What are the laboratory tests for von Willebrand (vWD) disease?

From the Guidelines

Von Willebrand disease diagnosis should include initial laboratory evaluation with a complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (PTT), followed by von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII) as the most important diagnostic tests, as recommended by the 2008 NHLBI/NIH guidelines 1. The initial evaluation aims to identify potential bleeding disorders, and if a mucocutaneous bleeding history is strong, VWD assays should be considered at the initial visit.

• Key laboratory tests for VWD diagnosis include:
  • VWF:Ag to measure the quantity of VWF protein
  • VWF:RCo to assess VWF function
  • FVIII activity, which is often reduced in VWD since VWF serves as its carrier protein
  • The ratio of VWF activity to VWF antigen, which helps determine the VWD type, with ratios below 0.7 suggesting type 2 VWD 1
• Multimer analysis is not recommended for initial VWD screening but can be used to further characterize the disease by examining the size distribution of VWF molecules if initial VWD testing identifies an abnormal result or clinical information suggests a high likelihood of abnormal VWF multimer analysis.
• It is essential to note that blood type O individuals typically have 25-35% lower VWF levels, and testing should be repeated at least once for confirmation, ideally when the patient is not under stress, pregnant, or taking estrogen-containing medications, as these conditions can temporarily increase VWF levels and mask the diagnosis 1.
• The VWF:RCo/VWF:Ag ratio of <0.5–0.7 is recommended to distinguish Type 1 vs. Type 2 VWD variants, and a cut-off of 30 IU/dL is suggested for the definite diagnosis of VWD, considering the high frequency of blood type O and the presence of bleeding symptoms in normal individuals 1.

From the FDA Drug Label

Laboratory tests for assessing patient status include levels of factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII von Willebrand factor antigen. The skin bleeding time may be helpful in following these patients.

The labs for Von Willebrand deficiency include:

• Factor VIII coagulant activity
• Factor VIII ristocetin cofactor activity
• Factor VIII von Willebrand factor antigen
• Skin bleeding time may also be helpful in following these patients 2

From the Research

Laboratory Tests for Von Willebrand Deficiency

• Von Willebrand disease (VWD) is a common bleeding disorder that requires laboratory diagnosis, which typically involves an initial test panel including antigen, activity, and factor VIII measurements 3.
• The diagnosis of VWD is made by laboratory investigation, which includes multiple assays to assess VWF levels and functions, such as VWF antigen (VWF:Ag) and VWF activity assays 4.
• VWF activity/antigen testing ratios are used to differentiate type 1 and type 2 disease, with recommended ratio cutoffs ranging from 0.5 to 0.7 3.
• VWF multimer analysis is a critical part of the laboratory testing to differentiate type 1, type 2 VWD, and subtypes of type 1 or 2 VWD, and can help to understand the underlying molecular mechanism of VWF synthesis, multimerization, and clearance defects in VWD 5, 6.

Types of Laboratory Tests

• Enzyme-linked immunosorbent assays (ELISA) and latex-enhanced immunoassays (LIA) are commonly used to assess VWF:Ag levels 7.
• VWF activity assays, such as ristocetin cofactor using platelets (VWF:RCo) or other particles incorporating recombinant glycoprotein I ('VWF:GPIbR'), or other GPI binding assays using gain-of-function mutations ('VWF:GPIbM'), or collagen binding (VWF:CB), are used to assess VWF function 5.
• VWF multimer analysis can be performed using manual or semi-automated electrophoresis and immunoblotting 6.

Interpretation of Laboratory Results

• The interpretation of laboratory results, including VWF antigen, VWF activity, and VWF multimer patterns, is critical for the diagnosis and subtyping of VWD 3, 6.
• The use of VWF activity/antigen ratios and VWF multimer analysis can help to identify the underlying molecular mechanism of VWF defects in VWD 5, 6.