Clinical features of pulmonary embolism in patients with lung cancer: A meta-analysis

Autoři: Xin Hua aff001;  Shu-Hua Han aff001;  Shu-Zhen Wei aff001;  Ying Wu aff001;  Jun Sha aff001;  Xiao-Li Zhu aff001
Působiště autorů: Department of Respiratory, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China aff001;  Medical School of Southeast University, Nanjing, Jiangsu, China aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223230



Pulmonary embolism (PE) is correlated with increased mortality among patients with lung cancer (LC). The characteristics of patients with LC presenting with PE have not been fully established, and our meta-analysis aims to comprehensively investigate the clinical characteristics associated with PE in patients with LC to help physicians identify PE earlier in these patients.


Multiple databases were searched, including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Wanfang. Odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were used as effect measures for dichotomous and continuous variables, respectively. Moreover, Egger’s test, Begg’s test and a sensitivity analysis were performed to assess the publication bias and reliability of the articles.


In total, 16 studies were included in our meta-analysis. The results indicated that history of chronic obstructive pulmonary disease (OR = 2.59, 95% CI: 1.09, 6.15; P = 0.03), adenocarcinoma (OR = 2.28, 95% CI: 1.88, 2.77; P < 0.01), advanced tumour stage (TNM III-IV vs. I-II, OR = 2.38, 95% CI: 1.99, 2.86; P < 0.01), history of central venous catheter (OR = 1.95, 95% CI: 1.36, 2.78; P < 0.01), history of chemotherapy (OR = 2.32, 95% CI: 1.80, 2.99, P < 0.01), high levels of D-dimer (WMD = 4.31, 95% CI: 2.53, 6.10; P < 0.01) and carcinoembryonic antigen (WMD = 10.30, 95% CI: 9.95, 10.64; P < 0.01) and a low level of partial pressure of oxygen (WMD = -25.97, 95% CI: -31.31, -20.62; P < 0.01) were clinical features of LC patients with PE compared to those without PE.


These results reveal that LC patients with PE have specific clinical features, including but not limited to several cancer- and treatment-related factors, that may help their early identification.

Klíčová slova:

Adenocarcinomas – Database searching – Chemotherapy – Chronic obstructive pulmonary disease – Lung and intrathoracic tumors – Publication ethics – Pulmonary embolism


1. Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293: 715–722. doi: 10.1001/jama.293.6.715 15701913

2. Abdol RNB, Jones G, Bhandari M, Berndt MC, Metharom P. Cancer-associated thrombosis: an overview of mechanisms, risk factors, and treatment. Cancers (Basel). 2018;10: E380.

3. Astruc N, Ianotto JC, Metges JP, Lacut K, Delluc A. External validation of the modified Ottawa score for risk stratification of recurrent cancer-associated thrombosis. Eur J Intern Med. 2016;36: e11–e12. doi: 10.1016/j.ejim.2016.08.001 27592403

4. Ay C, Unal UK. Epidemiology and risk factors for venous thromboembolism in lung cancer. Curr Opin Oncol. 2016;28: 145–149. doi: 10.1097/CCO.0000000000000262 26730487

5. Bartholomew JR. Update on the management of venous thromboembolism. Cleve Clin J Med. 2017;84: 39–46. doi: 10.3949/ccjm.84.s3.04 29257737

6. Wang H, Huang Y, Xu C-W, Lin L. Clinical analysis of tumor and non-tumor patients complicated with pulmonary embolism. Int J Clin Exp Med. 2015;8: 18729–18736. 26770488

7. Lee JW, Cha SI, Jung CY, Choi WI, Jeon KN, Yoo SS, et al. Clinical course of pulmonary embolism in lung cancer patients. Respiration. 2009;78: 42–48. doi: 10.1159/000176208 19023192

8. Xu X, Yang H, Qiao L, Tan Z, Jin J, Jin Y, et al. Clinical characteristic and outcomes of lung cancer patients with venous thromboembolism. Zhonghua Yi Xue Za Zhi. 2014;94: 2045–2049. 25312667

9. Sun W, Wang H, Wen Z, Ma N, Xiao Y, Ma L, et al. Clinical characteristics of lung cancer complicated with pulmonary embolism. Zhonghua Jie He Hu Xi Za Zhi. 2016;39: 198–202.

10. Chuang YM, Yu CJ. Clinical characteristics and outcomes of lung cancer with pulmonary embolism. Oncology. 2009;77: 100–106. doi: 10.1159/000229503 19622900

11. Nichols L, Saunders R, Knollmann FD. Causes of death of patients with lung cancer. Arch Pathol Lab Med. 2012;136: 1552–1557. doi: 10.5858/arpa.2011-0521-OA 23194048

12. Sun JM, Kim TS, Lee J, Park YH, Ahn JS, Kim H, et al. Unsuspected pulmonary emboli in lung cancer patients: the impact on survival and the significance of anticoagulation therapy. Lung Cancer. 2010;69: 330–336. doi: 10.1016/j.lungcan.2009.11.015 20007002

13. Ai P. Clinical analysis of risk factors and prognosis of lung cancer complicated with pulmonary embolism. Journal of Huaihai Medicine. 2017;35: 49–51.

