Circulating Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

Danielle Carole Roy; Tzu-Fei Wang; Ronda Lun; Amin Zahrai; Ranjeeta Mallick; Dylan Burger; Gabriele Zitikyte; Steven Hawken; Philip Wells

doi:10.1055/a-2330-1371

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2024; 124(12): 1117-1133
DOI: 10.1055/a-2330-1371

Stroke, Systemic or Venous Thromboembolism

Circulating Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

Danielle Carole Roy

¹Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada

,

Tzu-Fei Wang

¹Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada

²Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada

³The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

,

Ronda Lun

²Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada

³The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

⁴Vascular Neurology, Stanford Healthcare, Palo Alto, California, United States

,

Amin Zahrai

¹Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada

³The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

,

Ranjeeta Mallick

³The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

,

Dylan Burger

²Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada

³The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

,

Gabriele Zitikyte

⁵Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada

,

Steven Hawken^*

¹Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada

³The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

,

Philip Wells^*

¹Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada

²Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada

³The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

› Institutsangaben

Abstract

Background Cancer patients have an increased risk of venous thromboembolism (VTE). Currently, the availability of highly discriminatory prediction models for VTE in cancer patients is limited. The implementation of biomarkers in prediction models might lead to refined VTE risk prediction. In this systematic review and meta-analysis, we aimed to evaluate candidate biomarkers and their association with cancer-associated VTE.

Methods We searched Medline, EMBASE, and Cochrane Central for studies that evaluated biomarkers in adult cancer patients from inception to September 2022. We included studies reporting on VTE after a cancer diagnosis with biomarker measurements performed at a defined time point. Median/mean differences (for continuous measures) and odds ratios (for dichotomous measures) with 95% confidence intervals were estimated and pooled using random-effects models.

Results We included 113 studies in the systematic review. Of these, 50 studies were included in the meta-analysis. We identified two biomarkers at cancer diagnosis (factor VIII and time to peak thrombin), three biomarkers pre-chemotherapy (D-dimer, fibrinogen, and mean platelet volume), and one biomarker preoperatively (platelet count) that had significant median or mean differences. Additionally, we found that hemoglobin <100 g/L and white blood count >11 × 10⁹/L were significantly associated with future VTE risk only when measured at cancer diagnosis. Pre-chemotherapy neutrophil-to-lymphocyte ratio ≥3 and preoperative platelet count ≥400 × 10⁹/L were also found to be associated with future VTE risk.

Conclusion In conclusion, this study identified nine candidate blood biomarkers that may help in optimizing VTE prediction in cancer patients that should be further explored in future studies.

