{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:46:34Z","timestamp":1785919594050,"version":"3.56.0"},"reference-count":119,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"1","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":157,"URL":"https:\/\/www.science.org\/content\/page\/science-licenses-journal-article-reuse"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL154150,"],"award-info":[{"award-number":["R01HL154150,"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R21HL16850"],"award-info":[{"award-number":["R21HL16850"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM163243"],"award-info":[{"award-number":["R01GM163243"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["406212"],"award-info":[{"award-number":["406212"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Comput Struct Biotechnol J"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>The interplay between inflammation and coagulation is a central driver of thrombotic risk across various diseases. While mathematical models of blood coagulation are well established, there remains a critical gap in quantitative frameworks that capture inflammation-induced hypercoagulability. In this study, we develop a mathematical model that explicitly simulates the interaction between pro-inflammatory cytokines and the coagulation cascade. The model incorporates key mechanisms, including: (a) up-regulation of tissue factor by interleukin-1\ud835\udefd, interleukin-6, and tumor necrosis factor-\u03b1; (b) suppression of natural anticoagulants, namely, antithrombin III and tissue factor pathway inhibitor, by interleukin-6 and tumor necrosis factor-\u03b1; and (c) feedback amplification of pro-inflammatory cytokines by thrombin. By encoding the bidirectional feedback between inflammatory and coagulation pathways, the model captures essential features of inflammation-driven hypercoagulability and enables systematic quantification of how variability in inflammatory extent and duration result in heterogeneous thrombin generation (TG) dynamics. To evaluate its effectiveness, we integrate the model with TG assays and apply it to virtual patient cohorts representing 4 clinically distinct conditions: COVID-19, sickle cell disease, type 2 diabetes mellitus and hemophilia A. Model simulations predict that disease-specific inflammatory environments induce distinct shifts in TG dynamics. In COVID-19 and type 2 diabetes mellitus, elevated cytokine levels lead to shortened lag times and increased thrombin peak, whereas in sickle cell disease, shortened lag times are accompanied by a reduced thrombin peak. These effects are strongly modulated by both cytokine concentration and duration of exposure. These results demonstrate that the proposed computational model augments conventional TG assays by mechanistically linking inflammatory signaling to disease-specific coagulation responses. Collectively, the proposed computational framework extends conventional TG assays by considering the interplay between inflammation and coagulation, thereby providing a mechanistic exploratory platform for generating testable hypotheses regarding disease-specific thromboinflammatory regulation. This framework lays a foundation to support future clinical prediction or individualized therapeutic decision-making after validation using prospective patient-level longitudinal datasets.<\/jats:p>","DOI":"10.34133\/csbj.0180","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T20:14:03Z","timestamp":1783541643000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Computational Modeling of Pro-inflammatory Cytokine-Enhanced Blood Coagulation"],"prefix":"10.34133","volume":"35","author":[{"given":"Geli","family":"Li","sequence":"first","affiliation":[{"name":"School of Chemical, Materials, and Biomedical Engineering, \rUniversity of Georgia, Athens, GA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, \rNanjing Medical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galit H.","family":"Frydman","sequence":"additional","affiliation":[{"name":"Division of Comparative Medicine, Department of Biological Engineering, \rMassachusetts Institute of Technology, Cambridge, MA, USA."},{"name":"Division of Trauma, Emergency Surgery, and Surgical Critical Care, Massachusetts General Hospital","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemical, Materials, and Biomedical Engineering, \rUniversity of Georgia, Athens, GA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"4","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/01.moh.0000130308.37353.d4","article-title":"The blood coagulation cascade","volume":"11","author":"Schenone M","year":"2004","unstructured":"Schenone M, Furie BC, Furie B. The blood coagulation cascade. Curr Opin Hematol. 2004;11(4):272\u2013277.","journal-title":"Curr Opin Hematol"},{"issue":"7","key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1542\/pir.34.7.289","article-title":"Hemophilia: In review","volume":"34","author":"Zimmerman B","year":"2013","unstructured":"Zimmerman B, Valentino LA. Hemophilia: In review. Pediatr Rev. 2013;34(7):289\u2013295.","journal-title":"Pediatr Rev"},{"issue":"23","key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1182\/blood.2020006000","article-title":"COVID-19 and its implications for thrombosis and anticoagulation","volume":"135","author":"Connors JM","year":"2020","unstructured":"Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033\u20132040.","journal-title":"Blood"},{"issue":"2","key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/ajh.22206","article-title":"Thrombin generation reveals high procoagulant potential in the plasma of sickle cell disease children","volume":"87","author":"Noubouossie DF","year":"2012","unstructured":"Noubouossie DF, L\u00ea PQ, Corazza F, Debaugnies F, Rozen L, Ferster A, Demulder A. Thrombin generation reveals high procoagulant potential in the plasma of sickle cell disease children. Am J Hematol. 