Fibrin Clot Properties in Cancer: Impact on Cancer-Associated Thrombosis

 

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Abstract

Cancer is associated with a high risk of venous thromboembolism (VTE) and its recurrence. There is evidence that the prothrombotic fibrin clot phenotype, involving the formation of denser and stiffer clots relatively resistant to lysis, occurs in cancer patients, which is in part related to enhanced inflammation, oxidative stress, and coagulation activation, along with the release of neutrophil extracellular traps, indicating that fibrin-related mechanisms might contribute to cancer-associated thrombosis (CAT). Multiple myeloma and its therapy have been most widely explored in terms of altered fibrin characteristics, but prothrombotic fibrin clot features have also been reported in patients with active solid cancer, including lung cancer and gastrointestinal cancer. Patient-related factors such as advanced age, smoking, and comorbidities might also affect fibrin clot characteristics and the risk of CAT. Prothrombotic fibrin clot features have been shown to predict the detection of cancer in patients following VTE during follow-up. Cancer-specific therapies and anticoagulation can favorably modify the phenotype of a fibrin clot, which may alter the course of CAT. It is unclear whether the fibrin clot phenotype might help identify patients with CAT who are more likely to experience recurrent events. This narrative review summarizes the current knowledge on the role of fibrin clot structure and function in cancer patients in the context of CAT.

Author Contribution

M.Z. reviewed literature and drafted the manuscript and A.U. revised and edited the manuscript.

Data Availability

No new data were generated or analyzed in support of this research.

Publication History

Article published online:
23 June 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

