Malignant neoplasms and thromboses

Schulman S., Makatsaria N.A., Vorobyev A.V., Bitsadze V.O., Khizroeva D.Kh., Solopova A.G.

1) Research Institute of Thrombosis and Atherosclerosis, Faculty of Medicine, McMaster University, Hamilton, Ontario, Canada; 2) Obstetrics and Gynecology Department Two, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
Objective. To carry out a systems analysis of data on the relationship between cancer and thrombotic events and to analyze risk factors for thrombosis in cancer patients.
Material and methods. The review includes data from foreign and Russian articles published on this topic in the past 10 years, which were found in e-Library and Pubmed.
Results. The paper presents data on the possibilities of using anticoagulant therapy in cancer patients. It analyzes the features of managing patients with recurrent thromboses: a change in the dosage of low molecular weight heparin or the need for implantation of a cava filter into the inferior vena cava.
Conclusion. Activated coagulation may increase the risk of cancer and, conversely, the effect of anticoagulants may reduce the risk of developing certain types of cancer.

Keywords

malignant neoplasms
thrombotic events
hemostatic disorders
thrombophilia
pathogenesis of thrombotic events
prevention of thromboses
anticoagulant therapy

References

  1. Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood. 2007; 110(6): 1723-9.
  2. Trousseau A. Phlegmasia alba dolens. Clinique Medicale de l'Hotel-Dieu de Paris. 1865; 3: 490-515.
  3. Воробьев А.В., Макацария А.Д., Бреннер Б. Синдром Труссо: забытое прошлое или актуальное настоящее? Акушерство и гинекология. 2018; 2: 27-34. [Vorobev A.V., Makatsaria A.D., Brenner B. Trusso's syndrome: a forgotten past or an actual present? Akusherstvo i ginekologiya/Obstetrics and gynecology. 2018; 2: 27-34. (In Russian)]
  4. Prandoni P., Lensing A.W., Piccioli A., Bernardi E., Simioni P., Girolami B. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002; 100(10): 3484-8.
  5. Chew H.K., Wun T., Harvey D., Zhou H., White R.H. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch. Intern. Med. 2006; 166(4): 458-64.
  6. Prandoni P., Lensing A.W., Büller H.R., Cogo A., Prins M.H., Cattelan A.M. et al. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N. Engl. J. Med. 1992; 327(16): 1128-33.
  7. Carrier M., Le Gal G., Wells P.S., Fergusson D., Ramsay T., Rodger M.A. Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism? Ann. Intern. Med. 2008; 149(5): 323-33.
  8. Carrier M., Lazo-Langner A., Shivakumar S., Tagalakis V., Zarychanski R., Solymoss S. et al. Screening for occult cancer in unprovoked venous thromboembolism. N. Engl. J. Med. 2015; 373(8): 697-704.
  9. Piccioli A., Lensing A.W., Prins M.H., Falanga A., Scannapieco G.L., Ieran M. et al. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. J. Thromb. Haemost. 2004; 2(6): 884-9.
  10. Prandoni P., Bernardi E., Valle F.D., Visonà A., Tropeano P.F., Bova C. et al. Extensive computed tomography versus limited screening for detection of occult cancer in unprovoked venous thromboembolism: a multicenter, controlled, randomized clinical trial. Semin. Thromb. Hemost. 2016; 42(8): 884-90.
  11. Воробьев А.В., Макацария А.Д., Бицадзе В.О., Бреннер Б. Нарушения функции системы гемостаза и канцерогенез. Современное состояние вопроса. Акушерство и гинекология. 2017; 8: 28-33. [Vorobev A.V., Makatsariya A.D., Bitsadze V.O., Brenner B. Dysfunctions of the hemostasis system and carcinogenesis. The current state of the issue. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2017; 8: 28-33. (In Russian)]
  12. Khorana A.A., Kuderer N.M., Culakova E., Lyman G.H., Francis C.W. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008; 111(10): 4902-7.
  13. Ay C., Dunkler D., Marosi C., Chiriac A.L., Vormittag R., Simanek R. et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010; 116(24): 5377-82.
  14. Verso M., Agnelli G., Barni S., Gasparini G., LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern. Emerg. Med. 2012;7(3): 291-2.
  15. Pelzer U., Sinn M., Stieler J., Riess H. Primary pharmacological prevention of thromboembolic events in ambulatory patients with advanced pancreatic cancer treated with chemotherapy? Dtsch. Med. Wochenschr. 2013; 138(41): 2084-8.
  16. Vorobiev A.V., Makatsaria A.D., Chabrov A.M. Thrombophilia markers in cancer patients during chemotherapy and radiation therapy. Pathophysiol. Haemost. Thromb. 2006; 35(1-2): A20.
  17. van Es N., Di Nisio M., Cesarman G., Kleinjan A., Otten H.M., Mahé I. et al. Comparison of risk prediction scores for venous thromboembolism in cancer patients: a prospective cohort study. Haematologica. 2017; 102(9): 1494-501.
  18. Farge D., Debourdeau P., Beckers M., Baglin C., Bauersachs R.M., Brenner B. et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J. Thromb. Haemost. 2013; 11(1): 56-70.
  19. ENOXACAN Study Group. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double- blind randomized multicentre trial with venographic assessment. Br. J. Surg. 1997; 84(8): 1099-103.
  20. Agnelli G., Bolis G., Capussotti L., Scarpa R.M., Tonelli F., Bonizzoni E. et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann. Surg. 2006; 243(1): 89-95.
  21. Bergqvist D., Agnelli G., Cohen A.T., Eldor A., Nilsson P.E., Le Moigne-Amrani A., Dietrich-Neto F.; ENOXACAN II Investigators. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N. Engl. J. Med. 2002; 346(13): 975-80.
  22. Rasmussen M.S., Jorgensen L.N., Wille-Jørgensen P., Nielsen J.D., Horn A., Mohn A.C. 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.
  23. Kakkar V.V., Balibrea J.L., Martinez-Gonzalez J., Prandoni P. Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study. J. Thromb. Haemost. 2010; 8(6): 1223-9.
  24. Lyman G.H., Khorana A.A., Kuderer N.M., Lee A.Y., Arcelus J.I., Balaban E.P. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J. Clin. Oncol. 2013; 31(17): 2189-204.
  25. Mandala M., Falanga A., Roila F. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann. Oncol. 2011; 22(Suppl. 6): vi85-92.
