VENOUS THROMBOEMBOLIC COMPLICATIONS IN LYMPHOMA PATIENTS
Keywords:
lymphomas, VTE, thromboprophylaxis, LMWH, DOAC
Abstract
Lymphomas represent a heterogeneous group of malignant hematological diseases characterized by a high risk for development of venous thromboembolic complications (VTE). Consequently, VTE significantly impacts on the morbidity and mortality of these patients. Another concern is the financial burden of the health system caused by diagnostic and therapeutic procedures of cancer-associated thrombosis (CAT). The complex biology of lymphoma, in conjunction with patient and treatment related risk factors for the development of VTE, results in a procoagulant hemostatic dysregulation. Considering the incidence of VTE in patients with lymphoma, there is an emerging demand for both reliable risks assessment model (RAM) for prediction of VTE and for effective VTE prophylaxis and treatment. The clinical course of the patients with malignant diseases is accompanied by a wide range of potential treatment complications, therefore the task of prevention and treatment of VTE becomes even more challenging. In recent years, great progress has been achieved in understanding the pathophysiological mechanisms of thrombotic complications, while the significant number of randomized controlled trials (RCT) have provided us with standards of prophylaxis and treatment of VTE complications in patients with malignancy. In comparison to previous recommendations and guidelines for CAT, the use of direct oral anticoagulants (DOAC) has been gradually approaching low molecular weight heparins (LMWH) in terms of efficacy and safety profile in these indications. This systematic review is focused on the latest pathophysiological advances, risk factors assessment, prophylactic and therapeutic recommendations and guidelines concerning VTE in patients with lymphoma.
References
1. Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: Burden, mechanisms, and management. Thromb Haemost. 2017;117(2):219–30.
2. Donnellan E, Khorana AA. Cancer and Venous Thromboembolic Disease: A Review. Oncologist. 2017/02/07. 2017;22(2):199–207.
3. Falanga A, Marchetti M, Russo L. Venous thromboembolism in the hematologic malignancies. Curr Opin Oncol. 2012;24(6):702–10.
4. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.
5. Goldschmidt N, Linetsky E, Shalom E, Varon D, Siegal T. High incidence of thromboembolism in patients with central nervous system lymphoma. Cancer. 2003;98(6):1239–42.
6. Lekovic D, Miljic P, Mihaljevic B. Increased risk of venous thromboembolism in patients with primary mediastinal large B-cell lymphoma. Thromb Res. 2010;126(6):477–80.
7. Yokoyama K, Murata M, Ikeda Y, Okamoto S. Incidence and risk factors for developing venous thromboembolism in Japanese with diffuse large b-cell lymphoma. Thromb Res. 2012;130(1):7–11.
8. Caruso V, Di Castelnuovo A, Meschengieser S, Lazzari MA, de Gaetano G, Storti S, et al. Thrombotic complications in adult patients with lymphoma: a meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events. Blood. 2010;115(26):5322–8.
9. Borchmann S, Muller H, Hude I, Fuchs M, Borchmann P, Engert A. Thrombosis as a treatment complication in Hodgkin lymphoma patients: a comprehensive analysis of three prospective randomized German Hodgkin Study Group (GHSG) trials. Ann Oncol Off J Eur Soc Med Oncol. 2019;30(8):1329–34.
10. Zhou X, Teegala S, Huen A, Ji Y, Fayad L, Hagemeister FB, et al. Incidence and risk factors of venous Thromboembolic events in lymphoma. Am J Med. 2010;123(10):935–41.
11. Yıldız A, Albayrak M, Pala Ç, Afacan Öztürk HB, Maral S, Şahin O, et al. The incidence and risk factors of thrombosis and the need for thromboprophylaxis in lymphoma and leukemia patients: A 9-year single-center experience. J Oncol Pharm Pract. 2020;26(2):386–96.
12. Mohren M, Markmann I, Jentsch-Ullrich K, Koenigsmann M, Lutze G, Franke A. Increased risk of thromboembolism in patients with malignant lymphoma: A single-centre analysis. Br J Cancer. 2005;92(8):1349–51.