• References

• 1 Repetto O, De Re V. Coagulation and fibrinolysis in gastric cancer. Ann N Y Acad Sci 2017; 1404 (01) 27-48
  CrossrefPubMedGoogle Scholar
• 2 Canonico ME, Santoro C, Avvedimento M. et al. Venous thromboembolism and cancer: a comprehensive review from pathophysiology to novel treatment. Biomolecules 2022; 12 (02) 259
  CrossrefPubMedGoogle Scholar
• 3 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
  CrossrefPubMedGoogle Scholar
• 4 Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood 2017; 130 (13) 1499-1506
  CrossrefPubMedGoogle Scholar
• 5 Kwaan HC, Lindholm PF. Fibrin and fibrinolysis in cancer. Semin Thromb Hemost 2019; 45 (04) 413-422
  Article in Thieme ConnectPubMedGoogle Scholar
• 6 Dunn EJ, Ariëns RA, de Lange M. et al. Genetics of fibrin clot structure: a twin study. Blood 2004; 103 (05) 1735-1740
  CrossrefPubMedGoogle Scholar
• 7 Ząbczyk M, Ariëns RAS, Undas A. Fibrin clot properties in cardiovascular disease: from basic mechanisms to clinical practice. Cardiovasc Res 2023; 119 (01) 94-111
  CrossrefPubMedGoogle Scholar
• 8 Liu X, Shi B. Progress in research on the role of fibrinogen in lung cancer. Open Life Sci 2020; 15 (01) 326-330
  CrossrefPubMedGoogle Scholar
• 9 Perisanidis C, Psyrri A, Cohen EE. et al. Prognostic role of pretreatment plasma fibrinogen in patients with solid tumors: a systematic review and meta-analysis. Cancer Treat Rev 2015; 41 (10) 960-970
  CrossrefPubMedGoogle Scholar
• 10 Litvinov RI, Pieters M, de Lange-Loots Z, Weisel JW. Fibrinogen and fibrin. Subcell Biochem 2021; 96: 471-501
  CrossrefPubMedGoogle Scholar
• 11 de Vries JJ, Snoek CJM, Rijken DC, de Maat MPM. Effects of post-translational modifications of fibrinogen on clot formation, clot structure, and fibrinolysis: a systematic review. Arterioscler Thromb Vasc Biol 2020; 40 (03) 554-569
  CrossrefPubMedGoogle Scholar
• 12 Pieters M, Philippou H, Undas A, de Lange Z, Rijken DC, Mutch NJ. Subcommittee on Factor XIII and Fibrinogen, and the Subcommittee on Fibrinolysis. An international study on the feasibility of a standardized combined plasma clot turbidity and lysis assay: communication from the SSC of the ISTH. J Thromb Haemost 2018; 16 (05) 1007-1012
  CrossrefPubMedGoogle Scholar
• 13 Pieters M, Undas A, Marchi R, De Maat MP, Weisel J, Ariëns RA. Factor XIII And Fibrinogen Subcommittee Of The Scientific Standardisation Committee Of The International Society For Thrombosis And Haemostasis. An international study on the standardization of fibrin clot permeability measurement: methodological considerations and implications for healthy control values. J Thromb Haemost 2012; 10 (10) 2179-2181
  CrossrefPubMedGoogle Scholar
• 14 Ząbczyk M, Stachowicz A, Natorska J, Olszanecki R, Wiśniewski JR, Undas A. Plasma fibrin clot proteomics in healthy subjects: relation to clot permeability and lysis time. J Proteomics 2019; 208: 103487
  CrossrefPubMedGoogle Scholar
• 15 Bryk AH, Natorska J, Ząbczyk M, Zettl K, Wiśniewski JR, Undas A. Plasma fibrin clot proteomics in patients with acute pulmonary embolism: association with clot properties. J Proteomics 2020; 229: 103946
  CrossrefPubMedGoogle Scholar
• 16 Kristinsson SY, Pfeiffer RM, Björkholm M. et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood 2010; 115 (24) 4991-4998
  CrossrefPubMedGoogle Scholar
• 17 Lyon AR, López-Fernández T, Couch LS. et al; ESC Scientific Document Group. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J 2022; 43 (41) 4229-4361
  CrossrefPubMedGoogle Scholar
• 18 Praga C, Jean G, Cortellaro M. [Anomaly of clot formation in a case of IgG myeloma. Influence of the isolated paraprotein on coagulation and ultrastructural study of the clot]. Nouv Rev Fr Hematol 1967; 7 (03) 353-366
  PubMedGoogle Scholar
• 19 Lackner H, Hunt V, Zucker MB, Pearson J. Abnormal fibrin ultrastructure, polymerization, and clot retraction in multiple myeloma. Br J Haematol 1970; 18 (06) 625-636
  CrossrefPubMedGoogle Scholar
• 20 Carr Jr ME, Zekert SL. Abnormal clot retraction, altered fibrin structure, and normal platelet function in multiple myeloma. Am J Physiol 1994; 266 (3 Pt 2): H1195-H1201