  26. Gould M.K., Garcia D.A., Wren S.M., Karanicolas P.J., Arcelus J.I., Heit J.A., Samama C.M. 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, Suppl.): e227S-77S.
  27. Siragusa S., Cosmi B., Piovella F., Hirsh J., Ginsberg J.S. 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(3): 269-77.
  28. Kakkar A.K., Levine M.N., Kadziola Z., Lemoine N.R., Low V., Patel H.K. 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(10): 1944-8.
  29. van Doormaal F.F., Di Nisio M., Otten H.M., Richel D.J., Prins M., Buller H.R. Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J. Clin. Oncol. 2011; 29(15): 2071-6.
  30. Lee A., Julian J.A., Levine M.N., Baker R.I., Bowden C., Kakkar A.K. et al. Long-term treatment with dalteparin low-molecular-weight heparin (LMWH) may improve survival in patients with non-metastatic malignancy and venous thromboembolism (VTE). J. Thromb. Haemost. 2003; 2(Suppl.): OC004. (Abstr.).
  31. Meyer G., Marjanovic Z., Valcke J., Lorcerie B., Gruel Y., Solal-Celigny P. et al. Comparison low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer. Arch. Intern. Med. 2002; 162(15): 1729-35.
  32. Lee A.Y.Y., Kamphuisen P.W., Meyer G., Bauersachs R., Janas M.S., Jarner M.F., Khorana A.A.; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA. 2015; 314(7): 677-86.
  33. Louzada M.L., Majeed H., Wells P.S. Efficacy of low-molecular-weight-heparin versus vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: a systematic review of randomized controlled trials. Thromb. Res. 2009; 123(6): 837-44.
  34. Kearon C., Akl E.A., Ornelas J., Blaivas A., Jimenez D., Bounameaux H. et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016; 149(2): 315-52.
  35. van Es N., Coppens M., Schulman S., Middeldorp S., Buller H.R. Direct oral anticoagulants compared with vitamin K antagonists for acute symptomatic venous thromboembolism: evidence from phase 3 trials. Blood. 2014; 124(12): 1968-75.
  36. Raskob G.E., van Es N., Verhamme P., Carrier M., Di Nisio M., Garcia D. et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N. Engl. J. Med. 2017; 378(7): 615-24.
  37. Young A.M., Marshall A., Thirlwall J., Chapman O., Lokare A., Hill C. et al. Comparison of an oral factor Xa Inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J. Clin. Oncol. 2018; 36(20): 2017-23.
  38. McBane R.D., Wysokinski W.E., Le-Rademacher J., Ashrani A.A., Tafur A.J., Gundabolu K. et al. Apixaban, dalteparin, in active cancer associated venous thromboembolism, the ADAM VTE Trial. Blood. 2018; 132(Suppl. 1): Abstr. 421.
  39. Kim H.S., Preece S.R., Black J.H., Pham L.D., Streiff M.B. Safety of catheter-directed thrombolysis for deep venous thrombosis in cancer patients. J. Vasc. Surg. 2008; 47(2): 388-94.
  40. Maleux G., Marchal P., Palmers M., Heye S., Verhamme P., Vaninbroukx J., Verhaeghe R. Catheter-directed thrombolytic therapy for thoracic deep vein thrombosis is safe and effective in selected patients with and without cancer. Eur. Radiol. 2010; 20(9): 2293-300.
  41. Hutten B.A., Prins M.H., Gent M., Ginsberg J., Tijssen J.G., Büller H.R. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J. Clin. Oncol. 2000; 18(17): 3078-83.
  42. Palareti G., Legnani C., Lee A., Manotti C., Hirsh J., D'Angelo A. et al. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy. Thromb. Haemost. 2000; 84(5): 805-10.
  43. Schulman S., Zondag M., Linkins L., Pasca S., Cheung Y.W., de Sancho M. et al. Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis. J. Thromb. Haemost. 2015;13(6): 1010-8.
  44. Carrier M., Le Gal G., Cho R., Tierney S., Rodger M., Lee A.Y. Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients. J. Thromb. Haemost. 2009; 7(5): 760-5.
  45. Ihaddadene R., Le Gal G., Delluc A., Carrier M. Dose escalation of low molecular weight heparin in patients with recurrent cancer-associated thrombosis. Thromb. Res. 2014; 134: 93-5.
  46. Schulman S., Lindmarker P. Incidence of cancer after secondary prophylaxis against venous thromboembolism with warfarin. N. Engl. J. Med. 2000; 342(26): 1953-8.
  47. Zacharski L.R., Henderson W.G., Rickles F.R., Forman W.B., Cornell C.J. Jr., Forcier R.J. et al. Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75. JAMA. 1981; 245(8):831-5.
  48. Maurer L.H., Herndon J.E. 2nd, Hollis D.R., Aisner J., Carey R.W., Skarin A.T. 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(11):3378-87.
  49. Tagalakis V., Tamim H., Blostein M., Collet J.P., Hanley J.A., Kahn S.R. Use of warfarin and risk of urogenital cancer: a population-based, nested case-control study. Lancet Oncol. 2007; 8(5): 395-402.
  50. Pengo V., Noventa F., Denas G., Pengo M.F., Gallo U., Grion A.M. et al. Long-term use of vitamin K antagonists and incidence of cancer: a population-based study. Blood. 2011; 117(5): 1707-9.
  51. Miller G.J., Bauer K.A., Howarth D.J., Cooper J.A., Humphries S.E., Rosenberg R.D. Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway. J. Thromb. Haemost. 2004; 2(12): 2107-14.
  52. Макацария А.Д., Воробьев А.В. Гемостазиологические аспекты опухолевого роста. Акушерство и гинекология. 2016; 9: 28-36.[Makatsariya A.D., Vorobyev A.V. Hemostasiological aspects of tumor growth. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2016; 9: 28-36.(In Russian)]
  53. Taniguchi T., Kakkar A.K., Tuddenham E.G., Williamson R.C., Lemoine N.R. Enhanced expression of urokinase receptor induced through the tissue factor-factor VIIa pathway in human pancreatic cancer. Cancer Res. 1998; 58(9): 4461-7.
  54. Макацария А.Д., Воробьев А.В., Бицадзе В.О. Злокачественные новообразования, тромбофилия, тромбозы. Монография. М.: Триада-Х; 2008. 650 с. [Makatsariya A.D., Vorobyev A.V., Bitsadze V.O. Malignant neoplasms, thrombophilia, thrombosis. Monograph. M.: Triada-X; 2008. 650 p. (In Russian)]
  55. Fernandez-Patron C., Zhang Y., Radomski M.W., Hollenberg M.D., Davidge S.T. Rapid release of matrix metalloproteinase (MMP)-2 by thrombin in the rat aorta: modulation by protein tyrosine kinase/phosphatase. Thromb. Haemost. 1999; 82(4): 1353-7.

