Venous thromboembolism and lung cancer: a review

Carolina Vitale, Maria D'Amato, Paolo Calabrò, Anna Agnese Stanziola, Mauro Mormile, Antonio Molino, Carolina Vitale, Maria D'Amato, Paolo Calabrò, Anna Agnese Stanziola, Mauro Mormile, Antonio Molino

Abstract

Venous thromboembolism (VTE) is a common complication of malignancies and epidemiological studies suggest that lung cancer belonged to the group of malignancies with the highest incidence rates of VTE. Risk factors for VTE in lung cancer patients are adenocarcinoma, NSCLC in comparison with SCLC, advanced disease, pneumonectomy, chemotherapy including antiangiogenic therapy. Other risk factors are pretreatment platelet counts and increased release of TF-positive microparticles. Elevated D-dimer levels do not necessarily indicate an increased risk of VTE but have been shown to be predictive for a worse clinical outcome in lung cancer patients. Mechanisms responsible for the increase in venous thrombosis in patients with lung cancer are not understood. Currently no biomarker is recognized as a predictor for VTE in lung cancer patients. Although several clinical trials have reported the efficacy of antithrombotic prophylaxis in patients with lung cancer who are receiving chemotherapy, further trials are needed to assess the clinical benefit since these patients are at an increased risk of developing a thromboembolism.

Keywords: Lung cancer; Non small-cell lung cancer; Small-cell lung cancer; Thromboprophylaxis; Venous thromboembolism.

References

    1. Shinagare AB, Okajima Y, Oxnard GR, Dipiro PJ, Johnson BE, Hatabu H, Nishino M. Unsuspected pulmonary embolism in lung cancer patients: comparison of clinical characteristics and outcome with suspected pulmonary embolism. Lung Cancer. 2012;78(2):161–166. doi: 10.1016/j.lungcan.2012.08.007.
    1. Nordstrom M, Lindblad B, Bergqvist D, Kjellström T. A prospective study of the incidence of deep-vein thrombosis within a defined urban population. J Intern Med. 1992;232(2):155–160. doi: 10.1111/j.1365-2796.1992.tb00565.x.
    1. Falanga A. The incidence and risk of venous thromboembolism associated with cancer and nonsurgical cancer treatment. Cancer Investig. 2009;27(1):105–115. doi: 10.1080/07357900802563028.
    1. Lee AY. Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol. 2005;128:291–302. doi: 10.1111/j.1365-2141.2004.05292.x.
    1. Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R, Rimm AA. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy: risk analysis using Medicare claims data. Medicine (Baltimore) 1999;78:285–291. doi: 10.1097/00005792-199909000-00001.
    1. Shinagare AB, Guo M, Hatabu H, Krajewski KM, Andriole K, Van den Abbeele AD, DiPiro PJ, Nishino M. Incidence of pulmonary embolism in oncologic outpatients at a tertiary cancer center. Cancer. 2011;117(16):3860–6. doi: 10.1002/cncr.25941.
    1. Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost. 2002;87:575–57.
    1. Noble S, Pasi J. Epidemiologyand pathofisiology of cancer associated thrombosis. Br J Cancer. 2010;102:S2–S9. doi: 10.1038/sj.bjc.6605599.
    1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics 2010. CA Cancer J Clin. 2010;60(5):277–300. doi: 10.3322/caac.20073.
    1. Rickles FR. Thrombosis and lung cancer. Am Rev Respir Dis. 1989;140:573–575. doi: 10.1164/ajrccm/140.3.573.
    1. Gabazza EC, Taguchi O, Yamakami T, Machishi M, Ibata H, Suzuki S. Evaluating prethrombotic state in lung cancer using molecular markers. Chest. 1993;103(1):196–200. doi: 10.1378/chest.103.1.196.
    1. Tesselaar M, Osanto S. Risk of venous thromboembolism in lung cancer. Curr Opi Pul Med. 2007;13:362–367.
    1. Tagalakis V, Levi D, Agulnik JS, Cohen V, Kasymjanova G, Small D. High risk of deep vein thrombosis in patients with non-small cell lung cancer: a cohort study of 493 patients. J Thorac Oncol. 2007;2(8):729–34. doi: 10.1097/JTO.0b013e31811ea275.
