Cellular Components Contributing to the Development of Venous Thrombosis in Patients with Pancreatic Cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer and has a poor prognosis. Patients with PDAC are at high risk of developing thromboembolic events, which is a leading cause of morbidity and mortality following cancer progression. Plasma-derived coagulation is the most studied process in cancer-associated thrombosis. Other blood components, such as platelets, red blood cells, and white blood cells, have been gaining less attention. This narrative review addresses the literature on the role of cellular components in the development of venous thromboembolism (VTE) in patients with PDAC. Blood cells seem to play an important role in the development of VTE. Altered blood cell counts, i.e., leukocytosis, thrombocytosis, and anemia, have been found to associate with VTE risk. Tumor-related activation of leukocytes leads to the release of tissue factor-expressing microvesicles and the formation of neutrophil extracellular traps, initiating coagulation and forming a scaffold for thrombi. Tissue factor-expressing microvesicles are also thought to be released by PDAC cells. PDAC cells have been shown to stimulate platelet activation and aggregation, proposedly via the secretion of podoplanin and mucins. Hypofibrinolysis, partially explained by increased plasminogen activator inhibitor-1 activity, is observed in PDAC. In short, PDAC-associated hypercoagulability is a complex and multifactorial process. A better understanding of cellular contributions to hypercoagulability might lead to the improvement of diagnostic tests to identify PDAC patients at highest risk of VTE.

Keywords

pancreatic ductal adenocarcinoma - cancer-associated thrombosis - venous thromboembolism - red blood cells - platelets - white blood cells

^* Contributed equally and joint first authors.

Publication History

Article published online:
04 December 2023

• References

• 1 Ducreux M, Cuhna AS, Caramella C. et al; ESMO Guidelines Committee. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26 (Suppl. 05) v56-v68
• 2 Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin 2021; 71 (01) 7-33
• 3 Ferlay J, Colombet M, Soerjomataram I. et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356-387
• 4 Cho J, Petrov MS. Pancreatitis, pancreatic cancer, and their metabolic sequelae: projected burden to 2050. Clin Transl Gastroenterol 2020; 11 (11) e00251
• 5 Hu JX, Zhao CF, Chen WB. et al. Pancreatic cancer: a review of epidemiology, trend, and risk factors. World J Gastroenterol 2021; 27 (27) 4298-4321
• 6 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol 2005; 6 (06) 401-410
• 7 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 (03) 632-634
• 8 Wun T, White RH. Epidemiology of cancer-related venous thromboembolism. Best Pract Res Clin Haematol 2009; 22 (01) 9-23
• 9 Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer - a cohort study using linked United Kingdom databases. Eur J Cancer 2013; 49 (06) 1404-1413
• 10 Epstein AS, Soff GA, Capanu M. et al. Analysis of incidence and clinical outcomes in patients with thromboembolic events and invasive exocrine pancreatic cancer. Cancer 2012; 118 (12) 3053-3061
• 11 Blom JW, Osanto S, Rosendaal FR. High risk of venous thrombosis in patients with pancreatic cancer: a cohort study of 202 patients. Eur J Cancer 2006; 42 (03) 410-414
• 12 Ishigaki K, Nakai Y, Isayama H. et al. Thromboembolisms in advanced pancreatic cancer: a retrospective analysis of 475 patients. Pancreas 2017; 46 (08) 1069-1075
• 13 Mandalà M, Reni M, Cascinu S. et al. Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients. Ann Oncol 2007; 18 (10) 1660-1665
• 14 Menapace LA, Peterson DR, Berry A, Sousou T, Khorana AA. Symptomatic and incidental thromboembolism are both associated with mortality in pancreatic cancer. Thromb Haemost 2011; 106 (02) 371-378
• 15 Muñoz Martín AJ, García Alfonso P, Rupérez Blanco AB, Pérez Ramírez S, Blanco Codesido M, Martín Jiménez M. Incidence of venous thromboembolism (VTE) in ambulatory pancreatic cancer patients receiving chemotherapy and analysis of Khorana's predictive model. Clin Transl Oncol 2014; 16 (10) 927-930
• 16 Berger AK, Singh HM, Werft W. et al. High prevalence of incidental and symptomatic venous thromboembolic events in patients with advanced pancreatic cancer under palliative chemotherapy: a retrospective cohort study. Pancreatology 2017; 17 (04) 629-634
• 17 Kim JS, Kang EJ, Kim DS. et al. Early venous thromboembolism at the beginning of palliative chemotherapy is a poor prognostic factor in patients with metastatic pancreatic cancer: a retrospective study. BMC Cancer 2018; 18 (01) 1260
• 18 Laderman L, Sreekrishnanilayam K, Pandey RK. et al. Venous thromboembolism in metastatic pancreatic cancer. Eur J Haematol 2023; 110 (06) 706-714