2012;87(2):145\u2013149.","journal-title":"Am J Hematol"},{"issue":"2","key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3126\/ijasbt.v12i2.65863","article-title":"Examining the risk of clot formation in diabetes through computational analysis: An approach using mathematical modeling","volume":"12","author":"Singh A","year":"2024","unstructured":"Singh A, Arora K, Shah SR. Examining the risk of clot formation in diabetes through computational analysis: An approach using mathematical modeling. Int J Appl Sci Biotechnol. 2024;12(2):92\u201399.","journal-title":"Int J Appl Sci Biotechnol"},{"issue":"3","key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3126\/bibechana.v21i3.64973","article-title":"Computational analysis of clot formation risk in diabetes: A mathematical modeling approach","volume":"21","author":"Akbar S","year":"2024","unstructured":"Akbar S, Sharma RK, Sadique M, Jaiswal KM, Chaturvedi P, Kumar V, Shah SR. Computational analysis of clot formation risk in diabetes: A mathematical modeling approach. BIBECHANA. 2024;21(3):233\u2013240.","journal-title":"BIBECHANA"},{"issue":"1","key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00320240","article-title":"Clinical disorders of fibrinolysis: A critical review","volume":"59","author":"Francis RB","year":"1989","unstructured":"Francis RB Jr. Clinical disorders of fibrinolysis: A critical review. Blut. 1989;59(1):1\u201314.","journal-title":"Blut"},{"issue":"1","key":"e_1_3_4_9_2","first-page":"59","article-title":"Thrombophilia as a multigenic disease","volume":"84","author":"Zoller B","year":"1999","unstructured":"Zoller B, de Frutos PG, Hillarp AN, Dahlback B. Thrombophilia as a multigenic disease. Haematologica. 1999;84(1):59\u201370.","journal-title":"Haematologica"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00552-1"},{"issue":"2","key":"e_1_3_4_11_2","first-page":"34","article-title":"Does inflammation contribute to thrombotic events?","volume":"30","author":"Esmon CT","year":"2000","unstructured":"Esmon CT. Does inflammation contribute to thrombotic events? Haemostasis. 2000;30(2):34\u201340.","journal-title":"Haemostasis"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05753.x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181c98d21"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20220208"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.2147\/JIR.S504184","article-title":"The mechanisms of sepsis induced coagulation dysfunction and its treatment","volume":"18","author":"Zhu L","year":"2025","unstructured":"Zhu L, Dong H, Li L, Liu X. The mechanisms of sepsis induced coagulation dysfunction and its treatment. J Inflamm Res. 2025;18:1479\u20131495.","journal-title":"J Inflamm Res"},{"issue":"9","key":"e_1_3_4_16_2","first-page":"967","article-title":"Cytokines and hemostasis","volume":"85","author":"Grignani G","year":"2000","unstructured":"Grignani G, Maiolo A. Cytokines and hemostasis. Haematologica. 2000;85(9):967\u2013972.","journal-title":"Haematologica"},{"issue":"2","key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.vph.2014.05.005","article-title":"Regulation of tissue factor gene expression in monocytes and endothelial cells: Thromboxane A2 as a new player","volume":"62","author":"Bode M","year":"2014","unstructured":"Bode M, Mackman N. Regulation of tissue factor gene expression in monocytes and endothelial cells: Thromboxane A2 as a new player. Vascul Pharmacol. 2014;62(2):57\u201362.","journal-title":"Vascul Pharmacol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000131660.51520.9A"},{"issue":"3","key":"e_1_3_4_19_2","first-page":"254","article-title":"Inflammation, sepsis, and coagulation","volume":"84","author":"Esmon CT","year":"1999","unstructured":"Esmon CT, Fukudome K, Mather T, Bode W, Regan LM, Stearns-Kurosawa DJ, Kurosawa S. Inflammation, sepsis, and coagulation. Haematologica. 1999;84(3):254\u2013259.","journal-title":"Haematologica"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2021.734005","article-title":"Elevated plasma fibrinogen is associated with excessive inflammation and disease severity in COVID-19 patients","volume":"11","author":"Sui J","year":"2021","unstructured":"Sui J, Noubouossie DF, Gandotra S, Cao L. Elevated plasma fibrinogen is associated with excessive inflammation and disease severity in COVID-19 patients. Front Cell Infect Microbiol. 2021;11: Article 734005.","journal-title":"Front Cell Infect Microbiol"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2016.11.007"},{"issue":"11","key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1111\/jth.14578","article-title":"Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation","volume":"17","author":"Iba T","year":"2019","unstructured":"Iba T, Levy JH, Warkentin TE, Thachil J, van der Poll T, Levi M, Scientific and Standardization Committee on DIC, and the Scientific and Standardization Committee on Perioperative and Critical Care of the International Society on Thrombosis and Haemostasis. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019;17(11):1989\u20131994.","journal-title":"J Thromb Haemost"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/35025229"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3345"},{"issue":"3","key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.thromres.2011.10.010","article-title":"Platelet-leukocyte interactions in thrombosis","volume":"129","author":"Cerletti C","year":"2012","unstructured":"Cerletti C, Tamburrelli C, Izzi B, Gianfagna F, De Gaetano G. Platelet-leukocyte interactions in thrombosis. Thromb Res. 2012;129(3):263\u2013266.","journal-title":"Thromb Res"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12266"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-882993"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1TA1115-517RR"},{"issue":"4","key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1213\/ANE.0000000000006888","article-title":"Sepsis-induced coagulopathy: A comprehensive narrative review of pathophysiology, clinical presentation, diagnosis, and management strategies","volume":"138","author":"Williams B","year":"2024","unstructured":"Williams B, Zou L, Pittet J-F, Chao W. Sepsis-induced coagulopathy: A comprehensive narrative review of pathophysiology, clinical presentation, diagnosis, and management strategies. Anesth Analg. 2024;138(4):696\u2013711.","journal-title":"Anesth Analg"},{"issue":"2","key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3390\/life13020350","article-title":"Sepsis-induced coagulopathy: An update on pathophysiology, biomarkers, and current guidelines","volume":"13","author":"Tsantes AG","year":"2023","unstructured":"Tsantes AG, Parastatidou S, Tsantes EA, Bonova E, Tsante KA, Mantzios PG, Vaiopoulos AG, Tsalas S, Konstantinidi A, Houhoula D, et al. Sepsis-induced coagulopathy: An update on pathophysiology, biomarkers, and current guidelines. Life. 2023;13(2):350.","journal-title":"Life"},{"issue":"3","key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"918","DOI":"10.3390\/pharmaceutics15030918","article-title":"A review of quantitative systems pharmacology models of the coagulation cascade: Opportunities for improved usability","volume":"15","author":"Chung D","year":"2023","unstructured":"Chung D, Bakshi S, van der Graaf PH. A review of quantitative systems pharmacology models of the coagulation cascade: Opportunities for improved usability. Pharmaceutics. 2023;15(3):918.","journal-title":"Pharmaceutics"},{"issue":"12","key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"7707","DOI":"10.3934\/mbe.2024339","article-title":"Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review","volume":"21","author":"Al Bannoud M","year":"2024","unstructured":"Al Bannoud M, Martins TD, de Lima Montalv\u00e3o SA, Annichino-Bizzacchi JM, Maciel Filho R, Maciel MR. Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review. Math Biosci Eng. 2024;21(12):7707\u20137739.","journal-title":"Math Biosci Eng"},{"issue":"3","key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/S0006-3495(01)76085-7","article-title":"Surface-mediated control of blood coagulation: The role of binding site densities and platelet deposition","volume":"80","author":"Kuharsky AL","year":"2001","unstructured":"Kuharsky AL, Fogelson AL. Surface-mediated control of blood coagulation: The role of binding site densities and platelet deposition. Biophys J. 2001;80(3):1050\u20131074.","journal-title":"Biophys J"},{"issue":"2","key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000089930","article-title":"Coagulation under flow: The influence of flow-mediated transport on the initiation and inhibition of coagulation","volume":"34","author":"Fogelson AL","year":"2005","unstructured":"Fogelson AL, Tania N. Coagulation under flow: The influence of flow-mediated transport on the initiation and inhibition of coagulation. Pathophysiol Haemost Thromb. 2005;34(2\u20133):91\u2013108.","journal-title":"Pathophysiol Haemost Thromb"},{"issue":"1","key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/imammb\/20.1.105","article-title":"A mathematical model of lipid-mediated thrombin generation","volume":"20","author":"Bungay SD","year":"2003","unstructured":"Bungay SD, Gentry PA, Gentry RD. A mathematical model of lipid-mediated thrombin generation. Math Med Biol. 2003;20(1):105\u2013129.","journal-title":"Math Med Biol"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1642"},{"issue":"21","key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"18322","DOI":"10.1074\/jbc.M201173200","article-title":"A model for the stoichiometric regulation of blood coagulation","volume":"277","author":"Hockin MF","year":"2002","unstructured":"Hockin MF, Jones KC, Everse SJ, Mann KG. A model for the stoichiometric regulation of blood coagulation. J Biol Chem. 2002;277(21):18322\u201318333.","journal-title":"J Biol Chem"},{"issue":"19","key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"8744","DOI":"10.1073\/pnas.92.19.8744","article-title":"Mathematical analysis of activation thresholds in enzyme-catalyzed positive feedbacks: Application to the feedbacks of blood coagulation","volume":"92","author":"Beltrami E","year":"1995","unstructured":"Beltrami E, Jesty J. Mathematical analysis of activation thresholds in enzyme-catalyzed positive feedbacks: Application to the feedbacks of blood coagulation. Proc Natl Acad Sci USA. 1995;92(19):8744\u20138748.","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.10.011"},{"issue":"3","key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1080\/10255842.2022.2124858","article-title":"Computational