    1. Chew HK, Davies AM, Wun T, Harvey D, Zhou H, White RH, et al. The incidence of venous thromboembolism among patients with primary lung cancer. J Thromb Haemost. 2008;6(4):601–8. doi: 10.1111/j.1538-7836.2008.02908.x.
    1. Connolly GC, Dalal M, Lin J, Khorana AA. Incidence and predictors of venous thromboembolism (VTE) among ambulatory patients with lung cancer. Lung Cancer. 2012;78(3):253–8. doi: 10.1016/j.lungcan.2012.09.007.
    1. Crolow C, Samulowski M, Blum T, Kollmeier J, Schönfeld N, Bittner RC, Behr J, Bauer TT, Grüning W. Frequency of thromboembolic complications in patients with lung cancer. Pneumologie. 2013;67(8):442–7. doi: 10.1055/s-0033-1344341.
    1. Zhang Y, Yang Y, Chen W, Guo L, Liang L, Zhai Z, et al. Prevalence and associations of venous thromboembolism in patients with newly diagnosed lung cancer. Chest. 2014. Doi:10.1378/chest.13-2379.
    1. Kadlec J, Skrickova ZM. The incidence and predictors of thromboembolic events in patients with lung cancer. Sci World J. 2014;125706:9.
    1. Alexander M, Kirsa S, Wolfe R. Thromboembolism in lung cancer- an area of urgent unmet need. Lung Cancer. 2014;84(3):275–80. doi: 10.1016/j.lungcan.2014.02.009.
    1. White RH, Chew HK, Zhou H, Parikh-Patel A, Harris D, Harvey D, Wun T. Incidence of venous thromboembolism in the year before the diagnosis of cancer in 528,693 adults. Arch Intern Med. 2005;165:1782–1787. doi: 10.1001/archinte.165.15.1782.
    1. Connolly GC, Menapace L, Safadjou S, Francis CW, Khorana AA. Prevalence and clinical significance of incidental and clinically suspected venous thromboembolism in lung cancer patients. Clin Lung cancer. 2013;14(6):713–8. doi: 10.1016/j.cllc.2013.06.003.
    1. Calleias MF, Errazuriz JI, Castillo F, Otárola C, Riquelme C, Ortega C, Huete Á, Bächler P. Incidental venous thromboembolism detected by PET-CT in patients with cancer: prevalence and impact on serviva rate. Thromb Res. 2014;133(5):750–5. doi: 10.1016/j.thromres.2014.02.005.
    1. Hron G, Kollars M, Weber H, Sagaster V, Quehenberger P, Eichinger S, Kyrle PA, Weltermann A. Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost. 2007;97(1):119–123.
    1. Campello E, Spiezia L, Radu CM, Bulato C, Castelli M, Gavasso S, Simioni P. Endothelial, platelet, and tissue factor-bearing microparticles in cancer patients with and without venous thromboembolism. Thromb Res. 2011;127(5):473–477. doi: 10.1016/j.thromres.2011.01.002.
    1. Tesselaar ME, Romijn FP, Van Der Linden IK, Prins FA, Bertina RM, Osanto S. Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost. 2007;5:520–527. doi: 10.1111/j.1538-7836.2007.02369.x.
    1. Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncology. 2009;7(29):4839–4847. doi: 10.1200/JCO.2009.22.3271.
    1. Sousou T, Khorana A. New insights into cancer-associated thrombosis. Arterioscler Thromb Vasc Biol. 2009;29(3):316–320. doi: 10.1161/ATVBAHA.108.182196.
    1. Callander NS, Varki N, Rao LV. Immunohistochemical identification of tissue factor in solid tumors. Cancer. 1992;70:1194–1201. doi: 10.1002/1097-0142(19920901)70:5<1194::AID-CNCR2820700528>;2-E.
    1. Ornstein DL, Zacharski LR, Memoli VA, Kisiel W, Kudryk BJ, Hunt J, Rousseau SM, Stump DC. Coexisting macrophageassociated fibrin formation and tumor cell urokinase in squamous cell and adenocarcinoma of the lung tissues. Cancer. 1991;68:1061–1067. doi: 10.1002/1097-0142(19910901)68:5<1061::AID-CNCR2820680525>;2-D.