13. Lyman GH, Khorana AA, Falanga A. Thrombosis and Cancer: Emerging Data for the Practicing Oncologist. Am Soc Clin Oncol Educ B. 2013;(33):e337–45.
14. Sanfilippo KM, Wang TF, Gage BF, Luo S, Riedell P, Carson KR. Incidence of venous thromboembolism in patients with non-Hodgkin lymphoma. Thromb Res. 2016;143:86–90.
15. Kekre N, Connors JM. Venous thromboembolism incidence in hematologic malignancies. Blood Rev. 2019;33:24–32.
16. Dharmavaram G, Cao S, Sundaram S, Ayyapan S, Boughan K, Gallogly M, et al. Aggressive Lymphoma Subtype Is A Risk Factor for Venous Thrombosis. Development of Lymphoma – Specific Venous Thrombosis Prediction Models. Am J Hematol. 2020;
17. Metharom P, Falasca M, Berndt MC. The history of armand trousseau and cancer-associated thrombosis. Cancers (Basel). 2019;11(2):2–5.
18. Karimi M, Cohan N. Cancer-associated thrombosis. Open Cardiovasc Med J. 2010;4:78–82.
19. Falanga A, Russo L, Milesi V, Vignoli A. Mechanisms and risk factors of thrombosis in cancer. Crit Rev Oncol Hematol. 2017;118(August):79–83.
20. Khorana AA. Cancer and thrombosis: Implications of published guidelines for clinical practice. Ann Oncol. 2009;20(10):1619–30.
21. Elyamany G, Alzahrani AM, Bukhary E. Cancer-associated thrombosis: An overview. Clin Med Insights Oncol. 2014;8:129–37.
22. Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost. 2013;11(2):223–33.
23. Mukai M, Oka T. Mechanism and management of cancer-associated thrombosis. J Cardiol. 2018;72(2):89–93.
24. Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750.
25. Kim AS, Khorana AA, McCrae KR. Mechanisms and biomarkers of cancer-associated thrombosis. Transl Res. 2020;225:33–53.
26. Fuentes HE, Tafur AJ, Caprini JA. Cancer-associated thrombosis. Disease-a-Month. 2016;62(5):121–58.
27. Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood. 2017;130(13):1499–506.
28. Al-Samkari H, Song AB, Connors JM. Cancer-associated thrombosis: Where do we stand? Adv CELL GENE Ther. 2020;3(1):e73.
29. Mitrugno A, Tassi Yunga S, Sylman JL, Zilberman-Rudenko J, Shirai T, Hebert JF, et al. The role of coagulation and platelets in colon cancer-associated thrombosis. Am J Physiol Cell Physiol. 2019;316(2):C264–73.
30. Razak NBA, Jones G, Bhandari M, Berndt MC, Metharom P. Cancer-associated thrombosis: An overview of mechanisms, risk factors, and treatment. Cancers (Basel). 2018;10(10):1–21.
31. Charlotte T, Yohei H, Staffan L, Nigel M, Håkan W. Neutrophil Extracellular Traps. Arterioscler Thromb Vasc Biol. 2019;39(9):1724–38.
32. Aksu K, Donmez A, Keser G. Inflammation-induced thrombosis: mechanisms, disease associations and management. Curr Pharm Des. 2012;18(11):1478–93.
33. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.
34. Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15(11):e493-503.
35. Alfaro C, Teijeira A, Oñate C, Pérez G, Sanmamed MF, Andueza MP, et al. Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs). Clin cancer Res an Off J Am Assoc Cancer Res. 2016;22(15):3924–36.
36. Antic D, Milic N, Bontekoe E, Hoppensteadt D, Djurasinovic V, Vukovic V, et al. Biomarkers of Hemostatic Dysregulation and Inflammation in Lymphoma: Potential Relevance to Thrombogenesis. Blood. 2019;134(Supplement_1):4945.
37. Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol. 2009;27(29):4839–47.
38. Antic D, Jelicic J, Vukovic V, Nikolovski S, Mihaljevic B. Venous thromboembolic events in lymphoma patients: Actual relationships between epidemiology, mechanisms, clinical profile and treatment. Blood Rev. 2018;32(2):144–58.
