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      Therapeutics and Clinical Risk Management (submit here)

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      Clinical features of patients with lung cancer accompanied by thromboembolism or disseminated intravascular coagulation


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          Thromboembolism (TE) and disseminated intravascular coagulation (DIC) are often present concomitantly. This study aimed to investigate the clinical features of patients with lung cancer and TE and/or DIC.

          Patients and methods

          Data on 716 patients with pathologically confirmed diagnoses of lung cancer were retrospectively analyzed for TE/DIC.


          TE was identified in 16 patients (2.2%) and DIC was identified in 5 (0.7%) during the diagnosis of cancer. TE was more often observed in adenocarcinoma (4.0%). Both TE and DIC were more often observed in stage IV (4.7% and 1.5%, respectively). In patients with stage IV adenocarcinoma who received some systemic treatment, overall survival (OS) was significantly shorter in patients with TE (median 280 days) and with DIC (72 days) than in non-TE/DIC patients (538 days). Multivariate analysis showed that older age, poor performance status, greater number of metastatic organs, no EGFR mutation/ ALK fusion, presence of interstitial lung disease, and DIC were poor prognostic factors for OS. In 339 patients in stage IV, 25 (7.4%) and 21 (6.2%) patients had TE and DIC, respectively, during the course. Six patients exhibited both TE and DIC. TE was more often observed in adenocarcinoma (20 of 196 patients; 10.2%). Patients with DIC had extremely shorter survival (median 13 days) after onset. Cancer control by systemic therapy, such as chemotherapy and molecular-targeted therapy, contributed to long survival.


          Patients with TE/DIC had shorter OS than patients without TE/DIC. Control of lung cancer by systemic therapy was important for longer survival after the onset of events.

          Most cited references17

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          The incidence of venous thromboembolism among patients with primary lung cancer.

          The incidence of venous thromboembolism (VTE) by lung cancer histology and stage is unknown. To determine the incidence of VTE and the risk factors associated with development of VTE in a large population-based study of patients with non-small cell and small cell lung cancer. The California Cancer Registry was merged with the Patient Discharge Data Set to determine the incidence of VTE among lung cancer cases diagnosed between 1993 and 1999. Among 91 933 patients with newly diagnosed lung cancer, the 1-year and 2-year cumulative VTE incidences were 3.0% and 3.4%, respectively, with a person-time rate of 7.2 events/100 patient-years during the first 6 months. The 1-year incidence of VTE was significantly increased in comparison to the general population [standardized incidence ratio = 21.2, 95% confidence interval (CI) = 20.4-22.0]. In a multivariate model, significant predictors of developing VTE within 1 year of non-small cell lung cancer (NSCLC) diagnosis were: younger age, the number of chronic medical comorbidities [hazard ratio (HR) = 2.8 if 3 vs. 0, 95% CI = 2.5-3.1], advancing cancer stage (HR = 4.0 for metastatic vs. local disease, 95% CI = 3.4-4.6) and adenocarcinoma histology (HR = 1.9 vs. squamous cell, 95% CI = 1.7-2.1). In multivariate models, VTE was a significant predictor of death within 2 years for both NSCLC and small cell lung cancer (SCLC), HR = 2.3, 95% CI = 2.2-2.4, and HR = 1.5, 95% CI = 1.3-1.7, respectively. Approximately 3% of lung cancer patients developed VTE within 2 years. The diagnosis of VTE was associated with a higher risk of death within 2 years for NSCLC and SCLC.
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            The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma.

            Only limited data on the incidence of venous thrombosis in different types of malignancy are available. Patients with adenocarcinoma are believed to have the highest risk of developing venous thrombosis. To study the incidence of thrombosis in patients with lung cancer, with an emphasis on the comparison between adenocarcinoma and squamous cell carcinoma, we have performed a cohort study of patients with non-small-cell lung cancer. In addition the risk associated with treatment and extent of disease was assessed. A total of 537 patients with a first diagnosis of lung carcinoma were included. Patient and tumor characteristics as well as venous thrombotic events were recorded from the medical records and from the Anticoagulation Clinic. Thrombotic risk in lung cancer patients was 20-fold higher than in the general population (standardized morbidity ratio (SMR): 20.0 (14.6-27.4). In the group of patients with squamous cell cancer we found 10 (10/258) cases (incidence: 21.2 per 1000 years) of venous thrombosis whereas in the group of patients with adenocarcinoma 14 (14/133) cases (incidence: 66.7 per 1000 years) occurred. The crude adjusted hazard ratio was 3.1 (95% CI: 1.4-6.9). The risk increased during chemotherapy and radiotherapy and in the presence of metastases. The risk of venous thrombosis in lung cancer patients is increased 20-fold compared to the general population. Patients with adenocarcinoma have a higher risk than patients squamous cell carcinoma. During chemotherapy or radiotherapy and in the presence of metastases the risk is even higher.
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              Trousseau's syndrome: cancer-associated thrombosis.

              Trousseau's syndrome (cancer-associated thrombosis) is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is 4- to 7-fold higher in patients with cancer than in those without cancer. The causes of this impaired coagulation are associated with general patient-related risk factors, and other factors that are specific to the particular cancer or treatment. It is important to assess the risk of thrombotic events in cancer patients and administer effective prophylaxis and treatment. Effective prophylaxis and treatment of venous thromboembolism reduces morbidity and mortality, and improves patients' quality of life. Low molecular weight heparin is the first-line treatment for venous thromboembolism, as an effective and safe means for prophylaxis and treatment, according to guidelines released by international scientific societies. Oral anticoagulation therapy with warfarin is preferable to no therapy. However, warfarin has low efficacy and is associated with high rates of recurrence. If low molecular weight heparin is unavailable, some guidelines recommend the use of vitamin K antagonists that have a target international normalized ratio in the range of 2-3, as acceptable alternatives. Novel oral anticoagulants that directly inhibit factor Xa or thrombin are promising for the prophylaxis of high-risk cancer patients and in the long-term treatment of venous thromboembolism. However, to date, there is insufficient evidence to support the use of these new anticoagulants.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                01 August 2018
                : 14
                : 1361-1368
                [1 ]Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, kanaji@ 123456med.kagawa-u.ac.jp
                [2 ]Department of Respiratory Medicine, National Hospital Organization Takamatsu Medical Center
                [3 ]Department of Internal Medicine, Shodoshima Central Hospital, Kagawa, Japan
                Author notes
                Correspondence: Nobuhiro Kanaji, Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan, Tel +81 87 891 2145, Fax +81 87 891 2147, Email kanaji@ 123456med.kagawa-u.ac.jp
                © 2018 Kanaji et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                deep vein thrombosis,pulmonary embolism,survival,trousseau’s syndrome,venous thrombotic event,prognosis


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