2 VWD from simple quantity loss. To characterize type 2, you need tests that assess the structure and function of vWF, not just how much is present.

Multimer analysis by electrophoresis reveals the size distribution of vWF multimers. In many type 2 variants, there is loss or reduction of the high-molecular-weight multimers, which are most effective at supporting platelet adhesion. This pattern helps identify the specific subtype within type 2.

Ristocetin-induced platelet aggregation measures how well vWF can bridge platelets via the GPIb receptor in the presence of ristocetin. Abnormal aggregation patterns indicate a functional defect in vWF, as seen in type 2 VWD, and can help differentiate some subtypes.

The vWF propeptide level and the ratio of vWF propeptide to vWF antigen provide insight into whether the problem is decreased production/secretion or increased clearance of vWF, which has implications for distinguishing subtype mechanisms within type 2.

The vWF–collagen binding assay assesses how well vWF binds to collagen, a function impaired in several type 2 variants. Together, these tests give a comprehensive picture of both the structural and functional abnormalities characteristic of type 2 VWD.

Tests like platelet count and function tests, PT/INR, and D-dimer/fibrinogen assess general hemostasis or other pathways and do not characterize the qualitative defects of vWF that define type 2 VWD.