  PubMedGoogle Scholar
• 21 Carr Jr ME, Dent RM, Carr SL. Abnormal fibrin structure and inhibition of fibrinolysis in patients with multiple myeloma. J Lab Clin Med 1996; 128 (01) 83-88
  CrossrefPubMedGoogle Scholar
• 22 Kotlín R, Sobotková A, Riedel T. et al. Acquired dysfibrinogenemia secondary to multiple myeloma. Acta Haematol 2008; 120 (02) 75-81
  CrossrefPubMedGoogle Scholar
• 23 Undas A, Zubkiewicz-Usnarska L, Helbig G. et al. Altered plasma fibrin clot properties and fibrinolysis in patients with multiple myeloma. Eur J Clin Invest 2014; 44 (06) 557-566
  CrossrefPubMedGoogle Scholar
• 24 Undas A, Zubkiewicz-Usnarska L, Helbig G. et al. Induction therapy alters plasma fibrin clot properties in multiple myeloma patients: association with thromboembolic complications. Blood Coagul Fibrinolysis 2015; 26 (06) 621-627
  CrossrefPubMedGoogle Scholar
• 25 Arachchillage DR, Laffan M. Pathogenesis and management of thrombotic disease in myeloproliferative neoplasms. Semin Thromb Hemost 2019; 45 (06) 604-611
  Article in Thieme ConnectPubMedGoogle Scholar
• 26 Blann A, Caine G, Bareford D. Abnormal vascular, platelet and coagulation markers in primary thrombocythaemia are not reversed by treatments that reduce the platelet count. Platelets 2004; 15 (07) 447-449
  CrossrefPubMedGoogle Scholar
• 27 Tong D, Yu M, Guo L. et al. Phosphatidylserine-exposing blood and endothelial cells contribute to the hypercoagulable state in essential thrombocythemia patients. Ann Hematol 2018; 97 (04) 605-616
  CrossrefPubMedGoogle Scholar
• 28 Małecki R, Gacka M, Kuliszkiewicz-Janus M. et al. Altered plasma fibrin clot properties in essential thrombocythemia. Platelets 2016; 27 (02) 110-116
  PubMedGoogle Scholar
• 29 Morrissey JH, Smith SA. Polyphosphate as modulator of hemostasis, thrombosis, and inflammation. J Thromb Haemost 2015; 13 (01) S92-S97
  CrossrefPubMedGoogle Scholar
• 30 Amelot AA, Tagzirt M, Ducouret G, Kuen RL, Le Bonniec BF. Platelet factor 4 (CXCL4) seals blood clots by altering the structure of fibrin. J Biol Chem 2007; 282 (01) 710-720
  CrossrefPubMedGoogle Scholar
• 31 Pósán E, Ujj G, Kiss A, Telek B, Rák K, Udvardy M. Reduced in vitro clot lysis and release of more active platelet PAI-1 in polycythemia vera and essential thrombocythemia. Thromb Res 1998; 90 (02) 51-56
  CrossrefPubMedGoogle Scholar
• 32 Lim HY, Ng C, Rigano J. et al. An evaluation of global coagulation assays in myeloproliferative neoplasm. Blood Coagul Fibrinolysis 2018; 29 (03) 300-306
  CrossrefPubMedGoogle Scholar
• 33 Rusak T, Piszcz J, Misztal T, Brańska-Januszewska J, Tomasiak M. Platelet-related fibrinolysis resistance in patients suffering from PV. Impact of clot retraction and isovolemic erythrocytapheresis. Thromb Res 2014; 134 (01) 192-198
  CrossrefPubMedGoogle Scholar
• 34 Walker AJ, Baldwin DR, Card TR, Powell HA, Hubbard RB, Grainge MJ. Risk of venous thromboembolism in people with lung cancer: a cohort study using linked UK healthcare data. Br J Cancer 2016; 115 (01) 115-121
  CrossrefPubMedGoogle Scholar
• 35 Davies NA, Harrison NK, Morris RH. et al. Fractal dimension (df) as a new structural biomarker of clot microstructure in different stages of lung cancer. Thromb Haemost 2015; 114 (06) 1251-1259
  Article in Thieme ConnectPubMedGoogle Scholar
• 36 Piwkowski C, Gabryel P, Orłowski TM, Kowalewski J, Kużdżał J, Rzyman W. The impact of the COVID-19 pandemic on surgical treatment of lung cancer. Pol Arch Intern Med 2022; 132 (02) 16191
  PubMedGoogle Scholar
• 37 Ząbczyk M, Królczyk G, Czyżewicz G. et al. Altered fibrin clot properties in advanced lung cancer: strong impact of cigarette smoking. Med Oncol 2019; 36 (04) 37
  CrossrefPubMedGoogle Scholar
• 38 Winiarska A, Zareba L, Krolczyk G, Czyzewicz G, Zabczyk M, Undas A. Decreased levels of histidine-rich glycoprotein in advanced lung cancer: association with prothrombotic alterations. Dis Markers 2019; 2019: 8170759
  CrossrefPubMedGoogle Scholar
