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Cancer progression and tumor hypercoagulability: a platelet perspective

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Abstract

Venous thromboembolism, which is common in cancer patients and accompanies or even precedes malignant tumors, is known as cancer-related thrombosis and is an important cause of cancer- associated death. At present, the exact etiology of the elevated incidence of venous thrombosis in cancer patients remains elusive. Platelets play a crucial role in blood coagulation, which is intimately linked to the development of arterial thrombosis. Additionally, platelets contribute to tumor progression and facilitate immune evasion by tumors. Tumor cells can interact with the coagulation system through various mechanisms, such as producing hemostatic proteins, activating platelets, and directly adhering to normal cells. The relationship between platelets and malignant tumors is also significant. In this review article, we will explore these connections.

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The authors declare that no new data were created for this narrative review.

References

  1. Anderson E, Durstine JL (2019) Physical activity, exercise, and chronic diseases: a brief review. Sports Med Health Sci 1(1):3–10

    Article  PubMed  PubMed Central  Google Scholar 

  2. Curigliano G, Lenihan D, Fradley M et al (2020) Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol: Off J Eur Soc Med Oncol 31(2):171–190

    Article  CAS  Google Scholar 

  3. Tavares V, Neto BV, Vilas-Boas MI et al (2022) Impact of hereditary thrombophilia on cancer-associated thrombosis, tumour susceptibility and progression: a review of existing evidence. Biochim Biophys Acta 1877(5):188778

    CAS  Google Scholar 

  4. Elyamany G, Alzahrani AM, Bukhary E (2014) Cancer-associated thrombosis: an overview. Clin Med Insights Oncol 8:129–137

    Article  PubMed  PubMed Central  Google Scholar 

  5. Heit JA, Spencer FA, White RH (2016) The epidemiology of venous thromboembolism. J Thromb Thrombolysis 41(1):3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Laporte S, Mismetti P, Décousus H et al (2008) Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation 117(13):1711–1716

    Article  PubMed  Google Scholar 

  7. Farge D, Frere C, Connors JM et al (2019) 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 20(10):e566–e581

    Article  PubMed  Google Scholar 

  8. Khorana AA, Cohen AT, Carrier M et al (2020) Prevention of venous thromboembolism in ambulatory patients with cancer. ESMO Open 5(6):e000948

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gran OV, Smith EN, Brækkan SK et al (2016) Joint effects of cancer and variants in the factor 5 gene on the risk of venous thromboembolism. Haematologica 101(9):1046–1053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Reitsma PH, Versteeg HH, Middeldorp S (2012) Mechanistic view of risk factors for venous thromboembolism. Arterioscler Thromb Vasc Biol 32(3):563–568

    Article  CAS  PubMed  Google Scholar 

  11. Tavares V, Pinto R, Assis J et al (2020) Venous thromboembolism GWAS reported genetic makeup and the hallmarks of cancer: linkage to ovarian tumour behaviour. Biochim Biophys Acta 1873(1):188331

    CAS  Google Scholar 

  12. Skille H, Paulsen B, Hveem K et al (2021) Prothrombotic genotypes and risk of venous thromboembolism in occult cancer. Thromb Res 205:17–23

    Article  CAS  PubMed  Google Scholar 

  13. Buijs JT, Versteeg HH (2020) Genes and proteins associated with the risk for cancer-associated thrombosis. Thromb Res 191:S43–S49

    Article  CAS  PubMed  Google Scholar 

  14. Moik F, Chan W-SE, Wiedemann S et al (2021) Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy. Blood 137(12):1669–1678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sussman TA, Li H, Hobbs B et al (2021) Incidence of thromboembolism in patients with melanoma on immune checkpoint inhibitor therapy and its adverse association with survival. J Immunother Cancer 9(1):e001719

    Article  PubMed  PubMed Central  Google Scholar 

  16. Roopkumar J, Swaidani S, Kim AS et al (2021) Increased incidence of venous thromboembolism with cancer immunotherapy. Med (New York, NY) 2(4):423–434

    CAS  Google Scholar 

  17. Galmiche A, Rak J, Roumenina LT et al (2022) Coagulome and the tumor microenvironment: an actionable interplay. Trends Cancer 8(5):369–383

    Article  CAS  PubMed  Google Scholar 

  18. Falanga A, Schieppati F, Russo L (2019) Pathophysiology 1. Mechanisms of Thrombosis in Cancer Patients. Cancer Treat Res 179:11–36

    Article  CAS  PubMed  Google Scholar 

  19. Khorana AA (2010) Venous thromboembolism and prognosis in cancer. Thromb Res 125(6):490–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Posch F, Riedl J, Reitter E-M et al (2016) Hypercoagulabilty, venous thromboembolism, and death in patients with cancer. A multi-state model. Thromb Haemost 115(4):817–826

    Article  PubMed  Google Scholar 

  21. Riedl JM, Schwarzenbacher E, Moik F et al (2022) Patterns of thromboembolism in patients with advanced pancreatic cancer undergoing first-line chemotherapy with FOLFIRINOX or gemcitabine/nab-paclitaxel. Thromb Haemost 122(4):633–645

