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.
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References
Merriman L, Greaves M. Testing for thrombophilia: an evidence-based approach. Postgrad Med J. 2006;82(973):699–704.
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.
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.
Blom JW, Doggen CJ, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715–22.
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.
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.
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.
Gouda MA. Common pitfalls in reporting the use of SPSS software. Med Princ Pract. 2015;24:300. https://doi.org/10.1159/000381953
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.
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.
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.
Khan S, Dickerman JD. Hereditary thrombophilia. Thromb J. 2006;4:15.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Colucci G, Tsakiris DA. Thrombophilia screening. Clin Appl Thromb Hemost. 2017; https://doi.org/10.1177/1076029616683803.
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.
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.
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.
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.
Funding
This work was supported by the project of the Ministry of Health, Czech Republic (RVO-VFN64165 and NT 13251-4).
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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.
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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.
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Ulrych, J., Kvasnicka, T., Fryba, V. et al. The impact of hereditary thrombophilia on the incidence of postoperative venous thromboembolism in colorectal cancer patients: a prospective cohort study. Eur Surg 51, 5–12 (2019). https://doi.org/10.1007/s10353-018-0534-0
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DOI: https://doi.org/10.1007/s10353-018-0534-0