• 19 Lee JC, Ro YS, Cho J. et al. Characteristics of venous thromboembolism in pancreatic adenocarcinoma in east asian ethnics: a large population-based observational study. Medicine (Baltimore) 2016; 95 (17) e3472
• 20 Ouaïssi M, Frasconi C, Mege D. et al. Impact of venous thromboembolism on the natural history of pancreatic adenocarcinoma. Hepatobiliary Pancreat Dis Int 2015; 14 (04) 436-442
• 21 Mitry E, Taleb-Fayad R, Deschamps A. et al. Risk of venous thrombosis in patients with pancreatic adenocarcinoma. Gastroenterol Clin Biol 2007; 31 (12) 1139-1142
• 22 Walma MS, Brada LJ, Patuleia SIS. et al; Dutch Pancreatic Cancer Group. Treatment strategies and clinical outcomes in consecutive patients with locally advanced pancreatic cancer: a multicenter prospective cohort. Eur J Surg Oncol 2021; 47 (3 Pt B): 699-707
• 23 Katz MHG, Shi Q, Ahmad SA. et al. Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer: alliance for clinical trials in oncology trial A021101. JAMA Surg 2016; 151 (08) e161137-e161137
• 24 Krepline AN, Christians KK, George B. et al. Venous thromboembolism prophylaxis during neoadjuvant therapy for resectable and borderline resectable pancreatic cancer-Is it indicated?. J Surg Oncol 2016; 114 (05) 581-586
• 25 Hanna-Sawires RG, Groen JV, Hamming A. et al. Incidence, timing and risk factors of venous thromboembolic events in patients with pancreatic cancer. Thromb Res 2021; 207: 134-139
• 26 Barrau M, Maoui K, Le Roy B. et al. Early venous thromboembolism is a strong prognostic factor in patients with advanced pancreatic ductal adenocarcinoma. J Cancer Res Clin Oncol 2021; 147 (11) 3447-3454
• 27 Tahara J, Shimizu K, Otsuka N, Akao J, Takayama Y, Tokushige K. Gemcitabine plus nab-paclitaxel vs. FOLFIRINOX for patients with advanced pancreatic cancer. Cancer Chemother Pharmacol 2018; 82 (02) 245-250
• 28 Shaib W, Deng Y, Zilterman D, Lundberg B, Saif MW. Assessing risk and mortality of venous thromboembolism in pancreatic cancer patients. Anticancer Res 2010; 30 (10) 4261-4264
• 29 Mulder FI, Horváth-Puhó E, van Es N. et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood 2021; 137 (14) 1959-1969
• 30 Campello E, Bosch F, Simion C, Spiezia L, Simioni P. Mechanisms of thrombosis in pancreatic ductal adenocarcinoma. Best Pract Res Clin Haematol 2022; 35 (01) 101346
• 31 Kruger S, Haas M, Burkl C. et al. Incidence, outcome and risk stratification tools for venous thromboembolism in advanced pancreatic cancer - a retrospective cohort study. Thromb Res 2017; 157: 9-15
• 32 Frere C, Bournet B, Gourgou S. et al; BACAP Consortium. Incidence of venous thromboembolism in patients with newly diagnosed pancreatic cancer and factors associated with outcomes. Gastroenterology 2020; 158 (05) 1346-1358.e4
• 33 Moik F, Prager G, Thaler J. et al. Hemostatic biomarkers and venous thromboembolism are associated with mortality and response to chemotherapy in patients with pancreatic cancer. Arterioscler Thromb Vasc Biol 2021; 41 (11) 2837-2847
• 34 Maraveyas A, Waters J, Roy R. et al. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer 2012; 48 (09) 1283-1292
• 35 Pelzer U, Opitz B, Deutschinoff G. et al. Efficacy of prophylactic low-molecular weight heparin for ambulatory patients with advanced pancreatic cancer: outcomes from the CONKO-004 trial. J Clin Oncol 2015; 33 (18) 2028-2034
• 36 Khorana AA, Soff GA, Kakkar AK. et al; CASSINI Investigators. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med 2019; 380 (08) 720-728
• 37 Carrier M, Abou-Nassar K, Mallick R. et al; AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019; 380 (08) 711-719
• 38 Frere C, Crichi B, Bournet B. et al. Primary thromboprophylaxis in ambulatory pancreatic cancer patients receiving chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Cancers (Basel) 2020; 12 (08) 2028
• 39 Agnelli G, Gussoni G, Bianchini C. et al; PROTECHT Investigators. 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 (10) 943-949
• 40 Agnelli G, George DJ, Kakkar AK. et al; SAVE-ONCO Investigators. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366 (07) 601-609
• 41 Willems RAL, Michiels N, Lanting VR. et al. Venous thromboembolism and primary thromboprophylaxis in perioperative pancreatic cancer care. Cancers (Basel) 2023; 15 (14) 3546
• 42 Ladha D, Mallick R, Wang TF, Caiano L, Wells PS, Carrier M. Efficacy and safety of apixaban for primary prevention in gastrointestinal cancers: a post-hoc analysis of the AVERT trial. Thromb Res 2021; 202: 151-154
• 43 Vadhan-Raj S, McNamara MG, Venerito M. et al. Rivaroxaban thromboprohylaxis in ambulatory patients with pancreatic cancer: results from a prespecified subgroup analysis of the CASSINI study. J Clin Oncol 2019; 37 (15) 4016-4016