Keywords

venous thromboembolism - biomarkers - cancer - systematic review - meta-analysis

Volltext

Referenzen

References
1 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
2 Kyriazi V, Theodoulou E. Assessing the risk and prognosis of thrombotic complications in cancer patients. Arch Pathol Lab Med 2013; 137 (09) 1286-1295
3 Lyman GH, Culakova E, Poniewierski MS, Kuderer NM. Morbidity, mortality and costs associated with venous thromboembolism in hospitalized patients with cancer. Thromb Res 2018; 164 (Suppl. 01) S112-S118
4 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
5 Grosse SD, Nelson RE, Nyarko KA, Richardson LC, Raskob GE. The economic burden of incident venous thromboembolism in the United States: a review of estimated attributable healthcare costs. Thromb Res 2016; 137: 3-10
6 Arshad N, Bjøri E, Hindberg K, Isaksen T, Hansen JB, Braekkan SK. Recurrence and mortality after first venous thromboembolism in a large population-based cohort. J Thromb Haemost 2017; 15 (02) 295-303
7 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
8 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
9 Bosch FTM, Mulder FI, Kamphuisen PW. et al. Primary thromboprophylaxis in ambulatory cancer patients with a high Khorana score: a systematic review and meta-analysis. Blood Adv 2020; 4 (20) 5215-5225
10 Di Nisio M, Porreca E, Candeloro M, De Tursi M, Russi I, Rutjes AW. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev 2016; 12 (12) CD008500
11 Lyman GH, Carrier M, Ay C. et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 2021; 5 (04) 927-974
12 Farge D, Frere C, Connors JM. et al; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 2019; 20 (10) e566-e581
13 Streiff MB, Abutalib SA, Farge D, Murphy M, Connors JM, Piazza G. Update on guidelines for the management of cancer-associated thrombosis. Oncologist 2021; 26 (01) e24-e40
14 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
15 Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med 2012; 7 (03) 291-292
16 Pelzer U, Sinn M, Stieler J, Riess H. Primary pharmacological prevention of thromboembolic events in ambulatory patients with advanced pancreatic cancer treated with chemotherapy? [in German]. Dtsch Med Wochenschr 2013; 138 (41) 2084-2088
17 Cella CA, Di Minno G, Carlomagno C. et al. Preventing venous thromboembolism in ambulatory cancer patients: the ONKOTEV study. Oncologist 2017; 22 (05) 601-608
18 Pabinger I, van Es N, Heinze G. et al. A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts. Lancet Haematol 2018; 5 (07) e289-e298
19 van Es N, Di Nisio M, Cesarman G. et al. Comparison of risk prediction scores for venous thromboembolism in cancer patients: a prospective cohort study. Haematologica 2017; 102 (09) 1494-1501
20 Moik F, Englisch C, Pabinger I, Ay C. Risk assessment models of cancer-associated thrombosis - potentials and perspectives. Thromb Update 2021; 5: 100075
21 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
22 Kuderer NM, Poniewierski MS, Culakova E. et al. Predictors of venous thromboembolism and early mortality in lung cancer: results from a global prospective study (CANTARISK). Oncologist 2018; 23 (02) 247-255
23 Moher D, Shamseer L, Clarke M. et al; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4 (01) 1
24 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. PLoS Med 2021; 18 (03) e1003583
25 Definition of biomarker - NCI Dictionary of Cancer Terms - NCI. Published February 2, 2011. Accessed 1 March 2024 at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biomarker
26 McGrath S, Sohn H, Steele R, Benedetti A. Meta-analysis of the difference of medians. Biom J 2020; 62 (01) 69-98
27 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7 (03) 177-188
28 McGrath S, Sohn H, Steele R, Benedetti A. Two-sample aggregate data meta-analysis of medians. Biom J 2020; 62 (01) 69-98
