Advertisement

Biomarkers of Cancer-Associated Thromboembolism

Chapter
First Online:
Part of the Cancer Treatment and Research book series (CTAR, volume 179)

Abstract

Venous thromboembolism is known to be associated with an increase in morbidity and mortality in patients with malignancy. Predictive laboratory biomarkers of venous thromboembolism (VTE) have long been sought after to improve outcomes and help guide clinical decision making. Previously studied biomarkers include C reactive protein (CRP), tissue factor expressing microparticles (TF MP), D-dimer, soluble P-selectin (sP-selectin), plasminogen activator inhibitor 1 (PAI-1), factor VIII, platelet count, and leukocyte counts. This chapter will focus on these possible biomarkers for cancer-associated thrombosis (CAT) with particular emphasis on the pathophysiology behind thrombosis formation as well as data from clinical studies in patients with malignancy. The incorporation of the above biomarkers into risk assessment tools to predict CAT will also be reviewed, as will risk factors for recurrent VTE in patients with malignancy. Further studies are ongoing to develop readily available biomarkers that can be incorporated into future risk assessment models with the goal of reducing morbidity and mortality due to cancer-associated thrombosis.

Keywords

Biomarkers Venous thrombosis Tissue factor P-selectin D-dimer Factor VIII C reactive protein 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC (2013) Epidemiology of cancer-associated venous thrombosis. Blood 122(10):1712–1723PubMedCrossRefGoogle Scholar
  2. 2.
    Chew HK, Wun T, Harvey D, Zhou H, White RH (2006) Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 166(4):458–464PubMedCrossRefGoogle Scholar
  3. 3.
    Khorana AA, Liebman H, White R, Wun T, Lyman G (2008) The risk of venous thromboembolism in patients with cancer. American Society of Clinical Oncology educational book, pp 240–248Google Scholar
  4. 4.
    Chew HK, Wun T, Harvey DJ, Zhou H, White RH (2007) Incidence of venous thromboembolism and the impact on survival in breast cancer patients. J Clin Oncol 25(1):70–76PubMedCrossRefGoogle Scholar
  5. 5.
    Alcalay A, Wun T, Khatri V, Chew HK, Harvey D, Zhou H et al (2006) Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 24(7):1112–1118PubMedCrossRefGoogle Scholar
  6. 6.
    Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA (2000) Prognosis of cancers associated with venous thromboembolism. N Engl J Med 343(25):1846–1850PubMedCrossRefGoogle Scholar
  7. 7.
    Prandoni P, Falanga A, Piccioli A (2005) Cancer and venous thromboembolism. Lancet Oncol 6(6):401–410PubMedCrossRefGoogle Scholar
  8. 8.
    Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 5(3):632–634PubMedCrossRefGoogle Scholar
  9. 9.
    Vormittag R, Simanek R, Ay C, Dunkler D, Quehenberger P, Marosi C et al (2009) High factor VIII levels independently predict venous thromboembolism in cancer patients: the cancer and thrombosis study. Arterioscler Thromb Vasc Biol 29(12):2176–2181PubMedCrossRefGoogle Scholar
  10. 10.
    Walker AJ, Card TR, West J, Crooks C, Grainge MJ (2013) Incidence of venous thromboembolism in patients with cancer—a cohort study using linked United Kingdom databases. Eur J Cancer 49(6):1404–1413PubMedCrossRefGoogle Scholar
  11. 11.
    Horsted F, West J, Grainge MJ (2012) Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 9(7):e1001275PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 110(10):2339–2346PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE (2006) Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 119(1):60–68PubMedCrossRefGoogle Scholar
  14. 14.
    Virchow RLK (1856) “Thrombose und Embolie. Gefässentzündung und septische Infektion” GAzwMFaMVMS, 219–732. Translation in Matzdorff AC, Bell WR (1998) Thrombosis and embolie (1846-1856). Science History Publications, Canton, Massachusetts. ISBN 0-88135-113-XGoogle Scholar
  15. 15.
    Falati S, Liu Q, Gross P, Merrill-Skoloff G, Chou J, Vandendries E et al (2003) Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 197(11):1585–1598PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Muller I, Klocke A, Alex M, Kotzsch M, Luther T, Morgenstern E et al (2003) Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets. FASEB J 17(3):476–478PubMedCrossRefGoogle Scholar