• 44 Schünemann HJ, Ventresca M, Crowther M. et al. Evaluating prophylactic heparin in ambulatory patients with solid tumours: a systematic review and individual participant data meta-analysis. Lancet Haematol 2020; 7 (10) e746-e755
• 45 Bohlius J, Bohlke K, Castelli R. et al. Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update. J Clin Oncol 2019; 37 (15) 1336-1351
• 46 Streiff MB, Holmstrom B, Angelini D. et al. Cancer-associated venous thromboembolic disease, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2021; 19 (10) 1181-1201
• 47 Farge D, Frere C, Connors JM. et al; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol 2022; 23 (07) e334-e347
• 48 van Es N, Franke VF, Middeldorp S, Wilmink JW, Büller HR. The Khorana score for the prediction of venous thromboembolism in patients with pancreatic cancer. Thromb Res 2017; 150: 30-32
• 49 Campello E, Ilich A, Simioni P, Key NS. The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues. Br J Cancer 2019; 121 (05) 359-371
• 50 Vormittag R, Simanek R, Ay C. et al. High factor VIII levels independently predict venous thromboembolism in cancer patients: the cancer and thrombosis study. Arterioscler Thromb Vasc Biol 2009; 29 (12) 2176-2181
• 51 Sun W, Ren H, Gao CT. et al. Clinical and prognostic significance of coagulation assays in pancreatic cancer patients with absence of venous thromboembolism. Am J Clin Oncol 2015; 38 (06) 550-556
• 52 Wilts IT, Hutten BA, Meijers JCM, Spek CA, Büller HR, Kamphuisen PW. Association between protein C levels and mortality in patients with advanced prostate, lung and pancreatic cancer. Thromb Res 2017; 154: 1-6
• 53 Byrnes JR, Wolberg AS. Red blood cells in thrombosis. Blood 2017; 130 (16) 1795-1799
• 54 Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood 2017; 130 (13) 1499-1506
• 55 Swystun LL, Liaw PC. The role of leukocytes in thrombosis. Blood 2016; 128 (06) 753-762
• 56 Falanga A, Marchetti M. Cancer-associated thrombosis: enhanced awareness and pathophysiologic complexity. J Thromb Haemost 2023; 21 (06) 1397-1408
• 57 Abdol Razak NB, Jones G, Bhandari M, Berndt MC, Metharom P. Cancer-associated thrombosis: an overview of mechanisms, risk factors, and treatment. Cancers (Basel) 2018; 10 (10) 380
• 58 Rickles FR, Falanga A. Activation of clotting factors in cancer. Cancer Treat Res 2009; 148: 31-41
• 59 Lundbech M, Krag AE, Christensen TD, Hvas AM. Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients. Thromb Res 2020; 186: 80-85
• 60 Kwon HC, Oh SY, Lee S. et al. Plasma levels of prothrombin fragment F1+2, D-dimer and prothrombin time correlate with clinical stage and lymph node metastasis in operable gastric cancer patients. Jpn J Clin Oncol 2008; 38 (01) 2-7
• 61 Yu X, Hu F, Yao Q, Li C, Zhang H, Xue Y. Serum fibrinogen levels are positively correlated with advanced tumor stage and poor survival in patients with gastric cancer undergoing gastrectomy: a large cohort retrospective study. BMC Cancer 2016; 16 (01) 480
• 62 Falanga A, Giaccherini C, Marchetti M. et al. A thrombotic biomarker-based risk assessment scoring model for disease recurrence in breast cancer patient candidate to systemic chemotherapy. Blood 2019; 134 (Suppl. 01) 2426
• 63 Ay C, Vormittag R, Dunkler D. et al. 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 (25) 4124-4129
• 64 Qi Y, Hu X, Chen J, Ying X, Shi Y. The risk factors of VTE and survival prognosis of patients with malignant cancer: implication for nursing and treatment. Clin Appl Thromb Hemost 2020; 26: 1076029620971053
• 65 Stender MT, Larsen AC, Sall M, Thorlacius-Ussing O. D-Dimer predicts prognosis and non-resectability in patients with pancreatic cancer: a prospective cohort study. Blood Coagul Fibrinolysis 2016; 27 (05) 597-601
• 66 Arpaia G, Carpenedo M, Verga M. et al. D-dimer before chemotherapy might predict venous thromboembolism. Blood Coagul Fibrinolysis 2009; 20 (03) 170-175
• 67 Stender MT, Frøkjaer 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 (03) 446-451
• 68 Kodama J, Seki N, Masahiro S. et al. D-dimer level as a risk factor for postoperative venous thromboembolism in Japanese women with gynecologic cancer. Ann Oncol 2010; 21 (08) 1651-1656
• 69 Ferroni P, Martini F, Portarena I. et al. Novel high-sensitive D-dimer determination predicts chemotherapy-associated venous thromboembolism in intermediate risk lung cancer patients. Clin Lung Cancer 2012; 13 (06) 482-487
• 70 Kondo S, Sasaki M, Hosoi H. et al. Incidence and risk factors for venous thromboembolism in patients with pretreated advanced pancreatic carcinoma. Oncotarget 2018; 9 (24) 16883-16890
• 71 Iguchi T, Sugimachi K, Mano Y. et al. The preoperative prognostic nutritional index predicts the development of deep venous thrombosis after pancreatic surgery. Anticancer Res 2020; 40 (04) 2297-2301