modeling of hypercoagulability in COVID-19","volume":"26","author":"Zhu G","year":"2023","unstructured":"Zhu G, Modepalli S, Anand M, Li H. Computational modeling of hypercoagulability in COVID-19. Comput Methods Biomech Biomed Eng. 2023;26(3):338\u2013349.","journal-title":"Comput Methods Biomech Biomed Eng"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(96)00182-X"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.069062"},{"issue":"1","key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/imammb\/dqq005","article-title":"Grow with the flow: A spatial\u2013temporal model of platelet deposition and blood coagulation under flow","volume":"28","author":"Leiderman K","year":"2011","unstructured":"Leiderman K, Fogelson AL. Grow with the flow: A spatial\u2013temporal model of platelet deposition and blood coagulation under flow. Math Med Biol. 2011;28(1):47\u201384.","journal-title":"Math Med Biol"},{"issue":"8","key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1007\/s11538-012-9784-3","article-title":"The influence of hindered transport on the development of platelet thrombi under flow","volume":"75","author":"Leiderman K","year":"2013","unstructured":"Leiderman K, Fogelson AL. The influence of hindered transport on the development of platelet thrombi under flow. Bull Math Biol. 2013;75(8):1255\u20131283.","journal-title":"Bull Math Biol"},{"key":"e_1_3_4_45_2","unstructured":"Bouchnita A. Mathematical modelling of blood coagulation and thrombus formation under flow in normal and pathological conditions [thesis]. [Lyon (France)]: Universit\u00e9 de Lyon; 2017."},{"issue":"9","key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"873","DOI":"10.3390\/axioms12090873","article-title":"Thrombin generation thresholds for coagulation initiation under flow","volume":"12","author":"Bouchnita A","year":"2023","unstructured":"Bouchnita A, Yadav K, Llored J-P, Gurovich A, Volpert V. Thrombin generation thresholds for coagulation initiation under flow. Axioms. 2023;12(9):873.","journal-title":"Axioms"},{"issue":"7","key":"e_1_3_4_47_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0235392","article-title":"A mathematical model to quantify the effects of platelet count, shear rate, and injury size on the initiation of blood coagulation under venous flow conditions","volume":"15","author":"Bouchnita A","year":"2020","unstructured":"Bouchnita A, Terekhov K, Nony P, Vassilevski Y, Volpert V. A mathematical model to quantify the effects of platelet count, shear rate, and injury size on the initiation of blood coagulation under venous flow conditions. PLoS One. 2020;15(7): Article e0235392.","journal-title":"PLoS One"},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.compfluid.2019.03.021","article-title":"A multiscale model of platelet-fibrin thrombus growth in the flow","volume":"184","author":"Bouchnita A","year":"2019","unstructured":"Bouchnita A, Volpert V. A multiscale model of platelet-fibrin thrombus growth in the flow. Comput Fluids. 2019;184:10\u201320.","journal-title":"Comput Fluids"},{"issue":"1","key":"e_1_3_4_49_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005291","article-title":"A general shear-dependent model for thrombus formation","volume":"13","author":"Yazdani A","year":"2017","unstructured":"Yazdani A, Li H, Humphrey JD, Karniadakis GE. A general shear-dependent model for thrombus formation. PLoS Comput Biol. 2017;13(1): Article e1005291.","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1038\/s41598-018-20603-x","article-title":"Data-driven modeling of hemodynamics and its role on thrombus size and shape in aortic dissections","volume":"8","author":"Yazdani A","year":"2017","unstructured":"Yazdani A, Li H, Bersi MR, Achille PD, Insley J, Humphrey JD, Karniadakis GE. Data-driven modeling of hemodynamics and its role on thrombus size and shape in aortic dissections. Sci Rep. 2017;8(1):2515.","journal-title":"Sci Rep"},{"issue":"175","key":"e_1_3_4_51_2","doi-asserted-by":"crossref","first-page":"20200834","DOI":"10.1098\/rsif.2020.0834","article-title":"Integrating blood cell mechanics, platelet adhesive dynamics and coagulation cascade for modelling thrombus formation in normal and diabetic blood","volume":"18","author":"Yazdani A","year":"2021","unstructured":"Yazdani A, Deng Y, Li H, Javadi E, Li Z, Jamali S, Lin C, Humphrey JD, Mantzoros CS, Karniadakis GE. Integrating blood cell mechanics, platelet adhesive dynamics and coagulation cascade for modelling thrombus formation in normal and diabetic blood. J R Soc Interface. 2021;18(175):20200834.","journal-title":"J R Soc Interface"},{"issue":"3","key":"e_1_3_4_52_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1009892","article-title":"Multiphysics and multiscale modeling of microthrombosis in covid-19","volume":"18","author":"Li H","year":"2022","unstructured":"Li H, Deng Y, Li Z, Gallastegi AD, Mantzoros CS, Frydman GH, Karniadakis GE. Multiphysics and multiscale modeling of microthrombosis in covid-19. PLoS Comput Biol. 2022;18(3): Article e1009892.","journal-title":"PLoS Comput Biol"},{"issue":"14","key":"e_1_3_4_53_2","doi-asserted-by":"crossref","first-page":"8201","DOI":"10.3390\/app13148201","article-title":"Computational flow dynamic analysis in left atrial appendage thrombus formation risk: A review","volume":"13","author":"Valvez S","year":"2023","unstructured":"Valvez S, Oliveira-Santos M, Piedade AP, Gon\u00e7alves L, Amaro AM. Computational flow dynamic analysis in left atrial appendage thrombus formation risk: A review. Appl Sci. 2023;13(14):8201.","journal-title":"Appl Sci"},{"key":"e_1_3_4_54_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s10237-025-02039-1","article-title":"Sensitivity analysis of factors in a microfluidics CFD model of coagulation and cardiac applications","volume":"25","author":"Melidoro P","year":"2026","unstructured":"Melidoro P, Qureshi A, Williams SE, Lip GYH, Klis M, Aslanidi O, De Vecchi A. Sensitivity analysis of factors in a microfluidics CFD model of coagulation and cardiac applications. Biomech Model Mechanobiol. 