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      Tissue Factor Pathway Inhibitor-1 Is a Valuable Marker for the Prediction of Deep Venous Thrombosis and Tumor Metastasis in Patients with Lung Cancer

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          Abstract

          Activation of blood coagulation contributes to cancer progression. Tissue factor pathway inhibitor-1 (TFPI-1) is the main inhibitor of extrinsic coagulation pathway. The aim of this study is to assess the predicting significance of TFPI-1 for thrombotic complication and metastasis in lung cancer patients. Total of 188 non-small cell lung cancer (NSCLC) patients were included in this study. Plasma TFPI-1, D-dimer (D-D), antithrombin (AT), Fibrinogen (Fbg), and coagulating factor VIII activity (FVIII:C) were measured. In NSCLC patients, significantly decreased TFPI-1 and AT and increased D-D, Fbg, and FVIII:C levels were observed, and there was a significant correlation between TFPI-1 and other hemostatic parameters ( P < 0.001, resp.). NSCLC patients with deep venous thrombosis (DVT) or metastasis had significantly lower TFPI-1 levels than those without DVT or metastasis ( P < 0.01, resp.). Multivariate regression revealed that TFPI-1 acted as a predictor for DVT or tumor metastasis in NSCLC patients [OR: 4.15 or 3.28, P < 0.05, resp.]. The area under ROC curve of TFPI-1 was 0.905 (95% CI, 0.842~0.967) or 0.828 (95% CI, 0.742~0.915) for predicting DVT or metastasis ( P < 0.001, resp.). The optimal point of TFPI-1 was 57.7 or 54.3 ng/mL for predicting DVT or metastasis, respectively. Combination of TFPI-1 and D-D measurements can improve the predicting power for DVT or metastasis in NSCLC patients. Our findings suggested that TFPI-1 was a valuable predictor of DVT and tumor metastasis in NSCLC patients.

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          Coagulation and cancer: biological and clinical aspects.

          Malignancy affects the hemostatic system and the hemostatic system affects malignancy. In cancer patients there are a number of coagulation abnormalities which provide the background for an increased tendency of these patients to both thrombosis and hemorrhage. The causes of this coagulation impairment rely on general risk factors which are common to other categories of patients, and other factors which are specific to cancer, such as tumor type and disease stage. In addition, data from basic research indicate that the hemostatic components and the cancer biology are interconnected in multiple ways. Notably, while cancer cells are able to activate the coagulation system, the hemostatic factors play a role in tumor progression. This opens the way to the development of bifunctional therapeutic approaches that are both capable of attacking the malignant process and resolving the coagulation impairment. On the other hand, the management of thrombosis and hemorrhages in cancer patients can be different. To approach these problems, some guidelines have been released by prominent international scientific societies. Also actively investigated is the issue of identifying new biomarkers to classify the subjects at a higher risk, thus improving the prevention of thrombohemorrhagic events in these patients. Finally, novel prophylactic and therapeutic approaches are currently under development. This review provides an overview of the hemostatic complications in cancer, together with new insights into the interaction between hemostasis and cancer biology. We also review the assessment of the risk of thrombohemorrhagic events in cancer patients, and the prophylaxis and treatment of such manifestations. © 2012 International Society on Thrombosis and Haemostasis.
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            Assessing risk of venous thromboembolism in the patient with cancer.

            Patients with cancer are increasingly at risk for venous thromboembolism (VTE). Rates of VTE, however, vary markedly among patients with cancer. This review focuses on recent data derived from population-based, hospital-based, and outpatient cohort studies of patients with cancer that have identified multiple clinical risk factors as well as candidate laboratory biomarkers predictive of VTE. Clinical risk factors for cancer-associated VTE include primary tumor site, stage, initial period after diagnosis, presence and number of comorbidities, and treatment modalities including systemic chemotherapy, antiangiogenic therapy, and hospitalization. Candidate predictive biomarkers include elevated platelet or leukocyte counts, tissue factor, soluble P-selectin, and D-dimer. A recently validated risk model, incorporating some of these factors, can help differentiate patients at high or low risk for developing VTE while receiving chemotherapy. Identifying patients with cancer who are most at risk for VTE is essential to better target thromboprophylaxis, with the eventual goal of reducing the burden as well as the consequences of VTE for patients with cancer.
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              High D-dimer levels are associated with poor prognosis in cancer patients.

              Systemic activation of hemostasis is frequently observed in cancer patients, even in the absence of thrombosis. Moreover, this activation has been implicated in tumor progression, angiogenesis and metastatic spread. Increased levels of D-dimer, which is a degradation product of cross-linked fibrin, indicate a global activation of hemostasis and fibrinolysis. In a prospective and observational cohort study, we assessed the prognostic value of D-dimer levels for overall survival and mortality risk in 1178 cancer patients included in the Vienna Cancer and Thrombosis Study (CATS). Patients were followed over 2 years at regular intervals until occurrence of symptomatic venous thromboembolism or death. D-dimer levels were measured with a quantitative D-dimer latex agglutination assay The main solid tumors were malignancies of the lung (n=182), breast (n=157), lower gastrointestinal tract (n=133), pancreas (n=74), stomach (n=50), kidney (n=37), prostate (n=133), and brain (n=148); 201 of the patients had hematologic malignancies; 63 had other tumors. During a median follow-up of 731 days, 460 (39.0%) patients died. The overall survival probabilities for patients with D-dimer levels categorized into four groups based on the 1(st), 2(nd) and 3(rd) quartiles of the D-dimer distribution in the total study population were 88%, 82%, 66% and 53% after 1 year, and 78%, 66%, 50% and 30% after 2 years, respectively (P<0.001). The univariate hazard ratio of D-dimer (per double increase) for mortality was 1.5 (95% confidence interval: 1.4-1.6, P<0.001) and remained increased in multivariable analysis including tumor subgroups, age, sex and venous thromboembolism. High D-dimer levels were associated with poor overall survival and increased mortality risk in cancer patients.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2017
                26 January 2017
                : 2017
                : 8983763
                Affiliations
                Center of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou 310014, China
                Author notes

                Academic Editor: Noriyoshi Sawabata

                Author information
                http://orcid.org/0000-0002-5631-408X
                http://orcid.org/0000-0001-7042-3306
                http://orcid.org/0000-0002-2707-518X
                http://orcid.org/0000-0002-2060-6216
                Article
                10.1155/2017/8983763
                5299162
                28246607
                e9ccdc7c-bb2a-4667-934e-150d390382df
                Copyright © 2017 Xianming Fei et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 September 2016
                : 23 December 2016
                : 9 January 2017
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81301406
                Funded by: Natural Science Foundation of Zhejiang Province
                Award ID: LQ13H190005
                Categories
                Research Article

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