Prolonged Prophylaxis of Thromboembolic Disease in Patients with Colorectal Surgical Resections for Malignancy

Czech version

Authors: R. Brzežková; V. Frýba ^*; K. Chrz ^*; Z. Krška ^*; J. Kvasnička
Authors‘ workplace: Trombotické centrum a Centrální hematologické laboratoře, Ústav klinické biochemie a laboratorní diagnostiky ; I. chirurgická klinika, Všeobecná fakultní nemocnice a 1. LF UK v Praze ^*
Published in: Rozhl. Chir., 2009, roč. 88, č. 11, s. 642-648.
Category: Monothematic special - Original

Overview

Cancer patients have 6-fold higher risk of venous thromboembolism compared with patients without malignancy. This risk of VTE is further increased by cancer surgery.

Aim of the study:
The aim of our pilot study was to examine the changes in inflammatory reaction, changes of coagulation parameters and inhibition of FXa in patients with new diagnosed colorectal cancer. During 30 days of observation prophylactic dose of dalteparin 5000 UI subcutaneously once daily was administrated.

Patients and methods:
Patients who underwent surgical resection of the colon for new diagnosed colorectal cancer were included in the study.

Laboratory tests (blood count, acute phase proteins – alpfa-1-antitrypsin, transferin, prealbumin, alpfa-2-makroglobulin, orosomukoid and C reactive protein and coagulation laboratory tests – PT in INR, aPTT, TT, fibrinogen concentration, activity of antithrombinu and concentration of D-dimer) were performed before surgery and on day 3, 10 and 30 after surgery.

Results:
Inflammatory response reached highest level on day 3, lasted until day 10 after surgery than parameters returned to normal values (p < 0.05). Hypercoagulable tendency was already seen before surgery, highest value of D-dimer was measured on day 10 after surgery and after decrease it lasted until the day 30 after surgery (p < 0.05).

Inhibition of FXa varied between 0.02–0.7 IU/ml. The prophylactic range of FXa inhibition 0.2–0.4 IU/ml was reached in 48.1% of the samples, 20.4 % of the samples were over the range and 31.5 % were under the prophylactic range.

During 30 day of observation deep vein thrombosis was not detected in any patient as well as bleeding complication.

Conclusion:
The pilot study shows that prolonged prophylaxis of VTE is advisable in patients after cancer surgery. Variation of FXa inhibition will be in our study further examined.

Key words:
colorectal cancer – colorectal resection – venous thromboembolism – low-molecular-weight heparins

Sources

1. Trousseau, A. Lectures on clinical medicine (delivered at the Hotel-Dieu, Paris, France). The New Syndeham Society, London, 1872: p. 282–332.

2. Rickles, F. R., Levine, M., Edwards, R. L. Hemostatic alterations in cancer patients. Cancer Metastasis Rev., 1992, 11(3-4): p. 237–248.

3. Stein, P. D., Beemath, A., Meyers, F. A., Skaf, E., Sanchez, J., Olson, R. E. Incidence of venous thromboembolism in patients hospitalized with cancer. Am. J. Med., 2006. 119(1): p. 60–68.

4. Lee, A. Y., Levine, M. Venous thromboembolism and cancer: risks and outcomes. Circulation, 2003. 107(23 Suppl 1): p. 17–21.

5. Bergqvist, D. Venous thromboembolism and cancer: prevention of VTE. Thromb. Res., 2001. 102(6): p. V209–213.

6. Kakkar, A. K., Haas, S., Wolf, H., Encke, A. Evaluation of perioperative fatal pulmonary embolism and death in cancer surgical patients: the MC-4 cancer substudy. Thromb. Haemost., 2005. 94(4): p. 867–871.

7. Blom, J. W., Doggen, C. J. M., Osanto, S. Malignancies, Prothrombotic Mutations, and the Risk of Venous Thromobsis. JAMA, 2005, 293(6): p. 715–722.

8. Leizorovicz, A., Mismetti, P. Preventing venous thromboembolism in medical patients. Circulation, 2004, 110: p. 874–879.

9. Turpie, A. G. G. Thrombosis prophylaxis in the acutely ill medical patient: insights from the prophylaxis in medical patients with enoxaparin (MEDENOX) trial. Am. J. Cardiol., 2000, 86(12B): p. 48–52.

10. Bergqvist, D., Agnelli, G., Cohen, A. T., et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N. Engl. J. Med., 2002, 346(13): p. 975–980.

11. Rasmussen, M. S., Jorgensen, L., Wille-Jorgensen, 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): p. 2384–2390.

12. Cohen, A. T., Tapson, V., Bergmann, J. F., Goldhaber, S. Z., Kakkar, A. K., Deslandes, B., Huang, W., Zayaruzny, M., Emery, L., Anderson, F. A. Jr., ENDORSE Investigators Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet, 2008. 371(9610): p. 387–394.

13. Geerts, W. H., Bergqvist, D., Pineo, G. F., Heit, J. A., Samama, C. M., Lassen, M. R., Colwell, C. W., American College of Chest Physicians Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 2008, 133: p. 381–453.

14. van Aken, B. E., den Heijer, M., Bos, G. M., van Deventer, S. J., Reitsma, P. H. Recurrent venous thrombosis and markers of inflammation. Thromb. Haemost., 2000, 83(4): p. 536–539.

15. Battistelli, S., Stefanovi, M., Genovese, A. Prevalence of factor V Leiden and prothrombin G20210A in patients with gastric cancer. Worlds J. Gatroenterol., 2006, 12(26): p. 4179–4180.

16. Pihusch, R., Danzl, G., Scholz, M., Harich, D., Pihusch, M., Lohse, P., Hiller, E. Impact of thrombophilic gene mutations on thrombosis risk in patients with gastrointestinal carcinoma. Cancer, 2002, 94(12): p. 3120–3126.

17. Young, E., et al. Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb. Haemost., 1992. 67(6): p. 639–643.

18. Gruys, E., Toussaint, M., Niewold, T. A., Koopmans, S. J. Acute phase reaction and acute phase proteins. J. Zhejiang Univ. Sci. B., 2005, 6(11): p. 1045–1056.

19. Hirsh, J., Bauer, K. A., Donati, M. B., Gould, M., Samama, M. M., Weitz, J. I., American College of Chest Physicians Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest, 2008, 133(6 suppl): p. 141S–159S.