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Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

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Abstract

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.

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References

  1. Rickles FR, Falanga A. Molecular basis for the relationship between thrombosis and cancer. Thromb Res. 2001;102:V215–24.

    Article  PubMed  CAS  Google Scholar 

  2. Tieken C, Versteeg HH. Anticoagulants versus cancer. Thromb Res. 2016;140:S148–53.

    Article  PubMed  CAS  Google Scholar 

  3. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med. 2012;9:e1001275.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bochenek J, Puskulluoglu M, Krzemieniecki K. The antineoplastic effect of low-molecular-weight heparins—a literature review. Contemp Oncol. 2013;17:6–13.

    CAS  Google Scholar 

  5. Luzzatto G, Schafer AI. The prethrombotic state in cancer. Semin Oncol. 1990;17:147–59.

    PubMed  CAS  Google Scholar 

  6. Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation. 2003;107:I17–21.

    Article  PubMed  Google Scholar 

  7. Paschoa AF. Heparin: 100 years of pleiotropic effects. J Thromb Thrombolysis. 2016;41:636–43.

    Article  PubMed  CAS  Google Scholar 

  8. Noble S. Heparins and cancer survival: where do we stand? Thromb Res. 2014;133:S133–8.

    Article  PubMed  CAS  Google Scholar 

  9. Lever R, Mulloy B, Page CP. Heparin—a century of progress. Berlin: Springer; 2012.

    Book  Google Scholar 

  10. Borsig L. Antimetastatic activities of heparins and modified heparins. Experimental evidence. Thromb Res. 2010;125:S66–71.

    Article  PubMed  Google Scholar 

  11. Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C, et al. Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol. 2005;23:2123–9.

    Article  PubMed  CAS  Google Scholar 

  12. Boccaccio C, Comoglio PM. Genetic link between cancer and thrombosis. J Clin Oncol. 2009;27:4827–33.

    Article  PubMed  CAS  Google Scholar 

  13. Kuderer NM, Ortel TL, Francis CW. Impact of venous thromboembolism and anticoagulation on cancer and cancer survival. J Clin Oncol. 2009;27:4902–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Smorenburg SM, Van Noorden CJ. The complex effects of heparins on cancer progression and metastasis in experimental studies. Pharmacol Rev. 2001;53:93–105.

    PubMed  CAS  Google Scholar 

  15. Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol. 2005;6:401–10.

    Article  PubMed  Google Scholar 

  16. Falanga A, Gordon SG. Isolation and characterization of cancer procoagulant: a cysteine proteinase from malignant tissue. Biochemistry. 1985;24:5558–67.

    Article  PubMed  CAS  Google Scholar 

  17. Varki A. Trousseau’s syndrome: multiple definitions and multiple mechanisms. Blood. 2007;110:1723–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Bendas G, Borsig L. Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int J Cell Biol. 2012;2012:676731.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest. 2003;124:58S–68S.

    Article  PubMed  CAS  Google Scholar 

  20. Borensztajn KS, Spek CA. Protease-activated receptors, apoptosis and tumor growth. Pathophysiol Haemost Thromb. 2008;36:137–47.

    Article  PubMed  CAS  Google Scholar 

  21. Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA. 2001;98:3352–7.

    Article  PubMed  CAS  Google Scholar 

  22. Borsig L, Wong R, Hynes RO, Varki NM, Varki A. Synergistic effects of L-and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci USA. 2002;99:2193–8.

    Article  PubMed  CAS  Google Scholar 

  23. Hejna M, Raderer M, Zielinski CC. Inhibition of metastases by anticoagulants. J Natl Cancer Inst. 1999;91:22–36.

    Article  PubMed  CAS  Google Scholar 

  24. Au YP, Kenagy RD, Clowes MM, Clowes AW. Mechanisms of inhibition by heparin of vascular smooth muscle cell proliferation and migration. Haemostasis. 1993;23:177–82.

    PubMed  CAS  Google Scholar 

  25. Stevenson JL, Choi SH, Varki A. Differential metastasis inhibition by clinically relevant levels of heparins-correlation with selectin inhibition, not antithrombotic activity. Clin Cancer Res. 2005;11:7003–11.

