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Plasminogen activator inhibitor-1 gene promoter 4G/5G polymorphism and risks of peripherally inserted central catheter–related venous thrombosis in patients with lung cancer: a prospective cohort study

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Abstract

Purpose

This study investigated the influence of plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms and other contributing clinical factors on peripherally inserted central catheter–related venous thrombosis (PICC-RVT) in Chinese patients with lung cancer.

Methods

We conducted a prospective study of 237 participants. Blood samples were collected to detect the PAI-1 4G/5G genotype. Venous thromboembolism risk was calculated by the Caprini risk assessment model. Color Doppler ultrasonography was performed every 7 days for 3 weeks to confirm PICC-RVT.

Results

The rate of PICC-RVT was 13.50% (32/237). The 5G/5G, 4G/5G, and 4G/4G genotypes were found in 12.50% vs 17.56%, 59.38% vs 49.27%, and 28.12% vs 34.17% in the thrombus group and the non-thrombus group of the participants. No difference was observed in the distribution frequency of the three genotypes between the thrombus and non-thrombus groups. A higher fibrinogen level (OR 1.194, 95% CI 1.004–1.420, P = 0.045) and a higher Caprini score (OR 1.698, 95% CI 1.103–2.614, P = 0.016) were statistically significant risk factors for PICC-RVT. Compared with patients who underwent a pemetrexed/cisplatin regimen, those who were administered paclitaxel/cisplatin (OR 18.332, 95% CI 2.890–116.278, P = 0.002) or gemcitabine/cisplatin (OR 6.617, 95% CI 1.210–36.180, P = 0.029) were at increased risk of PICC-RVT.

Conclusion

Our finding suggested that there is no statistically significant influence of the PAI-1 4G/5G gene variant on PICC-RVT in Chinese patients with lung cancer. However, patients with higher Caprini scores and higher fibrinogen levels are at increased risk for PICC-RVT, as are patients receiving chemotherapy. Clinical staff should carefully perform a risk assessment for patients with PICC. Those with the above risk factors should pay close attention and take timely and effective preventive measures.

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References

  1. Chopra V, Kaatz S, Conlon A, Paje D, Grant PJ, Rogers MAM, Bernstein SJ, Saint S, Flanders SA (2017) The Michigan Risk Score to predict peripherally inserted central catheter-associated thrombosis. J Thromb Haemost 15(10):1951–1962. https://doi.org/10.1111/jth.13794

    Article  PubMed  CAS  Google Scholar 

  2. Kelly LJ, Green A, Hainey K (2015) Implementing a new teaching and learning strategy for CVAD care. Br J Nurs 24(8):S4-8–S9, S12. https://doi.org/10.12968/bjon.2015.24.Sup8.S4

    Article  Google Scholar 

  3. Harrold K, Martin A, Scarlett C (2016) Proactive PICC placement: evaluating the patient experience. Br J Nurs 25 (8):S4–S14. https://doi.org/10.12968/bjon.2016.25.8.S4

  4. Winters JP, Callas PW, Cushman M, Repp AB, Zakai NA (2015) Central venous catheters and upper extremity deep vein thrombosis in medical inpatients: the Medical Inpatients and Thrombosis (MITH) Study. J Thromb Haemost 13(12):2155–2160. https://doi.org/10.1111/jth.13131

    Article  PubMed  CAS  Google Scholar 

  5. Koo CM, Vissapragada R, Sharp R, Nguyen P, Ung T, Solanki C, Esterman A (2018) ABO blood group related venous thrombosis risk in patients with peripherally inserted central catheters. Br J Radiol 91(1082):20170560. https://doi.org/10.1259/bjr.20170560

    Article  PubMed  PubMed Central  Google Scholar 

  6. Austin RE, Shahriar S, Siavash B, Jeschke MG (2015) Peripherally inserted central venous catheter safety in burn care: a single-center retrospective cohort review. Journal of Burn Care & Research 36(1):111–117. https://doi.org/10.1097/BCR.0000000000000207

    Article  Google Scholar 

  7. Ahn DH, Illum HB, Wang DH, Sharma A, Dowell JE (2013) Upper extremity venous thrombosis in patients with cancer with peripherally inserted central venous catheters: a retrospective analysis of risk factors. J Oncol Pract 9(1):e8–e12. https://doi.org/10.1200/JOP.2012.000595

    Article  PubMed  Google Scholar 

  8. Paauw JD, Borders H, Ingalls N, Boomstra S, Lambke S, Fedeson B, Goldsmith A, Davis AT (2008) The incidence of PICC line-associated thrombosis with and without the use of prophylactic anticoagulants. JPEN J Parenter Enteral Nutr 32(4):443–447. https://doi.org/10.1177/0148607108319801