39. Connolly GC, Khorana AA. Emerging risk stratification approaches to cancer-associated thrombosis: risk factors, biomarkers and a risk score. Thromb Res. 2010;125 Suppl:S1–7.
40. Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016/01/16. 2016;41(1):3–14.
41. Shapiro SS. The lupus anticoagulant/antiphospholipid syndrome. Annu Rev Med. 1996;47:533–53.
42. Marlar RA, Husain S. The enigmas of the lupus anticoagulant: mechanisms, diagnosis, and management. Curr Rheumatol Rep. 2008;10(1):74–80.
43. Wahl DG, Guillemin F, De Maistre E, Perret-Guillaume C, Lecompte T, Thibaut G. Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus. 1998;7(1):15–22.
44. Lechner K, Simonitsch I, Haselböck J, Jäger U, Pabinger I. Acquired immune-mediated thrombophilia in lymphoproliferative disorders. Leuk Lymphoma. 2011;52(10):1836–43.
45. Gebhart J, Lechner K, Skrabs C, Sliwa T, Müldür E, Ludwig H, et al. Lupus anticoagulant and thrombosis in splenic marginal zone lymphoma. Thromb Res. 2014;134(5):980–4.
46. Moons KGM, Kengne AP, Grobbee DE, Royston P, Vergouwe Y, Altman DG, et al. Risk prediction models: II. External validation, model updating, and impact assessment. Heart. 2012;98(9):691–8.
47. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902–7.
48. Mulder FI, Candeloro M, Kamphuisen PW, Di Nisio M, Bossuyt PM, Guman N, et al. The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis. Haematologica. 2019;104(6):1277–87.
49. Rupa-Matysek J, Gil L, Kazmierczak M, Baranska M, Komarnicki M. Prediction of venous thromboembolism in newly diagnosed patients treated for lymphoid malignancies: validation of the Khorana Risk Score. Med Oncol. 2017;35(1):5.
50. Hohaus S, Bartolomei F, Cuccaro A, Maiolo E, Alma E, D’alò F, et al. Venous thromboembolism in lymphoma: Risk stratification and antithrombotic prophylaxis. Cancers (Basel). 2020;12(5):1–17.
51. Antic D, Milic N, Nikolovski S, Todorovic M, Bila J, Djurdjevic P, et al. Development and validation of multivariable predictive model for thromboembolic events in lymphoma patients. Am J Hematol. 2016;91(10):1014–9.
52. Antic D, Milic N, Mihaljevic B, Cheson B, Narkhede M, Abdel-Razeq H, et al. External Validation and Revision of Thrombosis Lymphoma /Throly/ Score. Blood. 2018;132(Supplement 1):140.
53. Moik F, Pabinger I, Ay C. How i treat cancer-associated thrombosis. ESMO Open. 2020;5(1).
54. Becattini C, Verso M, Muňoz A, Agnelli G. Updated meta-analysis on prevention of venous thromboembolism in ambulatory cancer patients. Haematologica. 2020;105(3):838–48.
55. Ramacciotti E, Agati LB, Caffaro RA, Volpiani GG, Lopes RD, Comerota AJ, et al. Direct Oral Anticoagulants and Cancer-Associated Thrombosis Management. Where Do We Stand in 2019? Clin Appl Thromb Hemost. 2019;25:1076029619856433–1076029619856433.
56. Farge D, Frere C. Recent advances in the treatment and prevention of venous thromboembolism in cancer patients: role of the direct oral anticoagulants and their unique challenges. F1000Research. 2019;8:F1000 Faculty Rev-974.
57. Li A, Garcia DA, Lyman GH, Carrier M. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thromb Res. 2019;173:158–63.
58. Bauersachs R, Khorana AA, Lee AYY, Soff G. Cancer-associated venous thromboembolism: Treatment and prevention with rivaroxaban. Res Pract Thromb Haemost. 2020;4(4):532–49.
59. Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, et al. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med. 2018;380(8):711–9.
60. Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, et al. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med. 2019;380(8):720–8.
61. Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496–520.
62. Farge D, Frere C, Connors JM, Ay C, Khorana AA, Munoz A, et al. 2019 International Clinical Practice Guidelines for the Treatment and Prophylaxis of Venous Thromboembolism in Patients With Cancer. Lancet Oncol. 2019;20(10):e566–81.
63. National Compehensive Cancer Network. Cancer-Associated Venous Thromboembolic Disease (Version 1.2020) [Internet]. 2020.
64. Zahir MN, Shaikh Q, Shabbir-Moosajee M, Jabbar AA. Incidence of Venous Thromboembolism in cancer patients treated with Cisplatin based chemotherapy — a cohort study. BMC Cancer. 2017;17(1):57.
65. Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman M V, Connors JM, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020;382(17):1599–607.
66. McBane II RD, Wysokinski WE, Le-Rademacher JG, Zemla T, Ashrani A, Tafur A, et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost. 2020;18(2):411–21.
67. Young AM, 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 Off J Am Soc Clin Oncol. 2018;36(20):2017–23.
68. Raskob GE, 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. 2018;378(7):615–24.
69. Kooiman J, den Exter PL, Cannegieter SC, le Cessie S, del Toro J, Sahuquillo JC, et al. Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer-associated venous thromboembolism during anticoagulant treatment. J Thromb Haemost. 2013;11(11):1968–76.
70. Lim W, Dentali F, Eikelboom JW, Crowther MA. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med. 2006;144(9):673–84.
71. Scotté F, Rey JB, Launay-Vacher V. Thrombosis, cancer and renal insufficiency: low molecular weight heparin at the crossroads. Support care cancer Off J Multinatl Assoc Support Care Cancer. 2012;20(12):3033–42.
72. Yeung J, Dix CHK, Ritchie AG, Kow M, Chen VMY. Tinzaparin for venous thromboembolism in patients with renal impairment - a single-centre, prospective pilot study. Intern Med J. 2020;
73. Woodruff S, Feugère G, Abreu P, Heissler J, Ruiz MT, Jen F. A post hoc analysis of dalteparin versus oral anticoagulant (VKA) therapy for the prevention of recurrent venous thromboembolism (rVTE) in patients with cancer and renal impairment. J Thromb Thrombolysis. 2016;42(4):494–504.
74. Bauersachs R, Lee AYY, Kamphuisen PW, Meyer G, Janas MS, Jarner MF, et al. Renal Impairment, Recurrent Venous Thromboembolism and Bleeding in Cancer Patients with Acute Venous Thromboembolism-Analysis of the CATCH Study. Thromb Haemost. 2018;118(5):914–21.
75. Martin K, Beyer-Westendorf J, Davidson BL, Huisman M V, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016/04/27. 2016;14(6):1308–13.
2. Donnellan E, Khorana AA. Cancer and Venous Thromboembolic Disease: A Review. Oncologist. 2017/02/07. 2017;22(2):199–207.
3. Falanga A, Marchetti M, Russo L. Venous thromboembolism in the hematologic malignancies. Curr Opin Oncol. 2012;24(6):702–10.
4. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.
5. Goldschmidt N, Linetsky E, Shalom E, Varon D, Siegal T. High incidence of thromboembolism in patients with central nervous system lymphoma. Cancer. 2003;98(6):1239–42.
6. Lekovic D, Miljic P, Mihaljevic B. Increased risk of venous thromboembolism in patients with primary mediastinal large B-cell lymphoma. Thromb Res. 2010;126(6):477–80.
7. Yokoyama K, Murata M, Ikeda Y, Okamoto S. Incidence and risk factors for developing venous thromboembolism in Japanese with diffuse large b-cell lymphoma. Thromb Res. 2012;130(1):7–11.
8. Caruso V, Di Castelnuovo A, Meschengieser S, Lazzari MA, de Gaetano G, Storti S, et al. Thrombotic complications in adult patients with lymphoma: a meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events. Blood. 2010;115(26):5322–8.
