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Von-Willebrand- und Upshaw-Schulman-Syndrom

Die zwei Seiten des Von-Willebrand-Faktors

Von Willebrand disease and Upshaw-Schulman syndrome

The two sides of von Willebrand factor

Zusammenfassung

Quantitative und qualitative Defekte des Von-Willebrand-Faktors (VWF) sind für die häufigste hereditäre Blutungsneigung, das Von-Willebrand-Syndrom (VWS), ursächlich, welches überwiegend autosomal-dominant, aber auch -rezessiv vererbt wird. Entsprechend der modularen Struktur des VWF, mit verschiedenen funktionell und strukturell wichtigen Domänen, besteht eine hochgradige Heterogenität sowohl der klinischen Symptomatik als auch der Pathomechanismen. Eine Überfunktion des VWF beruht auf der fehlenden Größenregulation durch seine spezifische Protease ADAMTS13, die mit dem lebensbedrohlichen Krankheitsbild der thrombotisch-thrombozytopenischen Purpura korreliert, einer Störung der Mikrozirkulation durch hyaline Thromben. Deren autosomal-rezessiv vererbte Form, das Upshaw-Schulman-Syndrom, steht auf der anderen Seite der vom VWF verursachten Störungen der Blutgerinnung. Das heutige Wissen um die Pathophysiologie des VWF und seiner Protease ADAMTS13 ermöglicht neben einer rationalen Therapie auch die Erfassung seiner Beteiligung an vaskulären Erkrankungen.

Abstract

Quantitative and qualitative defects of von Willebrand factor (VWF) cause von Willebrand disease (VWD), the most common inborn bleeding disorder inherited in a mainly autosomal-dominant but also recessive manner. According to its modular structure, which consists of distinct functional and structural domains, VWF defects correlate with considerable heterogeneity of clinical symptoms, biochemical parameters, and the underlying molecular mechanisms. Lack of functional regulation of VWF is observed in patients with life-threatening thrombotic thrombocytopenic purpura (TTP) due to hyaline thrombi in the microcirculation in the absence of the VWF-specific protease ADAMTS13. Upshaw-Schulman syndrome is the recessively inherited form of TTP caused by mutations in ADAMTS13 and is the other side of the coin representing VWF-related coagulation disorders. Current knowledge of the pathophysiology of VWF and its protease ADAMTS13 provides the basis for rational therapy and assessment of its contribution to vascular diseases.

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Correspondence to R. Schneppenheim.

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Schneppenheim, R., Budde, U. Von-Willebrand- und Upshaw-Schulman-Syndrom. medgen 20, 197–203 (2008). https://doi.org/10.1007/s11825-008-0106-y

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Schlüsselwörter

  • Von-Willebrand-Faktor
  • Von-Willebrand-Syndrom
  • ADAMTS13
  • Thrombotisch-thrombozytopenische Purpura
  • Upshaw-Schulman-Syndrom

Keywords

  • Von Willebrand factor
  • Von Willebrand disease
  • ADAMTS13
  • Thrombotic thrombocytopenic purpura
  • Upshaw-Schulman syndrome