Venous thrombosis and cancer: From mouse models to clinical trials

Journal of Thrombosis and Haemostasis

Volumn 13, Issue 8, 2015, Pages 1372-1382

  Hisada, Y ^a,b   Geddings, J E ^a   Ay, C ^c   Mackman, N ^a,b  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF TROMSØ   (Norway)

^c MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Cancer; Leukocytes; Platelets; Thrombosis; Tissue factor

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; ANTITHROMBOCYTIC AGENT; ANTIVITAMIN K; BETA THROMBOGLOBULIN; BLOOD CLOTTING FACTOR 8; CD40 LIGAND; CELL FREE DNA; CERTOPARIN; CLOPIDOGREL; D DIMER; DALTEPARIN; DNA; ENOXAPARIN; GRANULOCYTE COLONY STIMULATING FACTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 6; LOW MOLECULAR WEIGHT HEPARIN; NADROPARIN; PADGEM PROTEIN; PLACEBO; PROTHROMBIN; SEMULOPARIN; THROMBIN ANTITHROMBIN COMPLEX; THROMBOCYTE FACTOR 4; THROMBOPLASTIN; THROMBOPOIETIN; THROMBOSPONDIN 1; UNCLASSIFIED DRUG; FIBRINOLYTIC AGENT;

BLADDER CANCER; BLOOD CLOTTING; BRAIN CANCER; BREAST CANCER; CANCER PATIENT; CANCER SURVIVAL; CLINICAL TRIAL (TOPIC); COLON CANCER; DRUG EFFECT; DRUG EFFICACY; EXTRACELLULAR TRAP; HIGH RISK PATIENT; HUMAN; LEUKOCYTE ACTIVATION; LEUKOCYTE COUNT; LEUKOCYTE FUNCTION; LUNG CANCER; MEMBRANE MICROPARTICLE; META ANALYSIS (TOPIC); MOUSE; NEOPLASM; NEUTROPHILIA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK ASSESSMENT; RISK FACTOR; THROMBOCYTE ACTIVATION; THROMBOCYTE COUNT; THROMBOCYTE FUNCTION; THROMBOCYTOPOIESIS; THROMBOSIS PREVENTION; TUMOR DERIVED TISSUE FACTOR POSITIVE MICROVESICLE; VENOUS THROMBOEMBOLISM; ANIMAL; BLOOD; COMPLICATION; DISEASE MODEL; DRUG EFFECTS; PATHOLOGY; PROGNOSIS; VENOUS THROMBOSIS;

ANIMALS; ANTICOAGULANTS; BLOOD COAGULATION; DISEASE MODELS, ANIMAL; FIBRINOLYTIC AGENTS; HUMANS; MICE; NEOPLASMS; PROGNOSIS; RISK ASSESSMENT; RISK FACTORS; VENOUS THROMBOSIS;

EID: 84937973104     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.13009     Document Type: Review

References (102)

1. Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE. Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 2006; 119: 60-8.
2. Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood 2013; 122: 1712-23.
3. Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 2012; 9: e1001275.
4. Bouillard JB, Bouillaud S. De l'Obliteration des veines et de son influence sur la formation des hydropisies partielles: consideration sur la hydropisies passive et general. Arch Gen Med 1823; 1: 188-204.
5. Trousseau A. Phlegmasia alba dolens. Paris: Clinique Medicale de l'Hotel-Dieu de Paris, 1865: 654-712.
6. James TI, Matheson N. Thrombophlebitis in cancer. Practitioner 1935; 134: 683-4.
7. Agnelli G, Gussoni G, Bianchini C, Verso M, Mandala M, Cavanna L, Barni S, Labianca R, Buzzi F, Scambia G, Passalacqua R, Ricci S, Gasparini G, Lorusso V, Bonizzoni E, Tonato M, Investigators P. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009; 10: 943-9.
8. Agnelli G, George DJ, Kakkar AK, Fisher W, Lassen MR, Mismetti P, Mouret P, Chaudhari U, Lawson F, Turpie AG, Investigators S-O. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366: 601-9.
9. Falanga A, Russo L, Verzeroli C. Mechanisms of thrombosis in cancer. Thromb Res 2013; 131 (Suppl. 1): S59-62.
10. Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 2009; 27: 4839-47.
11. Khorana AA, Dalal M, Lin J, Connolly GC. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer 2013; 119: 648-55.
12. Young A, Chapman O, Connor C, Poole C, Rose P, Kakkar AK. Thrombosis and cancer. Nat Rev Clin Oncol 2012; 9: 437-49.
13. Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343: 1846-50.
14. Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166: 458-64.
15. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007; 5: 632-4.
16. Ogren M, Bergqvist D, Wahlander K, Eriksson H, Sternby NH. Trousseau's syndrome - what is the evidence? A population-based autopsy study Thromb Haemost 2006; 95: 541-5.
17. Falanga A, Marchetti M, Russo L. The mechanisms of cancer-associated thrombosis. Thromb Res 2015; 135 (Suppl. 1): S8-11.
18. Agnelli G, Bolis G, Capussotti L, Scarpa RM, Tonelli F, Bonizzoni E, Moia M, Parazzini F, Rossi R, Sonaglia F, Valarani B, Bianchini C, Gussoni G. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 2006; 243: 89-95.
19. Edwards RL, Klaus M, Matthews E, McCullen C, Bona RD, Rickles FR. Heparin abolishes the chemotherapy-induced increase in plasma fibrinopeptide A levels. Am J Med 1990; 89: 25-8.
20. Weitz IC, Israel VK, Waisman JR, Presant CA, Rochanda L, Liebman HA. Chemotherapy-induced activation of hemostasis: effect of a low molecular weight heparin (dalteparin sodium) on plasma markers of hemostatic activation. Thromb Haemost 2002; 88: 213-20.
21. Pabinger I, Ay C, Dunkler D, Thaler J, Reitter EM, Marosi C, Zielinski C, Mannhalter C. 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: 17-22.
22. Hanna DL, White RH, Wun T. Biomolecular markers of cancer-associated thromboembolism. Crit Rev Oncol Hematol 2013; 88: 19-29.
23. Rickles FR, Falanga A. Molecular basis for the relationship between thrombosis and cancer. Thromb Res 2001; 102: V215-24.
24. Levi M. Cancer-related coagulopathies. Thromb Res 2014; 133 (Suppl. 2): S70-5.
25. Pabinger I, Thaler J, Ay C. Biomarkers for prediction of venous thromboembolism in cancer. Blood 2013; 122: 2011-8.
26. Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA, van Delden JJ, Moons KG, Reitsma JB. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. BMJ 2013; 346: f2492.
27. Kodama J, Seki N, Masahiro S, Kusumoto T, Nakamura K, Hongo A, Hiramatsu Y. D-dimer level as a risk factor for postoperative venous thromboembolism in Japanese women with gynecologic cancer. Ann Oncol 2010; 21: 1651-6.
28. Stender MT, Frokjaer JB, Larsen TB, Lundbye-Christensen S, Thorlacius-Ussing O. Preoperative plasma D-dimer is a predictor of postoperative deep venous thrombosis in colorectal cancer patients: a clinical, prospective cohort study with one-year follow-up. Dis Colon Rectum 2009; 52: 446-51.
29. Ay C, Vormittag R, Dunkler D, Simanek R, Chiriac AL, Drach J, Quehenberger P, Wagner O, Zielinski C, Pabinger I. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2009; 27: 4124-9.
30. Iversen LH, Okholm M, Thorlacius-Ussing O. Pre- and postoperative state of coagulation and fibrinolysis in plasma of patients with benign and malignant colorectal disease-a preliminary study. Thromb Haemost 1996; 76: 523-8.