    Article  PubMed  CAS  Google Scholar 

  9. Maxim I, Mondshein JI, S William S, Shlansky-Goldberg RD, Soulen MC, Trerotola SO (2014) Peripherally inserted central catheter thrombosis—reverse tapered versus nontapered catheters: a randomized controlled study. Journal of Vascular & Interventional Radiology Jvir 25(1):85–91.e81. https://doi.org/10.1016/j.jvir.2013.10.009

    Article  Google Scholar 

  10. Noble S, Pasi J (2010) Epidemiology and pathophysiology of cancer-associated thrombosis. British Journal of Cancer 102 Suppl 1(Suppl 1):S2–S9. https://doi.org/10.1038/sj.bjc.6605599

    Article  Google Scholar 

  11. Shinagare AB, Guo M, Hatabu H, Krajewski KM, Andriole K, Van den Abbeele AD, DiPiro PJ, Nishino M (2011) Incidence of pulmonary embolism in oncologic outpatients at a tertiary cancer center. Cancer 117(16):3860–3866

    Article  Google Scholar 

  12. Connolly GC, Menapace L, Safadjou S, Francis CW, Khorana AA (2013) Prevalence and clinical significance of incidental and clinically suspected venous thromboembolism in lung cancer patients. Clin Lung Cancer 14(6):713–718. https://doi.org/10.1016/j.cllc.2013.06.003

    Article  PubMed  Google Scholar 

  13. Horsted F, West J, Grainge MJ (2012) Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 9(7):e1001275. https://doi.org/10.1371/journal.pmed.1001275

    Article  PubMed  PubMed Central  Google Scholar 

  14. Han T, Zhang G, Yan D, Yang H, Ma T, Ye Z (2016) Modulation of plasminogen activator inhibitor-1 (PAI-1) by the naphthoquinone shikonin. Fitoterapia 113:117–122. https://doi.org/10.1016/j.fitote.2016.07.010

    Article  PubMed  CAS  Google Scholar 

  15. Stegnar M, Uhrin P, Peternel P, Mavri A, Salobir-Pajnic B, Stare J, Binder BR (1998) The 4G/5G sequence polymorphism in the promoter of plasminogen activator inhibitor-1 (PAI-1) gene: relationship to plasma PAI-1 level in venous thromboembolism. Thromb Haemost 79(5):975–979. https://doi.org/10.1055/s-0037-1615105

    Article  PubMed  CAS  Google Scholar 

  16. Ossei-Gerning N, Mansfield MW, Stickland MH, Wilson IJ, Grant PJ (1997) Plasminogen activator inhibitor-1 promoter 4G/5G genotype and plasma levels in relation to a history of myocardial infarction in patients characterized by coronary angiography. Arterioscler Thromb Vasc Biol 17(1):33–37. https://doi.org/10.1161/01.ATV.17.1.33

    Article  PubMed  CAS  Google Scholar 

  17. Balta G, Altay C, Gurgey A (2002) PAI-1 gene 4G/5G genotype: a risk factor for thrombosis in vessels of internal organs. Am J Hematol 71(2):89–93. https://doi.org/10.1002/ajh.10192

    Article  PubMed  CAS  Google Scholar 

  18. Hooper WC, Lally C, Austin H, Renshaw M, Dilley A, Wenger NK, Phillips DJ, Whitsett C, Rawlins P, Evatt BL (2000) The role of the t-PA I/D and PAI-1 4G/5G polymorphisms in African-American adults with a diagnosis of myocardial infarction or venous thromboembolism. Thromb Res 99(3):223–230. https://doi.org/10.1016/S0049-3848(00)00236-X

    Article  PubMed  CAS  Google Scholar 

  19. Pan L, Zhao Q, Yang X (2014) Risk factors for venous thrombosis associated with peripherally inserted central venous catheters. Int J Clin Exp Med 7(12):5814–5819

    PubMed  PubMed Central  Google Scholar 

  20. Liu K, Zhou Y, Xie W, Gu Z, Jin Y, Ye X, Chen X, Fan B, Wang H, Cui Y (2018) Handgrip exercise reduces peripherally inserted central catheter-related venous thrombosis in patients with solid cancers: a randomized controlled trial. Int J Nurs Stud 86:99–106. https://doi.org/10.1016/j.ijnurstu.2018.06.004

    Article  PubMed  Google Scholar 

  21. Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, Samama CM (2012) Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(5):1369–1369. https://doi.org/10.1378/chest.11-2297 e277S

