Inflammatory and Thrombotic Mediators in Small Cell Lung Carcinoma: Potential Role in Thromboembolic Complications

Abstract

Abstract 2294 Introduction:Small Cell Lung Carcinoma (SCLC) patients exhibit a higher prevalence of thromboembolic complications. We hypothesized that in this malignancy, procoagulant and inflammatory mediators contribute to the pathogenesis of such complications and warfarin treatment may down regulate these levels. Methods: In a prospective, randomized, controlled study, patients with inoperable lung cancer (n=100) were randomized to receive chemotherapy and radiation with and without warfarin (INR 1.5 – 2.5). Blood samples were drawn prior to and after the 2nd treatment cycle with warfarin or control and retrospectively analyzed for microparticles and thrombin generation markers such as fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT) and prothrombin fragment F1.2 (F1.2). In addition, biochip array for C-reactive protein (CRP), D Dimer, neuron specific enolase (NSE), neutrophil gelatinase associated lipocalin (NGAL), tumor necrosis factor receptor 1 (TNFR1), and thrombomodulin (TM) were measured. The results were compared with a normal population (N=50).Results: The results are shown in the following table.MarkerLung CA PatientsNormal ControlsMeanSEMMeanSEMCRP9.030.512.650.21DD725.0100.959.67.5NSE37.13.613.41.2NGAL825.448.9307.310.6TNFR11.30.10.40.02TM3.30.31.60.2MP18.31.26.20.4The microparticles were markedly increased in the SCLC patients (3 fold increase) at baseline. Similarly, the thrombin generation markers showed variable increase (1.5–3.2 fold increase). In the biochip array analysis, variable increase was noted. CRP (2.4 fold), D DIMER (11.6 fold), NSE (1.8 fold), NGAL (1.7 fold), TNFR1 (2 fold) and TM (1.3 fold) were all increased as compared to normal controls. All of the markers exhibited a decrease after warfarin treatment with a most pronounced decrease in the D Dimer and TNFR1. Conclusions:These results validate the hypothesis that SCLC patients exhibit a hypercoagulable state that is associated with simultaneous upregulation of inflammatory mediators. Warfarin treatment results in a down regulation of these mediators. Our results provide a rationale for prophylactic anticoagulant therapy in this group of patients with conventional and newer oral anticoagulant drugs. Disclosures:No relevant conflicts of interest to declare.