31. Vormittag R, Simanek R, Ay C, Dunkler D, Quehenberger P, Marosi C, Zielinski C, Pabinger I. High factor VIII levels independently predict venous thromboembolism in cancer patients: the cancer and thrombosis study. Arterioscler Thromb Vasc Biol 2009; 29: 2176-81.
32. Falanga A. Thrombophilia in cancer. Semin Thromb Hemost 2005; 31: 104-10.
33. Geddings JE, Mackman N. Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood 2013; 122: 1873-80.
34. Callander NS, Varki N, Rao LV. Immunohistochemical identification of tissue factor in solid tumors. Cancer 1992; 70: 1194-201.
35. Khorana AA, Ahrendt SA, Ryan CK, Francis CW, Hruban RH, Hu YC, Hostetter G, Harvey J, Taubman MB. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res 2007; 13: 2870-5.
36. Kakkar AK, Lemoine NR, Scully MF, Tebbutt S, Williamson RC. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995; 82: 1101-4.
37. Wang JG, Geddings JE, Aleman MM, Cardenas JC, Chantrathammachart P, Williams JC, Kirchhofer D, Bogdanov VY, Bach RR, Rak J, Church FC, Wolberg AS, Pawlinski R, Key NS, Yeh JJ, Mackman N. Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer. Blood 2012; 119: 5543-52.
38. Uno K, Homma S, Satoh T, Nakanishi K, Abe D, Matsumoto K, Oki A, Tsunoda H, Yamaguchi I, Nagasawa T, Yoshikawa H, Aonuma K. Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer. Br J Cancer 2007; 96: 290-5.
39. Thaler J, Preusser M, Ay C, Kaider A, Marosi C, Zielinski C, Pabinger I, Hainfellner JA. Intratumoral tissue factor expression and risk of venous thromboembolism in brain tumor patients. Thromb Res 2013; 131: 162-5.
40. Yu JL, Rak JW. Shedding of tissue factor (TF)-containing microparticles rather than alternatively spliced TF is the main source of TF activity released from human cancer cells. J Thromb Haemost 2004; 2: 2065-7.
41. Yu JL, May L, Lhotak V, Shahrzad S, Shirasawa S, Weitz JI, Coomber BL, Mackman N, Rak JW. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 2005; 105: 1734-41.
42. Davila M, Amirkhosravi A, Coll E, Desai H, Robles L, Colon J, Baker CH, Francis JL. Tissue factor-bearing microparticles derived from tumor cells: impact on coagulation activation. J Thromb Haemost 2008; 6: 1517-24.
43. Thomas GM, Panicot-Dubois L, Lacroix R, Dignat-George F, Lombardo D, Dubois C. Cancer cell-derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo. J Exp Med 2009; 206: 1913-27.
44. Thaler J, Ay C, Mackman N, Bertina RM, Kaider A, Marosi C, Key NS, Barcel DA, Scheithauer W, Kornek G, Zielinski C, Pabinger I. Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients. J Thromb Haemost 2012; 10: 1363-70.
45. van Es N, Sturk A, Middeldorp S, Nieuwland R. Effects of cancer on platelets. Semin Oncol 2014; 41: 311-8.
46. Connolly GC, Phipps RP, Francis CW. Platelets and cancer-associated thrombosis. Semin Oncol 2014; 41: 302-10.
47. Riedl J, Pabinger I, Ay C. Platelets in cancer and thrombosis. Hamostaseologie 2014; 34: 54-62.
48. Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-9.
49. Simanek R, Vormittag R, Ay C, Alguel G, Dunkler D, Schwarzinger I, Steger G, Jaeger U, Zielinski C, Pabinger I. High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Haemost 2010; 8: 114-20.
50. Jensvoll H, Blix K, Braekkan SK, Hansen JB. Platelet count measured prior to cancer development is a risk factor for future symptomatic venous thromboembolism: the Tromso Study. PLoS One 2014; 9: e92011.
51. Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, Rupairmoole R, Armaiz-Pena GN, Pecot CV, Coward J, Deavers MT, Vasquez HG, Urbauer D, Landen CN, Hu W, Gershenson H, Matsuo K, Shahzad MM, King ER, Tekedereli I, et al. Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med 2012; 366: 610-8.
52. Shavit JA, Motto DG. Coagulation and metastasis - an unexpected role for von Willebrand factor. J Thromb Haemost 2006; 4: 517-8.
53. Vandendries ER, Furie BC, Furie B. Role of P-selectin and PSGL-1 in coagulation and thrombosis. Thromb Haemost 2004; 92: 459-66.
54. Ay C, Dunkler D, Marosi C, Chiriac AL, Vormittag R, Simanek R, Quehenberger P, Zielinski C, Pabinger I. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116: 5377-82.
55. Ay C, Simanek R, Vormittag R, Dunkler D, Alguel G, Koder S, Kornek G, Marosi C, Wagner O, Zielinski C, Pabinger I. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). Blood 2008; 112: 2703-8.