2026;25:19.","journal-title":"Biomech Model Mechanobiol"},{"key":"e_1_3_4_55_2","article-title":"Digital twins for predictive modelling of thrombosis and stroke risk: Current approaches and future directions","author":"De Vecchi A","year":"2026","unstructured":"De Vecchi A, Camara O, Cavarra R, Del Alamo JC, El-Bouri W, Ferro A, Henry Horng-Shing L, Melidoro P, Ogbomo-Harmitt S, Olier I, et al. Digital twins for predictive modelling of thrombosis and stroke risk: Current approaches and future directions. Thromb Haemost. 2026; 10.1055\/a-2761-5903.","journal-title":"Thromb Haemost"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-025-03837-5"},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00521-026-12047-6","article-title":"Accelerating hybrid ANN\u2013ODE frameworks using surrogate machine learning and metaheuristic optimization for predicting recurrent venous thromboembolism","volume":"38","author":"Al Bannoud M","year":"2026","unstructured":"Al Bannoud M, Martins TD, de Lima Montalv\u00e3o SA, Annichino-Bizzacchi JM, Filho RM, Maciel MR. Accelerating hybrid ANN\u2013ODE frameworks using surrogate machine learning and metaheuristic optimization for predicting recurrent venous thromboembolism. Neural Comput Appl. 2026;38:285.","journal-title":"Neural Comput Appl"},{"issue":"15","key":"e_1_3_4_58_2","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1161\/01.CIR.101.15.1767","article-title":"Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men","volume":"101","author":"Ridker PM","year":"2000","unstructured":"Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101(15):1767\u20131772.","journal-title":"Circulation"},{"issue":"8","key":"e_1_3_4_59_2","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1002\/eji.1830190821","article-title":"Fate and biological action of human recombinant interleukin 1\ud835\udefd in the rat in\u00a0vivo","volume":"19","author":"Klapproth J","year":"1989","unstructured":"Klapproth J, Castell J, Geiger T, Andus T, Heinrich PC. Fate and biological action of human recombinant interleukin 1\ud835\udefd in the rat in\u00a0vivo. Eur J Immunol. 1989;19(8):1485\u20131490.","journal-title":"Eur J Immunol"},{"issue":"2","key":"e_1_3_4_60_2","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2337\/db11-0727","article-title":"Potential role of tumor necrosis factor-\u03b1 in downregulating sex hormone\u2013binding globulin","volume":"61","author":"Sim\u00f3 R","year":"2012","unstructured":"Sim\u00f3 R, Barbosa-Desongles A, Lecube A, Hernandez C, Selva DM. Potential role of tumor necrosis factor-\u03b1 in downregulating sex hormone\u2013binding globulin. Diabetes. 2012;61(2):372\u2013382.","journal-title":"Diabetes"},{"issue":"4","key":"e_1_3_4_61_2","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.tcm.2015.12.001","article-title":"Tissue factor as a link between inflammation and coagulation","volume":"26","author":"Witkowski M","year":"2016","unstructured":"Witkowski M, Landmesser U, Rauch U. Tissue factor as a link between inflammation and coagulation. Trends Cardiovasc Med. 2016;26(4):297\u2013303.","journal-title":"Trends Cardiovasc Med"},{"issue":"2","key":"e_1_3_4_62_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.abb.2005.06.005","article-title":"Tissue factor mediates inflammation","volume":"440","author":"Chu AJ","year":"2005","unstructured":"Chu AJ. Tissue factor mediates inflammation. Arch Biochem Biophys. 2005;440(2):123\u2013132.","journal-title":"Arch Biochem Biophys"},{"issue":"10","key":"e_1_3_4_63_2","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.4049\/jimmunol.160.10.5130","article-title":"Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation","volume":"160","author":"Johnson K","year":"1998","unstructured":"Johnson K, Choi Y, DeGroot E, Samuels I, Creasey A, Aarden L. Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation. J Immunol. 1998;160(10):5130\u20135135.","journal-title":"J Immunol"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03413.x"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1137\/22M1469067"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2008.04.011"},{"issue":"7","key":"e_1_3_4_67_2","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/mrd.22489","article-title":"The ImageJ ecosystem: An open platform for biomedical image analysis","volume":"82","author":"Schindelin J","year":"2015","unstructured":"Schindelin J, Rueden CT, Hiner MC, Eliceiri KW. The ImageJ ecosystem: An open platform for biomedical image analysis. Mol Reprod Dev. 2015;82(7\u20138):518\u2013529.","journal-title":"Mol Reprod Dev"},{"issue":"2","key":"e_1_3_4_68_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000527581","article-title":"Association between thrombin generation and clinical characteristics in covid-19 patients","volume":"146","author":"Cohen O","year":"2023","unstructured":"Cohen O, Landau N, Avisahai E, Brutman-Barazani T, Budnik I, Livnat T, Asraf K, Doolman R, Levy-Mendelovich S, Efros O, et al. Association between thrombin generation and clinical characteristics in covid-19 patients. Acta Haematol. 