    Article  PubMed  CAS  Google Scholar 

  26. Amirkhosravi A, Mousa SA, Amaya M, Francis JL. Antimetastatic effect of tinzaparin, a low-molecular-weight heparin. J Thromb Haemost. 2003;1:1972–6.

    Article  PubMed  CAS  Google Scholar 

  27. Mousa SA, Fareed J, Iqbal O, Kaiser B. Tissue factor pathway inhibitor in thrombosis and beyond. Methods Mol Med. 2004;93:133–55.

    PubMed  CAS  Google Scholar 

  28. Mousa SA, Mohamed S. Inhibition of endothelial cell tube formation by the low molecular weight heparin, tinzaparin, is mediated by tissue factor pathway inhibitor. Thromb Haemost. 2004;92:627–33.

    PubMed  CAS  Google Scholar 

  29. Mousa SA, Mohamed S. Anti-angiogenic mechanisms and efficacy of the low molecular weight heparin, tinzaparin: anti-cancer efficacy. Oncol Rep. 2004;12:683–8.

    PubMed  CAS  Google Scholar 

  30. Khorana AA, Sahni A, Altland OD, Francis CW. Heparin inhibition of endothelial cell proliferation and organization is dependent on molecular weight. Arterioscler Thromb Vasc Biol. 2003;23:2110–5.

    Article  PubMed  CAS  Google Scholar 

  31. Jayson GC, Gallagher JT. Heparin oligosaccharides: inhibitors of the biological activity of bFGF on Caco-2 cells. Br J Cancer. 1997;75:9–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Li HL, Ye KH, Zhang HW, Luo YR, Ren XD, Xiong AH, et al. Effect of heparin on apoptosis in human nasopharyngeal carcinoma CNE2 cells. Cell Res. 2001;11:311–5.

    Article  PubMed  CAS  Google Scholar 

  33. Au YPT, Kenagy RD, Clowes MM, Clowes AW. Mechanisms of inhibition by heparin of vascular smooth muscle cell proliferation and migration. Haemostasis. 1993;23(suppl 1):177–82.

    PubMed  CAS  Google Scholar 

  34. Sylvester DM, Liu SY, Meadows GG. Augmentation of antimetastatic activity of interferon and tumor necrosis factor by heparin. Immunopharmacol Immunotoxicol. 1990;12:161–80.

    Article  PubMed  CAS  Google Scholar 

  35. Leculier C, Couprie N, Adeleine P, Leitienne P, Francina A, Richard M. The effects of high molecular weight- and low molecular weight-heparins on superoxide ion production and degranulation by human polymorphonuclear leukocytes. Thromb Res. 1993;69:519–31.

    Article  PubMed  CAS  Google Scholar 

  36. Gunji Y, Lewis J, Gorelik E. Fibrin formation inhibits the in vitro cytotoxic activity of human natural and lymphokine-activated killer cells. Blood Coagul Fibrinolysis. 1990;1:663–72.

    PubMed  CAS  Google Scholar 

  37. Angelini A, Di Febbo C, Ciofani G, Di Nisio M, Baccante G, Di Ilio C, et al. Inhibition of P-glycoprotein-mediated multidrug resistance by unfractionated heparin: a new potential chemosensitizer for cancer therapy. Cancer Biol Ther. 2005;4:313–7.

    Article  PubMed  CAS  Google Scholar 

  38. Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. N Engl J Med. 2000;342:1953–8.

    Article  PubMed  CAS  Google Scholar 

  39. Maurer LH, Herndon JE 2nd, Hollis DR, Aisner J, Carey RW, Skarin AT, et al. Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study. J Clin Oncol. 1997;15:3378–87.

    Article  PubMed  CAS  Google Scholar 

  40. Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell CJ Jr, Forcier RJ, et al. Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Cancer. 1984;53:2046–52.