    1. Sawada M, Miyake S, Ohdama S, Matsubara O, Masuda S, Yakumaru K, Yoshizawa Y. Expression of tissue factor in nonsmall-cell lung cancers and its relationship to metastasis. Br J Cancer. 1999;79(3–4):472–477. doi: 10.1038/sj.bjc.6690073.
    1. Goldin-Lang P, Tran QV, Fichtner I. Tissue factor expression pattern in human non-small cell lung cancer tissues indicate increased blood thrombogenicity and tumor metastasis. Oncol Rep. 2008;20(1):123–8.
    1. Minamiya Y, Matsuzaki I, Sageshima M, Saito H, Taguchi K, Nakagawa T, Ogawa J. Expression of tissue factor mRNA and invasion of blood vessels by tumor cells in non-small cell lung cancer. Surg Today. 2004;34:1–5. doi: 10.1007/s00595-003-2643-y.
    1. Sato T, Tsujino I, Ikeda D, Ieko M, Nishimura M. Trousseau’s syndrome associated with tissue factor produced by pulmonary adenocarcinoma. Thorax. 2006;61:1009–1010. doi: 10.1136/thx.2004.031492.
    1. Del Conde I, Bharwani LD, Dietzen DJ, Pendurthi U, Thiagarajan P, López JA. Microvesicle-associated tissue factor and Trousseau’s syndrome. J Thromb Haemost. 2007;5(1):70–4. doi: 10.1111/j.1538-7836.2006.02301.x.
    1. Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T. Prognostic impact of thrombocytosis in resectable non-small cell lung cancer. Interactive Cardiovascular Thoracic Surgery. 2008;7:613–5. doi: 10.1510/icvts.2007.174391.
    1. Pedersen LM, Milman N. Prognostic significance of thrombocytosis in patients with primary lung cancer. Eur Respiratory J. 1996;9:1826–30. doi: 10.1183/09031936.96.09091826.
    1. Maraz A, Furak J, Varga Z. Thrombocytosis has a negative prognostic value in lung cancer. Anticancer Res. 2013;33(4):1725–9.
    1. Haas S. Venous thromboembolism in medical patients—the scope of the problem. Semin Thromb Hemost. 2003;29(supplement 1):17–21. doi: 10.1055/s-2003-45413.
    1. Demirci NI, Turay UI, Ylmaz A, Erdogan Y, Biber Ç, Yücel H. A vascular events in lung cancer. Asian Pac J Cancer Prev. 2011;12(10):2685–7.
    1. Taguchi O, Gabazza E, Yasui H, Kobayashi T, Yoshida M, Kobayashi H. Prognostic significance of plasma D-dimer levels in patients with lung cancer. Thorax. 1997;52(6):563–565. doi: 10.1136/thx.52.6.563.
    1. Altiay G, Ciftci A, Demir M. High plasma D-dimer level is associated with decreased survival in patients with lung cancer. Clin Oncol (R Coll Radiol) 2007;19(7):494–8. doi: 10.1016/j.clon.2007.04.002.
    1. Ferroni P, Martini F, Portarena I. Novel high-sensitive D-dimer determination predicts chemotherapy-associated venous thromboembolism in intermediate risk lung cancer patients. Clin Lung Cancer. 2012;13(6):482–7. doi: 10.1016/j.cllc.2012.03.005.
    1. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902–4907. doi: 10.1182/blood-2007-10-116327.
    1. Zecchina G, Ghio P, Bosio S, Cravino M, Camaschella C, Scagliotti GV. Reactive thrombocytosis might contribute to chemotherapy-related thrombophilia in patients with lung cancer. Clinical Lung Cancer. 2007;8(4):264–267. doi: 10.3816/CLC.2007.n.004.
    1. Sack GH, Jr, Levin J, Bell WR. Trousseau’s syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine (Baltimore) 1977;56:1–37. doi: 10.1097/00005792-197756010-00001.
    1. Levi D, Tagalakis V, Cohen V, Kasymjanova G, Small D. The Risk of Deep Vein Thrombosis in Lung Cancer Patients [abstract] Atlanta: American Thoracic Society; 2006. p. Abstract 7159.
    1. 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.
    1. Lee YG, Kim I, Lee E, Bang SM, Kang CH, Kim YT, et al. Risk factors and prognostic impact of venous thromboembolism in Asian patients with non small cell lung cancer. Thromb Haemost. 2014;111(6):1112–20. doi: 10.1160/TH13-11-0956.