2023;146(2):151\u2013160.","journal-title":"Acta Haematol"},{"issue":"2","key":"e_1_3_4_69_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11239-010-0506-0","article-title":"Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay","volume":"31","author":"Tripodi A","year":"2011","unstructured":"Tripodi A, Branchi A, Chantarangkul V, Clerici M, Merati G, Artoni A, Mannucci PM. Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay. J Thromb Thrombolysis. 2011;31(2):165\u2013172.","journal-title":"J Thromb Thrombolysis"},{"issue":"4","key":"e_1_3_4_70_2","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1111\/bjh.13641","article-title":"Coagulation activation in sickle cell trait: An exploratory study","volume":"171","author":"Amin C","year":"2015","unstructured":"Amin C, Adam S, Mooberry MJ, Kutlar A, Kutlar F, Esserman D, Brittain JE, Ataga KI, Chang J-Y, Wolberg AS, et al. Coagulation activation in sickle cell trait: An exploratory study. Br J Haematol. 2015;171(4):638\u2013646.","journal-title":"Br J Haematol"},{"issue":"1","key":"e_1_3_4_71_2","doi-asserted-by":"crossref","first-page":"15572","DOI":"10.1038\/s41598-021-95066-8","article-title":"Tailoring the effect of antithrombin-targeting therapy in haemophilia A using in silico thrombin generation","volume":"11","author":"Laat-Kremers RMW","year":"2021","unstructured":"de Laat-Kremers RMW, Ninivaggi M, van Moort I, de Maat M, de Laat B. Tailoring the effect of antithrombin-targeting therapy in haemophilia A using in silico thrombin generation. Sci Rep. 2021;11(1):15572.","journal-title":"Sci Rep"},{"issue":"1","key":"e_1_3_4_72_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3390\/jcdd9010027","article-title":"Vitamin D inhibits IL-6 pro-atherothrombotic effects in human endothelial cells: A potential mechanism for protection against COVID-19 infection?","volume":"9","author":"Cimmino G","year":"2022","unstructured":"Cimmino G, Conte S, Morello M, Pellegrino G, Marra L, Morello A, Nicoletti G, De Rosa G, Golino P, Cirillo P. Vitamin D inhibits IL-6 pro-atherothrombotic effects in human endothelial cells: A potential mechanism for protection against COVID-19 infection? J Cardiovasc Dev Dis. 2022;9(1):27.","journal-title":"J Cardiovasc Dev Dis"},{"issue":"12","key":"e_1_3_4_73_2","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1161\/01.ATV.17.12.3399","article-title":"Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity","volume":"17","author":"Neumann F-J","year":"1997","unstructured":"Neumann F-J, Ott I, Marx N, Luther T, Kenngott S, Gawaz M, Kotzsch M, Sch\u00f6mig A. Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity. Arterioscler Thromb Vasc Biol. 1997;17(12):3399\u20133405.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"3","key":"e_1_3_4_74_2","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1055\/s-0038-1657691","article-title":"Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons","volume":"78","author":"Niessen RWLM","year":"1997","unstructured":"Niessen RWLM, Lamping RJ, Jansen PM, Prins MH, Peters M, Taylor FB Jr, De Vijlder JJM, Ten Cate JW, Hack CE, Sturk A. Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons. Thromb Haemost. 1997;78(3):1088\u20131092.","journal-title":"Thromb Haemost"},{"issue":"1","key":"e_1_3_4_75_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1479-5876-3-37","article-title":"Interleukin-1\ud835\udefd induced vascular permeability is dependent on induction of endothelial tissue factor (TF) activity","volume":"3","author":"Puhlmann M","year":"2005","unstructured":"Puhlmann M, Weinreich DM, Farma JM, Carroll NM, Turner EM, Alexander HR Jr. Interleukin-1\ud835\udefd induced vascular permeability is dependent on induction of endothelial tissue factor (TF) activity. J Transl Med. 2005;3(1):37.","journal-title":"J Transl Med"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11367"},{"key":"e_1_3_4_77_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.thromres.2021.07.002","article-title":"Differential procoagulatory response of microvascular, arterial and venous endothelial cells upon inflammation in\u00a0vitro","volume":"205","author":"Brandtner AK","year":"2021","unstructured":"Brandtner AK, Lehner GF, Pircher A, Feistritzer C, Joannidis M. Differential procoagulatory response of microvascular, arterial and venous endothelial cells upon inflammation in\u00a0vitro. Thromb Res. 2021;205:70\u201380.","journal-title":"Thromb Res"},{"issue":"6","key":"e_1_3_4_78_2","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/labinvest.3700550","article-title":"1,25(OH)2D3 blocks TNF-induced monocytic tissue factor expression by inhibition of transcription factors AP-1 and NF-\ud835\udf05B","volume":"87","author":"Chung J","year":"2007","unstructured":"Chung J, Koyama T, Ohsawa M, Shibamiya A, Hoshi A, Hirosawa S. 1,25(OH)2D3 blocks TNF-induced monocytic tissue factor expression by inhibition of transcription factors AP-1 and NF-\ud835\udf05B. Lab Invest. 2007;87(6):540\u2013547.","journal-title":"Lab Invest"},{"issue":"2","key":"e_1_3_4_79_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/aja.2008.12","article-title":"Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor pathway inhibitor downregulation via suppression of nuclear factor-kappa B in endothelial cells","volume":"11","author":"Jin H","year":"2009","unstructured":"Jin H, Qiu W-B, Mei Y-F, Wang D-M, Li Y-G, Tan X-R. Testosterone alleviates tumor necrosis factor-alpha-mediated tissue factor pathway inhibitor downregulation via suppression of nuclear factor-kappa B in endothelial cells. Asian J Androl. 