Received 30.03.2019

Accepted 19.04.2019

About the Authors

Sam Schulman, MD, PhD, Professor of the Thrombosis and Atherosclerosis Research Institute and Department of Medicine, McMaster University, Hamilton, Ontario, Canada, professor of the Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University; E-mail: schulms@mcmaster.ca
Makatsariya Aleksander, MD, corresponding member of the Russian Academy of Sciences, Professor, Head of the Department of Obstetrics and Gynecology,
The First I.M. Sechenov Moscow State Medical University; E-mail: gemostasis@mail.ru
Vorobev Alexander, PhD, Associate Professor of the Department of Obstetrics and Gynecology of the Faculty of Medical and Preventive, The First I.M. Sechenov Moscow State Medical University; E-mail: alvorobev@gmail.com
Bitsadze Viktoria, MD, Professor of the Russian Academy of Sciences, Professor of the Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University; E-mail: gemostasis@mail.ru
Khizroeva Jamilya, MD, Professor of the Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University; E-mail: gemostasis@mail.ru
Solopova Antonina, MD, Professor of the Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University;
E-mail: gemostasis@mail.ru

For citations: Schulman S., Makatsaria N.A., Vorobyev A.V., Bitsadze V.O., Khizroeva D.Kh., Solopova A.G. Malignant neoplasms and thromboses. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2019; (7): 14-23 (in Russian).
http://dx.doi.org/10.18565/aig.2019.7.14-23

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