56. Poruk KE, Firpo MA, Huerter LM, Scaife CL, Emerson LL, Boucher KM, Jones KA, Mulvihill SJ. Serum platelet factor 4 is an independent predictor of survival and venous thromboembolism in patients with pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2010; 19: 2605-10.
57. Riedl J, Hell L, Kaider A, Koder S, Marosi C, Zielinski C, Panzer S, Pabinger I, Ay C. Association of platelet activation markers with cancer-associated venous thromboembolism. Platelets 2015; [Epub ahead of print].
58. Shoenfeld Y, Tal A, Berliner S, Pinkhas J. Leukocytosis in non hematological malignancies-a possible tumor-associated marker. J Cancer Res Clin Oncol 1986; 111: 54-8.
59. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-7.
60. Pabinger I, Posch F. Flamethrowers: blood cells and cancer thrombosis risk. Hematology 2014; 2014: 410-7.
61. Thaler J, Ay C, Kaider A, Reitter EM, Haselbock J, Mannhalter C, Zielinski C, Marosi C, Pabinger I. Biomarkers predictive of venous thromboembolism in patients with newly diagnosed high-grade gliomas. Neuro Oncol 2014; 16: 1645-51.
62. Blix K, Jensvoll H, Braekkan SK, Hansen JB. White blood cell count measured prior to cancer development is associated with future risk of venous thromboembolism-the Tromso study. PLoS One 2013; 8: e73447.
63. Connolly GC, Khorana AA, Kuderer NM, Culakova E, Francis CW, Lyman GH. Leukocytosis, thrombosis and early mortality in cancer patients initiating chemotherapy. Thromb Res 2010; 126: 113-8.
64. von Bruhl ML, Stark K, Steinhart A, Chandraratne S, Konrad I, Lorenz M, Khandoga A, Tirniceriu A, Coletti R, Kollnberger M, Byrne RA, Laitinen I, Walch A, Brill A, Pfeiler S, Manukyan D, Braun S, Lange P, Riegger J, Ware J, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209: 819-35.
65. Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013; 13: 34-45.
66. Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 2007; 176: 231-41.
67. Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood 2014; 123: 2768-76.
68. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science 2004; 303: 1532-5.
69. Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, Keys EM, Allen-Vercoe E, Devinney R, Doig CJ, Green FH, Kubes P. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 2007; 13: 463-9.
70. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, Wrobleski SK, Wakefield TW, Hartwig JH, Wagner DD. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA 2010; 107: 15880-5.
71. Gould TJ, Vu TT, Swystun LL, Dwivedi DJ, Mai SH, Weitz JI, Liaw PC. Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms. Arterioscler Thromb Vasc Biol 2014; 34: 1977-84.
72. Brill A, Fuchs TA, Savchenko AS, Thomas GM, Martinod K, De Meyer SF, Bhandari AA, Wagner DD. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost 2012; 10: 136-44.
73. Martinod K, Demers M, Fuchs TA, Wong SL, Brill A, Gallant M, Hu J, Wang Y, Wagner DD. Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci USA 2013; 110: 8674-9.
74. Savchenko AS, Martinod K, Seidman MA, Wong SL, Borissoff JI, Piazza G, Libby P, Goldhaber SZ, Mitchell RN, Wagner DD. Neutrophil extracellular traps form predominantly during the organizing stage of human venous thromboembolism development. J Thromb Haemost 2014; 12: 860-70.
75. Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR, Fuchs TA, Scadden DT, Wagner DD. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci USA 2012; 109: 13076-81.
76. Demers M, Wagner DD. Neutrophil extracellular traps: a new link to cancer-associated thrombosis and potential implications for tumor progression. Oncoimmunology 2013; 2: e22946.
77. Demers M, Wagner DD. NETosis: a new factor in tumor progression and cancer-associated thrombosis. Semin Thromb Hemost 2014; 40: 277-83.
78. Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11: 426-37.
79. Gailani D, Renne T. The intrinsic pathway of coagulation: a target for treating thromboembolic disease? J Thromb Haemost 2007; 5: 1106-12.
80. Swystun LL, Mukherjee S, Liaw PC. Breast cancer chemotherapy induces the release of cell-free DNA, a novel procoagulant stimulus. J Thromb Haemost 2011; 9: 2313-21.
81. Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, De Bon E, Tormene D, Pagnan A, Prandoni P. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010; 8: 2450-7.
