Laboratory diagnosis of von Willebrand disease

Summary

Over the last decade, considerable progress has been made in the laboratory diagnosis of VWD. Precise, sensitive and automated VWF : Ag assays became widely available. The VWF : RCo performance was improved to a certain degree. However, the sensitivity, precision and general availability of automated applications is not yet optimal. Nevertheless, this type of assay is still recognized as superior to other activity assays, e. g. VWF : CBA assays and antibody-binding “activity” assays, for the detection of defects in VWF function.

A decision limit of either 30 or 40 IU dl-1 VWF (VWF:RCo or VWF:Ag) is recommended for a diagnosis of type 1 VWD. Type 2 VWD can be differentiated from type 1 by calculating the VWF:RCo/VWF:Ag ratio.

Improved and easier to perform multimer analysis and genetic testing are beginning to facilitate the diagnosis of the VWD type 1, 2A, 2B, 2N, 2M or 3. Within type 1 or 2, a decreased VWF survival can be detected by the VWFpp assay and its ratio to VWF : Ag.

A new type of VWF activity assay, based on the binding of VWF to a GPIb⟨-fragment, has been developed. One assay variant does not need ristocetin as a cofactor anymore. The performance investigations presented so far are very promising. It is probable that these GPIb⟨-binding assays will detect functional VWF defects as the VWF : RCo assay, but are much more sensitive and precise. Fully automated applications on routine analyzers are expected to be commercialized soon.

Zusammenfassung

In den vergangenen 10 Jahren sind erhebliche Fortschritte in der Labordiagnostik des von-Willebrand-Syndroms (VWS) zu verzeichnen. Präzise, sensitive und automatisierte VWF : Ag-Teste sind verfügbar. Die Leistungsfähigkeit des VWF : RCo-Tests ist zu einem gewissen Maß verbessert worden, aber die Sensitivität, Präzision und die allgemeine Verfügbarkeit von automatisierten Testapplikationen sind noch suboptimal. Nach wie vor ist der VWF : RCo-Test anerkanntermaßen besser zur Erkennung funktionaler Defekte als andere Aktivitäts -teste, z. B. VWF : CBA-Test oder Antikörper-benutzende “Aktivitäts”-Teste.

Zur Diagnose des VWS vom Typ 1 wird jetzt eine Entscheidungsgrenze von 30 oder 40 IU dl-1 empfohlen (VWF : RCo oder VWF : Ag). Eine Differenzierung von Typ 1 und 2 erlaubt die der Ratio-Bildung VWF : RCo/VWF : Ag.

Eine verbesserte und vereinfachte Multimerenanalyse sowie die Gendiagnostik beginnen gerade, die Diagnose der VWS-Typen 1, 2A, 2B, 2M, 2N und 3 zu erleichtern. Innerhalb der Typen 1 oder 2 kann der VWFpp-Test mittels der Ratio-Bildung zu VWF : Ag eine verringerte Überlebenszeit von VWF detektieren. Ein neuer Typ eines VWF-Aktivitätstests wurde entwickelt. Er basiert auf der Bindung von VWF an ein GPIb⟨-Fragment. Eine Variante dieses Tests kann auf Ristocetin als Kofaktor verzichten. Die Testeigenschaften, die vorgestellt wurden, sind vielversprechend. Mit hoher Wahrscheinlichkeit wird dieser neue Test funktionelle VWF-Defekte ähnlich gut wie der VWF : RCo-Test erkennen, doch wesentlich präziser und sensitiver sein. Voraussichtlich sind bald vollautomatisierte Applikationen auf Routinegeräten verfügbar.

Keywords

Von Willebrand disease - von Willebrand factor

Schlüsselwörter

Von-Willebrand-Syndrom - von-Willebrand-Faktor

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