• 39 Królczyk G, Ząbczyk M, Czyżewicz G. et al. Altered fibrin clot properties in advanced lung cancer: impact of chemotherapy. J Thorac Dis 2018; 10 (12) 6863-6872
  CrossrefPubMedGoogle Scholar
• 40 Mulder MB, Proctor KG, Valle EJ, Livingstone AS, Nguyen DM, Van Haren RM. Hypercoagulability After Resection Of Thoracic Malignancy: A Prospective Evaluation. World J Surg 2019; 43 (12) 3232-3238
  CrossrefPubMedGoogle Scholar
• 41 Gronostaj K, Richter P, Nowak W, Undas A. Altered plasma fibrin clot properties in patients with digestive tract cancers: links with the increased thrombin generation. Thromb Res 2013; 131 (03) 262-267
  CrossrefPubMedGoogle Scholar
• 42 Thaler J, Koder S, Kornek G, Pabinger I, Ay C. Microparticle-associated tissue factor activity in patients with metastatic pancreatic cancer and its effect on fibrin clot formation. Transl Res 2014; 163 (02) 145-150
  CrossrefPubMedGoogle Scholar
• 43 Cools-Lartigue J, Spicer J, Najmeh S, Ferri L. Neutrophil extracellular traps in cancer progression. Cell Mol Life Sci 2014; 71 (21) 4179-4194
  CrossrefPubMedGoogle Scholar
• 44 Fuchs TA, Brill A, Duerschmied D. et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A 2010; 107 (36) 15880-15885
  CrossrefPubMedGoogle Scholar
• 45 Yang C, Sun W, Cui W. et al. Procoagulant role of neutrophil extracellular traps in patients with gastric cancer. Int J Clin Exp Pathol 2015; 8 (11) 14075-14086
  PubMedGoogle Scholar
• 46 Hoek M, Schultz M, Alummoottil S, Aneck-Hahn N, Mathabe K, Bester J. Ex vivo Vitamin D supplementation improves viscoelastic profiles in prostate cancer patients. Clin Hemorheol Microcirc 2022; 81 (03) 221-232
  CrossrefPubMedGoogle Scholar
• 47 Hell L, Däullary T, Burghart V. et al. Extracellular vesicle-associated tissue factor activity in prostate cancer patients with disseminated intravascular coagulation. Cancers (Basel) 2021; 13 (07) 1487
  CrossrefPubMedGoogle Scholar
• 48 Winther-Larsen A, Sandfeld-Paulsen B, Hvas AM. New insights in coagulation and fibrinolysis in patients with primary brain cancer: a systematic review. Semin Thromb Hemost 2022; 48 (03) 323-337
  Article in Thieme ConnectPubMedGoogle Scholar
• 49 Dombret H, Scrobohaci ML, Ghorra P. et al. Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. Leukemia 1993; 7 (01) 2-9
  PubMedGoogle Scholar
• 50 Paneesha S, McManus A, Arya R. et al; VERITY Investigators. Frequency, demographics and risk (according to tumour type or site) of cancer-associated thrombosis among patients seen at outpatient DVT clinics. Thromb Haemost 2010; 103 (02) 338-343
  Article in Thieme ConnectPubMedGoogle Scholar
• 51 Imberti D, Agnelli G, Ageno W. et al; MASTER Investigators. Clinical characteristics and management of cancer-associated acute venous thromboembolism: findings from the MASTER Registry. Haematologica 2008; 93 (02) 273-278
  CrossrefPubMedGoogle Scholar
• 52 Undas A, Brozek J, Jankowski M, Siudak Z, Szczeklik A, Jakubowski H. Plasma homocysteine affects fibrin clot permeability and resistance to lysis in human subjects. Arterioscler Thromb Vasc Biol 2006; 26 (06) 1397-1404
  CrossrefPubMedGoogle Scholar
• 53 Siudut J, Iwaniec T, Plens K, Pieters M, Undas A. Determinants of plasma fibrin clot lysis measured using three different assays in healthy subjects. Thromb Res 2021; 197: 1-7
  CrossrefPubMedGoogle Scholar
• 54 Swanepoel AC, de Lange-Loots Z, Cockeran M, Pieters M. Lifestyle influences changes in fibrin clot properties over a 10-year period on a population level. Thromb Haemost 2022; 122 (01) 67-79
  Article in Thieme ConnectPubMedGoogle Scholar
• 55 Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist 2010; 15 (06) 556-565
  CrossrefPubMedGoogle Scholar
• 56 Fatah K, Silveira A, Tornvall P, Karpe F, Blombäck M, Hamsten A. Proneness to formation of tight and rigid fibrin gel structures in men with myocardial infarction at a young age. Thromb Haemost 1996; 76 (04) 535-540
  Article in Thieme ConnectPubMedGoogle Scholar
• 57 Eksteen P, Pieters M, de Lange Z, Kruger HS. The association of clot lysis time with total obesity is partly independent from the association of PAI-1 with central obesity in African adults. Thromb Res 2015; 136 (02) 415-421