    Article  PubMed  CAS  Google Scholar 

  41. Levine M, Hirsh J, Gent M, Arnold A, Warr D, Falanga A, et al. Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet. 1994;343:886–9.

    Article  PubMed  CAS  Google Scholar 

  42. Daly L. The first international urokinase/warfarin trial in colorectal cancer. Clin Exp Metastasis. 1991;9:3–11.

    Article  PubMed  CAS  Google Scholar 

  43. Chahinian AP, Propert KJ, Ware JH, Zimmer B, Perry MC, Hirsh V, et al. A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. J Clin Oncol. 1989;7:993–1002.

    Article  PubMed  CAS  Google Scholar 

  44. Smorenburg SM, Vink R, Otten HM, Swaneveld F, Buller HR. The effects of vitamin K-antagonists on survival of patients with malignancy: a systematic analysis. Thromb Haemost. 2001;86:1586–7.

    Article  PubMed  CAS  Google Scholar 

  45. Smorenburg SM, Hettiarachchi RJ, Vink R, Buller HR. The effects of unfractionated heparin on survival in patients with malignancy—a systematic review. Thromb Haemost. 1999;82:1600–4.

    Article  PubMed  CAS  Google Scholar 

  46. Lebeau B, Chastang C, Brechot JM, Capron F, Dautzenberg B, Delaisements C, et al. Subcutaneous heparin treatment increases survival in small cell lung cancer. Cancer. 1994;74:38–45.

    Article  PubMed  CAS  Google Scholar 

  47. Nitti D, Wils J, Sahmoud T, Curran D, Couvreur ML, Lise M, et al. Final results of a phase III clinical trial on adjuvant intraportal infusion with heparin and 5-fluorouracil (5-FU) in resectable colon cancer (EORTC GITCCG 1983–1987). Eur J Cancer. 1997;33:1209–15.

    Article  PubMed  CAS  Google Scholar 

  48. Papaioannou AN, Polychronis AP, Kozonis JA, Nomicos J, Tsamouri M, Plataniotis GA, et al. Chemotherapy with or without anticoagulation as initial management of patients with operable colorectal cancer: a prospective study with at least 5 years follow-up. Recent Results Cancer Res. 1986;103:135–41.

    Article  PubMed  CAS  Google Scholar 

  49. Fielding LP, Hittinger R, Grace RH, Fry JS. Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma. Lancet. 1992;340:502–6.

    Article  PubMed  CAS  Google Scholar 

  50. Kingston RD, Fielding JWL, Palmer MK. Peri-operative heparin: a possible adjuvant to surgery in colo-rectal cancer? Int J Colorectal Dis. 1993;8:111–5.

    Article  PubMed  CAS  Google Scholar 

  51. Kakkar A, Hedges R, Williamson R, Kakkar V. Perioperative heparin-therapy inhibits late death from metastatic cancer. Int J Oncol. 1995;6:885–8.

    PubMed  CAS  Google Scholar 

  52. Torngren S, Rieger A. The influence of heparin and curable resection on the survival of colorectal cancer. Acta Chir Scand. 1983;149:427–9.

    PubMed  CAS  Google Scholar 

  53. Kohanna FH, Sweeney J, Hussey S, Zacharski LR, Salzman EW. Effect of perioperative low-dose heparin administration on the course of colon cancer. Surgery. 1983;93:433–8.

    PubMed  CAS  Google Scholar 

  54. Prandoni P, Lensing AW, Buller HR, Carta M, Cogo A, Vigo M, et al. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet. 1992;339:441–5.

    Article  PubMed  CAS  Google Scholar 

  55. Green D, Hull RD, Brant R, Pineo GF. Lower mortality in cancer patients treated with low-molecular-weight versus standard heparin. Lancet. 1992;339:1476.

    Article  PubMed  CAS  Google Scholar 

  56. Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg JS. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med. 1996;100:269–77.

    Article  PubMed  CAS  Google Scholar 

  57. Hettiarachchi RJ, Smorenburg SM, Ginsberg J, Levine M, Prins MH, Buller HR. Do heparins do more than just treat thrombosis? The influence of heparins on cancer spread. Thromb Haemost. 1999;82:947–52.

