Das erworbene von-Willebrand-Syndrom

Zusammenfassung

Das von-Willebrand-Syndrom ist durch quantitative, qualitative oder kombinierte Defekte des von-Willebrand-Faktors charakterisiert und äußert sich klinisch als hämorrhagische Diathese. Neben dem angeborenen von-Willebrand-Syndrom kommt in seltenen Fällen bei hämatologischen Systemerkrankungen, Tumorerkrankungen, endokrinen Störungen, kardialen Vitien oder unter medikamentöser Therapie auch eine erworbene Form dieser Hämostasestörung vor. Pathogenetisch sind insbesondere Inhibitoren gegen den von-Willebrand-Faktor, Adsorption an maligne Zellen, gesteigerter proteolytischer Abbau und verminderte Synthese von Bedeutung. Die Diagnose dieses erworbenen von-Willebrand-Syndroms wird in Zusammenschau von Anamnese, klinischer Symptomatik und Laborbefunden gestellt. Charakteristisch ist eine erworbene hämorrhagische Diathese mit bevorzugtem Auftreten von Schleimhautblutungen in Kombination mit verlängerter Blutungszeit und verminderter Aktivität des von-Willebrand-Faktors. Häufig kann eine Reduktion der hochmolekularen Multimere des von-Willebrand-Faktors nachgewiesen werden. Grundsätzlich steht die Behandlung der Grunderkrankung im Vordergrund. Weitere Therapieoptionen beim erworbenen von-Willebrand-Syndrom beinhalten die Applikation des Vasopressin-Analogons Desmopressin, die Hämotherapie mit von-Willebrand-Faktor-haltigen Faktorenkonzentraten, die intravenöse Gabe von Immunglobulinen, immunsuppressive Maßnahmen und im Einzelfall die Immunadsorption. Die vorliegende Arbeit stellt den aktuellen Kenntnisstand über diese seltene erworbene Hämostasestörung dar. Insbesondere wird eine rationale Differenzialtherapie der Erkrankung diskutiert und anhand der Grunderkrankung und assoziierten Pathomechanismen begründet.

Summary

Von Willebrand disease is characterized by an increased risk of bleeding caused by quantitative, qualitative, or combined defects of von Willebrand factor. While hereditary von Willebrand disease is a frequent disorder of the hemostatic system, acquired von Willebrand syndrome is rare. This hemostatic defect is preferentially found in patients suffering from hematological malignancies, cancer, endocrine disorders, congenital or acquired heart valve defects, or in patients receiving drug therapy. The pathogenesis is heterogeneous, including inhibitors against von Willebrand factor, adsorption of von Willebrand factor onto malignant cells, increased proteolysis, and diminished synthesis of von Willebrand factor. The diagnostic work-up comprises the patient’s history, clinical symptoms, and laboratory findings. An acquired bleeding tendency with preferential mucocutaneous bleeding in combination with a prolonged bleeding time and decreased activity of von Willebrand factor are characteristic. Further analysis often reveals a reduction or loss of the high-molecular weight von Willebrand factor multimers. With regard to acquired von Willebrand syndrome, therapy of the underlying disease is mandatory. Further treatment options include application of desmopressin, hemotherapy with von Willebrand factor containing factor concentrates, intravenous application of immunoglobulins, immunosuppression, or immunoadsorption. This review summarizes the current knowledge of acquired von Willebrand syndrome. In particular, we discuss the differential therapy of this rare acquired hemostatic disorder based on the underlying disease and associated pathomechanisms.

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