    Article  PubMed  Google Scholar 

  22. Ay C, Pabinger I, Cohen AT (2017) Cancer-associated venous thromboembolism: Burden, mechanisms, and management. Thromb Haemost 117(2):219–230

    Article  PubMed  Google Scholar 

  23. Gao S, Ma J-J, Lu C (2014) Venous thromboembolism risk and erythropoiesis-stimulating agents for the treatment of cancer-associated anemia: a meta-analysis. Tumour Biol 35(1):603–613

    Article  CAS  PubMed  Google Scholar 

  24. Ashrani AA, Gullerud RE, Petterson TM et al (2016) Risk factors for incident venous thromboembolism in active cancer patients: a population based case-control study. Thromb Res 139:29–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cohen AT, Katholing A, Rietbrock S et al (2017) Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study. Thromb Haemost 117(1):57–65

    Article  PubMed  Google Scholar 

  26. Königsbrügge O, Pabinger I, Ay C (2014) Risk factors for venous thromboembolism in cancer: novel findings from the Vienna cancer and thrombosis study (CATS). Thromb Res 133(Suppl 2):S39–S43

    Article  PubMed  Google Scholar 

  27. Fiedler T, Rabe M, Mundkowski RG et al (2018) Adipose-derived mesenchymal stem cells release microvesicles with procoagulant activity. Int J Biochem Cell Biol 100:49–53

    Article  CAS  PubMed  Google Scholar 

  28. Farge D, Le Maignan C, Doucet L et al (2019) Women, thrombosis, and cancer. Thromb Res 181(Suppl 1):S47–S53

    Article  CAS  PubMed  Google Scholar 

  29. Würtz M, Grove EL, Corraini P et al (2020) Comorbidity and risk of venous thromboembolism after hospitalization for first-time myocardial infarction: a population-based cohort study. J Thromb Haemost 18(8):1974–1985

    Article  PubMed  Google Scholar 

  30. Chaturvedi S, Braunstein EM, Yuan X et al (2020) Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS. Blood 135(4):239–251

    Article  PubMed  PubMed Central  Google Scholar 

  31. Karasu A, Engbers MJ, Cushman M et al (2016) Genetic risk factors for venous thrombosis in the elderly in a case-control study. J Thromb Haemost 14(9):1759–1764

    Article  CAS  PubMed  Google Scholar 

  32. Ghouse J, Tragante V, Ahlberg G et al (2023) Genome-wide meta-analysis identifies 93 risk loci and enables risk prediction equivalent to monogenic forms of venous thromboembolism. Nat Genet 55(3):399–409

    Article  CAS  PubMed  Google Scholar 

  33. Raghunathan S, Rayes J, Sen Gupta A (2022) Platelet-inspired nanomedicine in hemostasis thrombosis and thromboinflammation. J Thromb Haemost 20(7):1535–1549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Levi M (2019) Disseminated intravascular coagulation in cancer: an update. Semin Thromb Hemost 45(4):342–347

    Article  PubMed  Google Scholar 

  35. Mitrugno A, Tassi Yunga S, Sylman JL et al (2019) The role of coagulation and platelets in colon cancer-associated thrombosis. Am J Physiol Cell Physiol 316(2):C264–C273

    Article  CAS  PubMed  Google Scholar 

  36. Ghoshal K, Bhattacharyya M (2014) Overview of platelet physiology: its hemostatic and nonhemostatic role in disease pathogenesis. Sci World J 2014:781857

    Article  Google Scholar 

  37. Wang S, Li Z, Xu R (2018) Human cancer and platelet interaction, a potential therapeutic target. Int J Mol Sci 19(4):1246. https://doi.org/10.3390/ijms19041246

  38. Levin J, Conley CL (1964) Thrombocytosis associated with malignant disease. Arch Intern Med 114:497–500

    Article  CAS  PubMed  Google Scholar 

  39. Wojtukiewicz MZ, Sierko E, Hempel D et al (2017) Platelets and cancer angiogenesis nexus. Cancer Metastasis Rev 36(2):249–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang X, Ran Y (2015) Prognostic role of elevated platelet count in patients with lung cancer: a systematic review and meta-analysis. Int J Clin Exp Med 8(4):5379–5387

    PubMed  PubMed Central  Google Scholar 

  41. Gu D, Szallasi A (2017) Thrombocytosis portends adverse prognosis in colorectal cancer: a meta-analysis of 5,619 patients in 16 individual studies. Anticancer Res 37(9):4717–4726

    PubMed  Google Scholar 

  42. Ji Y, Sheng L, Du X et al (2015) Elevated platelet count is a strong predictor of poor prognosis in stage I non-small cell lung cancer patients. Platelets 26(2):138–142

    Article  CAS  PubMed  Google Scholar 

  43. Harano K, Kogawa T, Wu J et al (2017) Thrombocytosis as a prognostic factor in inflammatory breast cancer. Breast Cancer Res Treat 166(3):819–832

    Article  CAS  PubMed  Google Scholar 

  44. Zarà M, Canobbio I, Visconte C et al (2018) Molecular mechanisms of platelet activation and aggregation induced by breast cancer cells. Cell Signal 48:45–53