    Article  PubMed  CAS  Google Scholar 

  58. Lazo-Langner A, Goss GD, Spaans JN, Rodger MA. The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials. J Thromb Haemost. 2007;5:729–37.

    Article  PubMed  CAS  Google Scholar 

  59. Altinbas M, Coskun HS, Er O, Ozkan M, Eser B, Unal A, et al. A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost. 2004;2:1266–71.

    Article  PubMed  CAS  Google Scholar 

  60. Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005;23:2130–5.

    Article  PubMed  CAS  Google Scholar 

  61. Kakkar AK, Levine MN, Kadziola Z, Lemoine NR, Low V, Patel HK, et al. Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol. 2004;22:1944–8.

    Article  PubMed  CAS  Google Scholar 

  62. Sideras K, Schaefer PL, Okuno SH, Sloan JA, Kutteh L, Fitch TR, et al. Low-molecular-weight heparin in patients with advanced cancer: a phase 3 clinical trial. Mayo Clin Proc. 2006;81:758–67.

    Article  PubMed  CAS  Google Scholar 

  63. Sanford D, Naidu A, Alizadeh N, Lazo-Langner A. The effect of low molecular weight heparin on survival in cancer patients: an updated systematic review and meta-analysis of randomized trials. J Thromb Haemost. 2014;12:1076–85.

    Article  PubMed  CAS  Google Scholar 

  64. Agnelli G, Gussoni G, Bianchini C, Verso M, Mandala M, Cavanna L, et al. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol. 2009;10:943–9.

    Article  PubMed  CAS  Google Scholar 

  65. Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012;366:601–9.

    Article  PubMed  CAS  Google Scholar 

  66. van Doormaal FF, Di Nisio M, Otten HM, Richel DJ, Prins M, Buller HR. Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J Clin Oncol. 2011;29:2071–6.

    Article  PubMed  CAS  Google Scholar 

  67. Perry JR, Julian JA, Laperriere NJ, Geerts W, Agnelli G, Rogers LR, et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost. 2010;8:1959–65.

    Article  PubMed  CAS  Google Scholar 

  68. Lecumberri R, Vivanco GL, Font A, Billalabeitia EG, Gurpide A, Codina JG, et al. Adjuvant therapy with bemiparin in patients with limited-stage small cell lung cancer: results from the ABEL study. Thromb Res. 2013;132:666–70.

    Article  PubMed  CAS  Google Scholar 

  69. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–66.

    Article  PubMed  CAS  Google Scholar 

  70. Pelzer U, Opitz B, Deutschinoff G, Stauch M, Reitzig PC, Hahnfeld S, et al. Efficacy of prophylactic low-molecular weight heparin for ambulatory patients with advanced pancreatic cancer: outcomes from the CONKO-004 trial. J Clin Oncol. 2015;33:2028–34.

    Article  PubMed  CAS  Google Scholar 

  71. Macbeth F, Noble S, Evans J, Ahmed S, Cohen D, Hood K, et al. Randomized phase III trial of standard therapy plus low molecular weight heparin in patients with lung cancer: FRAGMATIC trial. J Clin Oncol. 2016;34:488–94.

    Article  PubMed  CAS  Google Scholar 

  72. Ek L, Gezelius E, Bergman B, Bendahl PO, Anderson H, Sundberg J, et al. Randomized phase III trial of low molecular weight heparin enoxaparin in addition to standard treatment in small cell lung cancer: the RASTEN trial. Ann Oncol. 2017. https://doi.org/10.1093/annonc/mdx716.

    Article  PubMed Central  Google Scholar 

  73. Meyer G, Besse B, Doubre H, Charles-Nelson A, Aquilanti S, Izadifar A, et al. Effect of low molecular weight heparin on survival of patients with resected non-small cell lung cancer: the tinzaparin in lung tumors (TILT) randomized phase III trial. Presented at XXVI International Society on Thrombosis and Haemostasis (ISTH) Congress. Berlin, Germany, 8–13 July 2017.