  17. 17.
    Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y (2003) Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 9(4):458–462PubMedCrossRefGoogle Scholar
  18. 18.
    Zwicker JI (2008) Tissue factor-bearing microparticles and cancer. Semin Thromb Hemost 34(2):195–198PubMedCrossRefGoogle Scholar
  19. 19.
    Nijziel MR, van Oerle R, Hillen HF, Hamulyak K (2006) From trousseau to angiogenesis: the link between the haemostatic system and cancer. Neth J Med 64(11):403–410PubMedGoogle Scholar
  20. 20.
    Caine GJ, Stonelake PS, Lip GY, Kehoe ST (2002) The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia 4(6):465–473PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Kanz R, Vucokich T, Vormittag R, Dunkler D, Ay C, Thaler J, Haselbock K, Scheithauer W, Zielinksi C, Pabinger I (2011) Thrombosis risk and survival in cancer patients with elevated C-reactive protein. J Thromb Haemost 9(1):57–63PubMedCrossRefGoogle Scholar
  22. 22.
    Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM (1993) C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 82(2):513–520PubMedGoogle Scholar
  23. 23.
    Cirillo P, Golino P, Calabro P, Cali G, Ragni M, De Rosa S et al (2005) C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation. Cardiovasc Res 68(1):47–55PubMedCrossRefGoogle Scholar
  24. 24.
    Molins B, Pena E, Vilahur G, Mendieta C, Slevin M, Badimon L (2008) C-reactive protein isoforms differ in their effects on thrombus growth. Arterioscler Thromb Vasc Biol 28(12):2239–2246PubMedCrossRefGoogle Scholar
  25. 25.
    Lopez JA, Kearon C, Lee AY (2004) Deep venous thrombosis. Hematol Am Soc Hematol Educ Program 439–456CrossRefGoogle Scholar
  26. 26.
    Pabinger I, Ay C (2009) Biomarkers and venous thromboembolism. Arterioscler Thromb Vasc Biol 29(3):332–336PubMedCrossRefGoogle Scholar
  27. 27.
    Osborne NH, Wakefield TW, Henke PK (2008) Venous thromboembolism in cancer patients undergoing major surgery. Ann Surg Oncol 15(12):3567–3578PubMedCrossRefGoogle Scholar
  28. 28.
    Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW (2008) Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 111(10):4902–4907PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Ay C, Dunkler D, Marosi C, Chiriac AL, Vormittag R, Simanek R et al (2010) Prediction of venous thromboembolism in cancer patients. Blood 116(24):5377–5382PubMedCrossRefGoogle Scholar
  30. 30.
    Devaraj S, Dasu MR, Singh U, Rao LV, Jialal I (2009) C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo. Atherosclerosis 203(1):67–74PubMedCrossRefGoogle Scholar
  31. 31.
    Kroger K, Weiland D, Ose C, Neumann N, Weiss S, Hirsch C et al (2006) Risk factors for venous thromboembolic events in cancer patients. Ann Oncol 17(2):297–303PubMedCrossRefGoogle Scholar
  32. 32.
    Khorana AA, Ahrendt SA, Ryan CK, Francis CW, Hruban RH, Hu YC et al (2007) Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res 13(10):2870–2875PubMedCrossRefGoogle Scholar
  33. 33.
    Mackman N (2009) The many faces of tissue factor. J Thromb Haemost 7(Suppl 1):136–139PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Gardiner C, Harrison P, Belting M, Boing A, Campello E, Carter BS et al (2015) Extracellular vesicles, tissue factor, cancer and thrombosis—discussion themes of the ISEV 2014 educational day. J Extracell Vesicles 4:26901PubMedCrossRefGoogle Scholar
  35. 35.
    Davila M, Amirkhosravi A, Coll E, Desai H, Robles L, Colon J et al (2008) Tissue factor-bearing microparticles derived from tumor cells: impact on coagulation activation. J Thromb Haemost 6(9):1517–1524PubMedCrossRefGoogle Scholar
  36. 36.
    Geddings JE, Hisada Y, Boulaftali Y, Getz TM, Whelihan M, Fuentes R et al (2016) Tissue factor-positive tumor microvesicles activate platelets and enhance thrombosis in mice. J Thromb Haemost 14(1):153–166PubMedCrossRefGoogle Scholar
  37. 37.
