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Predictive factors for cancer-associated thrombosis in a large retrospective single-center study

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Abstract

Background

The relationship between cancer and thrombosis has been studied for years, but reliable guidelines for thromboprophylaxis in that situation are still unclear.

Methods

We retrospectively reviewed the files of 3159 consecutive patients with newly diagnosed solid tumors at Jules Bordet Institute from January 2008 to December 2011. Among them, 99 developed a symptomatic thromboembolic episode and were matched with 2 controls (nested case control). The aim was to identify risk factors of thromboembolic events and to validate in our setting the Khorana score.

Results

In the cohort study, nodal status ≥ 2, presence of metastases, and primary tumor site were found to be the most significant predictive factors of a thromboembolic event (n = 99; 3.1%) in the multivariate analysis. In the nested study (n = 265), hemoglobin < 13 g/dL or treatment with a red cell growth factor, CRP ≥ 31.6 mg/L, creatinine level > 0.96 mg/dL, chronic inflammatory disease, and personal or familial history of thromboembolic events were found to be the most significant predictive factors of a thromboembolic event in the multivariate analysis. In our population, the sensitivity, specificity, positive predictive value, and negative predictive value of the Khorana score were respectively 29%, 93%, 15%, and 96%.

Conclusion

We confirm the value of the risk factors identified in the literature with the additional presence of nodal involvement, elevated CRP, and creatinine levels, which may be helpful for patient risk stratification and should be considered in future clinical trials. Our results also suggest that the Khorana score might help to identify patients who can safely be spared of thromboprophylaxis.

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References

  1. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ (2000) Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 160(6):809–815

    Article  PubMed  CAS  Google Scholar 

  2. Falanga A, Panova-Noeva M, Russo L (2009) Procoagulant mechanisms in tumour cells. Best Pract Res Clin Haematol. 22(1):49–60

    Article  PubMed  CAS  Google Scholar 

  3. De Cicco M (2004) The prothrombotic state in cancer: pathogenic mechanisms. Crit Rev Oncol Hematol 50(3):187–196

    Article  PubMed  Google Scholar 

  4. Farge-Bancel D, Florea L, Bosquet L, Debourdeau P (2008) Treatment of venous thromboembolic disease in cancer patients. Pathol Biol (Paris) 56(4):220–228

    Article  CAS  Google Scholar 

  5. Connors JM (2014) Prophylaxis against venous thromboembolism in ambulatory patients with cancer. N Engl J Med. 370(26):2515-9

  6. Khorana AA (2010) Venous thromboembolism and prognosis in cancer. Thromb Res. 125(6):490–493

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Farge D, Bounameaux H, Brenner B, Cajfinger F, Debourdeau P, Khorana AA et al (2016) International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 17(10):e452–e466

    Article  PubMed  CAS  Google Scholar 

  8. Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP et al (2013) Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol Off J Am Soc Clin Oncol. 31(17):2189–2204

    Article  CAS  Google Scholar 

  9. Di Nisio M, Carrier M, Lyman GH, Khorana AA (2014) Subcommittee on Haemostasis and Malignancy. Prevention of venous thromboembolism in hospitalized medical cancer patients: guidance from the SSC of the ISTH. J Thromb Haemost JTH. 12(10):1746–1749

    Article  PubMed  Google Scholar 

  10. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA et al (2012) Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 141(2 Suppl):e195S–e226S

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW (2008) Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 111(10):4902–4907

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Khorana AA, Connolly GC (2009 Oct 10) Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol Off J Am Soc Clin Oncol. 27(29):4839–4847

    Article  CAS  Google Scholar 

  13. Richardson DB (2004) An incidence density sampling program for nested case-control analyses. Occup Environ Med. 61(12):e59

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Lyman GH, Eckert L, Wang Y, Wang H, Cohen A (2013) Venous thromboembolism risk in patients with cancer receiving chemotherapy: a real-world analysis. The Oncologist. 18(12):1321–1329

    Article  PubMed  PubMed Central  Google Scholar 

  15. Blom JW, Vanderschoot JPM, Oostindiër MJ, Osanto S, van der Meer FJM, Rosendaal FR (2006) Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost JTH. 4(3):529–535

    Article  PubMed  CAS  Google Scholar 

  16. Blom JW, Doggen CJM, Osanto S, Rosendaal FR (2005) 419 Malignancies, prothrombotic mutations, and the risk of venous 420 thrombosis. JAMA. 293(6):715–722

  17. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer. 110(10):2339–2346

    Article  PubMed  Google Scholar 

  18. Kröger K, Weiland D, Ose C, Neumann N, Weiss S, Hirsch C et al (2006) Risk factors for venous thromboembolic events in cancer patients. Ann Oncol Off J Eur Soc Med Oncol. 17(2):297–303

    Article  Google Scholar 

  19. Bucek RA, Reiter M, Quehenberger P, Minar E (2002) C-reactive protein in the diagnosis of deep vein thrombosis. Br J Haematol. 119(2):385–389

    Article  PubMed  CAS  Google Scholar 

  20. Fox EA, Kahn SR (2005) The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost. 94(2):362–365

    PubMed  CAS  Google Scholar 

  21. Lu H-Y, Liao K-M (2018) Increased risk of deep vein thrombosis in end-stage renal disease patients. BMC Nephrol [Internet].

  22. Cheung KL, Bouchard BA, Cushman M (2018) Venous thromboembolism, factor VIII and chronic kidney disease. Thromb Res. 170:10–19

    Article  PubMed  CAS  Google Scholar 

  23. Mansfield AS, Tafur AJ, Wang CE, Kourelis TV, Wysokinska EM, Yang P (2016) Predictors of active cancer thromboembolic outcomes: validation of the Khorana score among patients with lung cancer. J Thromb Haemost JTH. 14(9):1773–1778

    Article  PubMed  CAS  Google Scholar 

  24. Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R (2012) A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med. 7(3):291–292

    Article  PubMed  Google Scholar 

  25. Kuderer NM, Culakova E, Lyman GH, Francis C, Falanga A, 383 Khorana AA (2016) Avalidated risk score for venous thromboem- 384 bolism is predictive of cancer progression and mortality. The 385 Oncologist. 21(7):861–867

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Acknowledgements

The authors acknowledge the contribution of Ornella Martini for English-language editing of this manuscript.

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Authors and Affiliations

  1. Service de Médecine - Urgences, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium

    J. Haltout

  2. Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, 1 rue Heger Bordet, 1000, Brussels, Belgium

    A. Awada, J. Klastersky, G. Machiels, M. Ignatiadis & N. Kotecki

  3. Data Center, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

    M. Paesmans & M. Moreau

Authors
  1. J. Haltout
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  2. A. Awada
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  3. M. Paesmans
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  4. M. Moreau
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  5. J. Klastersky
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  6. G. Machiels
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  7. M. Ignatiadis
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  8. N. Kotecki
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Corresponding author

Correspondence to N. Kotecki.

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The study was approved by Jules Bordet Institute Ethics Committee.

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The authors declare that they have no conflict of interest.

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Appendix

Appendix

Table 7 Known venous thromboembolism risk factors collected for the nested cohort study
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Table 8 Contingency table for the Khorana score
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Haltout, J., Awada, A., Paesmans, M. et al. Predictive factors for cancer-associated thrombosis in a large retrospective single-center study. Support Care Cancer 27, 1163–1170 (2019). https://doi.org/10.1007/s00520-018-4602-6

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  • DOI: https://doi.org/10.1007/s00520-018-4602-6

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