  CrossrefPubMedGoogle Scholar
• 58 Paulsen B, Gran OV, Severinsen MT. et al. Association of smoking and cancer with the risk of venous thromboembolism: the Scandinavian Thrombosis and Cancer cohort. Sci Rep 2021; 11 (01) 18752
  CrossrefPubMedGoogle Scholar
• 59 Undas A, Topór-Madry R, Tracz W, Pasowicz M. Effect of cigarette smoking on plasma fibrin clot permeability and susceptibility to lysis. Thromb Haemost 2009; 102 (06) 1289-1291
  PubMedGoogle Scholar
• 60 Barua RS, Sy F, Srikanth S. et al. Effects of cigarette smoke exposure on clot dynamics and fibrin structure: an ex vivo investigation. Arterioscler Thromb Vasc Biol 2010; 30 (01) 75-79
  CrossrefPubMedGoogle Scholar
• 61 Tavares V, Neto BV, Vilas-Boas MI, Pereira D, Medeiros R. Impact of hereditary thrombophilia on cancer-associated thrombosis, tumour susceptibility and progression: A review of existing evidence. Biochim Biophys Acta Rev Cancer 2022; 1877 (05) 188778
  CrossrefPubMedGoogle Scholar
• 62 Meltzer ME, Lisman T, Doggen CJ, de Groot PG, Rosendaal FR. Synergistic effects of hypofibrinolysis and genetic and acquired risk factors on the risk of a first venous thrombosis. PLoS Med 2008; 5 (05) e97
  CrossrefPubMedGoogle Scholar
• 63 Janion-Sadowska A, Natorska J, Siudut J, Ząbczyk M, Stanisz A, Undas A. Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban. Thromb Haemost 2017; 117 (09) 1739-1749
  Article in Thieme ConnectPubMedGoogle Scholar
• 64 Natorska J, Corral J, de la Morena-Barrio ME. et al. Antithrombin deficiency is associated with prothrombotic plasma fibrin clot phenotype. Thromb Haemost 2023; (e-pub ahead of print) DOI: 10.1055/s-0043-1768712.
  Article in Thieme ConnectPubMedGoogle Scholar
• 65 Larsen JB, Hvas AM. Fibrin clot properties in coronary artery disease: new determinants and prognostic markers. Pol Arch Intern Med 2021; 131 (11) 16113
  PubMedGoogle Scholar
• 66 Jaworska-Wilczyńska M, Natorska J, Siudut J. et al. Patients scheduled for TAVI tend to form abnormal fibrin clots more resistant to lysis: the impact of age. Kardiol Pol 2021; 79 (7-8): 796-803
  CrossrefPubMedGoogle Scholar
• 67 Undas A, Ariëns RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011; 31 (12) e88-e99
  CrossrefPubMedGoogle Scholar
• 68 Hess K, Alzahrani SH, Mathai M. et al. A novel mechanism for hypofibrinolysis in diabetes: the role of complement C3. Diabetologia 2012; 55 (04) 1103-1113
  CrossrefPubMedGoogle Scholar
• 69 Matusik PT, Leśniak WJ, Heleniak Z, Undas A. Thromboembolism and bleeding in patients with atrial fibrillation and stage 4 chronic kidney disease: impact of biomarkers. Kardiol Pol 2021; 79 (10) 1086-1092
  CrossrefPubMedGoogle Scholar
• 70 Sun LM, Chung WS, Lin CL, Liang JA, Kao CH. Unprovoked venous thromboembolism and subsequent cancer risk: a population-based cohort study. J Thromb Haemost 2016; 14 (03) 495-503
  CrossrefPubMedGoogle Scholar
• 71 Delluc A, Wang TF. How to treat incidental pulmonary embolism in cancer patients? Recent advances. Kardiol Pol 2021; 79 (12) 1305-1310
  CrossrefPubMedGoogle Scholar
• 72 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
  CrossrefPubMedGoogle Scholar
• 73 Cieslik J, Mrozinska S, Broniatowska E, Undas A. Altered plasma clot properties increase the risk of recurrent deep vein thrombosis: a cohort study. Blood 2018; 131 (07) 797-807
  CrossrefPubMedGoogle Scholar
• 74 Undas KW, Siudut J, Ząbczyk M. Unfavorably altered fibrin clot properties are associated with recurrent venous thromboembolism in patients following post–discharge events. Pol Arch Intern Med 2022; 132 (09) 16326
  PubMedGoogle Scholar
• 75 Mrozinska S, Cieslik J, Broniatowska E, Malinowski KP, Undas A. Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P-selectin predict occult cancer after unprovoked venous thromboembolism. J Thromb Haemost 2019; 17 (11) 1912-1922
  CrossrefPubMedGoogle Scholar
• 76 Mauracher LM, 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
  CrossrefPubMedGoogle Scholar