14. O'Connell CL, Boswell WD, Duddalwar V, Caton A, Mark LS, Vigen C, et al. Unsuspected pulmonary emboli in cancer patients: clinical correlates and relevance. J Clin Oncol. 2006;24: 4928–4932. doi: 10.1200/JCO.2006.06.5870 17050877

15. Malgor RD, Bilfinger TV, Labropoulos N. A systematic review of pulmonary embolism in patients with lung cancer. Ann Thorac Surg. 2012;94: 311–316. doi: 10.1016/j.athoracsur.2012.03.025 22626760

16. Li Y, Shang Y, Wang W, Ning S, Chen H. Lung cancer and pulmonary embolism: what is the relationship? A review. J Cancer. 2018;9: 3046–3057. doi: 10.7150/jca.26008 30210627

17. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25: 603–605. doi: 10.1007/s10654-010-9491-z 20652370

18. Asimit J, Day-Williams A, Zgaga L, Rudan I, Boraska V, Zeggini E. An evaluation of different meta-analysis approaches in the presence of allelic heterogeneity. Eur J Hum Genet. 2012;20: 709–12. doi: 10.1038/ejhg.2011.274 22293689

19. Tie X, Lang B, Shen F, Liu P, Li N, Zuo Z, et al. Analysis of clinical manifestation and predisposing factors in lung cancer patients with pulmonary embolism. Oncology Progress. 2018;16: 526–528.

20. Tang K. Risk factors and prognosis of lung cancer complicated with pulmonary embolism. Clinical Pulmonary Medicine Journal. 2017;22: 1477–1480.

21. Na J, Ma X, Zhou W. Analysis of clinical characteristics of primary lung cancer complicated with pulmonary embolism. Journal of Clinical Pulmonary Medicine. 2017;22: 817–821.

22. Tian X, Huang J. Risk factors of pulmonary embolism in patients with lung cancer. PJCCPVD. 2017;25: 50–52.

23. Zhao N, Wei Y. Influencing factors of pulmonary embolism in patients with non-small-cell lung cancer. PJCCPVD. 2017;25: 46–49.

24. Luo T, Zhao J. Risk factors for complicated with pulmonary embolism in lung cancer patients and their impact on prognosis. Contemporary Medicine Forum. 2017;15: 85–86.

25. Ma L, Wen Z. Risk factors and prognosis of pulmonary embolism in patients with lung cancer. Medicine (Baltimore). 2017;96: e6638.

26. Xiong W, Zhao Y, Xu M, Guo J, Pudasaini B, Wu X, et al. The relationship between tumor markers and pulmonary embolism in lung cancer. Oncotarget. 2017;8: 41412–41421. doi: 10.18632/oncotarget.17916 28575869

27. Zhu Y, Chen W, Dai H. Risk factors of pulmonary embolism in patients with lung cancer and its influence on prognosis. Journal of Clinical Medicine in Practice. 2016;20: 25–28.

28. Zhang L. Clinical prognosis and risk factors of lung cancer complicated with pulmonary embolism. Hainan Med J. 2015;26: 1598–1600.

29. Shi Z-H, Shi G-Y, Sun Z, Zhao X. Case-control study on the risk factors of lung cancer combined pulmonary thromboembolism. Chin J Cancer Prev Treat. 2015;22: 863–866.

30. Xiong L. Clinical analysis of risk factors for lung cancer complicated with pulmonary embolism. Modern Diagnosis & Treatment. 2014;25: 3302–3303.

31. Zhang Y, Yang Y, Chen W, Guo L, Liang L, Zhai Z, et al. Prevalence and associations of VTE in patients with newly diagnosed lung cancer. Chest. 2014;146: 650–658. doi: 10.1378/chest.13-2379 24676401

32. Wang J, Zhou W, Xu L, Yang M, Meng L, Fan W, et al. Risk factors and prognosis of lung cancer combined with pulmonary embolism. Zhongguo Fei Ai Za Zhi. 2011;14: 780–784. doi: 10.3779/j.issn.1009-3419.2011.10.03 22008107

33. Wahrenbrock M, Borsig L, Le D, Varki N, Varki A. Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas. J Clin Invest. 2003;112: 853–862. doi: 10.1172/JCI18882 12975470

34. Blom JW, Osanto S, Rosendaal FR. The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma. J Thromb Haemost. 2004;2: 1760–1765. doi: 10.1111/j.1538-7836.2004.00928.x 15456487

