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The impact of hereditary thrombophilia on the incidence of postoperative venous thromboembolism in colorectal cancer patients: a prospective cohort study

Hereditary thrombophilia and VTE in colorectal cancer surgery
  • Jan Ulrych
  • Tomas Kvasnicka
  • Vladimir Fryba
  • Martin Komarc
  • Ivana Malikova
  • Radka Brzezkova
  • Jan Kvasnicka Jr
  • Zdenek Krska
  • Jan Briza
  • Jan Kvasnicka
original article

Summary

Background

Hereditary thrombophilia may play an important role in the rate of postoperative venous thromboembolism (VTE). We focused on the impact of hereditary thrombophilia on VTE incidence in colorectal cancer surgery patients within a 1-year postoperative period.

Methods

Preoperatively, identifying of colorectal cancer patients with thrombotic mutations (PTM+) and without thrombotic mutations (PTM−) was performed by screening of factor V Leiden (FVL) and prothrombin G20210A mutation. Within prophylactic period (0–28 days postoperatively), coagulation markers (platelets, fibrinogen, D‑dimer) were measured and symptomatic VTE was observed. Within post-prophylactic period (2–12 months after surgery), symptomatic VTE was observed.

Results

In all, 202 patients were assessed and hereditary thrombophilia was detected in 9.9% (FVL 8.4%; prothrombin G20210A mutation 1.5%). In the prophylactic period, VTE incidence in PTM+ and PTM− was 0.0% and 1.6%, respectively (p = 0.730). Levels of coagulation markers were comparable in both patient cohorts within 28 days postoperatively. In the post-prophylactic period, VTE incidence in PTM+ and PTM− was 15.0% and 5.5%, respectively (p = 0.125), and detailed incidence of deep vein thrombosis (DVT) in PTM+ and PTM− was 15.0% and 3.3%, respectively (p = 0.048). We observed significantly increased incidence of lower extremity DVT in such patients with FVL (17.6%).

Conclusion

The standard regimen of extended-duration VTE prophylaxis is adequate for colorectal cancer patients with thrombotic mutations and more intensified VTE prophylaxis within the 28-day postoperative period is not justified. However, the ongoing postoperative pharmacologic prophylaxis (>28 days) should be considered in patients with hereditary thrombophilia, especially with FVL.

Keywords

Factor V Leiden Prothrombin mutation Colorectal neoplasms Venous thrombosis Risk assessment 

Notes

Funding

This work was supported by the project of the Ministry of Health, Czech Republic (RVO-VFN64165 and NT 13251-4).

Compliance with ethical guidelines

Conflict of interest

J. Ulrych, T. Kvasnicka, V. Fryba, M. Komarc, I. Malikova, R. Brzezkova, J. Kvasnicka Jr, Z. Krska, J. Briza, and J. Kvasnicka declare that they have no competing interests.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The study was approved by the ethics committee of General University Hospital in Prague. Informed consent was obtained from all patients for being included in the study.

