Von Willebrand Disease (VWD)
Part 2: NHLBI Diagnosis Guidelines

VWD — Initial Laboratory Evaluation

May 2011

How well do the initial 3 VWD tests perform? The short answer is: fair to poor performance overall, with the ristocetin cofactor assay being especially problematic.

The VWF ristocetin cofactor activity functional assay has poor performance characteristics, reflecting limited sensitivity for detecting very low activity (below 6 to12 % or IU/dL), and a high coefficient of variation (CV) of up to 30%, indicating poor precision. Multiple different methods have been described, based on using washed and/or fixed normal platelets, patient test plasma, and ristocetin (which “activates” VWF, exposing its platelet GPIb binding domain), with measurement of platelet agglutination response by aggregometry or other detection methods. The VWF antigen assay, based on immunoassay procedures such as ELISA (enzyme-linked immunosorbant) or automated LIA (latex immunoassay) methods, generally has fairly good performance (CV ~10-20%) and sensitivity for detection down to approximately 1 to 3 IU/dL (%). The ratio of VWF ristocetin cofactor activity to VWF antigen is used to screen for or help exclude Types 2A, 2B or 2M VWF – but especially the poor performance characteristics of the VWF ristocetin cofactor assay limit the utility of the VWF ristocetin cofactor VWF antigen ratio for this purpose, and for detecting the loss of VWF high molecular weight multimers that can occur in some cases of acquired von Willebrand syndrome (AVWS). Factor VIII coagulant activity assays are mainly based on modifications of the PTT (aPTT) test, and have fairly good performance (CV ~10 to 20%) with good sensitivity (detection limit as low as 1 IU/dL (%) factor VIII. But, factor VIII activity is labile, with the potential for false low results, especially if frozen-thawed plasma is tested and/or sample processing, storage or transportation conditions are suboptimal.

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Jump to section:

• Introduction
• Objectives—Part 2
• VWD NHLBI Guidelines (2008)¹
• VWD Classification — ISTH^1,2
• VWD NHLBI Guidelines (2008) Initial Patient Evaluation — Laboratory¹
• VWD NHLBI Guidelines 2008 Initial Patient Evaluation — Laboratory¹
• VWD — Initial Laboratory Evaluation
• VWD NHLBI Guidelines (2008) Subsequent Patient Evaluation—Laboratory¹
• Additional VWD Testing — Laboratory¹
• VWF Multimer Analysis: Intermediate Resolution³
• VWF Multimer Analysis: Recommendations⁴
• VWF Multimer Analysis: Recommendations⁴
• Expected Laboratory Values in VWD¹
• Typical Patterns of Laboratory Test Results for VWD Diagnosis and Classification¹
• VWD NHLBI Guidelines (2008) "Low VWF" versus "VWD Type 1"
• VWD Diagnosis (Especially Type 1)
• VWD NHLBI Guidelines ABO Blood Group & VWF/VWD^1,5
• VWD NHLBI Guidelines ABO Blood Group and VWF/VWD: Soft Recommendations
• VWD NHLBI Guidelines (2008): Collection and Handling of Samples for Laboratory Testing¹
• VWD NHLBI Guidelines (2008): Collection and Handling of Samples for Laboratory Testing¹
• VWD NHLBI Guidelines (2008): Collection and Handling of Samples for Laboratory Testing¹
• VWD NHLBI Guidelines: Collection and Handling of Samples for Laboratory Testing^1,4
• VWD NHLBI Guidelines (2008) Summary of Laboratory Recommendations
• VWD NHLBI Guidelines (2008) Summary of Laboratory Recommendations
• References
• VWD Profile
• Questions?