The Hemostasis Apparatus in Pancreatic Cancer and Its Importance beyond Thrombosis

Abstract

Laboratory evidence of aberrant coagulation is found in the majority of patients with advanced pancreatic cancer and a clinical consequence of this is the high incidence and prevalence of vascular thromboembolic events. Other sequelae are hypothesized to be the facilitation and acceleration of mechanisms that define the malignant phenotype, such as invasion, trafficking and anchoring, establishing the metastatic niche and inducing angiogenesis. We review the in vitro and preclinical evidence that supports the role of the coagulation apparatus in the metastatic process of pancreatic cancer, with a particular emphasis on interaction of this pathway with clinically-targeted growth factor receptor pathways. Links between hemostasis, angiogenesis and epidermal growth factor pathways and their significance as therapeutic targets are considered.

Clinical significance of plasma D-dimer in ovarian cancer

“…The association between VTE and malignancy was first recognized by Trousseau in 1865. [ 51 ] VTE includes deep vein thrombosis and pulmonary embolism and can significantly affect OS of patients. [ 52 ] Up to now, quite a lot of studies demonstrated the high incidence of VTE in cancer patients, [ 53 – 55 ] and they have confirmed that VTE was a common complication in malignant tumors.…”

Coagulation Disorders in Pancreatic Cancer

“…The activity of TF is regulated by several factors. The most important is TF pathway inhibitor which is composed of three different domains: the first inhibits FVII, the second inhibits FX and the function of the last one is still unknown (Broze, 1995;Girard et al, 1989;Echrish et al, 2011). TF pathway inhibitor is secreted by endothelial cells.…”

“…Proteins of coagulation are involved in angiogenesis in two different ways, one clotting dependent and the other one clotting independent (Echrish et al, 2011). The clotting dependent mechanism is initiated by the activation of TF receptors.…”

“…TF activates then the coagulation cascade that leading to fibrin formation and platelet activation (Falanga & Rickles, 1999). Activated platelets release mediators that promote angiogenesis such as VEGF, beta fibroblast growth factor (β-FGF) and platelet grows factor (PGF) (Palumbo et al, 2000;Echrish et al, 2011). In clotting independent mechanism thrombin plays a very important role by inducing the proteolytic cleavage of proteaseactivated receptors (PAR) (Traynelis & Trejo, 2007).…”

“…), history of venous thrombosis (Offord et al, 2004;Echrish et al, 2011). Also, the local effects of a great tumour, such as venous compression, that can predispose to an increased risk of thromboembolism (Dumitrascu et al, 2010) .…”