Pathophysiology of Trousseau’s syndrome

Summary

Clinically relevant clotting abnormalities in cancer patients are referred to as Trousseau’s syndrome. While thrombotic complications such as venous thromboembolism are most frequent in every day’s practice, cancer patients may also experience severe bleeding symptoms due to complex systemic coagulopathies, including disseminated intravascular coagulation, haemolytic thrombotic microangiopathy, and hyperfibrinolysis. The pathophysiology of Trousseau’s syndrome involves all aspects of Virchow’s triad, but previous basic research has mainly focused on the cellular and molecular mechanisms underlying blood hypercoagulability in solid cancers and haematological malignancies. In this regard, over-expression of tissue factor (TF), the principal initiator of the extrinsic coagulation pathway, by primary tumour cells and increased shedding of TF-bearing plasma microparticles are critical to both thrombus formation and cancer progression. However, novel findings on intrinsic contact activation in vivo, such as the release of polyphosphates or DNA by activated platelets and neutrophils, respectively, have pointed to additional pathways in the complex pathophysiology of Trousseau’s syndrome.

Zusammenfassung

Klinisch relevante Gerinnungsstörungen bei Tumorpatienten werden unter dem Begriff Trousseau-Syndrom zusammengefasst. Während im Alltag thrombotische Komplikationen wie die venöse Thromboembolie im Vordergrund stehen, können als Folge komplexer Koagulopathien (z. B. DIC, hämolytische thrombotische Mikroangiopathie oder Hyperfibrinolyse) auch schwerste Blutungen auftreten. Die Pathophysiologie des Trousseau-Syndroms betrifft zwar sämtliche Aspekte der Virchow-Trias; die Grundlagenforschung hat sich aber vor allem mit der Hyperkoagulabilität des Blutes bei soliden und hämatologischen Malignomen beschäftigt. Diesbezüglich sind die Expression von Tissue-Faktor (TF), dem Initiator der extrinsischen Gerinnungskaskade, durch die Tumorzellen und die Freisetzung von TF-positiven Mikropartikeln sowohl für die Thrombusentstehung als auch für die Tumorprogression von zentraler Bedeutung. Neue Erkenntnisse über die molekularen Grundlagen der Kontaktaktivierung in vivo (z. B. Freisetzung von Polyphosphaten oder DNA aus aktivierten Plättchen und neutrophilen Granulozyten) deuten auf weitere Mechanismen in der komplexen Pathophysiologie des Trousseau-Syndroms hin.

Keywords

Cancer - thrombosis - tissue factor - factor VII - microparticles

Schlüsselwörter

Tumor - Thrombose - Tissue-Faktor - Faktor VII - Mikropartikel

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