    Article  PubMed  Google Scholar 

  45. Reddel CJ, Tan CW, Chen VM (2019) Thrombin generation and cancer: contributors and consequences. Cancers (Basel) 11(1):100. https://doi.org/10.3390/cancers11010100

  46. Chang J, Jiang L, Wang Y et al (2015) 12/15 Lipoxygenase regulation of colorectal tumorigenesis is determined by the relative tumor levels of its metabolite 12-HETE and 13-HODE in animal models. Oncotarget 6(5):2879–2888

    Article  PubMed  Google Scholar 

  47. Heinmöller E, Weinel RJ, Heidtmann HH et al (1996) Studies on tumor-cell-induced platelet aggregation in human lung cancer cell lines. J Cancer Res Clin Oncol 122(12):735–744

    Article  PubMed  Google Scholar 

  48. Nilsson RJA, Balaj L, Hulleman E et al (2011) Blood platelets contain tumor-derived RNA biomarkers. Blood 118(13):3680–3683

    Article  PubMed  PubMed Central  Google Scholar 

  49. Nilsson RJA, Karachaliou N, Berenguer J et al (2016) Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer. Oncotarget 7(1):1066–1075

    Article  PubMed  Google Scholar 

  50. Sabrkhany S, Kuijpers MJE, van Kuijk SMJ et al (2017) A combination of platelet features allows detection of early-stage cancer. Eur J Cancer 80:5–13. https://doi.org/10.1016/j.ejca.2017.04.010

  51. Yao L, Dong H, Luo Y et al (2014) Net platelet angiogenic activity (NPAA) correlates with progression and prognosis of non-small cell lung cancer. PLoS One 9(4):e96206

    Article  PubMed  PubMed Central  Google Scholar 

  52. Alkozai EM, Porte RJ, Adelmeijer J et al (2015) Levels of angiogenic proteins in plasma and platelets are not different between patients with hepatitis B/C-related cirrhosis and patients with cirrhosis and hepatocellular carcinoma. Platelets 26(6):577–582

    Article  CAS  PubMed  Google Scholar 

  53. Kim SJ, Choi IK, Park KH et al (2004) Serum vascular endothelial growth factor per platelet count in hepatocellular carcinoma: correlations with clinical parameters and survival. Jpn J Clin Oncol 34(4):184–190

    Article  PubMed  Google Scholar 

  54. Peterson JE, Zurakowski D, Italiano JE et al (2012) VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients. Angiogenesis 15(2):265–273

    Article  CAS  PubMed  Google Scholar 

  55. Duvernay MT, Temple KJ, Maeng JG et al (2017) Contributions of protease-activated receptors PAR1 and PAR4 to thrombin-induced GPIIbIIIa activation in human platelets. Mol Pharmacol 91(1):39–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Reitter EM, Kaider A, Ay C et al (2016) Longitudinal analysis of hemostasis biomarkers in cancer patients during antitumor treatment. J Thromb Haemost 14(2):294–305

    Article  PubMed  Google Scholar 

  57. Arnout J, Hoylaerts MF, Lijnen HR (2006) Haemostasis. Handb Exp Pharmacol 176(Pt 2):1–41. https://doi.org/10.1007/3-540-36028-x_1

  58. Gardiner C, Harrison P, Belting M et al (2015) Extracellular vesicles, tissue factor, cancer and thrombosis - discussion themes of the ISEV 2014 Educational Day. J Extracell Vesicles 4:26901

    Article  PubMed  Google Scholar 

  59. Mackman N, Tilley RE, Key NS (2007) Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol 27(8):1687–1693

    Article  CAS  PubMed  Google Scholar 

  60. Gregory SA, Morrissey JH, Edgington TS (1989) Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 9(6):2752–2755

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Geddings JE, Mackman N (2013) Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood 122(11):1873–1880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tang X, Zhang Z, Fang M et al (2020) Transferrin plays a central role in coagulation balance by interacting with clotting factors. Cell Res 30(2):119–132

    Article  CAS  PubMed  Google Scholar 

  63. György B, Szabó TG, Pásztói M et al (2011) Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci: CMLS 68(16):2667–2688

    Article  PubMed  Google Scholar 

  64. Reddy EC, Rand ML (2020) Procoagulant phosphatidylserine-exposing platelets and. Front Cardiovasc Med 7:15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tesselaar MET, Romijn FPHTM, Van Der Linden IK et al (2007) Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost 5(3):520–527

    Article  CAS  PubMed  Google Scholar 

  66. Mulder FI, Horváth-Puhó E, van Es N et al (2021) Venous thromboembolism in cancer patients: a population-based cohort study. Blood 137(14):1959–1969

    Article  CAS  PubMed  Google Scholar 

  67. Gomes T, Várady CBS, Lourenço AL et al (2019) IL-1β blockade attenuates thrombosis in a neutrophil extracellular trap-dependent breast cancer model. Front Immunol 10:2088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Reusswig F, Fazel Modares N, Brechtenkamp M et al (2021) Efficiently restored thrombopoietin production by Ashwell-Morell receptor and IL-6R induced Janus Kinase 2/Signal transducer and activator of transcription signaling early after partial hepatectomy. Hepatology 74(1):411–427