2009;11(2):266\u2013271.","journal-title":"Asian J Androl"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1161\/hq1101.098489"},{"issue":"7","key":"e_1_3_4_81_2","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1182\/blood.V94.7.2169.419k22_2169_2178","article-title":"\u201cNormal\u201d thrombin generation","volume":"94","author":"Butenas S","year":"1999","unstructured":"Butenas S, van\u2019t Veer C, Mann KG. \u201cNormal\u201d thrombin generation. Blood. 1999;94(7):2169\u20132178.","journal-title":"Blood"},{"issue":"16","key":"e_1_3_4_82_2","doi-asserted-by":"crossref","first-page":"12563","DOI":"10.3390\/ijms241612563","article-title":"The crossroads of the coagulation system and the immune system: Interactions and connections","volume":"24","author":"Wilhelm G","year":"2023","unstructured":"Wilhelm G, Mertowska P, Mertowski S, Przysucha A, Stru\u017cyna J, Grywalska E, Torres K. The crossroads of the coagulation system and the immune system: Interactions and connections. Int J Mol Sci. 2023;24(16):12563.","journal-title":"Int J Mol Sci"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-024-05630-1"},{"issue":"7","key":"e_1_3_4_84_2","doi-asserted-by":"crossref","DOI":"10.1038\/cti.2016.39","article-title":"Platelets and coagulation in infection","volume":"5","author":"Davis RP","year":"2016","unstructured":"Davis RP, Miller-Dorey S, Jenne CN. Platelets and coagulation in infection. Clin Transl Immunol. 2016;5(7): Article e89.","journal-title":"Clin Transl Immunol"},{"issue":"5","key":"e_1_3_4_85_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1080\/10245330600841287","article-title":"Plasma levels of some blood coagulation parameters in Nigerian homozygous sickle cell patients (HbSS) in steady state","volume":"11","author":"Buseri FI","year":"2006","unstructured":"Buseri FI, Jeremiah ZA, Shokunbi WA. Plasma levels of some blood coagulation parameters in Nigerian homozygous sickle cell patients (HbSS) in steady state. Hematology. 2006;11(5\u20136):375\u2013379.","journal-title":"Hematology"},{"issue":"10","key":"e_1_3_4_86_2","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1111\/jth.13416","article-title":"Thrombin generation and cell-dependent hypercoagulability in sickle cell disease","volume":"14","author":"Whelihan MF","year":"2016","unstructured":"Whelihan MF, Lim MY, Mooberry MJ, Piegore MG, Ilich A, Wogu A, Cai J, Monroe DM, Ataga KI, Mann KG, et al. Thrombin generation and cell-dependent hypercoagulability in sickle cell disease. J Thromb Haemost. 2016;14(10):1941\u20131952.","journal-title":"J Thromb Haemost"},{"issue":"10","key":"e_1_3_4_87_2","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.3324\/haematol.2019.239350","article-title":"The molecular basis for the prothrombotic state in sickle cell disease","volume":"105","author":"Shet AS","year":"2020","unstructured":"Shet AS, Lizarralde-Iragorri MA, Naik RP. The molecular basis for the prothrombotic state in sickle cell disease. Haematologica. 2020;105(10):2368\u20132379.","journal-title":"Haematologica"},{"issue":"1","key":"e_1_3_4_88_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0014-5793(92)81139-D","article-title":"IL-4 inhibits LPS-, IL-1\ud835\udefd-and TNF\u03b1-induced expression of tissue factor in endothelial cells and monocytes","volume":"310","author":"Herbert JM","year":"1992","unstructured":"Herbert JM, Savi P, Laplace MC, Lale A. IL-4 inhibits LPS-, IL-1\ud835\udefd-and TNF\u03b1-induced expression of tissue factor in endothelial cells and monocytes. FEBS Lett. 1992;310(1):31\u201333.","journal-title":"FEBS Lett"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1160\/th14-02-0167"},{"issue":"405","key":"e_1_3_4_90_2","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aam5441","article-title":"Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy","volume":"9","author":"Schechter ME","year":"2017","unstructured":"Schechter ME, Andrade BB, He T, Richter GH, Tosh KW, Policicchio BB, Singh A, Raehtz KD, Sheikh V, Ma D, et al. Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy. Sci Transl Med. 2017;9(405): Article eaam5441.","journal-title":"Sci Transl Med"},{"issue":"2","key":"e_1_3_4_91_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.rpth.2023.100062","article-title":"In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype","volume":"7","author":"Verhagen MJA","year":"2023","unstructured":"Verhagen MJA, van Heerde WL, van der Bom JG, Beckers EAM, Blijlevens NMA, Coppens M, Gouw SC, Jansen JH, Leebeek FWG, van Vulpen LFD, et al. In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype. Res Pract Thromb Haemost. 2023;7(2): Article 100062.","journal-title":"Res Pract Thromb Haemost"},{"issue":"7","key":"e_1_3_4_92_2","doi-asserted-by":"crossref","DOI":"10.1002\/rth2.12611","article-title":"Global coagulation assays in patients with diabetes mellitus","volume":"5","author":"Lim HY","year":"2021","unstructured":"Lim HY, Lui B, Tacey M, Kwok A, Varadarajan S, Donnan G, Nandurkar H, Ho P. Global coagulation assays in patients with diabetes mellitus. Res Pract Thromb Haemost. 