Prospective Assessment of Clinical Risk Factors and Biomarkers of Hypercoagulability for the Identification of Patients with Lung Adenocarcinoma at Risk for Cancer Associated Thrombosis. the Observational Roadmap-CAT Study

INTRODUCTION: The aim of this prospective longitudinal study was to identify the most clinically relevant hypercoagulability biomarkers in lung adenocarcinoma patients for elaboration of an improved risk assessment model (RAM) for venous thromboembolism (VTE).

METHODS: 150 ambulatory patients with lung adenocarcinoma were prospectively enrolled as well as a control group comprised of 30 healthy age & sex-matched individuals. Thrombin generation parameters, procoagulant phospholipid-dependent clotting time (Procoag-PPL), tissue factor activity (TFa), factor VIIa (FVIIa), factor V (FV), antithrombin (AT), D-Dimers (DDi), P-selectin and heparanase levels were assessed in platelet-poor plasma (PPP) at inclusion (baseline) and at the end of the 3rd chemotherapy cycle (acute phase). Cox regression analysis was used to identify independent VTE predictors.

RESULTS: At baseline, patients had significantly attenuated thrombin generation, shorter Procoag-PPL, higher levels of TFa, D-Dimers and heparanase, and lower levels of FVIIa and P-selectin, compared to controls. A significant increase in Procoag-PPL, FV and FVIIa and a decrease of P-selectin levels was observed between baseline and the acute phase. Hospitalization within the last 3 months prior to assessment, time since cancer diagnosis less than 6 months, mean rate index of thrombin generation (MRI) and Procoag-PPL were independently associated with symptomatic VTE. Accordingly, a prediction model including the above parameters had improved discriminating capacity (area under the curve/AUC: 0.84).

CONCLUSIONS: Ambulatory patients with lung adenocarcinoma may display pronounced blood hypercoagulability due to decreased Procoag-PPL, increased endothelial cell activation and increased degradation of fibrin. Incorporation of Procoag-PPL and MRI of thrombin generation may improve the accuracy of a VTE RAM in the above setting.