    Thomas GM, Panicot-Dubois L, Lacroix R, Dignat-George F, Lombardo D, Dubois C (2009) Cancer cell-derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo. J Exp Med 206(9):1913–1927PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Wang JG, Geddings JE, Aleman MM, Cardenas JC, Chantrathammachart P, Williams JC et al (2012) Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer. Blood 119(23):5543–5552PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Thomas GM, Brill A, Mezouar S, Crescence L, Gallant M, Dubois C et al (2015) Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice. J Thromb Haemost 13(7):1310–1319PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Hisada Y, Ay C, Auriemma AC, Cooley BC, Mackman N (2017) Human pancreatic tumors grown in mice release tissue factor-positive microvesicles that increase venous clot size. J Thromb Haemost 15(11):2208–2217PubMedCrossRefGoogle Scholar
  41. 41.
    Tesselaar ME, Romijn FP, van der Linden IK, Bertina RM, Osanto S (2009) Microparticle-associated tissue factor activity in cancer patients with and without thrombosis. J Thromb Haemost 7(8):1421–1423PubMedCrossRefGoogle Scholar
  42. 42.
    Geddings JE, Mackman N (2013) Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood 122(11):1873–1880PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Hisada Y, Mackman N (2017) Cancer-associated pathways and biomarkers of venous thrombosis. Blood 130(13):1499–1506PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Magnus N, Gerges N, Jabado N, Rak J (2013) Coagulation-related gene expression profile in glioblastoma is defined by molecular disease subtype. J Thromb Haemost 11(6):1197–1200PubMedCrossRefGoogle Scholar
  45. 45.
    Thaler J, Ay C, Mackman N, Bertina RM, Kaider A, Marosi C et al (2012) Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients. J Thromb Haemost 10(7):1363–1370PubMedCrossRefGoogle Scholar
  46. 46.
    Zwicker JI, Liebman HA, Neuberg D, Lacroix R, Bauer KA, Furie BC et al (2009) Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 15(22):6830–6840PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Zwicker JI, Liebman HA, Bauer KA, Caughey T, Campigotto F, Rosovsky R et al (2013) Prediction and prevention of thromboembolic events with enoxaparin in cancer patients with elevated tissue factor-bearing microparticles: a randomized-controlled phase II trial (the microtec study). Br J Haematol 160(4):530–537PubMedCrossRefGoogle Scholar
  48. 48.
    Khorana AA, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF et al (2017) Tissue factor as a predictor of recurrent venous thromboembolism in malignancy: biomarker analyses of the CATCH trial. J Clin Oncol 35(10):1078–1085PubMedCrossRefGoogle Scholar
  49. 49.
    Tesselaar ME, Romijn FP, Van Der Linden IK, Prins FA, Bertina RM, Osanto S (2007) Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost 5(3):520–527PubMedCrossRefGoogle Scholar
  50. 50.
    Kohli M, Fink LM, Spencer HJ, Zent CS (2002) Advanced prostate cancer activates coagulation: a controlled study of activation markers of coagulation in ambulatory patients with localized and advanced prostate cancer. Blood Coagul Fibrinolysis 13(1):1–5PubMedCrossRefGoogle Scholar
  51. 51.
    Hanzal E, Tatra G (1993) Prothrombin fragment F 1+2 plasma concentrations in patients with gynecologic malignancies. Gynecol Oncol 49(3):373–376PubMedCrossRefGoogle Scholar
  52. 52.
    Ay C, Vormittag R, Dunkler D, Simanek R, Chiriac AL, Drach J et al (2009) 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 27(25):4124–4129PubMedCrossRefGoogle Scholar
  53. 53.
    Eichinger S, Heinze G, Jandeck LM, Kyrle PA (2010) Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation 121(14):1630–1636PubMedCrossRefGoogle Scholar
  54. 54.
    Tosetto A, Iorio A, Marcucci M, Baglin T, Cushman M, Eichinger S et al (2012) Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 10(6):1019–1025PubMedCrossRefGoogle Scholar
  55. 55.
    Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al (2006) D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 355(17):1780–1789PubMedCrossRefGoogle Scholar
  56. 56.
    Ay C, Simanek R, Vormittag R, Dunkler D, Alguel G, Koder S et al (2008) 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 112(7):2703–2708PubMedCrossRefGoogle Scholar
  57. 57.
    Chen M, Geng JG (2006) P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp (Warsz) 54(2):75–84CrossRefGoogle Scholar
  58. 58.
    Geng JG, Chen M, Chou KC (2004) P-selectin cell adhesion molecule in inflammation, thrombosis, cancer growth and metastasis. Curr Med Chem 11(16):2153–2160PubMedCrossRefGoogle Scholar
