What is the least useful laboratory test in the diagnosis of von Willebrand disease (vWD)?

The Prothrombin Time (PT) is the Least Useful Laboratory Test in Diagnosing von Willebrand Disease

The Prothrombin Time (PT) is the least useful laboratory test in the diagnosis of von Willebrand Disease (vWD) among the options listed. 1

Diagnostic Value of Each Test Option

Prothrombin Time (PT)

• PT is considered part of the "initial hemostasis tests" but does not evaluate for vWD specifically
• It is only used to suggest whether other coagulation factor deficiencies might be the potential cause of clinical bleeding
• The 2008 NHLBI/NIH guidelines classify PT as a grade C recommendation, indicating its limited utility in vWD diagnosis 1

Activated Partial Thromboplastin Time (APTT)

• While also classified as a grade C recommendation along with PT, APTT can be abnormal in approximately 25% of vWD patients 2
• APTT has demonstrated a significant correlation with von Willebrand factor antigen levels 3
• In one study, APTT showed excellent diagnostic sensitivity (100%) and satisfactory specificity (85%) for identifying isolated vWD deficiencies 3

Factor VIII Activity

• Factor VIII coagulant activity (FVIII) is one of the three recommended initial tests for vWD diagnosis (grade B recommendation) 1
• FVIII levels are typically decreased in Type 3 vWD and Type 2N vWD 4
• Abnormal in approximately 33% of vWD patients 2

Platelet Aggregation in Response to Ristocetin

• This test measures VWF ristocetin cofactor activity (VWF:RCo), which is one of the three essential initial tests for vWD diagnosis (grade B recommendation) 1
• Receiver-operating-characteristic analysis has shown VWF activity (ristocetin cofactor activity) to be superior to either VWF antigen or factor VIII:c in establishing the diagnosis of vWD 2
• Abnormal in approximately 79% of vWD patients, making it the most sensitive individual test 2

Bleeding Time

• While not one of the three recommended initial tests, bleeding time can be abnormal in approximately 43% of vWD patients 2
• The NHLBI/NIH guidelines note that "there are conflicting data with regard to sensitivity and specificity for VWD, and current evidence does not support their routine use as screening tests for VWD" 1
• However, when combined with VWF activity and APTT, bleeding time contributes to identifying 92% of vWD patients 2

Recommended Diagnostic Approach for vWD

The optimal laboratory approach for diagnosing vWD includes:

1. Initial three VWD tests (grade B recommendations) 1:

   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII)

2. Additional testing if initial results are abnormal:

   • VWF multimer analysis to determine VWD subtype
   • Specialized VWD assays if VWF:RCo to VWF:Ag ratio is abnormally low (below 0.5–0.7)

Common Pitfalls in vWD Diagnosis

• Relying solely on PT or APTT for diagnosis or exclusion of vWD
• Failing to order the three essential tests (VWF:Ag, VWF:RCo, and FVIII)
• Not considering that VWF levels can be affected by various conditions (pregnancy, stress, inflammation)
• Overlooking the need for correlation between laboratory findings and clinical bleeding history
• Using bleeding time or platelet function analyzer (PFA-100) as the sole screening test for vWD

In conclusion, while all the tests mentioned have some utility in the broader evaluation of bleeding disorders, the PT is the least useful specifically for diagnosing vWD, as it primarily evaluates the extrinsic coagulation pathway which is not directly affected by VWF deficiencies or abnormalities.