82. Zakai NA, Callas PW, Repp AB, Cushman M. Venous thrombosis risk assessment in medical inpatients: the medical inpatients and thrombosis (MITH) study. J Thromb Haemost 2013; 11: 634-41.
83. Kyrle PA. Predicting recurrent venous thromboembolism in cancer: is it possible? Thromb Res 2014; 133 (Suppl. 2): S17-22.
84. Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Prestrud AA, Falanga A, American Society of Clinical Oncology Clinical P. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31: 2189-204.
85. Mandala M, Falanga A, Roila F, Group EGW. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2011; 22 (Suppl. 6): vi85-92.
86. Franchini M, Mannucci PM. Thrombin and cancer: from molecular basis to therapeutic implications. Semin Thromb Hemost 2012; 38: 95-101.
87. Haas SK, Freund M, Heigener D, Heilmann L, Kemkes-Matthes B, von Tempelhoff GF, Melzer N, Kakkar AK, Investigators T. Low-molecular-weight heparin versus placebo for the prevention of venous thromboembolism in metastatic breast cancer or stage III/IV lung cancer. Clin Appl Thromb Hemost 2012; 18: 159-65.
88. Maraveyas A, Waters J, Roy R, Fyfe D, Propper D, Lofts F, Sgouros J, Gardiner E, Wedgwood K, Ettelaie C, Bozas G. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer 2012; 48: 1283-92.
89. Riess H, Pelzer U, Deutschinoff G, Opitz B, Stauch M, Reitzig P, Hahnfeld S, Hilbig A, Stieler J, Oettle H. A prospective, randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC): results of the CONKO 004 trial. J Clin Oncol 2009; 27 (Suppl.): abstr LBA4506.
90. Chee CE, Ashrani AA, Marks RS, Petterson TM, Bailey KR, Melton LJ 3rd, Heit JA. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study. Blood 2014; 123: 3972-8.
91. Simes J, Becattini C, Agnelli G, Eikelboom JW, Kirby AC, Mister R, Prandoni P, Brighton TA, Investigators IS. Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation 2014; 130: 1062-71.
92. Brill A, Fuchs TA, Chauhan AK, Yang JJ, De Meyer SF, Kollnberger M, Wakefield TW, Lammle B, Massberg S, Wagner DD. von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood 2011; 117: 1400-7.
93. Shai A, Rennert HS, Rennert G, Sagi S, Leviov M, Lavie O. Statins, aspirin and risk of thromboembolic events in ovarian cancer patients. Gynecol Oncol 2014; 133: 304-8.
94. Shai A, Rennert HS, Lavie O, Ballan-Haj M, Bitterman A, Steiner M, Keren S, Rennert G. Statins, aspirin and risk of venous thromboembolic events in breast cancer patients. J Thromb Thrombolysis 2014; 38: 32-8.
95. Palumbo A, Cavo M, Bringhen S, Zamagni E, Romano A, Patriarca F, Rossi D, Gentilini F, Crippa C, Galli M, Nozzoli C, Ria R, Marasca R, Montefusco V, Baldini L, Elice F, Callea V, Pulini S, Carella AM, Zambello R, et al. Aspirin, warfarin, or enoxaparin thromboprophylaxis in patients with multiple myeloma treated with thalidomide: a phase III, open-label, randomized trial. J Clin Oncol 2011; 29: 986-93.
96. Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, et al. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood 2012; 119: 933-9; quiz 1093.
97. Mezouar S, Darbousset R, Dignat-George F, Panicot-Dubois L, Dubois C. Inhibition of platelet activation prevents the P-selectin and integrin-dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo. Int J Cancer 2015; 136: 462-75.
98. Rahimi K, Bhala N, Kamphuisen P, Emberson J, Biere-Rafi S, Krane V, Robertson M, Wikstrand J, McMurray J. Effect of statins on venous thromboembolic events: a meta-analysis of published and unpublished evidence from randomised controlled trials. PLoS Med 2012; 9: e1001310.
99. Khemasuwan D, Divietro ML, Tangdhanakanond K, Pomerantz SC, Eiger G. Statins decrease the occurrence of venous thromboembolism in patients with cancer. Am J Med 2010; 123: 60-5.
100. Lotsch F, Konigsbrugge O, Posch F, Zielinski C, Pabinger I, Ay C. Statins are associated with low risk of venous thromboembolism in patients with cancer: a prospective and observational cohort study. Thromb Res 2014; 134: 1008-13.
101. Lee AY, Peterson EA. Treatment of cancer-associated thrombosis. Blood 2013; 122: 2310-7.
102. Carrier M, Lazo-Langner A, Shivakumar S, Tagalakis V, Gross PL, Blais N, Butts CA, Crowther M. Clinical challenges in patients with cancer-associated thrombosis: Canadian expert consensus recommendations. Curr Oncol 2015; 22: 49-59.