• 72 Sylman JL, Mitrugno A, Tormoen GW, Wagner TH, Mallick P, McCarty OJT. Platelet count as a predictor of metastasis and venous thromboembolism in patients with cancer. Converg Sci Phys Oncol 2017; 3 (02) 023001
• 73 Simanek R, Vormittag R, Ay C. et al. High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Haemost 2010; 8 (01) 114-120
• 74 Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104 (12) 2822-2829
• 75 Mulder FI, Candeloro M, Kamphuisen PW. et al; CAT-prediction collaborators. The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis. Haematologica 2019; 104 (06) 1277-1287
• 76 Boone BA, Zenati MS, Rieser C. et al. Risk of venous thromboembolism for patients with pancreatic ductal adenocarcinoma undergoing preoperative chemotherapy followed by surgical resection. Ann Surg Oncol 2019; 26 (05) 1503-1511
• 77 Hsu C, Patell R, Zwicker JI. The prevalence of thrombocytopenia in patients with acute cancer-associated thrombosis. Blood Adv 2023; 7 (17) 4721-4727
• 78 Poruk KE, Firpo MA, Huerter LM. et al. Serum platelet factor 4 is an independent predictor of survival and venous thromboembolism in patients with pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2010; 19 (10) 2605-2610
• 79 Fiedler GM, Leichtle AB, Kase J. et al. Serum peptidome profiling revealed platelet factor 4 as a potential discriminating Peptide associated with pancreatic cancer. Clin Cancer Res 2009; 15 (11) 3812-3819
• 80 Merten M, Thiagarajan P. P-selectin expression on platelets determines size and stability of platelet aggregates. Circulation 2000; 102 (16) 1931-1936
• 81 Ay C, Simanek R, Vormittag R. et al. 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 (07) 2703-2708
• 82 Sadler JE. New concepts in von Willebrand disease. Annu Rev Med 2004; 56: 173-191
• 83 Sadler JE. von Willebrand factor: two sides of a coin. J Thromb Haemost 2005; 3 (08) 1702-1709
• 84 Wang WS, Lin JK, Lin TC. et al. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma. World J Gastroenterol 2005; 11 (14) 2166-2170
• 85 Röhsig LM, Damin DC, Stefani SD, Castro Jr CG, Roisenberg I, Schwartsmann G. von Willebrand factor antigen levels in plasma of patients with malignant breast disease. Braz J Med Biol Res 2001; 34 (09) 1125-1129
• 86 Gadducci A, Baicchi U, Marrai R, Del Bravo B, Fosella PV, Facchini V. Pretreatment plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand factor (vWF) in patients with ovarian carcinoma. Gynecol Oncol 1994; 53 (03) 352-356
• 87 Obermeier HL, Riedl J, Ay C. et al. The role of ADAMTS-13 and von Willebrand factor in cancer patients: results from the Vienna Cancer and Thrombosis Study. Res Pract Thromb Haemost 2019; 3 (03) 503-514
• 88 Pépin M, Kleinjan A, Hajage D. et al. ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer. J Thromb Haemost 2016; 14 (02) 306-315
• 89 Heinmöller E, Schropp T, Kisker O, Simon B, Seitz R, Weinel RJ. Tumor cell-induced platelet aggregation in vitro by human pancreatic cancer cell lines. Scand J Gastroenterol 1995; 30 (10) 1008-1016
• 90 Palacios-Acedo AL, Mège D, Crescence L, Dignat-George F, Dubois C, Panicot-Dubois L. Platelets, thrombo-inflammation, and cancer: collaborating with the enemy. Front Immunol 2019; 10: 1805
• 91 Hirayama K, Kono H, Nakata Y. et al. Expression of podoplanin in stromal fibroblasts plays a pivotal role in the prognosis of patients with pancreatic cancer. Surg Today 2018; 48 (01) 110-118
• 92 Suzuki-Inoue K, Kato Y, Inoue O. et al. Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells. J Biol Chem 2007; 282 (36) 25993-26001
• 93 Mege D, Panicot-Dubois L, Ouaissi M. et al. The origin and concentration of circulating microparticles differ according to cancer type and evolution: a prospective single-center study. Int J Cancer 2016; 138 (04) 939-948
• 94 Kaur S, Kumar S, Momi N, Sasson AR, Batra SK. Mucins in pancreatic cancer and its microenvironment. Nat Rev Gastroenterol Hepatol 2013; 10 (10) 607-620
• 95 Yiannakou JY, Newland P, Calder F, Kingsnorth AN, Rhodes JM. Prospective study of CAM 17.1/WGA mucin assay for serological diagnosis of pancreatic cancer. Lancet 1997; 349 (9049) 389-392
• 96 Shao B, Wahrenbrock MG, Yao L. et al. Carcinoma mucins trigger reciprocal activation of platelets and neutrophils in a murine model of Trousseau syndrome. Blood 2011; 118 (15) 4015-4023
• 97 Key NS, Khorana AA, Kuderer NM. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol 2023; 41 (16) 3063-3071
• 98 Larocca A, Cavallo F, Bringhen S. et al. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood 2012; 119 (04) 933-939 , quiz 1093
• 99 Palumbo A, Cavo M, Bringhen S. 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 (08) 986-993
• 100 Callander NS, Baljevic M, Adekola K. et al. NCCN Guidelines® insights: multiple myeloma, version 3.2022. J Natl Compr Canc Netw 2022; 20 (01) 8-19