    Article  CAS  Google Scholar 

  22. Zhou H, Hu Y, Li X, Wang L, Wang M, Xiao J, Yi Q (2018) Assessment of the Risk of venous thromboembolism in medical inpatients using the Padua Prediction Score and Caprini risk assessment model. J Atheroscler Thromb 25(11):1091–1104. https://doi.org/10.5551/jat.43653

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, Samama CM (2012) Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141((2, Supplement)):e227S–e277S. https://doi.org/10.1378/chest.11-2297

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Pannucci CJ, Swistun L, Macdonald JK, Henke PK, Brooke BS (2017) Individualized venous thromboembolism risk stratification using the 2005 Caprini score to identify the benefits and harms of chemoprophylaxis in surgical patients: a meta-analysis. Ann Surg 265(6):1094–1103. https://doi.org/10.1097/SLA.0000000000002126

    Article  PubMed  Google Scholar 

  25. Haixia Z, Lan W, Xiaoling W, Yongjiang T, Jing Y, Bo W, Yu Y, Binmiao L, Ke W, Xuemei O (2014) Validation of a venous thromboembolism risk assessment model in hospitalized chinese patients: a case-control study. J Atheroscler Thromb 21(3):261–272. https://doi.org/10.5551/jat.20891

    Article  Google Scholar 

  26. Brown NJ, Murphey LJ, Srikuma N, Koschachuhanan N, Williams GH, Vaughan DE (2001) Interactive effect of PAI-1 4G/5G genotype and salt intake on PAI-1 antigen. Arterioscler Thromb Vasc Biol 21(6):1071–1077. https://doi.org/10.1161/01.atv.21.6.1071

    Article  PubMed  CAS  Google Scholar 

  27. Kain K, Catto AJ, Carter AM, Young J, Bamford J, Bavington J, Grant PJ (2001) Decreased fibrinolytic potential in South Asian women with ischaemic cerebrovascular disease. Br J Haematol 114(1):155–161. https://doi.org/10.1046/j.1365-2141.2001.02916.x

    Article  PubMed  CAS  Google Scholar 

  28. WUBULI G, MAHEMUTI A, TUNIYAZI G, XIA Y, HU X, Y ZHANG (2014) Asociation betwen PAI-1activity and its polymorphism in Uygur patients with venous thromboembolism of Xinjiang. Journal of Clinical Cardiology 30(7):576–582. https://doi.org/10.13201/j.issn.1001-1439.2014.07.007

    Article  CAS  Google Scholar 

  29. Prabhudesai A, Shetty S, Ghosh K, Kulkarni B (2017) Investigation of Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G promoter polymorphism in Indian venous thrombosis patients: a case-control study. Eur J Haematol 99(3):249–254. https://doi.org/10.1111/ejh.12912

    Article  PubMed  CAS  Google Scholar 

  30. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Miletich JP (1997) Arterial and venous thrombosis is not associated with the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor gene in a large cohort of US men. Circulation 95(1):59–62. https://doi.org/10.1161/01.CIR.95.1.59

    Article  PubMed  CAS  Google Scholar 

  31. Akar N, Yilmaz E, Akar E, Avcu F, Yalcin A, Cin S (2000) Effect of plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish deep vein thrombotic patients with and without FV1691 G-A. Thromb Res 97(4):227–230

    Article  CAS  Google Scholar 

  32. Song C, Burgess S, Eicher JD, O’Donnell CJ, Johnson AD (2017) Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease. J Am Heart Assoc 6(6). https://doi.org/10.1161/JAHA.116.004918

  33. Barnard SA, Pieters M, De Lange Z (2016) The contribution of different adipose tissue depots to plasma plasminogen activator inhibitor-1 (PAI-1) levels. Blood Rev 30(6):421–429. https://doi.org/10.1016/j.blre.2016.05.002

    Article  PubMed  CAS  Google Scholar 

  34. Mayerhofer K, Stolzlechner J, Yildiz S, Haider K, Heinzl H, Jakesz R, Pecherstorfer M, Rosen H, Sevelda P, Zeillinger R, Speiser P (1996) Plasminogen activator inhibitor 1 and prognosis in breast carcinoma. Geburtshilfe Frauenheilkd 56(1):23–27. https://doi.org/10.1055/s-2007-1023244

    Article  PubMed  CAS  Google Scholar 

  35. Abdullah BJ, Mohammad N, Sangkar JV, Abd Aziz YF, Gan GG, Goh KY, Benedict I (2005) Incidence of upper limb venous thrombosis associated with peripherally inserted central catheters (PICC). Br J Radiol 78(931):596–600. https://doi.org/10.1259/bjr/32639616