29 Cai S, Zhou J, Pan J. Estimating the sample mean and standard deviation from order statistics and sample size in meta-analysis. Stat Methods Med Res 2021; 30 (12) 2701-2719
30 Granholm A, Alhazzani W, Møller MH. Use of the GRADE approach in systematic reviews and guidelines. Br J Anaesth 2019; 123 (05) 554-559
31 McGrath S, Zhao X, Katzenschlager S, Ozturk O, Steele R, Benedetti A. Metamedian: Meta-analysis of Medians. Published online 2023. Accessed 24 May 2024 at: https://CRAN.R-project.org/package=metamedian
32 Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health 2019; 22 (04) 153-160
33 Kaida S, Miyake T, Murata S. et al. A prospective multicenter observational study of venous thromboembolism after gastric cancer surgery (SHISA-1601). Eur Surg Res 2021; 62 (01) 10-17
34 Chen Y, Wang Y, Xie S. et al. A risk of venous thromboembolism algorithm as a predictor of venous thromboembolism in patients with colorectal cancer. Clin Appl Thromb Hemost 2021 ;27:10760296211064900
35 Norris LA, Ward MP, O'Toole SA. et al. A risk score for prediction of venous thromboembolism in gynecologic cancer: the Thrombogyn score. Res Pract Thromb Haemost 2020; 4 (05) 848-859
36 Li D, Pise MN, Overman MJ. et al. ABO non-O type as a risk factor for thrombosis in patients with pancreatic cancer. Cancer Med 2015; 4 (11) 1651-1658
37 Mandalà M, Barni S, Prins M. et al. Acquired and inherited risk factors for developing venous thromboembolism in cancer patients receiving adjuvant chemotherapy: a prospective trial. Ann Oncol 2010; 21 (04) 871-876
38 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
39 Tabernero J, Hozak RR, Yoshino T. et al. Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study. Ann Oncol 2018; 29 (03) 602-609
40 von Tempelhoff GF, Nieman F, Heilmann L, Hommel G. Association between blood rheology, thrombosis and cancer survival in patients with gynecologic malignancy. Clin Hemorheol Microcirc 2000; 22 (02) 107-130
41 Königsbrügge O, Posch F, Riedl J. et al. Association between decreased serum albumin with risk of venous thromboembolism and mortality in cancer patients. Oncologist 2016; 21 (02) 252-257
42 Moeini A, Machida H, Takiuchi T. et al. Association of nonalcoholic fatty liver disease and venous thromboembolism in women with endometrial cancer. Clin Appl Thromb Hemost 2017; 23 (08) 1018-1027
43 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
44 Almasi M, Sevcikova S, Slaby O. et al. Association study of selected genetic polymorphisms and occurrence of venous thromboembolism in patients with multiple myeloma who were treated with thalidomide. Clin Lymphoma Myeloma Leuk 2011; 11 (05) 414-420
45 Khorana AA, Barnard J, Wun T. et al. Biomarker signatures in cancer patients with and without venous thromboembolism events: a substudy of CASSINI. Blood Adv 2022; 6 (04) 1212-1221
46 Faille D, Bourrienne MC, de Raucourt E. et al. Biomarkers for the risk of thrombosis in pancreatic adenocarcinoma are related to cancer process. Oncotarget 2018; 9 (41) 26453-26465
47 Thaler J, Ay C, Kaider A. et al. Biomarkers predictive of venous thromboembolism in patients with newly diagnosed high-grade gliomas. Neuro-oncol 2014; 16 (12) 1645-1651
48 von Tempelhoff GF, Dietrich M, Niemann F, Schneider D, Hommel G, Heilmann L. Blood coagulation and thrombosis in patients with ovarian malignancy. Thromb Haemost 1997; 77 (03) 456-461
49 von Tempelhoff GF, Niemann F, Schneider DM, Kirkpatrick CJ, Hommel G, Heilmann L. Blood rheology during chemotherapy in patients with ovarian cancer. Thromb Res 1998; 90 (02) 73-82
50 López-Salazar J, Ramírez-Tirado LA, Gómez-Contreras N. et al. Cancer-associated prothrombotic pathways: leucocytosis, but not thrombocytosis, correlates with venous thromboembolism in women with ovarian cancer. Intern Med J 2020; 50 (03) 366-370
51 Liang H, Guo X, Li Y. Cervical cancer associated biomarkers of identify high risk of venous thrombosis. Clin Lab 2020; 66 (05) 771-777