• 101 Shai A, Rennert HS, Lavie O. et al. Statins, aspirin and risk of venous thromboembolic events in breast cancer patients. J Thromb Thrombolysis 2014; 38 (01) 32-38
• 102 Altman R, Luciardi HL, Muntaner J, Herrera RN. The antithrombotic profile of aspirin. Aspirin resistance, or simply failure?. Thromb J 2004; 2 (01) 1
• 103 King R, Schaefer J, Sahai V, Griffith KA, Sood SL. Retrospective cohort analysis of aspirin use and venous thromboembolism in patients with pancreatic cancer and an indwelling central venous catheter. TH Open 2022; 6 (03) e221-e229
• 104 Madeddu C, Gramignano G, Astara G. et al. Pathogenesis and treatment options of cancer related anemia: perspective for a targeted mechanism-based approach. Front Physiol 2018; 9 (SEP): 1294
• 105 Ludwig H, Van Belle S, Barrett-Lee P. et al. The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer 2004; 40 (15) 2293-2306
• 106 Ludwig H, Müldür E, Endler G, Hübl W. Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol 2013; 24 (07) 1886-1892
• 107 Serna Thome MG, Padilla Rosciano AE, Mendoza Pablo PA, Lopez Basave HN, Garcia Matus R. Prevalence of anemia in patients with pancreas, liver and biliary cancers and their relationship with the inflammatory response. HPB (Oxford) 2019; 21: S500-S501
• 108 Yamai T, Ikezawa K, Hiraga E. et al. Early detection of venous thromboembolism after the initiation of chemotherapy predicts a poor prognosis in patients with unresectable metastatic pancreatic cancer who underwent first-line chemotherapy with gemcitabine plus nab-paclitaxel. PLoS One 2022; 17 (03) e0264653
• 109 Conroy T, Desseigne F, Ychou M. et al; Groupe Tumeurs Digestives of Unicancer, PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364 (19) 1817-1825
• 110 Conroy T, Hammel P, Hebbar M. et al; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 2018; 379 (25) 2395-2406
• 111 Von Hoff DD, Ervin T, Arena FP. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369 (18) 1691-1703
• 112 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111 (10) 4902-4907
• 113 Dutia M, White RH, Wun T. Risk assessment models for cancer-associated venous thromboembolism. Cancer 2012; 118 (14) 3468-3476
• 114 Riedl J, Posch F, Königsbrügge O. et al. Red cell distribution width and other red blood cell parameters in patients with cancer: association with risk of venous thromboembolism and mortality. PLoS One 2014; 9 (10) e111440
• 115 Wang PF, Song SY, Guo H, Wang TJ, Liu N, Yan CX. Prognostic role of pretreatment red blood cell distribution width in patients with cancer: a meta-analysis of 49 studies. J Cancer 2019; 10 (18) 4305-4317
• 116 İlhan A, Gurler F, Yilmaz F, Eraslan E, Dogan M. The relationship between hemoglobin-RDW ratio and clinical outcomes in patients with advanced pancreas cancer. Eur Rev Med Pharmacol Sci 2023; 27 (05) 2060-2067
• 117 Bennett CL, Silver SM, Djulbegovic B. et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008; 299 (08) 914-924
• 118 Zhan P, Wang Q, Qian Q, Yu LK. Risk of venous thromboembolism with the erythropoiesis-stimulating agents (ESAs) for the treatment of cancer-associated anemia: a meta-analysis of randomized control trials. Chin Clin Oncol 2012; 1 (02) 19
• 119 Tonia T, Mettler A, Robert N. et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev 2012; 12 (12) CD003407
• 120 Bohlius J, Wilson J, Seidenfeld J. et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 2006; 98 (10) 708-714
• 121 Ramsey G, Lindholm PF. Thrombosis risk in cancer patients receiving red blood cell transfusions. Semin Thromb Hemost 2019; 45 (06) 648-656
• 122 Khorana AA, Francis CW, Blumberg N, Culakova E, Refaai MA, Lyman GH. Blood transfusions, thrombosis, and mortality in hospitalized patients with cancer. Arch Intern Med 2008; 168 (21) 2377-2381
• 123 Semeraro F, Ammollo CT, Esmon NL, Esmon CT. Histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells. J Thromb Haemost 2014; 12 (10) 1697-1702
• 124 Du VX, Huskens D, Maas C, Al Dieri R, de Groot PG, de Laat B. New insights into the role of erythrocytes in thrombus formation. Semin Thromb Hemost 2014; 40 (01) 72-80
• 125 Wan J, Roberts LN, Hendrix W. et al. Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay. J Thromb Haemost 2020; 18 (04) 834-843
• 126 Wan J, Konings J, Yan Q. et al. A novel assay for studying the involvement of blood cells in whole blood thrombin generation. J Thromb Haemost 2020; 18 (06) 1291-1301
• 127 Wan J, Konings J, de Laat B, Hackeng TM, Roest M. Added value of blood cells in thrombin generation testing. Thromb Haemost 2021; 121 (12) 1574-1587
• 128 Sun S, Campello E, Zou J. et al. Crucial roles of red blood cells and platelets in whole blood thrombin generation. Blood Adv 2023; 7 (21) 6717-6731
• 129 Koshiar RL, Somajo S, Norström E, Dahlbäck B. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation. PLoS One 2014; 9 (08) e104200