References

  1. 1.
    Merriman L, Greaves M. Testing for thrombophilia: an evidence-based approach. Postgrad Med J. 2006;82(973):699–704.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Weingarz L, Schwonberg J, Schindewolf M, et al. Prevalence of thrombophilia according to age at the first manifestation of venous thromboembolism: results from the MAISTHRO registry. Br J Haematol. 2013;163(5):655–65.  https://doi.org/10.1111/bjh.12575.CrossRefPubMedGoogle Scholar
  3. 3.
    Kvasnička T, Hájková J, Bobčíková P, et al. The frequencies of six important thrombophilic mutations in a population of the Czech Republic. Physiol Res. 2014;63(2):245–53.PubMedGoogle Scholar
  4. 4.
    Blom JW, Doggen CJ, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715–22.CrossRefPubMedGoogle Scholar
  5. 5.
    Pabinger I, Ay C, Dunkler D, et al. Factor V Leiden mutation increases the risk for venous thromboembolism in cancer patients—results from the Vienna Cancer And Thrombosis Study (CATS). J Thromb Haemost. 2015;13(1):17–22.  https://doi.org/10.1111/jth.12778.CrossRefPubMedGoogle Scholar
  6. 6.
    Gould MK, Garcia DA, Wren SM, American College of Chest Physicians, et al. 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. 2012;141(2):e227S–e77S.  https://doi.org/10.1378/chest.11-2297.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997;350(9094):1795–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Gouda MA. Common pitfalls in reporting the use of SPSS software. Med Princ Pract. 2015;24:300.  https://doi.org/10.1159/000381953 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Colorectal Writing Group for Surgical Care and Outcomes Assessment Program, Comparative Effectiveness Research Translation Network (SCOAP-CERTAIN) Collaborative, Nelson DW, Simianu VV, Bastawrous AL, et al. Thromboembolic complications and prophylaxis patterns in colorectal surgery. JAMA Surg. 2015;150(8):712–20.  https://doi.org/10.1001/jamasurg.2015.1057.CrossRefGoogle Scholar
  10. 10.
    Alcalay A, Wun T, Khatri V, et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol. 2006;24(7):1112–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Walker AJ, West J, Card TR, et al. Variation in the risk of venous thromboembolism in people with colorectal cancer: a population-based cohort study from England. J Thromb Haemost. 2014;12(5):641–9.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Khan S, Dickerman JD. Hereditary thrombophilia. Thromb J. 2006;4:15.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ho WK, Hankey GJ, Quinlan DJ, et al. Risk of recurrent venous thromboembolism in patients with common thrombophilia: a systematic review. Arch Intern Med. 2006;166(7):729–36.CrossRefPubMedGoogle Scholar
  14. 14.
    Bergqvist D, Agnelli G, Cohen AT, et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002;346(13):975–80.CrossRefPubMedGoogle Scholar
  15. 15.
    Rasmussen MS, Jorgensen LN, Wille-Jørgensen P, et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost. 2006;4(11):2384–90.CrossRefPubMedGoogle Scholar
  16. 16.
    Akl EA, Terrenato I, Barba M, et al. Extended perioperative thromboprophylaxis in patients with cancer. A systematic review. Thromb Haemost. 2008;100(6):1176–80.PubMedGoogle Scholar
  17. 17.
    Sweetland S, Green J, Liu B, et al. Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: prospective cohort study. BMJ. 2009;339:b4583.  https://doi.org/10.1136/bmj.b4583.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Rooden CJ, Tesselaar ME, Osanto S, et al. Deep vein thrombosis associated with central venous catheters—a review. J Thromb Haemost. 2005;3(11):2409–19.CrossRefPubMedGoogle Scholar
  19. 19.
    Malinoski D, Ewing T, Bhakta A, et al. Which central venous catheters have the highest rate of catheter-associated deep venous thrombosis: a prospective analysis of 2,128 catheter days in the surgical intensive care unit. J Trauma Acute Care Surg. 2013;74(2):454–60.  https://doi.org/10.1097/TA.0b013e31827a0b2f. discussion 461–2.CrossRefPubMedGoogle Scholar
  20. 20.
    Shivakumar SP, Anderson DR, Couban S. Catheter-associated thrombosis in patients with malignancy. J Clin Oncol. 2009;27(29):4858–64.  https://doi.org/10.1200/JCO.2009.22.6126.CrossRefPubMedGoogle Scholar
  21. 21.
    Mäkelburg AB, Veeger NJ, Middeldorp S, et al. Different risk of deep vein thrombosis and pulmonary embolism in carriers with factor V Leiden compared with non-carriers, but not in other thrombophilic defects. Results from a large retrospective family cohort study. Haematologica. 2010;95(6):1030–3.  https://doi.org/10.3324/haematol.2009.017061.CrossRefPubMedGoogle Scholar
  22. 22.
    Hirmerova J, Seidlerova J, Subrt I. The association of factor V Leiden with various clinical patterns of venous thromboembolism-the factor V Leiden paradox. QJM. 2014;107(9):715–20.  https://doi.org/10.1093/qjmed/hcu055.CrossRefPubMedGoogle Scholar
  23. 23.
    Stevens SM, Woller SC, Bauer KA, et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis. 2016;41(1):154–64.  https://doi.org/10.1007/s11239-015-1316-1.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Colucci G, Tsakiris DA. Thrombophilia screening. Clin Appl Thromb Hemost. 2017;  https://doi.org/10.1177/1076029616683803.PubMedCrossRefGoogle Scholar
  25. 25.
    Wu O, Robertson L, Twaddle S, et al. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technol Assess. 2006;10(11):1–110.CrossRefPubMedGoogle Scholar
  26. 26.
    Becattini C, Rondelli F, Vedovati MC, et al. Incidence and risk factors for venous thromboembolism after laparoscopic surgery for colorectal cancer. Haematologica. 2015;100(1):e35–e8.  https://doi.org/10.3324/haematol.2014.109843.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lee E, Kang SB, Choi SI, et al. Prospective study on the incidence of postoperative venous thromboembolism in Korean patients with colorectal cancer. Cancer Res Treat. 2016;48(3):978–89.  https://doi.org/10.4143/crt.2015.311.CrossRefPubMedGoogle Scholar
  28. 28.
    Khorana AA. Cancer-associated thrombosis: updates and controversies. Hematology Am Soc Hematol Educ Program. 2012;2012:626–30.  https://doi.org/10.1182/asheducation-2012.1.626.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Jan Ulrych
    • 1
  • Tomas Kvasnicka
    • 2
  • Vladimir Fryba
    • 1
  • Martin Komarc
    • 3
    • 4
  • Ivana Malikova
    • 2
  • Radka Brzezkova
    • 2
  • Jan Kvasnicka Jr
    • 1
  • Zdenek Krska
    • 1
  • Jan Briza
    • 1
  • Jan Kvasnicka
    • 2
  1. 1.1st Department of Surgery—Department of Abdominal, Thoracic Surgery and Traumatology; First Faculty of Medicine, General University HospitalCharles UniversityPragueCzech Republic
  2. 2.Thrombotic Centre of Institute of Medical Biochemistry and Laboratory Diagnostics, General University HospitalCharles UniversityPragueCzech Republic
  3. 3.Institute of Biophysics and Informatics, First Faculty of MedicineCharles UniversityPragueCzech Republic
  4. 4.Department of Methodology, Faculty of Physical Education and SportCharles UniversityPragueCzech Republic

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