Venous thromboembolism in cancer patients: an underestimated major health problem

Abstract

Venous thromboembolism (VTE) is a major health problem among patients with cancer, its incidence in this particular population is widely increasing. Although VTE is associated with high rates of mortality and morbidity in cancer patients, its severity is still underestimated by many oncologists. Thromboprophylaxis of VTE now considered as a standard of care is still not prescribed in many institutions; the appropriate treatment of an established VTE is not yet well known by many physicians and nurses in the cancer field. Patients are also not well informed about VTE and its consequences. Many studies and meta-analyses have addressed this question so have many guidelines that dedicated a whole chapter to clarify and expose different treatment strategies adapted to this particular population. There is a general belief that the prevention and treatment of VTE cannot be optimized without a complete awareness by oncologists and patients. The aim of this article is to make VTE a more clear and understood subject.

Figure 1

Hemostasis genes promote tumor progression. Activated oncogenes (MET*, RAS*), hypoxia-inducible factor-1 (HIF-1), and loss of tumor suppressor genes (PTEN-, P53-) induce transcriptional programs (nuclear heatmap) including tissue factor (TF), cyclo-oxygenase 2 (COX-2), and plasminogen-activator inhibitor 1 (PAI-1) upregulation. These, in turn, promote hemostasis activation and fibrin deposition. Fibrin forms a provisional matrix that favors angiogenesis and supports integrin-mediated cell adhesion and migration. Coagulation proteases activate hepatocyte growth factor (HGF), and thus the receptor encoded by the MET proto-oncogene (c-MET), which is expressed by endothelial and cancer cells. TF and thrombin generated by the coagulation cascade activate cell surface receptors (protease-activated receptors [PAR]-1 and −2). COX-2 catalyzes the synthesis of prostacyclin and thromboxane, which modulate platelet aggregation, and prostaglandin E2 (PGE2). The latter binds cell surface E-series prostaglandin receptors (EP). Besides inhibiting plasmin and fibrin degradation, PAI-1 promotes integrin recycling. MET, TF, PARs, EP, vascular endothelial growth factor receptor (VEGFR), and integrins cooperate in regulating cancer cell invasive growth and angiogenesis [23]