52 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
53 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
54 Yang Y, Zhou Z, Niu XM. et al. Clinical analysis of postoperative venous thromboembolism risk factors in lung cancer patients. J Surg Oncol 2012; 106 (06) 736-741
55 Bagratuni T, Kastritis E, Politou M. et al. Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide-based regimens. Am J Hematol 2013; 88 (09) 765-770
56 Guadagni F, Riondino S, Formica V. et al. Clinical significance of glycemic parameters on venous thromboembolism risk prediction in gastrointestinal cancer. World J Gastroenterol 2017; 23 (28) 5187-5195
57 Gezelius E, Flou Kristensen A, Bendahl PO. et al. Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer: a sub-study of RASTEN - a randomized trial with low molecular weight heparin. PLoS One 2018; 13 (11) e0207387
58 Dranichnikov P, Mahteme H, Cashin PH, Graf W. Coagulopathy and venous thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 2021; 28 (12) 7772-7782
59 Cui LN, Li N, Fu S, Zhang X, Wang X, Wang RT. Combination of preoperative D-dimer and mean platelet volume predicts postoperative deep venous thrombosis in breast cancer patients. Cancer Biomark 2018; 21 (04) 909-913
60 Huang Y, Ding H, Luo M. et al. Combined analysis of clinical and laboratory markers to predict the risk of venous thromboembolism in patients with IDH1 wild-type glioblastoma. Support Care Cancer 2022; 30 (07) 6063-6069
61 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
62 Arpaia G, Carpenedo M, Verga M. et al. D-dimer before chemotherapy might predict venous thromboembolism. Blood Coagul Fibrinolysis 2009; 20 (03) 170-175
63 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
64 Riedl J, Kaider A, Marosi C. et al. Decreased platelet reactivity in patients with cancer is associated with high risk of venous thromboembolism and poor prognosis. Thromb Haemost 2017; 117 (01) 90-98
65 Li J, Yi J, Hua L. et al. Development and validation of a predictive score for venous thromboembolism in newly diagnosed non-small cell lung cancer. Thromb Res 2021; 208: 45-51
66 Li J, Qiang WM, Wang Y, Wang XY. Development and validation of a risk assessment nomogram for venous thromboembolism associated with hospitalized postoperative Chinese breast cancer patients. J Adv Nurs 2021; 77 (01) 473-483
67 Posch F, Riedl J, Reitter EM. et al. Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: a prospective study. J Thromb Haemost 2020; 18 (06) 1348-1356
68 Ferroni P, Martini F, Portarena I. et al. Early changes of a novel APC-dependent thrombin generation assay during chemotherapy independently predict venous thromboembolism in cancer patients–a pilot study. Support Care Cancer 2012; 20 (11) 2713-2720
69 Ay C, Posch F, Kaider A, Zielinski C, Pabinger I. Estimating risk of venous thromboembolism in patients with cancer in the presence of competing mortality. J Thromb Haemost 2015; 13 (03) 390-397
70 Jianlong M, Diansheng Z, Jing R. Estimation of venous thromboembolism risk with thrombotic biomarkers in cancer patients [in Chinese]. Zhonghua Zhong Liu Za Zhi 2015; 37 (04) 283-289
71 Schorling RM, Pfrepper C, Golombek T. et al. Evaluation of biomarkers for the prediction of venous thromboembolism in ambulatory cancer patients. Oncol Res Treat 2020; 43 (09) 414-427
72 Ferroni P, Guadagni F, Riondino S. et al. Evaluation of mean platelet volume as a predictive marker for cancer-associated venous thromboembolism during chemotherapy. Haematologica 2014; 99 (10) 1638-1644
73 Rupa-Matysek J, Lembicz M, Rogowska EK, Gil L, Komarnicki M, Batura-Gabryel H. Evaluation of risk factors and assessment models for predicting venous thromboembolism in lung cancer patients. Med Oncol 2018; 35 (05) 63
74 Wu X, Xue X, Tang J. et al. Evaluation of risk factors for venous thromboembolism in Chinese women with epithelial ovarian cancer. Int J Gynecol Cancer 2013; 23 (01) 65-72