• 130 Hess JR. Red cell changes during storage. Transfus Apheresis Sci 2010; 43 (01) 51-59
• 131 Dinkla S, Peppelman M, Van Der Raadt J. et al. Phosphatidylserine exposure on stored red blood cells as a parameter for donor-dependent variation in product quality. Blood Transfus 2014; 12 (02) 204-209
• 132 Kang TH, Park JH, Yang A. et al. Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment. Nat Commun 2020; 11 (01) 1137
• 133 Tulyte S, Characiejus D, Matuzeviciene R. et al. The effects of treatment on peripheral blood immune cell profile in pancreatic ductal adenocarcinoma (PDAC). Anticancer Res 2022; 42 (06) 3067-3073
• 134 Venkatesulu BP, Mallick S, Lin SH, Krishnan S. A systematic review of the influence of radiation-induced lymphopenia on survival outcomes in solid tumors. Crit Rev Oncol Hematol 2018; 123: 42-51
• 135 Reddy AV, Hill CS, Sehgal S. et al. Post-radiation neutrophil-to-lymphocyte ratio is a prognostic marker in patients with localized pancreatic adenocarcinoma treated with anti-PD-1 antibody and stereotactic body radiation therapy. Radiat Oncol J 2022; 40 (02) 111-119
• 136 Pabinger I, Posch F. Flamethrowers: blood cells and cancer thrombosis risk. Hematology (Am Soc Hematol Educ Program) 2014; 2014 (01) 410-417
• 137 Blix K, Jensvoll H, Brækkan SK, Hansen JB. White blood cell count measured prior to cancer development is associated with future risk of venous thromboembolism–the Tromsø study. PLoS One 2013; 8 (09) e73447
• 138 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 (02) 113-118
• 139 Trujillo-Santos J, Di Micco P, Iannuzzo M. et al; RIETE Investigators, Findings from the RIETE Registry. Elevated white blood cell count and outcome in cancer patients with venous thromboembolism. Thromb Haemost 2008; 100 (05) 905-911
• 140 Brinkmann V, Reichard U, Goosmann C. et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303 (5663) 1532-1535
• 141 Gregory SA, Morrissey JH, Edgington TS. Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 1989; 9 (06) 2752-2755
• 142 Demers M, Wagner DD. Neutrophil extracellular traps: a new link to cancer-associated thrombosis and potential implications for tumor progression. OncoImmunology 2013; 2 (02) e22946
• 143 Demers M, Wong SL, Martinod K. et al. Priming of neutrophils toward NETosis promotes tumor growth. OncoImmunology 2016; 5 (05) e1134073
• 144 Olsson AK, Cedervall J. NETosis in cancer - platelet-neutrophil crosstalk promotes tumor-associated pathology. Front Immunol 2016; 7: 373
• 145 Massberg S, Grahl L, von Bruehl ML. et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 2010; 16 (08) 887-896
• 146 Pratt HG, Steinberger KJ, Mihalik NE. et al. Macrophage and neutrophil interactions in the pancreatic tumor microenvironment drive the pathogenesis of pancreatic cancer. Cancers (Basel) 2021; 14 (01) 194
• 147 Abdol Razak N, Elaskalani O, Metharom P. Pancreatic cancer-induced neutrophil extracellular traps: a potential contributor to cancer-associated thrombosis. Int J Mol Sci 2017; 18 (03) 487
• 148 Boone BA, Schapiro NE, Neal MD, Ellis JT, Lotze MT, Zeh HJ. Neutrophil extracellular traps (NETs) are upregulated in pancreatic cancer as a result of autophagy and promote hypercoagulability. J Surg Res 2014; 186 (02) 638
• 149 Jung HS, Gu J, Kim JE, Nam Y, Song JW, Kim HK. Cancer cell-induced neutrophil extracellular traps promote both hypercoagulability and cancer progression. PLoS One 2019; 14 (04) e0216055
• 150 Yu M, Li T, Li B. et al. Phosphatidylserine-exposing blood cells, microparticles and neutrophil extracellular traps increase procoagulant activity in patients with pancreatic cancer. Thromb Res 2020; 188: 5-16
• 151 Wang Y, Li M, Stadler S. et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol 2009; 184 (02) 205-213
• 152 Li P, Li M, Lindberg MR, Kennett MJ, Xiong N, Wang Y. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med 2010; 207 (09) 1853-1862
• 153 Demers M, Krause DS, Schatzberg D. et al. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci U S A 2012; 109 (32) 13076-13081
• 154 Mauracher L-M, Posch F, Martinod K. et al. Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients. J Thromb Haemost 2018; 16 (03) 508-518
• 155 Krenn-Pilko S, Langsenlehner U, Thurner EM. et al. The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients. Br J Cancer 2014; 110 (10) 2524-2530
• 156 Li W, Tao L, Lu M, Xiu D. Prognostic role of platelet to lymphocyte ratio in pancreatic cancers: a meta-analysis including 3028 patients. Medicine (Baltimore) 2018; 97 (08) e9616
• 157 Templeton AJ, McNamara MG, Šeruga B. et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 2014; 106 (06) dju124
• 158 Yang JJ, Hu ZG, Shi WX, Deng T, He SQ, Yuan SG. Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: a meta-analysis. World J Gastroenterol 2015; 21 (09) 2807-2815