  59. 59.
    Cambien B, Wagner DD (2004) A new role in hemostasis for the adhesion receptor P-selectin. Trends Mol Med 10(4):179–186PubMedCrossRefGoogle Scholar
  60. 60.
    Furie B, Furie BC (2004) Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation. Trends Mol Med 10(4):171–178PubMedCrossRefGoogle Scholar
  61. 61.
    Meltzer ME, Lisman T, de Groot PG, Meijers JC, le Cessie S, Doggen CJ et al (2010) Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood 116(1):113–121PubMedCrossRefGoogle Scholar
  62. 62.
    Andren-Sandberg A, Lecander I, Martinsson G, Astedt B (1992) Peaks in plasma plasminogen activator inhibitor-1 concentration may explain thrombotic events in cases of pancreatic carcinoma. Cancer 69(12):2884–2887CrossRefGoogle Scholar
  63. 63.
    Sciacca FL, Ciusani E, Silvani A, Corsini E, Frigerio S, Pogliani S et al (2004) Genetic and plasma markers of venous thromboembolism in patients with high grade glioma. Clin Cancer Res 10(4):1312–1317PubMedCrossRefGoogle Scholar
  64. 64.
    Chen N, Ren M, Li R, Deng X, Li Y, Yan K et al (2015) Bevacizumab promotes venous thromboembolism through the induction of PAI-1 in a mouse xenograft model of human lung carcinoma. Mol Cancer 14:140PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Yigit E, Gonullu G, Yucel I, Turgut M, Erdem D, Cakar B (2008) Relation between hemostatic parameters and prognostic/predictive factors in breast cancer. Eur J Intern Med 19(8):602–607PubMedCrossRefGoogle Scholar
  66. 66.
    Battistelli S, Stefanoni M, Lorenzi B, Dell’avanzato R, Varrone F, Pascucci A et al (2008) Coagulation factor levels in non-metastatic colorectal cancer patients. Int J Biol Markers 23(1):36–41PubMedCrossRefGoogle Scholar
  67. 67.
    Minnema MC, Fijnheer R, De Groot PG, Lokhorst HM (2003) Extremely high levels of von Willebrand factor antigen and of procoagulant factor VIII found in multiple myeloma patients are associated with activity status but not with thalidomide treatment. J Thromb Haemost 1(3):445–449PubMedCrossRefGoogle Scholar
  68. 68.
    Levin J, Conley CL (1964) Thrombocytosis associated with malignant disease. Arch Intern Med 114:497–500PubMedCrossRefGoogle Scholar
  69. 69.
    Connolly GC, Phipps RP, Francis CW (2014) Platelets and cancer-associated thrombosis. Semin Oncol 41(3):302–310PubMedCrossRefGoogle Scholar
  70. 70.
    Mezouar S, Darbousset R, Dignat-George F, Panicot-Dubois L, Dubois C (2015) 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 136(2):462–475PubMedCrossRefGoogle Scholar
  71. 71.
    Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A et al (2012) Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood 119(4):933–939; quiz 1093PubMedCrossRefGoogle Scholar
  72. 72.
    Shai A, Rennert HS, Lavie O, Ballan-Haj M, Bitterman A, Steiner M et al (2014) Statins, aspirin and risk of venous thromboembolic events in breast cancer patients. J Thromb Thrombolysis 38(1):32–38PubMedCrossRefGoogle Scholar
  73. 73.
    Shai A, Rennert HS, Rennert G, Sagi S, Leviov M, Lavie O (2014) Statins, aspirin and risk of thromboembolic events in ovarian cancer patients. Gynecol Oncol 133(2):304–308PubMedCrossRefGoogle Scholar
  74. 74.
    Khorana AA, Francis CW, Culakova E, Lyman GH (2005) Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 104(12):2822–2829PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Simanek R, Vormittag R, Ay C, Alguel G, Dunkler D, Schwarzinger I et al (2010) High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Haemost 8(1):114–120PubMedCrossRefGoogle Scholar
  76. 76.
    Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS et al (2004) Neutrophil extracellular traps kill bacteria. Science 303(5663):1532–1535PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr et al (2010) Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A 107(36):15880–15885PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Brill A, Suidan GL, Wagner DD (2013) Hypoxia, such as encountered at high altitude, promotes deep vein thrombosis in mice. J Thromb Haemost 11(9):1773–1775PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Demers M, Wagner DD (2013) Neutrophil extracellular traps: a new link to cancer-associated thrombosis and potential implications for