75 Sanfilippo KM, Carson KR, Wang TF. et al. Evaluation of the Khorana score for prediction of venous thromboembolism in patients with multiple myeloma. Res Pract Thromb Haemost 2022; 6 (01) e12634
76 Rupa-Matysek J, Brzeźniakiewicz-Janus K, Gil L, Krasiński Z, Komarnicki M. Evaluation of the ThroLy score for the prediction of venous thromboembolism in newly diagnosed patients treated for lymphoid malignancies in clinical practice. Cancer Med 2018; 7 (07) 2868-2875
77 Posch F, Hofer S, Thaler J. et al. Ex vivo properties of plasma clot formation and lysis in patients with cancer at risk for venous thromboembolism, arterial thrombosis, and death. Transl Res 2020; 215: 41-56
78 Roy DC, Wang TF, Mallick R. et al. Growth differentiation factor-15, high-sensitivity cardiac troponin T, and N-terminal pro-B-type natriuretic peptide for predicting risk of venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Thromb Haemost 2022; 122 (07) 1169-1176
79 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
80 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
81 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
82 Posch F, Riedl J, Reitter EM. et al. Hypercoagulabilty, venous thromboembolism, and death in patients with cancer. A Multi-State Model. Thromb Haemost 2016; 115 (04) 817-826
83 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
84 Zhou Q, Zhu C, Shen Z. et al. Incidence and potential predictors of thromboembolic events in epithelial ovarian carcinoma patients during perioperative period. Eur J Surg Oncol 2020; 46 (05) 855-861
85 Park K, Ryoo BY, Ryu MH. et al. Incidence of venous thromboembolism and the role of D-dimer as predictive marker in patients with advanced gastric cancer receiving chemotherapy: a prospective study. World J Gastrointest Oncol 2017; 9 (04) 176-183
86 Shi S, Cheng J, Zhao Y, Chen W. Incidence, and preoperative and intraoperative prognostic factors of deep venous thrombosis in patients with glioma following craniotomy. Clin Neurol Neurosurg 2021; 210: 106998
87 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
88 Khan S, Kelly KJ, Veerapong J, Lowy AM, Baumgartner JM. Incidence, risk factors, and prevention strategies for venous thromboembolism after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 2019; 26 (07) 2276-2284
89 Reitter EM, Ay C, Kaider A. et al. Interleukin levels and their potential association with venous thromboembolism and survival in cancer patients. Clin Exp Immunol 2014; 177 (01) 253-260
90 Kirwan CC, McCollum CN, McDowell G, Byrne GJ. Investigation of proposed mechanisms of chemotherapy-induced venous thromboembolism: endothelial cell activation and procoagulant release due to apoptosis. Clin Appl Thromb Hemost 2015; 21 (05) 420-427
91 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
92 Fotiou D, Sergentanis TN, Papageorgiou L. et al. Longer procoagulant phospholipid-dependent clotting time, lower endogenous thrombin potential and higher tissue factor pathway inhibitor concentrations are associated with increased VTE occurrence in patients with newly diagnosed multiple myeloma: results of the prospective ROADMAP-MM-CAT study. Blood Cancer J 2018; 8 (11) 102
93 Mir Seyed Nazari P, Marosi C, Moik F. et al. Low systemic levels of chemokine C-C motif ligand 3 (CCL3) are associated with a high risk of venous thromboembolism in patients with glioma. Cancers (Basel) 2019; 11 (12) 2020
94 Streetly M, Hunt BJ, Parmar K, Jones R, Zeldis J, Schey S. Markers of endothelial and haemostatic function in the treatment of relapsed myeloma with the immunomodulatory agent Actimid (CC-4047) and their relationship with venous thrombosis. Eur J Haematol 2005; 74 (04) 293-296
95 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
96 Oto J, Plana E, Solmoirago MJ. et al. microRNAs and markers of neutrophil activation as predictors of early incidental post-surgical pulmonary embolism in patients with intracranial tumors. Cancers (Basel) 2020; 12 (06) 1536