  74. Akaogi K, Okabe Y, Sato J, Nagashima Y, Yasumitsu H, Sugahara K, et al. Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells. Proc Natl Acad Sci USA. 1996;93:8384–9.

    Article  PubMed  CAS  Google Scholar 

  75. Christianson HC, van Kuppevelt TH, Belting M. ScFv anti-heparan sulfate antibodies unexpectedly activate endothelial and cancer cells through p38 MAPK: implications for antibody-based targeting of heparan sulfate proteoglycans in cancer. PLoS ONE. 2012;7:e49092.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Svensson KJ, Kucharzewska P, Christianson HC, Skold S, Lofstedt T, Johansson MC, et al. Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. Proc Natl Acad Sci USA. 2011;108:13147–52.

    Article  PubMed  Google Scholar 

  77. Zhao P, Gao C, Dykema K, Furge K, Feng Z, Cao B. Repeated hepatocyte growth factor neutralizing antibody treatment leads to HGF/SF unresponsiveness in human glioblastoma multiforme cells. Cancer Lett. 2010;291:209–16.

    Article  PubMed  CAS  Google Scholar 

  78. Lund EL, Olsen MW, Lipson KE, McMahon G, Howlett AR, Kristjansen PE. Improved effect of an antiangiogenic tyrosine kinase inhibitor (SU5416) by combinations with fractionated radiotherapy or low molecular weight heparin. Neoplasia. 2003;5:155–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Robins HI, O’Neill A, Gilbert M, Olsen M, Sapiente R, Berkey B, et al. Effect of dalteparin and radiation on survival and thromboembolic events in glioblastoma multiforme: a phase II ECOG trial. Cancer Chemother Pharmacol. 2008;62:227–33.

    Article  PubMed  CAS  Google Scholar 

  80. Zincircioglu SB, Kaplan MA, Isikdogan A, Cil T, Karadayi B, Dirier A, et al. Contribution of low-molecular weight heparin addition to concomitant chemoradiotherapy in the treatment of glioblastoma multiforme. J Balk Union Oncol. 2012;17:124–7.

    CAS  Google Scholar 

  81. Maraveyas A, Waters J, Roy R, Fyfe D, Propper D, Lofts F, et al. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer. 2012;48:1283–92.

    Article  PubMed  CAS  Google Scholar 

  82. Haas SK, Freund M, Heigener D, Heilmann L, Kemkes-Matthes B, von Tempelhoff GF, 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;18:159–65.

    Article  PubMed  CAS  Google Scholar 

  83. Weber C, Merminod T, Herrmann FR, Zulian GB. Prophylactic anti-coagulation in cancer palliative care: a prospective randomised study. Support Care Cancer. 2008;16:847–52.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

    I. García-Escobar

  2. Medical Oncology GU and Breast Cancer Department, Hospital Universitario Virgen Macarena, Seville, Spain

    C. Beato-Zambrano

  3. Medical Oncology, Hospital Universitario La Fe, Valencia, Spain

    J. Muñoz Langa

  4. Medical Oncology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain

    E. Brozos Vázquez

  5. Medical Oncology, Hospital Universitario Infanta Leonor, Madrid, Spain

    B. Obispo Portero

  6. Medical Oncology, Hospital Universitario de Fuenlabrada, Madrid, Spain

    D. Gutiérrez-Abad

  7. Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    A. J. Muñoz Martín

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  1. I. García-Escobar
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On behalf of the Cancer and Thrombosis Working Group of the Spanish Society of Medical Oncology (SEOM)

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Dr. Muñoz Langa has been consultant or member of the advisory boards of LEO Pharma, Pfizer, and Novartis. Dr. Muñoz Martín has been consultant or member of the advisory boards of Sanofi Rovi and LEO Pharma. The remaining authors have no conflict of interest to declare.

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García-Escobar, I., Beato-Zambrano, C., Muñoz Langa, J. et al. Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?. Clin Transl Oncol 20, 1097–1108 (2018). https://doi.org/10.1007/s12094-018-1835-2

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