Initial Testing for von Willebrand Disease

Primary Testing Panel

The initial laboratory evaluation for von Willebrand disease should include three specific tests: VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII), as recommended by the National Heart, Lung, and Blood Institute (NHLBI) 1, 2, 3
VWF antigen (VWF:Ag) measures the quantity of von Willebrand factor protein in plasma, which is an important aspect of diagnosing von Willebrand disease in patients with bleeding symptoms 1
VWF ristocetin cofactor activity (VWF:RCo) assesses the functional ability of VWF to bind to platelets, a critical step in the diagnosis of von Willebrand disease in individuals with a history of mucocutaneous bleeding 1, 3
Factor VIII coagulant activity (FVIII) evaluates the level of factor VIII, which is carried and protected by VWF, and is essential for diagnosing von Willebrand disease in patients with suspected coagulopathy 1, 4

The 2008 NHLBI/NIH guidelines recommend that these three tests be ordered together as the initial evaluation panel when von Willebrand disease is suspected, with a grade B recommendation for their use in patients with bleeding symptoms 2, 3
If mucocutaneous bleeding history is strong, proceed directly to VWD-specific testing, as recommended by the American College of Medical Genetics 2, 5
For patients with less clear presentation, initial hemostasis tests (e.g., complete blood count, prothrombin time, partial thromboplastin time) may be ordered first to rule out other causes of bleeding 3

VWF multimer analysis is not recommended for initial screening but should be reserved for cases where initial testing shows abnormalities, as stated by the International Society on Thrombosis and Haemostasis 1, 4
Bleeding time and platelet function analyzer (PFA-100) tests are sometimes used but have conflicting data regarding sensitivity and specificity, and current evidence does not support their routine use as screening tests, according to the American Society of Hematology 2, 3
Testing should ideally be performed in the absence of conditions that elevate baseline VWF (such as pregnancy, inflammation, or stress), as recommended by the National Institute of Health 3, 5
Laboratory variability can affect results, so careful attention to blood specimen collection, processing, transportation, and storage is essential, as emphasized by the College of American Pathologists 3, 6

Relying on a single test for von Willebrand disease diagnosis - no single laboratory test can screen for all forms of von Willebrand disease, as stated by the World Federation of Hemophilia 3
Ordering VWF multimer analysis as part of initial screening - this complex test should be reserved for reflex testing when initial results are abnormal, as recommended by the European Association for Haemophilia and Allied Disorders 1, 4
Failing to consider timing of testing - VWF levels can be affected by various physiological and pathological conditions, such as inflammation or stress, as noted by the American College of Medical Genetics 3, 5
For patients with abnormal initial test results, consultation with a hemostasis specialist is recommended for further evaluation and management, as advised by the International Society on Thrombosis and Haemostasis 3, 6

A structured bleeding history assessment using specific screening questions is recommended to identify patients who would benefit from laboratory testing, with initial three screening questions to identify potential bleeding disorders, and if positive, proceeding to nine additional questions focused on VWD symptoms, as suggested by the American Journal of Hematology 7, 8
The likelihood of VWD increases with the number of positive responses to the screening questions 9
Physical examination should focus on evidence of bleeding, such as ecchymoses, hematomas, and petechiae, as well as signs suggesting other causes, like liver disease, splenomegaly, joint/skin laxity, and telangiectasia, with a gynecologic examination in females to identify anatomic lesions 9

Initial hemostasis tests, including complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (PTT), can suggest other coagulation disorders, but do not evaluate for VWD 9
If mucocutaneous bleeding history is strong, proceeding directly to the three core VWD assays, including VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII), is recommended 9
All three tests are necessary to establish diagnosis and suggest VWD type and severity, with abnormal results including low VWF:Ag, VWF:RCo, and FVIII, or a discrepant VWF:RCo to VWF:Ag ratio below 0.5-0.7 9

Reflexive testing, including VWF multimer analysis, collagen binding assay (VWF:CB), and ristocetin-induced platelet aggregation (RIPA), may be considered if initial VWD testing identifies abnormalities 9

Patient conditions, such as stress, exercise, inflammation, ABO blood group, pregnancy, or estrogen therapy, can affect test results, with stress, exercise, and inflammation falsely elevating VWF levels, and ABO blood group O having 25% lower VWF levels 8
Sample handling considerations, including transport at room temperature, prompt separation of plasma, and freezing at or below -40°C if not tested within 2 hours, are crucial to avoid false results 8
Bleeding time and platelet function analyzer (PFA-100) tests have conflicting data regarding sensitivity and specificity and are not recommended for routine screening, as stated by the American Journal of Hematology 10