    Article  CAS  PubMed  Google Scholar 

  69. Zucchella M, Dezza L, Pacchiarini L et al (1989) Human tumor cells cultured “in vitro” activate platelet function by producing ADP or thrombin. Haematologica 74(6):541–545

    CAS  PubMed  Google Scholar 

  70. Stone RL, Nick AM, McNeish IA et al (2012) Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med 366(7):610–618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. van Es N, Le Gal G, Otten H-M et al (2017) Screening for occult cancer in patients with unprovoked venous thromboembolism: a systematic review and meta-analysis of individual patient data. Ann Intern Med 167(6):410–417

    Article  PubMed  Google Scholar 

  72. Sierko E, Wojtukiewicz MZ (2004) Platelets and angiogenesis in malignancy. Semin Thromb Hemost 30(1):95–108. https://doi.org/10.1055/s-2004-822974

  73. Pihusch R, Danzl G, Scholz M et al (2002) Impact of thrombophilic gene mutations on thrombosis risk in patients with gastrointestinal carcinoma. Cancer 94(12):3120–3126

    Article  CAS  PubMed  Google Scholar 

  74. Tinholt M, Viken MK, Dahm AE et al (2014) Increased coagulation activity and genetic polymorphisms in the F5, F10 and EPCR genes are associated with breast cancer: a case-control study. BMC Cancer 14:845

    Article  PubMed  PubMed Central  Google Scholar 

  75. Maragoudakis ME, Tsopanoglou NE, Andriopoulou P et al (2000) Effects of thrombin/thrombosis in angiogenesis and tumour progression. Matrix Biol: J Int Soc Matrix Biol 19(4):345–351

    Article  CAS  Google Scholar 

  76. Green D (2010) Karpatkin S Role of thrombin as a tumor growth factor. Cell Cycle (Georgetown, Tex). 9(4):656–661

    Article  CAS  PubMed  Google Scholar 

  77. Eroğlu A, Oztürk A, Akar N (2011) Association between the -402GA, -401GT, and -323ins10-bp polymorphisms of factor VII gene and breast cancer. Breast Cancer (Tokyo, Japan) 18(4):282–285

    Article  PubMed  Google Scholar 

  78. Fang J, Yuan Q, Du Z et al (2021) Contribution of factor VII polymorphisms to coagulopathy in patients with isolated traumatic brain injury. Clin Neurol Neurosurg 208:106836

    Article  PubMed  Google Scholar 

  79. Ken-Dror G, Drenos F, Humphries SE et al (2010) Haplotype and genotype effects of the F7 gene on circulating factor VII, coagulation activation markers and incident coronary heart disease in UK men. J Thromb Haemost 8(11):2394–2403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. DuPre SA, Hunter KW (2007) Murine mammary carcinoma 4T1 induces a leukemoid reaction with splenomegaly: association with tumor-derived growth factors. Exp Mol Pathol 82(1):12–24

    Article  CAS  PubMed  Google Scholar 

  81. Kowanetz M, Wu X, Lee J 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):21248-21255

  82. Demers M, Krause DS, Schatzberg D 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):13076-13081

  83. Jensvoll H, Blix K, Brækkan SK et al (2014) Platelet count measured prior to cancer development is a risk factor for future symptomatic venous thromboembolism: the Tromsø Study. PLoS One 9(3):e92011

    Article  PubMed  PubMed Central  Google Scholar 

  84. Khorana AA, Francis CW, Culakova E et al (2005) Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 104(12):2822–2829

    Article  PubMed  Google Scholar 

  85. Simanek R, Vormittag R, Ay C 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):114–120

    Article  CAS  PubMed  Google Scholar 

  86. Thaler J, Ay C, Kaider A et al (2014) Biomarkers predictive of venous thromboembolism in patients with newly diagnosed high-grade gliomas. Neuro-oncology 16(12):1645–1651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Riedl J, Preusser M, Nazari PMS et al (2017) Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism. Blood 129(13):1831–1839

    Article  CAS  PubMed  Google Scholar 

  88. Khorana AA, Kuderer NM, Culakova E et al (2008) Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 111(10):4902–4907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Granger JM, Kontoyiannis DP (2009) Etiology and outcome of extreme leukocytosis in 758 nonhematologic cancer patients: a retrospective, single-institution study. Cancer 115(17):3919–3923

    Article  PubMed  Google Scholar 

  90. Kasuga I, Makino S, Kiyokawa H et al (2001) Tumor-related leukocytosis is linked with poor prognosis in patients with lung carcinoma. Cancer 92(9):2399–2405

    Article  CAS  PubMed  Google Scholar 

  91. Ruka W, Rutkowski P, Kaminska J et al (2001) Alterations of routine blood tests in adult patients with soft tissue sarcomas: relationships to cytokine serum levels and prognostic significance. Ann Oncol: Off J Eur Soc Med Oncol 12(10):1423–1432

    Article  CAS  Google Scholar 

  92. Blix K, Jensvoll H, Brækkan SK et al (2013) White blood cell count measured prior to cancer development is associated with future risk of venous thromboembolism–the Tromsø study. PLoS One 8(9):e73447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Pabinger I, Posch F (2014) Flamethrowers: blood cells and cancer thrombosis risk. Hematol Am Soc Hematol Educ Program 2014(1):410–417

