Cancer and thromboembolism: from biology to clinics.
The association between cancer and thromboembolic disease is a well-known phenomenon and can contribute significantly to the morbidity and mortality of cancer patients. Recent studies evidenced that malignant growth has also been linked to activity of heparin-like glycosoaminoglycans, to neoangiogenesis, to protease activity, to immune function and gene expression in addition with activation of coagulation and fibrinolysis. These evidences suggest that antithrombotic drugs may play an additional role in tumour cell growth and in cancer dissemination. The spectrum of thromboembolic manifestations in cancer patients includes deep vein thrombosis, pulmonary embolism, but also intravascular disseminated coagulation and abnormalities in the clotting system in the absence of clinical manifestations. Antithrombotic drugs such as unfractioned heparin (UFH) and, particularly, low molecular weight heparins (LMWH) in addition with dicumaroids, are widely used for the prevention and treatment of thromboembolic manifestations that commonly accompanies malignancies. The aims of the study are to review the pathogenetic mechanisms of thromboembolic disease in cancer patients, the efficiency of antithrombotic drugs in preventing and treating of cancer related thromboembolic complications and review the thromboprophylaxis strategies to prevent thromboembolic complications of cancer patients. Meta-analyses comparing UFH and LMWH for the treatment of deep vein thrombosis have shown better outcome with reduction of major bleeding complications in patients treated with LMWH. Many studies have demonstrated the efficiency and the safeness of antithrombotic agents in the prophylaxis and in the treatment of thromboembolic complication that accompanies malignancies. Many experimental studies, reviewed in this paper, support the hypothesis that antithrombotic agents, but especially heparins can affect cancer progression in many of the different steps of cancer biology. First of all, due to their anticoagulant effect, antithrombotic agents may interfere with thrombin generation and with fibrin formation induced by cancer cells, thus inhibiting the mechanism of metastasis.
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Dipartimento di Medicina e delle Specialità Mediche, Divisione di Medicina Generale, RCCS Fondazione Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Via Pace 5, 20122 Milan, Italy. Castelli39@interfree.it
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D000925:Anticoagulants / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D013923:Thromboembolism / Q000097:blood / Q000209:etiology*; D020246:Venous Thrombosis / Q000209:etiology / Q000517:prevention & control
D000925:Anticoagulants; D006493:Heparin