tumor progression. Oncoimmunology 2(2):e22946PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Demers M, Wong SL, Martinod K, Gallant M, Cabral JE, Wang Y et al (2016) Priming of neutrophils toward NETosis promotes tumor growth. Oncoimmunology 5(5):e1134073PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Olsson AK, Cedervall J (2016) NETosis in cancer—platelet-neutrophil crosstalk promotes tumor-associated pathology. Front Immunol 7:373PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR, Fuchs TA et al (2012) Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci U S A 109(32):13076–13081PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Kowanetz M, Wu X, Lee J, Tan M, Hagenbeek T, Qu X et al (2010) Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G + Ly6C + granulocytes. Proc Natl Acad Sci U S A 107(50):21248–21255PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Blix K, Jensvoll H, Braekkan SK, Hansen JB (2013) White blood cell count measured prior to cancer development is associated with future risk of venous thromboembolism–the tromso study. PLoS ONE 8(9):e73447PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Connolly GC, Khorana AA, Kuderer NM, Culakova E, Francis CW, Lyman GH (2010) Leukocytosis, thrombosis and early mortality in cancer patients initiating chemotherapy. Thromb Res 126(2):113–118PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B et al (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100(10):3484–3488CrossRefGoogle Scholar
  87. 87.
    Trujillo-Santos J, Prandoni P, Rivron-Guillot K, Roman P, Sanchez R, Tiberio G et al (2008) Clinical outcome in patients with venous thromboembolism and hidden cancer: findings from the RIETE registry. J Thromb Haemost 6(2):251–255PubMedCrossRefGoogle Scholar
  88. 88.
    Lee AYY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF et al (2015) Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA 314(7):677–686PubMedCrossRefGoogle Scholar
  89. 89.
    van Es N, Louzada M, Carrier M, Tagalakis V, Gross PL, Shivakumar S et al (2018) Predicting the risk of recurrent venous thromboembolism in patients with cancer: a prospective cohort study. Thromb Res 163:41–46PubMedCrossRefGoogle Scholar
  90. 90.
    Young L, Ockelford P, Milne D, Rolfe-Vyson V, McKelvie S, Harper P (2006) Post-treatment residual thrombus increases the risk of recurrent deep vein thrombosis and mortality. J Thromb Haemost 4(9):1919–1924PubMedCrossRefGoogle Scholar
  91. 91.
    Mazetto BM, Orsi FLA, Silveira SAF, Bittar LF, Flores-Nascimento MMC, Zapponi KCS et al (2017) Residual vein thrombosis echogenicity is associated to the risk of DVT recurrence: a cohort study. Clin Appl Thromb Hemost 1076029617700997Google Scholar
  92. 92.
    Piovella F, Crippa L, Barone M, Vigano D’Angelo S, Serafini S, Galli L et al (2002) Normalization rates of compression ultrasonography in patients with a first episode of deep vein thrombosis of the lower limbs: association with recurrence and new thrombosis. Haematologica 87(5):515–522PubMedGoogle Scholar
  93. 93.
    Napolitano M, Saccullo G, Malato A, Sprini D, Ageno W, Imberti D et al (2014) Optimal duration of low molecular weight heparin for the treatment of cancer-related deep vein thrombosis: the cancer-DACUS study. J Clin Oncol 32(32):3607–3612PubMedCrossRefGoogle Scholar
  94. 94.
    Khorana AA, Rubens D, Francis CW (2014) Screening high-risk cancer patients for VTE: a prospective observational study. Thromb Res 134(6):1205–1207PubMedCrossRefGoogle Scholar
  95. 95.
    Louzada ML, Carrier M, Lazo-Langner A, Dao V, Kovacs MJ, Ramsay TO et al (2012) Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation 126(4):448–454PubMedCrossRefGoogle Scholar
  96. 96.
    Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349(2):146–153PubMedCrossRefGoogle Scholar
  97. 97.
    Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P et al (2002) Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med 162(15):1729–1735PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Hematology and Oncology, UC Davis School of MedicineUC Davis Cancer CenterSacramentoUSA
  2. 2.UC Davis School of MedicineClinical and Translational Sciences Center (CTSC)SacramentoUSA

Personalised recommendations

Cite chapter

Buy options