    Article  Google Scholar 

  94. Khorana AA, Francis CW, Menzies KE et al (2008) Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost 6(11):1983–1985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Thaler J, Ay C, Mackman N 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):1363–1370

    Article  CAS  PubMed  Google Scholar 

  96. Bharthuar A, Khorana AA, Hutson A et al (2013) Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers. Thromb Res 132(2):180–184

    Article  CAS  PubMed  Google Scholar 

  97. Verheul HM, Hoekman K, Lupu F et al (2000) Platelet and coagulation activation with vascular endothelial growth factor generation in soft tissue sarcomas. Clin Cancer Res: Off J Am Assoc Cancer Res 6(1):166–171

    CAS  Google Scholar 

  98. Gordon SG, Mielicki WP (1997) Cancer procoagulant: a factor X activator, tumor marker and growth factor from malignant tissue. Blood Coagul Fibrinolysis: Int J Haemost Thromb 8(2):73–86

    Article  CAS  Google Scholar 

  99. Tinholt M, Vollan HKM, Sahlberg KK et al (2015) Tumor expression, plasma levels and genetic polymorphisms of the coagulation inhibitor TFPI are associated with clinicopathological parameters and survival in breast cancer, in contrast to the coagulation initiator TF. Breast Cancer Res: BCR 17(1):44

    Article  PubMed  PubMed Central  Google Scholar 

  100. Bazzarelli AK, Scheer AS, Tai LH et al (2016) Tissue factor pathway inhibitor gene polymorphism -33T → C predicts improved disease-free survival in colorectal cancer. Ann Surg Oncol 23(7):2274–2280

    Article  CAS  PubMed  Google Scholar 

  101. Han N, Jin K, He K et al (2011) Protease-activated receptors in cancer: a systematic review. Oncol Lett 2(4):599–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Ruf W (2007) Tissue factor and PAR signaling in tumor progression. Thromb Res 120(Suppl 2):S7-12

    Article  PubMed  Google Scholar 

  103. Tumors DHF (2019) Wounds that do not heal—a historical perspective with a focus on the fundamental roles of increased vascular permeability and clotting. Semin Thromb Hemost 45(06):576–592

    Article  Google Scholar 

  104. Hisada Y, Mackman N (2017) Cancer-associated pathways and biomarkers of venous thrombosis. Blood 130(13):1499–1506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Lundbech M, Krag AE, Christensen TD et al (2020) Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients. Thromb Res 186:80–85

    Article  CAS  PubMed  Google Scholar 

  106. Orcutt SJ, Pietropaolo C, Krishnaswamy S (2002) Extended interactions with prothrombinase enforce affinity and specificity for its macromolecular substrate. J Biol Chem 277(48):46191–46196

    Article  CAS  PubMed  Google Scholar 

  107. Cosmi B, Legnani C, Libra A et al (2023) D-Dimers in diagnosis and prevention of venous thrombosis: recent advances and their practical implications. Pol Arch Intern Med 133(11):16604. https://doi.org/10.20452/pamw.16604

  108. Ronchetti L, Terrenato I, Ferretti M et al (2023) Correction: circulating cell free DNA and citrullinated histone H3 as useful biomarkers of NETosis in endometrial cancer. J Exp Clin Cancer Res 42(1):278

    Article  PubMed  PubMed Central  Google Scholar 

  109. Wurtzel JGT, Lazar S, Askari S et al (2024) Plasma growth factors maintain constitutive translation in platelets to regulate reactivity and thrombotic potential. Blood Adv 8(6):1550–1566. https://doi.org/10.1182/bloodadvances.2023011734

  110. Palacios-Acedo A-L, Langiu M, Crescence L et al (2022) Platelet and cancer-cell interactions modulate cancer-associated thrombosis risk in different cancer types. Cancers (Basel) 14(3):730. https://doi.org/10.3390/cancers14030730

  111. Kansas GS (1996) Selectins and their ligands: current concepts and controversies. Blood 88(9):3259–3287

    Article  CAS  PubMed  Google Scholar 

  112. Vandendries ER, Furie BC, Furie B (2004) Role of P-selectin and PSGL-1 in coagulation and thrombosis. Thromb Haemost 92(3):459–466

    Article  CAS  PubMed  Google Scholar 

  113. Michelson AD, Barnard MR, Hechtman HB et al (1996) In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. Proc Natl Acad Sci U S A 93(21):11877-11882

  114. Palabrica T, Lobb R, Furie BC et al (1992) Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 359(6398):848–851

    Article  CAS  PubMed  Google Scholar 

  115. Frenette PS, Johnson RC, Hynes RO et al (1995) Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci U S A 92(16):7450-7454

  116. Chong BH, Murray B, Berndt MC et al (1994) Plasma P-selectin is increased in thrombotic consumptive platelet disorders. Blood 83(6):1535–1541

    Article  CAS  PubMed  Google Scholar 

  117. Glassman D, Bateman NW, Lee S et al (2022) Molecular Correlates of venous thromboembolism (VTE) in ovarian cancer. Cancers (Basel) 14(6):1496. https://doi.org/10.3390/cancers14061496