    Article  PubMed  CAS  Google Scholar 

  36. Sterbling HM, Rosen AK, Hachey KJ, Vellanki NS, Hewes PD, Rao SR, Pinjic E, Fernando HC, Litle VR (2018) Caprini risk model decreases venous thromboembolism rates in thoracic surgery cancer patients. Ann Thorac Surg 105(3):879–885. https://doi.org/10.1016/j.athoracsur.2017.10.013

    Article  PubMed  Google Scholar 

  37. Wolny-Rokicka E, Brzeźniakiewicz-Janus K, Wydmański J, Tukiendorf A, Zembroń-Łacny A (2018) Analysis of haemostasis biomarkers in patients with advanced stage lung cancer during hypofractionated radiotherapy treatment. J Int Med Res 46(5):1876–1883. https://doi.org/10.1177/0300060517750976

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zecchina G, Ghio P, Bosio S, Cravino M, Camaschella C, Scagliotti GV (2007) Reactive thrombocytosis might contribute to chemotherapy-related thrombophilia in patients with lung cancer. Clinical Lung Cancer 8(4):264–267. https://doi.org/10.3816/CLC.2007.n.004

    Article  PubMed  CAS  Google Scholar 

  39. Kadlec B, Skrickova J, Merta Z, Dusek L, Jarkovsky J (2014) The incidence and predictors of thromboembolic events in patients with lung cancer. Sci World J 2:125706. https://doi.org/10.1155/2014/125706

    Article  Google Scholar 

  40. Hao N, Xie X, Zhou Z, Li J, Kang L, Wu H, Guo P, Dang C, Zhang H (2017) Nomogram predicted risk of peripherally inserted central catheter related thrombosis. Sci Rep 7(1):6344. https://doi.org/10.1038/s41598-017-06609-x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Kang JR, Long LH, Yan SW, Wei WW, Jun HZ, Chen W (2017) Peripherally inserted central catheter-related vein thrombosis in patients with lung cancer. Clin Appl Thromb Hemost 23(2):181–186. https://doi.org/10.1177/1076029615595880

    Article  PubMed  Google Scholar 

  42. Moore RA, Adel N, Riedel E, Bhutani M, Feldman DR, Tabbara NE, Soff G, Parameswaran R, Hassoun H (2011) High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol 29(25):3466–3473. https://doi.org/10.1200/JCO.2011.35.5669

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Nakayama M, Munemura Y, Kanaya N, Tsuchida H, Namiki A (2001) Efficacy of alkalinized lidocaine for reducing pain on intravenous and epidural catheterization. J Anesth 15(4):201–203. https://doi.org/10.1007/s005400170003

    Article  PubMed  CAS  Google Scholar 

  44. Nelson AL (1995) Neutralizing pH of lidocaine reduces pain during Norplant system insertion procedure. Contraception 51(5):299–301. https://doi.org/10.1016/0010-7824(95)00078-O

    Article  PubMed  CAS  Google Scholar 

  45. Liu Y, Gao Y, Wei L, Chen W, Ma X, Song L (2015) Peripherally inserted central catheter thrombosis incidence and risk factors in cancer patients: a double-center prospective investigation. Ther Clin Risk Manag 11:153–160. https://doi.org/10.2147/TCRM.S73379

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Dr. Jianxin Xue, Dr. Hongyan Zhou, and Dr. Zhoupeng Wu for editorial assistance.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Not applicable.

Funding

This work was supported by the major research and development projects of the Sichuan Provincial Science and Technology Department (No. 2018SZ0203).

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Author notes

  1. Yan Fu, Qiufen Xiang and Lingling Xie contributed equally to this work.

Authors and Affiliations

  1. West China School of Nursing/Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Yue Feng

  2. Department of Thoracic Oncology, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, China

    Yan Fu, Qiufen Xiang, Lingling Xie, Chunhua Yu & Junying Li

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  1. Yue Feng
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Contributions

Yue Feng: Formal analysis; writing—original draft

Yan Fu: Resources; supervision

Qiufen Xiang: Investigation; resources

Lingling Xie: Investigation; data curation

Chunhua Yu: Conceptualization; resources; writing—review and editing

Junying Li: Methodology; writing—review and editing; funding acquisition

Corresponding authors

Correspondence to Chunhua Yu or Junying Li.

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The study protocol was approved by the Medical Ethics Committee of our hospital (2018-345). All patients involved in this study gave their informed consent.

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Patients signed informed consent regarding publishing their data.

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The authors declare no competing interests.

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Feng, Y., Fu, Y., Xiang, Q. et al. Plasminogen activator inhibitor-1 gene promoter 4G/5G polymorphism and risks of peripherally inserted central catheter–related venous thrombosis in patients with lung cancer: a prospective cohort study. Support Care Cancer 29, 6431–6439 (2021). https://doi.org/10.1007/s00520-021-06207-8

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