35. Li G, Li Y, Ma S. Lung cancer complicated with asymptomatic pulmonary embolism: clinical analysis of 84 patients. Technol Cancer Res Treat. 2017;16: 1130–1135. doi: 10.1177/1533034617735930 29332446

36. Papageorgiou C, Vandreden P, Marret E, Bonnet F, Robert F, Spyropoulos A, et al. Lobectomy and postoperative thromboprophylaxis with enoxaparin improve blood hypercoagulability in patients with localized primary lung adenocarcinoma. Thromb Res. 2013;132: 584–591. doi: 10.1016/j.thromres.2013.07.005 24094602

37. Verso M, Chiari R, Mosca S, Franco L, Fischer M, Paglialunga L, et al. Incidence of Ct scan-detected pulmonary embolism in patients with oncogene-addicted, advanced lung adenocarcinoma. Thromb Res. 2015;136: 924–927. doi: 10.1016/j.thromres.2015.09.006 26377037

38. Wieshammer S, Dreyhaupt J, Muller D, Momm F, Jakob A. Venous thromboembolism and persistent pulmonary hypertension in cancer patients: a cross-sectional study. Thromb J. 2016;14: 3. doi: 10.1186/s12959-016-0077-1 26858584

39. Davies NA, Harrison NK, Sabra A, Lawrence MJ, Noble S, Davidson SJ, et al. Application of ROTEM to assess hypercoagulability in patients with lung cancer. Thromb Res. 2015;135: 1075–1080. doi: 10.1016/j.thromres.2015.03.021 25895846

40. Donati MB, Falanga A. Pathogenetic mechanisms of thrombosis in malignancy. Acta Haematol. 2001;106: 18–24. doi: 10.1159/000046585 11549773

41. Ma R, Bi Y, Kou J, Zhou J, Shi J. Enhanced procoagulant activity of platelets after chemotherapy in non-small cell lung cancer. Cancer Biol Ther. 2017;18: 627–634. doi: 10.1080/15384047.2017.1345387 28718695

42. Lysov Z, Swystun LL, Kuruvilla S, Arnold A, Liaw PC. Lung cancer chemotherapy agents increase procoagulant activity via protein disulfide isomerase-dependent tissue factor decryption. Blood Coagul Fibrinolysis. 2015;26: 36–45. doi: 10.1097/MBC.0000000000000145 24911456

43. Wang C, Xu X, Zhai C. Risk factors and clinical observation of 48 lung cancer patients complicated with pulmonary embolism. China Health Care and Nutrition. 2016;26: 154.

44. Xiao F, Guo Q, Qi X. Risk factors and clinical prognosis of lung cancer complicated with pulmonary embolism. For All health. 2017;11: 28–29.

45. Zhu L, Qin S, Wu Y. Analysis of risk factors for lung cancer combined with pulmonary embolism. Journal of Guangxi Medical University. 2018;35: 476–479.

46. Lv Y. The 29 cases of clinical characteristics and risk factors analysis of lung cancer combined with pulmonary embolism. Dissertation. Dalian Medical University. 2016.

47. Li N, Wang Y. Clinical features in 23 lung cancer patients complicated with pulmonary thromboembolism. Zhongguo Fei Ai Za Zhi. 2014;17: 254–259. doi: 10.3779/j.issn.1009-3419.2014.03.12 24667264

48. van Herk-Sukel MP, Shantakumar S, Penning-Van Beest FJ, Kamphuisen PW, Majoor CJ, Overbeek LI, et al. Pulmonary embolism, myocardial infarction, and ischemic stroke in lung cancer patients: results from a longitudinal study. Lung. 2013;191: 501–509. doi: 10.1007/s00408-013-9485-1 23807721

49. Li H. Retrospective analysis of clinical features of lung cancer with pulmonary embolism. World Latest Medicine Information. 2018;18: 1–4.

50. Wan J, Li H, Zhou X, et al. Analysis for risk factors of pulmonary thromboembolism in the stage IV of lung cancer. Practical Oncology Journal. 2018;32: 241–244.

Článek vyšel v časopise


2019 Číslo 9

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Zvyšte si kvalifikaci online z pohodlí domova

Antiseptika a prevence ve stomatologii
nový kurz
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Citikolin v neuroprotekci a neuroregeneraci: od výzkumu do klinické praxe nejen očních lékařů
Autoři: MUDr. Petr Výborný, CSc., FEBO

Zánětlivá bolest zad a axiální spondylartritida – Diagnostika a referenční strategie
Autoři: MUDr. Monika Gregová, Ph.D., MUDr. Kristýna Bubová

Diagnostika a léčba deprese pro ambulantní praxi
Autoři: MUDr. Jan Hubeňák, Ph.D

Význam nemocničního alert systému v době SARS-CoV-2
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D., prim. MUDr. Václava Adámková

Všechny kurzy
Kurzy Doporučená témata