  118. Tawil N, Bassawon R, Meehan B et al (2021) Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles. Blood Adv 5(6):1682–1694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Suzuki-Inoue K, Kato Y, Inoue O et al (2007) Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells. J Biol Chem 282(36):25993–26001

    Article  CAS  PubMed  Google Scholar 

  120. Mege D, Aubert M, Lacroix R et al (2019) Involvement of platelets in cancers. Semin Thromb Hemost 45(6):569–575

    Article  CAS  PubMed  Google Scholar 

  121. Cedervall J, Hamidi A, Olsson A-K (2018) Platelets, NETs and cancer. Thromb Res 164(Suppl 1):S148–S152

    Article  CAS  PubMed  Google Scholar 

  122. Connolly GC, Phipps RP, Francis CW (2014) Platelets and cancer-associated thrombosis. Semin Oncol 41(3):302–310

    Article  CAS  PubMed  Google Scholar 

  123. Riedl J, Pabinger I, Ay C (2014) Platelets in cancer and thrombosis. Hamostaseologie 34(1):54–62

    Article  CAS  PubMed  Google Scholar 

  124. Larocca A, Cavallo F, Bringhen S et al (2012) Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood 119(4):933–939

    Article  CAS  PubMed  Google Scholar 

  125. Shai A, Rennert HS, Rennert G et al (2014) Statins, aspirin and risk of thromboembolic events in ovarian cancer patients. Gynecol Oncol 133(2):304–308

    Article  CAS  PubMed  Google Scholar 

  126. Shai A, Rennert HS, Lavie O et al (2014) Statins, aspirin and risk of venous thromboembolic events in breast cancer patients. J Thromb Thrombolysis 38(1):32–38. https://doi.org/10.1007/s11239-013-1015-8

  127. Riedl J, Hell L, Kaider A et al (2016) Association of platelet activation markers with cancer-associated venous thromboembolism. Platelets 27(1):80–85

    Article  CAS  PubMed  Google Scholar 

  128. Poruk KE, Firpo MA, Huerter LM et al (2010) Serum platelet factor 4 is an independent predictor of survival and venous thromboembolism in patients with pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev: Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 19(10):2605–2610

    Article  CAS  Google Scholar 

  129. Mezouar S, Darbousset R, Dignat-George F et al (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):462–475

    Article  CAS  PubMed  Google Scholar 

  130. Geddings JE, Hisada Y, Boulaftali Y et al (2016) Tissue factor-positive tumor microvesicles activate platelets and enhance thrombosis in mice. J Thromb Haemost 14(1):153–166

    Article  CAS  PubMed  Google Scholar 

  131. Medina C, Harmon S, Inkielewicz I et al (2012) Differential inhibition of tumour cell-induced platelet aggregation by the nicotinate aspirin prodrug (ST0702) and aspirin. Br J Pharmacol 166(3):938–949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Bastida E, Ordinas A, Jamieson GA (1981) Differing platelet aggregating effects by two tumor cell lines: absence of role for platelet-derived ADP. Am J Hematol 11(4):367–378

    Article  CAS  PubMed  Google Scholar 

  133. Boukerche H, Berthier-Vergnes O, Penin F et al (1994) Human melanoma cell lines differ in their capacity to release ADP and aggregate platelets. Br J Haematol 87(4):763–772

    Article  CAS  PubMed  Google Scholar 

  134. Bastida E, Escolar G, Almirall L et al (1986) Platelet activation induced by a human neuroblastoma tumor cell line is reduced by prior administration of ticlopidine. Thromb Haemost 55(3):333–337

    Article  CAS  PubMed  Google Scholar 

  135. Camez A, Dupuy E, Bellucci S et al (1986) Human platelet-tumor cell interactions vary with the tumor cell lines. Invasion Metastasis 6(6):321–334

    CAS  PubMed  Google Scholar 

  136. Alonso-Escolano D, Strongin AY, Chung AW et al (2004) Membrane type-1 matrix metalloproteinase stimulates tumour cell-induced platelet aggregation: role of receptor glycoproteins. Br J Pharmacol 141(2):241–252

    Article  CAS  PubMed  Google Scholar 

  137. Jurasz P, Sawicki G, Duszyk M et al (2001) Matrix metalloproteinase 2 in tumor cell-induced platelet aggregation: regulation by nitric oxide. Can Res 61(1):376–382

    CAS  Google Scholar 

  138. Palacios-Acedo AL, Mezouar S, Mège D et al (2021) P2RY12-inhibitors reduce cancer-associated thrombosis and tumor growth in pancreatic cancers. Front Oncol 11:704945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Ballerini P, Dovizio M, Bruno A et al (2018) P2Y receptors in tumorigenesis and metastasis. Front Pharmacol 9:66. https://doi.org/10.3389/fphar.2018.00066

  140. Ishikawa S, Miyashita T, Inokuchi M et al (2016) Platelets surrounding primary tumor cells are related to chemoresistance. Oncol Rep 36(2):787–794

