Die thrombotisch-thrombozytopenische Purpura (TTP) und das hämolytisch-urämische Syndrom (HUS) sind durch eine Thrombozytopenie, hämolytische Anämie und durch Organdysfunktionen, wovon vor allem das zentrale Nervensystem (ZNS) und die Niere betroffen sind, gekennzeichnet. Bis vor 25 Jahren gingen diese Erkrankungen mit einer Mortalität von bis zu 90 % einher, die jedoch mit der Einführung der Plasmaseparationstherapie drastisch gesenkt werden konnte. Eine Vielzahl auslösender Faktoren ist bislang bekannt, allerdings lässt sich nicht bei allen Patienten eine Ursache finden. Neue Untersuchungen konnten bei Patienten mit thrombotisch-thrombozytopenischer Purpura eine verminderte Aktivität der von-Willebrand-Faktor-cleaving-Protease ADAMTS13 nachweisen, die normalerweise ungewöhnlich große von-Willebrand-Faktor-(ULvWF)-Multimere spaltet und dadurch die Adhäsion und Aggregation von Thrombozyten in der Mikrostrombahn verhindert. Bei Patienten mit hämolytisch-urämischem Syndrom bestehen Mutationen in Genen einiger Proteine des Komplementsystems. Betroffen sind hier vor allem der Faktor H, das „membrane cofactor protein” (MCP/CD46) oder der „serine protease factor I”. Dieses Wissen macht es heute möglich, Patienten mit thrombotisch-thrombozytopenischer Pupura und hämolytisch-urämischen Syndrom auf molekularbiologischer Basis voneinander zu unterscheiden.
Thrombotic-thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are characterized by thrombocytopenia, hemolytic anemia, and organ dysfunction, especially of the central nervous system and the kidney. 25 years ago the mortality of these disorders was as high as 90% until it was drastically decreased by the use of plasma exchange therapy. Various agents have been identified to cause thrombotic-thrombocytopenic purpura and hemolytic-uremic syndrome but the underlying cause is not obvious in many patients. Recent studies demonstrated a decrease in von Willebrand factor cleaving protease ADAMTS13 activity in patients with TTP. ADAMTS13 breaks up unusually large von Willebrand factor (ULvWF) multimers and inhibits adhesion and aggregation of thrombocytes in the microvasculature. Patients with hemolytic-uremic syndrome were found to be carriers of mutations in genes encoding proteins of the complement system, particularly factor H, membrane cofactor protein (MCP/CD46) or serine protease factor I. These findings help to differentiate patients with thrombotic-thrombocytopenic purpura or hemolytic-uremic syndrome on the molecular level.
Key Words
thrombotic microangiopathy - hemolytic uremic syndrome - thrombotic thrombocytopenic purpura - plasma therapy
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Anschrift für die Verfasser
PD Dr. Christine E. Kurschat
Klinik für Nephrologie, Heinrich-Heine-Universität Düsseldorf
Moorenstr. 5
40225 Düsseldorf
