Platelet-dependent von Willebrand factor activity - an important constituent of the diagnostic repository to classify von Willebrand syndrome.

O. Tiebel, K. Trautmann, U. Platzbecker, R. Knöfler, G. Siegert (Dresden, Germany)

Laboratory tests
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: von Willebrand syndrome (vWS) is the most common inherited bleeding disorder. Acquired von Willebrand syndrome (avWS) comprises a deficiency or defect in von Willebrand factor (vWF). Diagnosis of vWS as well as avWS is difficult last but not lost due to limitations in test procedures and suffers from over- as well as under-diagnosis. The historical assay for evaluating the platelet dependent VWF function (vWF:RCo) is known for a high imprecision and low sensitivity. The new generation assays offer more reliable results. According to the new nomenclature they differentiate between vWF:GPIbR (ristocetin-induced binding of vWF to a recombinant wildtype GPIb fragment) and vWF:GPIbM (spontaneous binding of vWF to a gain-of-function mutant GPIb fragment).

Methods: 45 routine samples vWF-Antigen (vWF:Ag), vWF-Collagen-binding-activity (vWF:CB) and vWF-Ristocetin-induced-binding (vWF:GP1bR) were determined applying HemosIL AcuStar-Assays (Instrumentation Laboratory, Werfen Group, Kirchheim) including the calculation of vWF:GP1bR /Ag- and vWF:CB/Ag-ratio. The vWF-binding in the vWF: GP1bR-Assay is proportionally compared to the former ristocetin cofactor activity. The assay overcomes the limitations of the vWF:RCo-Assay, based on the agglutination of formalin-fixed normal platelets in presence of Ristocetin.

Results: The samples contained 35 normal, 7 Type I, 1 Type IIa, 1 Type IIb and 1 avWS. In all normal and Type I cases vWF:GPIbR /Ag- as well as vWF:CB/Ag-ratio was 0,7. In the Type IIa and Type IIb case both ratios were <0,7. In the avWS case vWF:CB/Ag-ratio was >0,7 whereas vWF:GPIbR /Ag-ratio <0,7.

Conclusion: The results are in concordance with the algorithmic approach published by Favaloro in 2015. They underline the importance to include a test covering the glycoprotein GP1b-activity within the primary test-panel. The secondary differentiation of Type IIa and IIb cases with an identical pattern of vWF:CB/Ag- and vWF:Ac/Ag-ratio could be achieved by Light Transmission Aggregometry applying low- and high-dose Ristocetin. Analysis of vWF-multimers than belongs rather on the end of diagnostic strategy. Reference: Favaloro, E. J. Recent advances in laboratory-aided diagnosis of von Willebrand disease. Expert Opinion on Orphan Drugs, 2015, 3, 975-995