9. Borchmann S, Muller H, Hude I, Fuchs M, Borchmann P, Engert A. Thrombosis as a treatment complication in Hodgkin lymphoma patients: a comprehensive analysis of three prospective randomized German Hodgkin Study Group (GHSG) trials. Ann Oncol Off J Eur Soc Med Oncol. 2019;30(8):1329–34.
10. Zhou X, Teegala S, Huen A, Ji Y, Fayad L, Hagemeister FB, et al. Incidence and risk factors of venous Thromboembolic events in lymphoma. Am J Med. 2010;123(10):935–41.
11. Yıldız A, Albayrak M, Pala Ç, Afacan Öztürk HB, Maral S, Şahin O, et al. The incidence and risk factors of thrombosis and the need for thromboprophylaxis in lymphoma and leukemia patients: A 9-year single-center experience. J Oncol Pharm Pract. 2020;26(2):386–96.
12. Mohren M, Markmann I, Jentsch-Ullrich K, Koenigsmann M, Lutze G, Franke A. Increased risk of thromboembolism in patients with malignant lymphoma: A single-centre analysis. Br J Cancer. 2005;92(8):1349–51.
13. Lyman GH, Khorana AA, Falanga A. Thrombosis and Cancer: Emerging Data for the Practicing Oncologist. Am Soc Clin Oncol Educ B. 2013;(33):e337–45.
14. Sanfilippo KM, Wang TF, Gage BF, Luo S, Riedell P, Carson KR. Incidence of venous thromboembolism in patients with non-Hodgkin lymphoma. Thromb Res. 2016;143:86–90.
15. Kekre N, Connors JM. Venous thromboembolism incidence in hematologic malignancies. Blood Rev. 2019;33:24–32.
16. Dharmavaram G, Cao S, Sundaram S, Ayyapan S, Boughan K, Gallogly M, et al. Aggressive Lymphoma Subtype Is A Risk Factor for Venous Thrombosis. Development of Lymphoma – Specific Venous Thrombosis Prediction Models. Am J Hematol. 2020;
17. Metharom P, Falasca M, Berndt MC. The history of armand trousseau and cancer-associated thrombosis. Cancers (Basel). 2019;11(2):2–5.
18. Karimi M, Cohan N. Cancer-associated thrombosis. Open Cardiovasc Med J. 2010;4:78–82.
19. Falanga A, Russo L, Milesi V, Vignoli A. Mechanisms and risk factors of thrombosis in cancer. Crit Rev Oncol Hematol. 2017;118(August):79–83.
20. Khorana AA. Cancer and thrombosis: Implications of published guidelines for clinical practice. Ann Oncol. 2009;20(10):1619–30.
21. Elyamany G, Alzahrani AM, Bukhary E. Cancer-associated thrombosis: An overview. Clin Med Insights Oncol. 2014;8:129–37.
22. Falanga A, Marchetti M, Vignoli A. Coagulation and cancer: biological and clinical aspects. J Thromb Haemost. 2013;11(2):223–33.
23. Mukai M, Oka T. Mechanism and management of cancer-associated thrombosis. J Cardiol. 2018;72(2):89–93.
24. Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750.
25. Kim AS, Khorana AA, McCrae KR. Mechanisms and biomarkers of cancer-associated thrombosis. Transl Res. 2020;225:33–53.
26. Fuentes HE, Tafur AJ, Caprini JA. Cancer-associated thrombosis. Disease-a-Month. 2016;62(5):121–58.
27. Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood. 2017;130(13):1499–506.
28. Al-Samkari H, Song AB, Connors JM. Cancer-associated thrombosis: Where do we stand? Adv CELL GENE Ther. 2020;3(1):e73.
29. Mitrugno A, Tassi Yunga S, Sylman JL, Zilberman-Rudenko J, Shirai T, Hebert JF, et al. The role of coagulation and platelets in colon cancer-associated thrombosis. Am J Physiol Cell Physiol. 2019;316(2):C264–73.
30. Razak NBA, Jones G, Bhandari M, Berndt MC, Metharom P. Cancer-associated thrombosis: An overview of mechanisms, risk factors, and treatment. Cancers (Basel). 2018;10(10):1–21.