    Article  CAS  PubMed  Google Scholar 

  141. Brass S (2001) Cardiovascular biology. Small cells, big issues. Nature 409(6817):145–147

    Article  CAS  PubMed  Google Scholar 

  142. Rolfes V, Idel C, Pries R et al (2018) PD-L1 is expressed on human platelets and is affected by immune checkpoint therapy. Oncotarget 9(44):27460–27470

    Article  PubMed  PubMed Central  Google Scholar 

  143. Zamora C, Cantó E, Nieto JC et al (2017) Binding of platelets to lymphocytes: a potential anti-inflammatory therapy in rheumatoid arthritis. J Immunol (Baltimore, Md: 1950) 198(8):3099–3108

    Article  CAS  Google Scholar 

  144. Metelli A, Wu BX, Riesenberg B et al (2020) Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β. Sci Transl Med 12(525):eaay4860. https://doi.org/10.1126/scitranslmed.aay4860

  145. Dahmani A, Delisle J-S (2018) TGF-β in T cell biology: implications for cancer immunotherapy. Cancers (Basel) 10(6):194. https://doi.org/10.3390/cancers10060194

  146. Lisman T (2018) Platelet-neutrophil interactions as drivers of inflammatory and thrombotic disease. Cell Tissue Res 371(3):567–576

    Article  CAS  PubMed  Google Scholar 

  147. Coffelt SB, Kersten K, Doornebal CW et al (2015) IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature 522(7556):345–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. de Kleijn S, Langereis JD, Leentjens J et al (2013) IFN-γ-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1. PLoS One 8(8):e72249

    Article  PubMed  PubMed Central  Google Scholar 

  149. Scully M, Cataland SR, Peyvandi F et al (2019) Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 380(4):335–346. https://doi.org/10.1056/NEJMoa1806311

  150. Corvigno S, Johnson AM, Wong K-K et al (2022) Novel markers for liquid biopsies in cancer management: circulating platelets and extracellular vesicles. Mol Cancer Ther 21(7):1067–1075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Strauss J, Heery CR, Schlom J et al (2018) Phase I trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFβ, in advanced solid tumors. Clin Cancer Res: Off J Am Assoc Cancer Res 24(6):1287–1295

    Article  CAS  Google Scholar 

  152. Goshua G, Sinha P, Hendrickson JE et al (2021) Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura. Blood 137(7):969–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Loschi M, Porcher R, Barraco F et al (2016) Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study. Am J Hematol 91(4):366–370

    Article  CAS  PubMed  Google Scholar 

  154. Cofiell R, Kukreja A, Bedard K et al (2015) Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood 125(21):3253–3262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Afshar-Kharghan V (2017) The role of the complement system in cancer. J Clin Invest 127(3):780–789. https://doi.org/10.1172/JCI90962

  156. Scully M, Knöbl P, Kentouche K et al (2017) Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood 130(19):2055–2063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Wang T-F, Li A, Garcia D (2018) Managing thrombosis in cancer patients. Res Pract Thromb Haemost 2(3):429–438

    Article  PubMed  PubMed Central  Google Scholar 

  158. Huang J, Li X, Shi X et al (2019) Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting. J Hematol Oncol 12(1):26

    Article  PubMed  PubMed Central  Google Scholar 

  159. Giordano A, Musumeci G, D’Angelillo A et al (2016) Effects of glycoprotein IIb/IIIa antagonists: anti platelet aggregation and beyond. Curr Drug Metab 17(2):194–203

    Article  CAS  PubMed  Google Scholar 

  160. Ulrichts H, Silence K, Schoolmeester A et al (2011) Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs. Blood 118(3):757–765

    Article  CAS  PubMed  Google Scholar 

  161. Callewaert F, Roodt J, Ulrichts H et al (2012) Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood 120(17):3603–3610

    Article  CAS  PubMed  Google Scholar 

  162. Scully M, Cataland SR, Peyvandi F et al (2019) Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 380(4):335–346

    Article  CAS  PubMed  Google Scholar 

  163. Völker LA, Kaufeld J, Balduin G et al (2023) Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura. J Thromb Haemost 21(3):559–572

    Article  PubMed  Google Scholar 

  164. Peyvandi F, Scully M, Kremer Hovinga JA et al (2016) Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med 374(6):511–522

    Article  CAS  PubMed  Google Scholar 

  165. Whilding LM, Halim L, Draper B et al (2019) CAR T-cells targeting the integrin αvβ6 and co-expressing the chemokine receptor CXCR2 demonstrate enhanced homing and efficacy against several solid malignancies. Cancers (Basel) 11(5):674. https://doi.org/10.3390/cancers11050674

  166. Haider T, Sandha KK, Soni V et al (2020) Recent advances in tumor microenvironment associated therapeutic strategies and evaluation models. Mater Sci Eng C Mater Biol Appl 116:111229

    Article  CAS  PubMed  Google Scholar 

  167. Wang H, Liu H, Sun C et al (2021) Nanoparticles dual targeting both myeloma cells and cancer-associated fibroblasts simultaneously to improve multiple myeloma treatment. Pharm 13(2):274. https://doi.org/10.3390/pharmaceutics13020274