97 Oto J, Navarro S, Larsen AC. et al. MicroRNAs and neutrophil activation markers predict venous thrombosis in pancreatic ductal adenocarcinoma and distal extrahepatic cholangiocarcinoma. Int J Mol Sci 2020; 21 (03) 840
98 Rojnuckarin P, Uaprasert N, Sriuranpong V. Monocyte count associated with subsequent symptomatic venous thromboembolism (VTE) in hospitalized patients with solid tumors. Thromb Res 2012; 130 (06) e279-e282
99 Muñoz Martín AJ, Ortega I, Font C. et al. Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer. Br J Cancer 2018; 118 (08) 1056-1061
100 Unruh D, Schwarze SR, Khoury L. et al. Mutant IDH1 and thrombosis in gliomas. Acta Neuropathol 2016; 132 (06) 917-930
101 Wang JK, Boorjian SA, Frank I. et al. Non-O blood type is associated with an increased risk of venous thromboembolism after radical cystectomy. Urology 2014; 83 (01) 140-145
102 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
103 Fuentes HE, Paz LH, Wang Y, Oramas DM, Simons CR, Tafur AJ. Performance of current thromboembolism risk assessment tools in patients with gastric cancer and validity after first treatment. Clin Appl Thromb Hemost 2018; 24 (05) 790-796
104 Wang Y, Attar BM, Fuentes HE, Yu J, Zhang H, Tafur AJ. Performance of Khorana risk score for prediction of venous thromboembolism in patients with hepatocellular carcinoma. Clin Appl Thromb Hemost 2018; 24 (03) 471-476
105 Conteduca V, Scarpi E, Wetterskog D. et al. Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration-resistant cancer patients. Int J Cancer 2022; 150 (07) 1166-1173
106 Merkow RP, Bilimoria KY, McCarter MD. et al. Post-discharge venous thromboembolism after cancer surgery: extending the case for extended prophylaxis. Ann Surg 2011; 254 (01) 131-137
107 Sonaglia F, Agnelli G, Baroni M, Severi P, Quintavalla R, D'Angelo SV. Pre-operative plasma levels of soluble fibrin polymers correlate with the development of deep vein thrombosis after elective neurosurgery. Blood Coagul Fibrinolysis 1999; 10 (08) 459-463
108 Zwicker JI, Liebman HA, Bauer KA. et al. 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 2013; 160 (04) 530-537
109 Ay C, Dunkler D, Simanek R. et al. Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2011; 29 (15) 2099-2103
110 Chalayer E, Talbot A, Frenzel L. et al. Prediction of venous thromboembolism in patients with multiple myeloma treated with lenalidomide, bortezomib, dexamethasone, and transplantation: lessons from the substudy of IFM/DFCI 2009 cohort. J Thromb Haemost 2022; 20 (08) 1859-1867
111 Roselli M, Ferroni P, Portarena I. et al. Predictive value of high-sensitive D-dimer determination for chemotherapy-associated venous thromboembolism in gastrointestinal cancer patients. Thromb Haemost 2012; 108 (06) 1243-1245
112 Mansfield AS, Tafur AJ, Wang CE, Kourelis TV, Wysokinska EM, Yang P. Predictors of active cancer thromboembolic outcomes: validation of the Khorana score among patients with lung cancer. J Thromb Haemost 2016; 14 (09) 1773-1778
113 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
114 Abu Saadeh F, Langhe R, Galvin DM. et al. Procoagulant activity in gynaecological cancer patients; the effect of surgery and chemotherapy. Thromb Res 2016; 139: 135-141
115 Casadei Gardini A, Carloni S, Scarpi E. et al. Prognostic role of serum concentrations of high-sensitivity C-reactive protein in patients with metastatic colorectal cancer: results from the ITACa trial. Oncotarget 2016; 7 (09) 10193-10202
116 Hoke M, Dieckmann K, Koppensteiner R, Schillinger M, Marosi C, Mlekusch W. Prognostic value of plasma d-dimer levels in patients with glioblastoma multiforme - results from a pilot study. Wien Klin Wochenschr 2011; 123 (7-8): 199-203
