Coagulation inhibition and activation in pancreatic cancer. Changes during progress of disease

Abstract

Background. To elucidate the disturbed hemostatic balance in patients with pancreatic cancer, the levels of plasma coagulation inhibition and coagulation activation were determined. Methods. Twenty‐one patients with adenocarcinoma of the pancreas were followed from time of diagnosis until death, using plasma analyses of coagulation inhibitors and a molecular marker of coagulation activation (thrombin‐antithrombin complex, TAT). Results. TAT was increased significantly at the time of diagnosis of pancreatic cancer compared with age‐adjusted healthy control subjects (mean, 6.2 ± 4.6 μg/1 [standard deviation] versus 2.0 ± 0.7 μg/l). It increased with disease progression (mean in the terminal phase, 14.1 μg/l; P < 0.05). Plasma levels of tissue factor pathway inhibitor (TFPI) also were increased significantly at the time of diagnosis compared with the control group (mean, 176 ± 80% versus 127 ± 29%; P < 0.05). The TFPI decreased to normal levels (121 ± 40%) after surgical removal of the pancreatic tumor (n = 4) or relief of the cholestasis using a bypass procedure (n = 6). The TFPI levels increased significantly as the malignant disease progressed (from 1‐3 months postoperatively to the terminal phase of disease; mean, 114 ± 52% versus 154 ± 60%). There was a significant positive correlation between TFPI levels and bilirubin levels; the correlation coefficient at diagnosis was 0.70 (P < 0.001). The levels of the coagulation inhibitors antithrombin, heparin cofactor II, protein C, and free protein S decreased significantly with disease progression compared with the normal values found at diagnosis. Conclusions. The mechanism for TFPI increase in cancer is not known. It may be related to the preoperative cholestasis seen in this study, but the increased degree of coagulation activation also may contribute.

Elevated TFPI in malignant disease: relation to cancer type and hypercoagulation

“…High plasma levels of TFPI have been found in patients with advanced colon cancer and pancreatic cancer (Lindahl et al, 1989(Lindahl et al, , 1992a. Although TFPI is not an acute-phase reactant , TFPI levels were found to increase with progression of the malignant disease.…”

“…Although TFPI is not an acute-phase reactant , TFPI levels were found to increase with progression of the malignant disease. In contrast, the plasma concentration of the other coagulation inhibitors decreased with progression of the malignancy (Lindahl et al, 1989(Lindahl et al, , 1992a. In less severe DIC (Brandtzaeg et al, 1989), and in patients with ischaemic heart disease (Sandset et al, 1989b), TFPI was normal to moderately elevated.…”

Factor VII-Targeted Photodynamic Therapy for Breast Cancer and Its Therapeutic Potential for Other Solid Cancers and Leukemia

“…Several groups showed that TF expression was found on pancreatic cancer tissues or cell lines (Cohen and Burtness, 2006;Haas et al, 2006;Hobbs et al, 2007;Iijima et al, 1991;Kakkar et al, 1995a;Kakkar et al, 1995b;Khorana et al, 2007;Khorana and Fine, 2004;Lindahl et al, 1993;Lindahl et al, 1992;Nitori et al, 2005;Silberberg et al, 1989;Taniguchi et al, 1998;Tesselaar et al, 2007;Ueda et al, 2001), but not in normal pancreatic cells (Cohen and Burtness, 2006;Kakkar et al, 1995a). Kakkar et al in 1995 reported that TF expression was detected in 29 of 55 (53%) pancreatic tumors (Kakkar et al, 1995a).…”

Epidemiology and diagnosis of the pancreatic cancer: Epidemiología y diagnóstico

“…In this sense increased plasma levels of TFPI (tissue factor pathway inhibitor) have been reported (63). Regenerating proteins, the expression of the reg gene, are useful markers of acinar cell differentiation (64).…”

“…En este sentido se ha demostrado un incremento de los niveles plasmáticos de TFPI (factor insular inhibidor de coagulación) (63). Las proteínas regenerantes, expresión del gen reg, son un marcador útil para la diferenciación celular acinar (64).…”