Hämostaseologische Aspekte in der Onkologie

Zusammenfassung

Der klinische Zusammenhang zwischen Tumor und Thrombose ist spätestens seit den Beobachtungen von Armand Trousseau (1865) bekannt. Die Aktivierung der Hämostase und Fibrinolyse spielt nicht nur in der Ätiologie des Trousseau-Syndroms eine wichtige Rolle, sondern fördert auch direkt die Progression maligner Erkrankungen. Insbesondere der Gewebefaktor (Tissue-Faktor) ist für das primäre Tumorwachstum und die hämatogene Metastasierung von Bedeutung. Dabei unterliegen die bei Krebspatienten beobachteten Gerinnungsstörungen zumindest teilweise der Kontrolle durch definierte (in)aktivierende Mutationen von Tumorsuppressor- oder Onkogenen.

Während die langfristige Antikoagulation mit niedermolekularem Heparin (NMH) etablierte Standardtherapie der tumorassoziierten venösen Thromboembolie (VTE) ist, müssen die medikamentöse VTE-Prophylaxe bei ambulanten onkologischen Patienten und das Management von komplexen Hämostase- störungen individuell und risikoadaptiert erfolgen. (Tier)experimentelle Studien legen zudem nahe, dass NMH in der Therapie von Krebspatienten effektiv sein könnte. Dieser Zusatznutzen konnte jedoch bisher nicht zweifelsfrei durch randomisierte Studien belegt werden.

Summary

The clinical link between cancer and thrombosis has been recognized by Armand Trousseau in 1865. It has become clear that activation of coagulation and fibrinolysis plays an important role not only in the pathophysiology of Trousseau’s syndrome, but also in the progression of solid malignancies. In particular, tissue factor is critical for both primary tumour growth and haematogenous metastasis. Haemostatic perturbations in cancer patients are, at least in part, controlled by defined genetic events in molecular tumourigenesis, including activating and inactivating mutations of oncogenes and tumour suppressor genes, respectively.

While long-term treatment with low-molecular-weight heparin (LMWH) is considered standard therapy for established venous thromboembolism (VTE), pharmacological VTE prophylaxis in ambulatory cancer patients and the management of complex systemic coagulopathies remain a challenge and have to be decided on an individual basis and in a risk-adapted manner. Experimental and preclinical studies further suggest that LMWH may be beneficial in cancer therapy, but this innovative concept has not yet been proven beyond doubt in rigorously designed clinical trials.

Schlüsselwörter

Tumor - Thrombose - Trousseau-Syndrom - Tissue-Faktor - niedermolekulares Heparin

Keywords

Cancer - thrombosis - Trousseau’s syndrome - tissue factor - low-molecular-weight heparin

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