117 Syrigos K, Grapsa D, Sangare R. et al. Prospective assessment of clinical risk factors and biomarkers of hypercoagulability for the identification of patients with lung adenocarcinoma at risk for cancer-associated thrombosis: the observational ROADMAP-CAT study. Oncologist 2018; 23 (11) 1372-1381
118 Tafur AJ, Dale G, Cherry M. et al. Prospective evaluation of protein C and factor VIII in prediction of cancer-associated thrombosis. Thromb Res 2015; 136 (06) 1120-1125
119 Sinnamon AJ, Tong JKC, Bailey EA. et al. Prospective implementation of a standardized screening protocol for deep venous thrombosis in abdominal surgical oncology patients. J Surg Oncol 2018; 118 (03) 568-573
120 Lee E, Kang SB, Choi SI. et al. Prospective study on the incidence of postoperative venous thromboembolism in Korean patients with colorectal cancer. Cancer Res Treat 2016; 48 (03) 978-989
121 Dickmann B, Ahlbrecht J, Ay C. et al. Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study. Haematologica 2013; 98 (08) 1309-1314
122 Iversen LH, Thorlacius-Ussing O. Relationship of coagulation test abnormalities to tumour burden and postoperative DVT in resected colorectal cancer. Thromb Haemost 2002; 87 (03) 402-408
123 Kuk A, Magnowska M, Suchy W. et al. Retrospective evaluation of thromboembolism risk in ovarian cancer patients treated with bevacizumab. Target Oncol 2017; 12 (04) 495-503
124 Yu I, Chen L, Ruan JY, Chang JT, Cheung WY. Risk and management of venous thromboembolisms in bevacizumab-treated metastatic colorectal cancer patients. Support Care Cancer 2016; 24 (03) 1199-1208
125 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
126 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
127 Matsuo K, Ross MS, Im DD. et al. Significance of venous thromboembolism in women with uterine carcinosarcoma. Gynecol Oncol 2018; 148 (02) 267-274
128 Posch F, Thaler J, Zlabinger GJ. et al. Soluble vascular endothelial growth factor (sVEGF) and the risk of venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study (CATS). Clin Cancer Res 2016; 22 (01) 200-206
129 Cini M, Zamagni E, Valdré L. et al. Thalidomide-dexamethasone as up-front therapy for patients with newly diagnosed multiple myeloma: thrombophilic alterations, thrombotic complications, and thromboprophylaxis with low-dose warfarin. Eur J Haematol 2010; 84 (06) 484-492
130 Kovacs MJ, Davies GA, Chapman JAW. et al. Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY.10. Br J Haematol 2015; 168 (04) 511-517
131 Wang J, Hu B, Li T. et al. The EGFR-rearranged adenocarcinoma is associated with a high rate of venous thromboembolism. Ann Transl Med 2019; 7 (23) 724-724
132 Rink M, Riethdorf S, Yu H. et al. The impact of circulating tumor cells on venous thromboembolism and cardiovascular events in bladder cancer patients treated with radical cystectomy. J Clin Med 2020; 9 (11) 3478
133 Kusunoki M, Miyake K, Shindo T. et al. The incidence of deep vein thrombosis in Japanese patients undergoing endoscopic submucosal dissection. Gastrointest Endosc 2011; 74 (04) 798-804
134 Piketty AC, Fléchon A, Laplanche A. et al. The risk of thrombo-embolic events is increased in patients with germ-cell tumours and can be predicted by serum lactate dehydrogenase and body surface area. Br J Cancer 2005; 93 (08) 909-914
135 Albertin CL, Uppal S, Al-Niaimi AN, Seo S, Hinshaw JL, Hartenbach EM. Thrombocytosis is predictive of postoperative pulmonary embolism in patients with gynecologic cancer. Int J Gynecol Cancer 2015; 25 (06) 1096-1101
136 Von Tempelhoff GF, Heilmann L. Thrombosis and Hemorheology in Patients with Breast Cancer and Adjuvant Chemotherapy. Clin Hemorheol 1995; 15 (03) 311-323
137 Kanz R, Vukovich T, Vormittag R. et al. Thrombosis risk and survival in cancer patients with elevated C-reactive protein. J Thromb Haemost 2011; 9 (01) 57-63
138 Ahlbrecht J, Dickmann B, Ay C. et al. Tumor grade is associated with venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2012; 30 (31) 3870-3875