• 159 Yang W, Liu Y. Platelet-lymphocyte ratio is a predictor of venous thromboembolism in cancer patients. Thromb Res 2015; 136 (02) 212-215
• 160 Tham T, Rahman L, Persaud C, Olson C, Costantino P. Venous thromboembolism risk in head and neck cancer: significance of the preoperative platelet-to-lymphocyte ratio. Otolaryngol Head Neck Surg 2018; 159 (01) 85-91
• 161 Yamagata K, Fukuzawa S, Uchida F, Ishibashi-Kanno N, Yanagawa T, Bukawa H. Is Preoperative plate-lymphocyte ratio a predictor of deep vein thrombosis in patients with oral cancer during surgery?. J Oral Maxillofac Surg 2021; 79 (04) 914-924
• 162 Grilz E, Posch F, Königsbrügge O. et al. Association of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio with the risk of thromboembolism and mortality in patients with cancer. Thromb Haemost 2018; 118 (11) 1875-1884
• 163 Ferroni P, Riondino S, Formica V. et al. Venous thromboembolism risk prediction in ambulatory cancer patients: clinical significance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. Int J Cancer 2015; 136 (05) 1234-1240
• 164 Otasevic V, Mihaljevic B, Milic N. et al. Immune activation and inflammatory biomarkers as predictors of venous thromboembolism in lymphoma patients. Thromb J 2022; 20 (01) 20
• 165 Nemerson Y. The tissue factor pathway of blood coagulation. Semin Hematol 1992; 29 (03) 170-176
• 166 Semeraro N, Colucci M. Tissue factor in health and disease. Thromb Haemost 1997; 78 (01) 759-764
• 167 Rambaldi A, Alessio G, Casali B. et al. Induction of monocyte-macrophage procoagulant activity by transformed cell lines. J Immunol 1986; 136 (10) 3848-3855
• 168 Granger V, Faille D, Marani V. et al. Human blood monocytes are able to form extracellular traps. J Leukoc Biol 2017; 102 (03) 775-781
• 169 Dâmaso S, Paiva R, Pinho I. et al. P-265 High peripheral monocyte count is associated with increased risk of venous thromboembolism in patients with advanced pancreatic cancer. Ann Oncol 2022; 33: S341-S342
• 170 van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018; 19 (04) 213-228
• 171 Gardiner C, Harrison P, Belting M. et al. Extracellular vesicles, tissue factor, cancer and thrombosis - discussion themes of the ISEV 2014 Educational Day. J Extracell Vesicles 2015; 4 (04) 26901
• 172 Clancy JW, Zhang Y, Sheehan C, D'Souza-Schorey C. An ARF6-Exportin-5 axis delivers pre-miRNA cargo to tumour microvesicles. Nat Cell Biol 2019; 21 (07) 856-866
• 173 D'Souza-Schorey C, Clancy JW. Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes Dev 2012; 26 (12) 1287-1299
• 174 Zhu S, Li S, Yi M, Li N, Wu K. Roles of microvesicles in tumor progression and clinical applications. Int J Nanomedicine 2021; 16: 7071-7090
• 175 Beck S, Hochreiter B, Schmid JA. Extracellular vesicles linking inflammation, cancer and thrombotic risks. Front Cell Dev Biol 2022; 10: 859863
• 176 Davila M, Amirkhosravi A, Coll E. et al. Tissue factor-bearing microparticles derived from tumor cells: impact on coagulation activation. J Thromb Haemost 2008; 6 (09) 1517-1524
• 177 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 (11) 2065-2067
• 178 Bastida E, Ordinas A, Escolar G, Jamieson GA. Tissue factor in microvesicles shed from U87MG human glioblastoma cells induces coagulation, platelet aggregation, and thrombogenesis. Blood 1984; 64 (01) 177-184
• 179 Geddings JE, Hisada Y, Boulaftali Y. et al. Tissue factor-positive tumor microvesicles activate platelets and enhance thrombosis in mice. J Thromb Haemost 2016; 14 (01) 153-166
• 180 Grover SP, Mackman N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arterioscler Thromb Vasc Biol 2018; 38 (04) 709-725
• 181 Andersen H, Greenberg DL, Fujikawa K, Xu W, Chung DW, Davie EW. Protease-activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity. Proc Natl Acad Sci U S A 1999; 96 (20) 11189-11193
• 182 Nitori N, Ino Y, Nakanishi Y. et al. Prognostic significance of tissue factor in pancreatic ductal adenocarcinoma. Clin Cancer Res 2005; 11 (07) 2531-2539
• 183 Kakkar AK, Lemoine NR, Scully MF, Tebbutt S, Williamson RCN. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995; 82 (08) 1101-1104
• 184 Khorana AA, Ahrendt SA, Ryan CK. et al. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res 2007; 13 (10) 2870-2875
• 185 Hisada Y, Mackman N. Cancer cell-derived tissue factor-positive extracellular vesicles: biomarkers of thrombosis and survival. Curr Opin Hematol 2019; 26 (05) 349-356
• 186 Campello E, Zanetto A, Spiezia L. et al. Hypercoagulability detected by circulating microparticles in patients with hepatocellular carcinoma and cirrhosis. Thromb Res 2016; 143: 118-121
• 187 van Es N, Hisada Y, Di Nisio M. et al. Extracellular vesicles exposing tissue factor for the prediction of venous thromboembolism in patients with cancer: a prospective cohort study. Thromb Res 2018; 166: 54-59