31. Charlotte T, Yohei H, Staffan L, Nigel M, Håkan W. Neutrophil Extracellular Traps. Arterioscler Thromb Vasc Biol. 2019;39(9):1724–38.
32. Aksu K, Donmez A, Keser G. Inflammation-induced thrombosis: mechanisms, disease associations and management. Curr Pharm Des. 2012;18(11):1478–93.
33. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.
34. Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15(11):e493-503.
35. Alfaro C, Teijeira A, Oñate C, Pérez G, Sanmamed MF, Andueza MP, et al. Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs). Clin cancer Res an Off J Am Assoc Cancer Res. 2016;22(15):3924–36.
36. Antic D, Milic N, Bontekoe E, Hoppensteadt D, Djurasinovic V, Vukovic V, et al. Biomarkers of Hemostatic Dysregulation and Inflammation in Lymphoma: Potential Relevance to Thrombogenesis. Blood. 2019;134(Supplement_1):4945.
37. Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol. 2009;27(29):4839–47.
38. Antic D, Jelicic J, Vukovic V, Nikolovski S, Mihaljevic B. Venous thromboembolic events in lymphoma patients: Actual relationships between epidemiology, mechanisms, clinical profile and treatment. Blood Rev. 2018;32(2):144–58.
39. Connolly GC, Khorana AA. Emerging risk stratification approaches to cancer-associated thrombosis: risk factors, biomarkers and a risk score. Thromb Res. 2010;125 Suppl:S1–7.
40. Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016/01/16. 2016;41(1):3–14.
41. Shapiro SS. The lupus anticoagulant/antiphospholipid syndrome. Annu Rev Med. 1996;47:533–53.
42. Marlar RA, Husain S. The enigmas of the lupus anticoagulant: mechanisms, diagnosis, and management. Curr Rheumatol Rep. 2008;10(1):74–80.
43. Wahl DG, Guillemin F, De Maistre E, Perret-Guillaume C, Lecompte T, Thibaut G. Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus. 1998;7(1):15–22.
44. Lechner K, Simonitsch I, Haselböck J, Jäger U, Pabinger I. Acquired immune-mediated thrombophilia in lymphoproliferative disorders. Leuk Lymphoma. 2011;52(10):1836–43.
45. Gebhart J, Lechner K, Skrabs C, Sliwa T, Müldür E, Ludwig H, et al. Lupus anticoagulant and thrombosis in splenic marginal zone lymphoma. Thromb Res. 2014;134(5):980–4.
46. Moons KGM, Kengne AP, Grobbee DE, Royston P, Vergouwe Y, Altman DG, et al. Risk prediction models: II. External validation, model updating, and impact assessment. Heart. 2012;98(9):691–8.
47. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902–7.
48. Mulder FI, Candeloro M, Kamphuisen PW, Di Nisio M, Bossuyt PM, Guman N, et al. The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis. Haematologica. 2019;104(6):1277–87.
49. Rupa-Matysek J, Gil L, Kazmierczak M, Baranska M, Komarnicki M. Prediction of venous thromboembolism in newly diagnosed patients treated for lymphoid malignancies: validation of the Khorana Risk Score. Med Oncol. 2017;35(1):5.
50. Hohaus S, Bartolomei F, Cuccaro A, Maiolo E, Alma E, D’alò F, et al. Venous thromboembolism in lymphoma: Risk stratification and antithrombotic prophylaxis. Cancers (Basel). 2020;12(5):1–17.
51. Antic D, Milic N, Nikolovski S, Todorovic M, Bila J, Djurdjevic P, et al. Development and validation of multivariable predictive model for thromboembolic events in lymphoma patients. Am J Hematol. 2016;91(10):1014–9.
52. Antic D, Milic N, Mihaljevic B, Cheson B, Narkhede M, Abdel-Razeq H, et al. External Validation and Revision of Thrombosis Lymphoma /Throly/ Score. Blood. 2018;132(Supplement 1):140.