139 Kitayama H, Kondo T, Sugiyama J. et al. Venous thromboembolism in hospitalized patients receiving chemotherapy for malignancies at Japanese community hospital: prospective observational study. BMC Cancer 2017; 17 (01) 351
140 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
141 Matsuo K, Hasegawa K, Yoshino K. et al. Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma. Eur J Cancer 2015; 51 (14) 1978-1988
142 Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth 2014; 58 (05) 515-523
143 Mutlu H, Artış TA, Erden A, Akca Z. Alteration in mean platelet volume and platicrit values in patients with cancer that developed thrombosis. Clin Appl Thromb Hemost 2013; 19 (03) 331-333
144 Lippi G, Buonocore R, Cervellin G. The mean platelet volume is decreased in patients diagnosed with venous thromboembolism in the emergency department. Semin Thromb Hemost 2016; 42 (06) 632-635
145 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
146 Malaponte G, Signorelli SS, Bevelacqua V. et al. Increased levels of NF-kB-Dependent markers in cancer-associated deep venous thrombosis. PLoS One 2015; 10 (07) e0132496
147 Park MS, Spears GM, Bailey KR. et al. Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma: a prospective cohort study. J Trauma Acute Care Surg 2017; 83 (03) 381-387
148 Wang Z, Chen X, Wu J. et al. Low mean platelet volume is associated with deep vein thrombosis in older patients with hip fracture. Clin Appl Thromb Hemost 2022 ;28:10760296221078837
149 Hansen ES, Edvardsen MS, Aukrust P. et al. Combined effect of high factor VIII levels and high mean platelet volume on the risk of future incident venous thromboembolism. J Thromb Haemost 2023; 21 (10) 2844-2853
150 Evensen LH, Folsom AR, Pankow JS. et al. Hemostatic factors, inflammatory markers, and risk of incident venous thromboembolism: the Multi-Ethnic Study of Atherosclerosis. J Thromb Haemost 2021; 19 (07) 1718-1728
151 Koster T, Rosendaal FR, Reitsma PH, van der Velden PA, Briët E, Vandenbroucke JP. Factor VII and fibrinogen levels as risk factors for venous thrombosis. A case-control study of plasma levels and DNA polymorphisms–the Leiden Thrombophilia Study (LETS). Thromb Haemost 1994; 71 (06) 719-722
152 Ay C, Dunkler D, Marosi C. et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116 (24) 5377-5382
153 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
154 van Es N, Ventresca M, Di Nisio M. et al; IPDMA Heparin Use in Cancer Patients Research Group. The Khorana score for prediction of venous thromboembolism in cancer patients: an individual patient data meta-analysis. J Thromb Haemost 2020; 18 (08) 1940-1951
155 Naggara O, Raymond J, Guilbert F, Roy D, Weill A, Altman DG. Analysis by categorizing or dichotomizing continuous variables is inadvisable: an example from the natural history of unruptured aneurysms. AJNR Am J Neuroradiol 2011; 32 (03) 437-440
156 Eggemann H, Ehricke J, Ignatov T. et al. Platelet count after chemotherapy is a predictor for outcome for ovarian cancer patients. Cancer Invest 2015; 33 (05) 193-196
157 Nurgalieva Z, Liu CC, Du XL. Chemotherapy use and risk of bone marrow suppression in a large population-based cohort of older women with breast and ovarian cancer. Med Oncol 2011; 28 (03) 716-725
158 Săftescu S, Popovici D, Oprean C. et al. Endurance of erythrocyte series in chemotherapy. Exp Ther Med 2020; 20 (06) 214
159 Riva N, Donadini MP, Ageno W. Epidemiology and pathophysiology of venous thromboembolism: similarities with atherothrombosis and the role of inflammation. Thromb Haemost 2015; 113 (06) 1176-1183
160 Malte AL, Højbjerg JA, Larsen JB. Platelet parameters as biomarkers for thrombosis risk in cancer: a systematic review and meta-analysis. Semin Thromb Hemost 2024; 50 (03) 360-383
161 Ten Berg MJ, van den Bemt PMLA, Shantakumar S. et al. Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study. Drug Saf 2011; 34 (12) 1151-1160

Zusatzmaterial

Supplementary Material