    1. Paesmans M. Benefits of chemotherapy for quality of life in patients with advanced non small cell lung cancer. Curr Opin Oncol. 2002;14:389–393. doi: 10.1097/00001622-200207000-00003.
    1. Crivellari G, Monfardini S, Stragliotto S, Marino D, Aversa SM. Increasing chemotherapy in small-cell lung cancer: from dose intensity and density to megadoses. Oncologist. 2007;12:79–89. doi: 10.1634/theoncologist.12-1-79.
    1. Heit JA. Risk factors for venous thromboembolism. Clin Chest Med. 2003;24:1–12. doi: 10.1016/S0272-5231(02)00077-1.
    1. Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy- associated venous thromboembolism in a prospective observational study. Cancer. 2005;104:2822–2829. doi: 10.1002/cncr.21496.
    1. Hicks LK, Cheung MC, Ding K, Hasan B, Seymour L, Le Maître A, et al. Venous thromboembolism and nonsmall cell lung cancer: a pooled analysis of National Cancer Institute of Canada Clinical Trials Group. Trials Cancer. 2009;115:5516–25. doi: 10.1002/cncr.24596.
    1. Numico G, Garrone O, Dongiovanni V, Silvestris N, Colantonio I, Di Costanzo G, et al. Prospective evaluation of major vascular events in patients with nonsmall cell lung carcinoma treated with cisplatin and gemcitabine. Cancer. 2005;103:994–999. doi: 10.1002/cncr.20893.
    1. Huang H, Korn JR, Mallick R, Friedman M, Nichols C, Menzin J. Incidence of venous thromboembolism among chemotherapy-treated patients with lung cancer and its association with mortality: a retrospective database study. J Thromb Thrombolysis. 2012;34(4):446–56. doi: 10.1007/s11239-012-0741-7.
    1. Shah MA, Ilson D, Kelsen DP. Thromboembolic events in gastric cancer: high incidence in patients receiving irinotecan- and bevacizumab- based therapy. J Clin Oncol. 2005;23:2574–2576. doi: 10.1200/JCO.2005.81.908.
    1. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342. doi: 10.1056/NEJMoa032691.
    1. Scappaticci F, Skillings J, Holden S, Gerber HP, Miller K, Kabbinavar F, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemiotherapy and bevacizumab. J Natl Cancer Inst. 2007;99(16):1232–9. doi: 10.1093/jnci/djm086.
    1. Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA. 2008;300:2277–2285. doi: 10.1001/jama.2008.656.
    1. Yang Y, Zhou Z, Niu XM, Li ZM, Chen ZW, Jian H, Ai XH, Cheng BJ, Liao ML, Lu S. Clinical analysis of postoperative venous thromboembolism risk factors in lung cancer patients. J Surg Oncol. 2012;106(6):736–41. doi: 10.1002/jso.23190.
    1. Behrendt CE, Ruiz RB. Venous thromboembolism among patients with advanced lung cancer randomized to prinomastat or placebo, plus chemotherapy. Thromb Haemost. 2003;90:734–737.
    1. Paz-Ares L, Douillard JY, Koralewski P, Manegold C, Smit EF, Reyes JM, et al. Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage nonsmall-cell lung cancer. J Clin Oncol. 2006;24:1428–1434. doi: 10.1200/JCO.2005.04.3299.
    1. ENOXACAN Study Group Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg. 1997;84:1099–1103. doi: 10.1002/bjs.1800840817.
    1. Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients. Results of meta-analysis. Ann Surg. 1988;208(2):227–40. doi: 10.1097/00000658-198808000-00016.
    1. White RH, Zhou H, Romanos PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost. 2003;90:446–455.
    1. Ziomek S, Read RC, Tobler HG, Harrell JE, Jr, Gocio JC, Fink LM, Ranval TJ, et al. Thromboembolism in patients undergoing thoracotomy. Ann Thorac Surg. 1993;56:223–6. doi: 10.1016/0003-4975(93)91151-C.
    1. Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, Jahanzeb M, et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol. 2007;25:490–505. doi: 10.1200/JCO.2007.14.1283.