• 77 Iding AFJ, Ten Cate-Hoek AJ. How to optimize the prevention of post–thrombotic syndrome: recent advances. Pol Arch Intern Med 2022; 132 (7-8): 16288
  PubMedGoogle Scholar
• 78 Ilich A, Kumar V, Henderson M. et al. Biomarkers in cancer patients at risk for venous thromboembolism: data from the AVERT study. Thromb Res 2020; 191 (Suppl. 01) S31-S36
  CrossrefPubMedGoogle Scholar
• 79 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
  CrossrefPubMedGoogle Scholar
• 80 Key NS, Khorana AA, Kuderer NM. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol 2020; 38 (05) 496-520
  CrossrefPubMedGoogle Scholar
• 81 Meyer G, Marjanovic Z, Valcke J. et al. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med 2002; 162 (15) 1729-1735
  CrossrefPubMedGoogle Scholar
• 82 Lee AYY, Kamphuisen PW, Meyer G. et al; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA 2015; 314 (07) 677-686
  CrossrefPubMedGoogle Scholar
• 83 Ząbczyk M, Natorska J, Malinowski KP, Undas A. Effect of enoxaparin on plasma fibrin clot properties and fibrin structure in patients with acute pulmonary embolism. Vascul Pharmacol 2020; 133-134: 106783
  CrossrefPubMedGoogle Scholar
• 84 Baker SR, Halliday G, Ząbczyk M. et al. Plasma from patients with pulmonary embolism show aggregates that reduce after anticoagulation. Commun Med (Lond) 2023; 3 (01) 12
  CrossrefPubMedGoogle Scholar
• 85 Yeromonahos C, Marlu R, Polack B, Caton F. Antithrombin-independent effects of heparins on fibrin clot nanostructure. Arterioscler Thromb Vasc Biol 2012; 32 (05) 1320-1324
  CrossrefPubMedGoogle Scholar
• 86 Voigtlaender M, Beckmann L, Schulenkorf A. et al. Effect of myeloperoxidase on the anticoagulant activity of low molecular weight heparin and rivaroxaban in an in vitro tumor model. J Thromb Haemost 2020; 18 (12) 3267-3279
  CrossrefPubMedGoogle Scholar
• 87 Stevens SM, Woller SC, Kreuziger LB. et al. Antithrombotic therapy for VTE disease: second update of the CHEST Guideline and Expert Panel Report. Chest 2021; 160 (06) e545-e608
  CrossrefPubMedGoogle Scholar
• 88 Sabatino J, De Rosa S, Polimeni A, Sorrentino S, Indolfi C. Direct oral anticoagulants in patients with active cancer: a systematic review and meta-analysis. JACC Cardiooncol 2020; 2 (03) 428-440
  CrossrefPubMedGoogle Scholar
• 89 Akpan IJ, Cuker A. Laboratory assessment of the direct oral anticoagulants: who can benefit?. Kardiol Pol 2021; 79 (06) 622-630
  PubMedGoogle Scholar
• 90 Frączek P, Krzysztofik M, Stanisz A, Undas A. Clinical outcomes and plasma clot permeability and lysability in patients with venous thromboembolism on rivaroxaban: a cohort study. Pol Arch Intern Med 2019; 129 (06) 377-385
  PubMedGoogle Scholar
• 91 Ammollo CT, Semeraro F, Incampo F, Semeraro N, Colucci M. Dabigatran enhances clot susceptibility to fibrinolysis by mechanisms dependent on and independent of thrombin-activatable fibrinolysis inhibitor. J Thromb Haemost 2010; 8 (04) 790-798
  CrossrefPubMedGoogle Scholar
• 92 Blombäck M, He S, Bark N, Wallen HN, Elg M. Effects on fibrin network porosity of anticoagulants with different modes of action and reversal by activated coagulation factor concentrate. Br J Haematol 2011; 152 (06) 758-765
  CrossrefPubMedGoogle Scholar
• 93 Gauer JS, Riva N, Page EM. et al. Effect of anticoagulants on fibrin clot structure: a comparison between vitamin K antagonists and factor Xa inhibitors. Res Pract Thromb Haemost 2020; 4 (08) 1269-1281
  CrossrefPubMedGoogle Scholar
• 94 Varin R, Mirshahi S, Mirshahi P. et al. Improvement of thrombolysis by rivaroxaban, an anti Xa inhibitor. Potential therapeutic importance in patients with thrombosis. Blood 2008; 112: 3031
  CrossrefPubMedGoogle Scholar
• 95 Carter RLR, Talbot K, Hur WS. et al. Rivaroxaban and apixaban induce clotting factor Xa fibrinolytic activity. J Thromb Haemost 2018; 16 (11) 2276-2288
  CrossrefPubMedGoogle Scholar
• 96 Evans VJ, Lawrence M, Whitley J. et al. The treatment effect of rivaroxaban on clot characteristics in patients who present acutely with first time deep vein thrombosis. Clin Hemorheol Microcirc 2022; 80 (02) 139-151
  CrossrefPubMedGoogle Scholar