Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura

U. Budde; R. Schneppenheim

doi:10.5482/HAMO-13-08-0045

Hämostaseologie, Table of Contents

Hamostaseologie 2014; 34(03): 215-225
DOI: 10.5482/HAMO-13-08-0045

Review

Schattauer GmbH

Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura

Interaktionen zwischen dem von-Willebrand- Faktor und ADAMTS13 am Beispiel des von- Willebrand-Syndroms und der thrombotischthrombozytopenischen Purpura

U. Budde

¹Medilys Laborgesellschaft Hamburg, Germany

,

R. Schneppenheim

²Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany

› Author Affiliations

Abstract

Summary

The function of von Willebrand factor (VWF), a huge multimeric protein and a key factor in platelet dependent primary haemostasis, is regulated by its specific protease ADAMTS13. The ADAMTS13 dependent degradation of VWF to its proteolytic fragments can be visualized as a characteristic so-called triplet structure of individual VWF oligomers by multimer analysis. Lack of VWF high molecular weight multimers (VWF-HMWM) or their pathologically enhanced degradation under - lies a particular type of von Willebrand disease, VWD type 2A with a significant bleeding tendency, and may also be observed in acquired von Willebrand syndrome due to cardiovascular disease. In these conditions multimer analysis is an obligatory and powerful tool for diagnosis of VWD. The opposite condition, the persistence of ultralarge VWF (UL-VWF) multimers may cause the microangiopathic life-threatening disorder thrombotic thrombocytopenic purpura (TTP). During the course of active TTP, UL-VWF is consumed in the hyaline thrombi formed in the microvasculature which will ultimately result in the loss of UL-VWF and VWF-HMWM. Therefore, VWF multimer analysis is not a valid tool to diagnose TTP in the active phase of disease but may be helpful for the diagnosis of TTP patients in remission.

Zusammenfassung

Der von-Willebrand-Faktors (VWF), ein riesiges multimeres Protein ist ein Schlüsselfaktor für die Thrombozyten-abhängige primäre Hämostase und wird über seine spezifische Protease ADAMTS13 reguliert. Die ADAMTS13-abhängige Degradierung des VWF in seine proteolytischen Fragmente zeigt sich als charakteristische so genannte Triplet-Struktur der einzelnen VWF-Oligomere in der Multimer-Analyse. Das Fehlen hochmolekularer VWF-Multimere oder deren pathologisch verstärkte Degradierung charakterisiert einen besonderen Typ des VWS, den Typ 2A mit einer signifikanten Blutungsneigung, die auch bei einer erworbenen Form im Rahmen kardiovaskulärer Erkrankungen beobachtet wird. In diesen Fällen ist die VWFMultimeranalyse ein notwendiges und diagnostisch hilfreiches Mittel. Die gegensätz - liche Situation, die Persistenz von „ultragroßen” VWF-(UL-VWF-)Multimeren kann zu der mikroangiopathischen und lebensbedrohenden thrombotisch-thrombozytopenischen Purpura (TTP) führen. Während einer aktiven TTP wird jedoch der besonders aktive hochmolekulare VWF in den entstehenden hyalinen Mikrothromben verbraucht. Dies führt schließlich zum Verlust der UL- und der hochmolekularen VWF-Multimere. Daher ist in der aktiven Phase einer TTP die VWF-Multimeranalyse in der Regel nicht weiterführend, kann aber hilfreich sein bei TTP-Patienten in Remission.

Keywords

Triplet pattern - phenotype-genotype relation - animal models

Schlüsselwörter

Triplet-Struktur - Phänotyp-Genotyp- Beziehung - Tiermodelle

Full Text

References

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