    1. Swiniarska J, Zekanowska E, Dancewicz M, Bella M, Szczesny TJ, Kowalewski J. J. Pneumonectomy due to lung cancer results in a more pronounced activation of coagulation system than lobectomy. Eur J Cardiothorac Surg. 2009;36:1064–8. doi: 10.1016/j.ejcts.2009.04.070.
    1. Mason DP, Quader MA, Blackstone EH, Rajeswaran J, DeCamp MM, Murthy SC, Quader AK, Rice TW. Thromboembolism after pneumonectomy for malignancy: an indipendent marker of poor outcome. J Thorac Cardiovasc Surg. 2006;131:711–718. doi: 10.1016/j.jtcvs.2005.10.027.
    1. Dentali F, Malato A, Ageno W, Imperatori A, Cajozzo M, Rotolo N, Douketis J, Siragusa S, Crowther M. Incidence of venous thromboembolism in patients undergoing thoracotomy for lung cancer. J Thorac Cardiovasc Surg. 2008;135:705–6. doi: 10.1016/j.jtcvs.2007.10.036.
    1. Gómez-Hernández T, Rodríguez-Pérez M, Novoa-Valentín N, Jiménez-López M, Aranda-Alcaide JL, Varela-Simó G. Prevalence of venous thromboembolism in elective thoracic surgery maría. Arch Bronconeumol. 2013;49(7):297–302. doi: 10.1016/j.arbres.2013.01.011.
    1. Christensen TD, Vad H, Pedersen S, Hvas AM, Wotton R, Naidu B, Larsen TB. Venous thromboembolism in patients undergoing operations for lung cancer: a systematic review. Ann Thorac Surg. 2014;97(2):394–400. doi: 10.1016/j.athoracsur.2013.10.074.
    1. Kalweit G, Huwer H, Volkmer I, Petzold T, Gams E. Pulmonary embolism: a frequent cause of acute fatality after lung resection. Eur J Cardiothorac Surg. 1996;10:242–246. doi: 10.1016/S1010-7940(96)80146-1.
    1. Weder W, Collaud S, Eberhardt WE, Hillinger S, Welter S, Stahel R, Stamatis G. Pneumonectomy is a valuable treatment option after neoadjuvant therapy for stage iii non-small-cell lung cancer. J Thorac Cardiovasc Surg. 2010;139:1424–30. doi: 10.1016/j.jtcvs.2010.02.039.
    1. Haas SK, Freund M, Heigener D, Heilmann L, Kemkes-Matthes B, von Tempelhoff GF, Melzer N, Kakkar AK, et al. Low-molecular-weight heparin versus placebo for the prevention of venous thromboembolism in metastatic breast cancer or stage III/IV lung cancer. Clin Appl Thromb Hemost. 2012;18(2):159–65. doi: 10.1177/1076029611433769.
    1. Zhang J, Zhang YL, Ma KX, QU JM. Efficacy and safety of adjunctive anticoagulation in patients with lung cancer without indication for anticoagulants : a systematic review and metanalysis. Thorax. 2013;68(5):442–50. doi: 10.1136/thoraxjnl-2012-202592.
    1. Si G, Lee A, Lee US, Choi HJ, Kang MH, Kang JH, et al. Clinical significance of neutrophil-lymphocyte ratio in venous thromboembolism patients with lung cancer. Lung Cancer. 2014;84(1):79–85. doi: 10.1016/j.lungcan.2014.01.014.
    1. Sevestre MA, Belizna C, Durant C, Bosson JL, Vedrine L, Cajfinger F, et al. Compliance with recommendations of clinical practice in the management of venous thromboembolism in cancer: the CARMEN study. J Mal Vasc. 2014;39(3):161–8. doi: 10.1016/j.jmv.2014.03.001.
    1. Alexander M, Kirska S, MacManaus M, Ball D, Solomon B, Burbury K. Thromboprophylaxis for lung cancer patients-multimodality assessment of clinician practices, perceptions and decision support tools. Support Care Cancer. 2014;22(7):1915–22. doi: 10.1007/s00520-014-2170-y.
    1. Steuer CE, Behera M, Kim S, Patel N, Chen Z, Pillai R, et al. Predictors and outcomes of venous thromboembolism in hospitalized lung cancer patients: a Nationwide Inpatient Sample database analysis. Lung Cancer. 2015;88:80–84. doi: 10.1016/j.lungcan.2015.01.022.

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