• 188 Bharthuar A, Khorana AA, Hutson A. et al. Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers. Thromb Res 2013; 132 (02) 180-184
• 189 van Doormaal F, Kleinjan A, Berckmans RJ. et al. Coagulation activation and microparticle-associated coagulant activity in cancer patients. An exploratory prospective study. Thromb Haemost 2012; 108 (01) 160-165
• 190 Khorana AA, Francis CW, Menzies KE. et al. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost 2008; 6 (11) 1983-1985
• 191 Thaler J, Ay C, Mackman N. et al. Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients. J Thromb Haemost 2012; 10 (07) 1363-1370
• 192 Zwicker JI, Liebman HA, Neuberg D. et al. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 2009; 15 (22) 6830-6840
• 193 Ståhl AL, Johansson K, Mossberg M, Kahn R, Karpman D. Exosomes and microvesicles in normal physiology, pathophysiology, and renal diseases. Pediatr Nephrol 2019; 34 (01) 11-30
• 194 Woei-A-Jin FJSH, Tesselaar MET, Garcia Rodriguez P, Romijn FPHTM, Bertina RM, Osanto S. Tissue factor-bearing microparticles and CA19.9: two players in pancreatic cancer-associated thrombosis?. Br J Cancer 2016; 115 (03) 332-338
• 195 Longstaff C, Kolev K. Basic mechanisms and regulation of fibrinolysis. J Thromb Haemost 2015; 13 (Suppl. 01) S98-S105
• 196 Sillen M, Declerck PJ. A narrative review on plasminogen activator inhibitor-1 and its (patho)physiological role: to target or not to target?. Int J Mol Sci 2021; 22 (05) 1-16
• 197 Mahmood N, Rabbani SA. Fibrinolytic system and cancer: diagnostic and therapeutic applications. Int J Mol Sci 2021; 22 (09) 4358
• 198 Kwaan HC, Lindholm PF. Fibrin and fibrinolysis in cancer. Semin Thromb Hemost 2019; 45 (04) 413-422
• 199 Südhoff T, Schneider W. Fibrinolytic mechanisms in tumor growth and spreading. Clin Investig 1992; 70 (08) 631-636
• 200 Sawai H, Liu J, Reber HA, Hines OJ, Eibl G. Activation of peroxisome proliferator-activated receptor-γ decreases pancreatic cancer cell invasion through modulation of the plasminogen activator system. Mol Cancer Res 2006; 4 (03) 159-167
• 201 Hisada Y, Mackman N. Mechanisms of cancer-associated thrombosis. Res Pract Thromb Haemost 2023; 7 (03) 100123
• 202 Andrén-Sandberg A, Lecander I, Martinsson G, Åstedt B. Peaks in plasma plasminogen activator inhibitor-1 concentration may explain thrombotic events in cases of pancreatic carcinoma. Cancer 1992; 69 (12) 2884-2887
• 203 Hisada Y, Garratt KB, Maqsood A. et al. Plasminogen activator inhibitor 1 and venous thrombosis in pancreatic cancer. Blood Adv 2021; 5 (02) 487-495
• 204 Liu WJ, Zhou L, Liang ZY. et al. Plasminogen activator inhibitor 1 as a poor prognostic indicator in resectable pancreatic ductal adenocarcinoma. Chin Med J (Engl) 2018; 131 (24) 2947-2952
• 205 Scheer FAJL, Shea SA. Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle. Blood 2014; 123 (04) 590-593
• 206 Hildenbrand R, Niedergethmann M, Marx A. et al. Amplification of the urokinase-type plasminogen activator receptor (uPAR) gene in ductal pancreatic carcinomas identifies a clinically high-risk group. Am J Pathol 2009; 174 (06) 2246-2253
• 207 Smith R, Xue A, Gill A. et al. High expression of plasminogen activator inhibitor-2 (PAI-2) is a predictor of improved survival in patients with pancreatic adenocarcinoma. World J Surg 2007; 31 (03) 493-502 , discussion 503
• 208 de Geus SW, Baart VM, Boonstra MC. et al. prognostic impact of urokinase plasminogen activator receptor expression in pancreatic cancer: malignant versus stromal cells. Biomark Insights 2017; 12: 1177271917715443
• 209 Harris NLE, Vennin C, Conway JRW. et al; Australian Pancreatic Cancer Genome Initiative. SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene 2017; 36 (30) 4288-4298
• 210 Nielsen A, Scarlett CJ, Samra JS. et al. Significant overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma using real-time quantitative reverse transcription polymerase chain reaction. J Gastroenterol Hepatol 2005; 20 (02) 256-263
• 211 Díaz VM, Planagumà J, Thomson TM, Reventós J, Paciucci R. Tissue plasminogen activator is required for the growth, invasion, and angiogenesis of pancreatic tumor cells. Gastroenterology 2002; 122 (03) 806-819
• 212 Goldenberg N, Kahn SR, Solymoss S. Markers of coagulation and angiogenesis in cancer-associated venous thromboembolism. J Clin Oncol 2003; 21 (22) 4194-4199
• 213 Gi T, Yamashita A, Aman M. et al. Tissue factor expression and tumor-infiltrating T lymphocytes in ovarian carcinomas and their association with venous thromboembolism. Pathol Int 2021; 71 (04) 261-266
• 214 Mege D, Crescence L, Ouaissi M. et al. Fibrin-bearing microparticles: marker of thrombo-embolic events in pancreatic and colorectal cancers. Oncotarget 2017; 8 (57) 97394-97406