53. Moik F, Pabinger I, Ay C. How i treat cancer-associated thrombosis. ESMO Open. 2020;5(1).
54. Becattini C, Verso M, Muňoz A, Agnelli G. Updated meta-analysis on prevention of venous thromboembolism in ambulatory cancer patients. Haematologica. 2020;105(3):838–48.
55. Ramacciotti E, Agati LB, Caffaro RA, Volpiani GG, Lopes RD, Comerota AJ, et al. Direct Oral Anticoagulants and Cancer-Associated Thrombosis Management. Where Do We Stand in 2019? Clin Appl Thromb Hemost. 2019;25:1076029619856433–1076029619856433.
56. Farge D, Frere C. Recent advances in the treatment and prevention of venous thromboembolism in cancer patients: role of the direct oral anticoagulants and their unique challenges. F1000Research. 2019;8:F1000 Faculty Rev-974.
57. Li A, Garcia DA, Lyman GH, Carrier M. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thromb Res. 2019;173:158–63.
58. Bauersachs R, Khorana AA, Lee AYY, Soff G. Cancer-associated venous thromboembolism: Treatment and prevention with rivaroxaban. Res Pract Thromb Haemost. 2020;4(4):532–49.
59. Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A, et al. Apixaban to Prevent Venous Thromboembolism in Patients with Cancer. N Engl J Med. 2018;380(8):711–9.
60. Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, et al. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med. 2019;380(8):720–8.
61. Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496–520.
62. Farge D, Frere C, Connors JM, Ay C, Khorana AA, Munoz A, et al. 2019 International Clinical Practice Guidelines for the Treatment and Prophylaxis of Venous Thromboembolism in Patients With Cancer. Lancet Oncol. 2019;20(10):e566–81.
63. National Compehensive Cancer Network. Cancer-Associated Venous Thromboembolic Disease (Version 1.2020) [Internet]. 2020.
64. Zahir MN, Shaikh Q, Shabbir-Moosajee M, Jabbar AA. Incidence of Venous Thromboembolism in cancer patients treated with Cisplatin based chemotherapy — a cohort study. BMC Cancer. 2017;17(1):57.
65. Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman M V, Connors JM, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020;382(17):1599–607.
66. McBane II RD, Wysokinski WE, Le-Rademacher JG, Zemla T, Ashrani A, Tafur A, et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost. 2020;18(2):411–21.
67. Young AM, 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 Off J Am Soc Clin Oncol. 2018;36(20):2017–23.
68. Raskob GE, 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. 2018;378(7):615–24.
69. Kooiman J, den Exter PL, Cannegieter SC, le Cessie S, del Toro J, Sahuquillo JC, et al. Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer-associated venous thromboembolism during anticoagulant treatment. J Thromb Haemost. 2013;11(11):1968–76.
70. Lim W, Dentali F, Eikelboom JW, Crowther MA. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med. 2006;144(9):673–84.
71. Scotté F, Rey JB, Launay-Vacher V. Thrombosis, cancer and renal insufficiency: low molecular weight heparin at the crossroads. Support care cancer Off J Multinatl Assoc Support Care Cancer. 2012;20(12):3033–42.
72. Yeung J, Dix CHK, Ritchie AG, Kow M, Chen VMY. Tinzaparin for venous thromboembolism in patients with renal impairment - a single-centre, prospective pilot study. Intern Med J. 2020;
73. Woodruff S, Feugère G, Abreu P, Heissler J, Ruiz MT, Jen F. A post hoc analysis of dalteparin versus oral anticoagulant (VKA) therapy for the prevention of recurrent venous thromboembolism (rVTE) in patients with cancer and renal impairment. J Thromb Thrombolysis. 2016;42(4):494–504.
74. Bauersachs R, Lee AYY, Kamphuisen PW, Meyer G, Janas MS, Jarner MF, et al. Renal Impairment, Recurrent Venous Thromboembolism and Bleeding in Cancer Patients with Acute Venous Thromboembolism-Analysis of the CATCH Study. Thromb Haemost. 2018;118(5):914–21.
75. Martin K, Beyer-Westendorf J, Davidson BL, Huisman M V, Sandset PM, Moll S. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2016/04/27. 2016;14(6):1308–13.