  168. Liu Y, Castro Bravo KM, Liu J (2021) Targeted liposomal drug delivery: a nanoscience and biophysical perspective. Nanoscale Horiz 6(2):78–94

    Article  CAS  PubMed  Google Scholar 

  169. Shao J, Zaro J, Shen Y (2020) Advances in exosome-based drug delivery and tumor targeting: from tissue distribution to intracellular fate. Int J Nanomedicine 15:9355–9371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Roopkumar J, Swaidani S, Kim AS et al (2021) Increased incidence of venous thromboembolism with cancer immunotherapy - ScienceDirect. Med 2(4):423–434. https://doi.org/10.1016/j.medj.2021.02.002

  171. Abe K, Yoshimura H, Tanaka H et al (2004) Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events. Neuroradiology 46(2):113–117

    Article  CAS  PubMed  Google Scholar 

  172. Crescente M, Mezzasoma AM, Del Pinto M et al (2011) Incomplete inhibition of platelet function as assessed by the platelet function analyzer (PFA-100) identifies a subset of cardiovascular patients with high residual platelet response while on aspirin. Platelets 22(3):179–187

    Article  CAS  PubMed  Google Scholar 

  173. Paniccia R, Antonucci E, Gori AM et al (2007) Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients. J Thromb Haemost 5(9):1839–1847

    Article  CAS  PubMed  Google Scholar 

  174. Lele M, Sajid M, Wajih N et al (2001) Eptifibatide and 7E3, but not tirofiban, inhibit alpha(v)beta(3) integrin-mediated binding of smooth muscle cells to thrombospondin and prothrombin. Circulation 104(5):582–587

    Article  CAS  PubMed  Google Scholar 

  175. Kujovich JL Factor V (2011) Leiden thrombophilia. Genet Med 13(1):1–16. https://doi.org/10.1097/GIM.0b013e3181faa0f2

  176. Mori J, Pearce AC, Spalton JC et al (2008) G6b-B inhibits constitutive and agonist-induced signaling by glycoprotein VI and CLEC-2. J Biol Chem 283(51):35419–35427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Perrault C, Mangin P, Santer M et al (2003) Role of the intracellular domains of GPIb in controlling the adhesive properties of the platelet GPIb/V/IX complex. Blood 101(9):3477–3484

    Article  CAS  PubMed  Google Scholar 

  178. Saidak Z, Soudet S, Lottin M et al (2021) A pan-cancer analysis of the human tumor coagulome and its link to the tumor immune microenvironment. Cancer Immunol Immunother: CII 70(4):923–933

    Article  CAS  PubMed  Google Scholar 

  179. Posch F, Riedl J, Reitter E-M et al (2020) Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: a prospective study. J Thromb Haemost 18(6):1348–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Marchetti M, Giaccherini C, Masci G et al (2020) Thrombin generation predicts early recurrence in breast cancer patients. J Thromb Haemost 18(9):2220–2231

    Article  CAS  PubMed  Google Scholar 

  181. Pantel K, Alix-Panabières C (2019) Liquid biopsy and minimal residual disease - latest advances and implications for cure. Nat Rev Clin Oncol 16(7):409–424

    Article  CAS  PubMed  Google Scholar 

  182. Keller L, Pantel K (2019) Unravelling tumour heterogeneity by single-cell profiling of circulating tumour cells. Nat Rev Cancer 19(10):553–567

    Article  CAS  PubMed  Google Scholar 

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Funding

The present study was funded by the National Natural Science Foundation of China (82172776), Tianjin Science and Technology Plan Project (19ZXDBSY00060), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-061B), and Diversified Input Project of Tianjin National Natural Science Foundation (21JCYBJC01770).

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Authors and Affiliations

  1. Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China

    Yifan Zhang, Jingtong Zeng, Shihao Bao, Bo Zhang, Xianjie Li, Hanqing Wang, Yuan Cheng, Hao Zhang, Lingling Zu, Song Xu & Zuoqing Song

  2. Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

    Yifan Zhang, Jingtong Zeng, Shihao Bao, Bo Zhang, Xianjie Li, Hanqing Wang, Yuan Cheng, Hao Zhang, Lingling Zu, Song Xu & Zuoqing Song

  3. Colleges of Nursing, Tianjin Medical University, Tianjin, China

    Xiaohong Xu

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  1. Yifan Zhang
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  11. Song Xu
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Contributions

Conceptualization, Y.-F.Z., J.-T.Z., B.Z., S.-H.B., X.-J.L., H.-Q.W., Y.C. and H.Z.; L.-L.Z., X.-H.X., S.X., Z.-Q.S. methodology, Y.-F.Z., J.-T.Z., B.Z., S.-H.B., X.-J.L., H.-Q.W., Y.C. and H.Z.; L.-L.Z., X.-H.X., S.X., Z.-Q.S.; writing—original draft preparation, Y.-F.Z.; writing—review and editing, Y.-F.Z. and J.-T.Z. contributed equally to this study. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Song Xu or Zuoqing Song.

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Zhang, Y., Zeng, J., Bao, S. et al. Cancer progression and tumor hypercoagulability: a platelet perspective. J Thromb Thrombolysis (2024). https://doi.org/10.1007/s11239-024-02993-0

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