2021;5(7): Article e12611.","journal-title":"Res Pract Thromb Haemost"},{"key":"e_1_3_4_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00762-9"},{"issue":"23","key":"e_1_3_4_94_2","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1016\/j.jacc.2020.04.031","article-title":"COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review","volume":"75","author":"Bikdeli B","year":"2020","unstructured":"Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Der Nigoghossian C, Ageno W, Madjid M, Guo Y, et al. COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(23):2950\u20132973.","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"e_1_3_4_95_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12933-019-0870-9","article-title":"Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation","volume":"18","author":"Randeria SN","year":"2019","unstructured":"Randeria SN, Thomson GJA, Nell TA, Roberts T, Pretorius E. Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation. Cardiovasc Diabetol. 2019;18(1):72.","journal-title":"Cardiovasc Diabetol"},{"key":"e_1_3_4_96_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.thromres.2021.11.027","article-title":"Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19","volume":"209","author":"Willems LH","year":"2022","unstructured":"Willems LH, Nagy M, Ten Cate H, Spronk HMH, Groh LA, Leentjens J, Janssen NAF, Netea MG, Thijssen DHJ, Hannink G, et al. Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19. Thromb Res. 2022;209:106\u2013114.","journal-title":"Thromb Res"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2023.2288154"},{"issue":"10","key":"e_1_3_4_98_2","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.3324\/haematol.2019.239343","article-title":"Thromboinflammatory mechanisms in sickle cell disease\u2013challenging the hemostatic balance","volume":"105","author":"Conran N","year":"2020","unstructured":"Conran N, De Paula EV. Thromboinflammatory mechanisms in sickle cell disease\u2013challenging the hemostatic balance. Haematologica. 2020;105(10):2380.","journal-title":"Haematologica"},{"issue":"2","key":"e_1_3_4_99_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41569-018-0080-2","article-title":"Prevention of atherothrombotic events in patients with diabetes mellitus: From antithrombotic therapies to new-generation glucose-lowering drugs","volume":"16","author":"Patti G","year":"2019","unstructured":"Patti G, Cavallari I, Andreotti F, Calabro P, Cirillo P, Denas G, Galli M, Golia E, Maddaloni E, Marcucci R, et al. Prevention of atherothrombotic events in patients with diabetes mellitus: From antithrombotic therapies to new-generation glucose-lowering drugs. Nat Rev Cardiol. 2019;16(2):113\u2013130.","journal-title":"Nat Rev Cardiol"},{"issue":"3","key":"e_1_3_4_100_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.bvth.2025.100079","article-title":"Global coagulation assays for patients with diabetes and their utility in the prediction of atherothrombotic events","volume":"2","author":"Brook R","year":"2025","unstructured":"Brook R, Suleiman M, Lui B, Ajjan RA, Nandurkar H, Varadarajan S, Ho P, Lim HY. Global coagulation assays for patients with diabetes and their utility in the prediction of atherothrombotic events. Blood Vessel Thromb Hemost. 2025;2(3): Article 100079.","journal-title":"Blood Vessel Thromb Hemost"},{"issue":"1","key":"e_1_3_4_101_2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/hep.26027","article-title":"Interferon-\u03b3\u2013mediated tissue factor expression contributes to T-cell-mediated hepatitis through induction of hypercoagulation in mice","volume":"57","author":"Kato J","year":"2013","unstructured":"Kato J, Okamoto T, Motoyama H, Uchiyama R, Kirchhofer D, Van Rooijen N, Enomoto H, Nishiguchi S, Kawada N, Fujimoto J, et al. Interferon-\u03b3\u2013mediated tissue factor expression contributes to T-cell-mediated hepatitis through induction of hypercoagulation in mice. Hepatology. 2013;57(1):362\u2013372.","journal-title":"Hepatology"},{"key":"e_1_3_4_102_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02592.x"},{"issue":"1","key":"e_1_3_4_103_2","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/bjh.15020","article-title":"Interleukin-12 and its procoagulant effect on erythrocytes, platelets and fibrin(ogen): The lesser known side of inflammation","volume":"180","author":"Page MJ","year":"2018","unstructured":"Page MJ, Bester J, Pretorius E. Interleukin-12 and its procoagulant effect on erythrocytes, platelets and fibrin(ogen): The lesser known side of inflammation. Br J Haematol. 2018;180(1):110\u2013117.","journal-title":"Br J Haematol"},{"key":"e_1_3_4_104_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1051-9"},{"key":"e_1_3_4_105_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.09.029"},{"issue":"12","key":"e_1_3_4_106_2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1089\/jir.1995.15.1061","article-title":"Serum interleukin-6 levels in the steady state of sickle cell disease","volume":"15","author":"Taylor SC","year":"1995","unstructured":"Taylor SC, Shacks SJ, Mitchell RA, Banks A. Serum interleukin-6 levels in the steady state of sickle cell disease. J Interferon Cytokine Res. 1995;15(12):1061\u20131064.","journal-title":"J Interferon Cytokine Res"},{"issue":"4","key":"e_1_3_4_107_2","first-page":"172","article-title":"Levels of tumor necrosis factor \u03b1\/cachectin (TNF\u03b1) in sera from patients with sickle cell disease","volume":"90","author":"Malav\u00e9 I","year":"1993","unstructured":"Malav\u00e9 I, Perdomo Y, Escalona E, Rodriguez E, Anchustegui M, Malav\u00e9 H, Arends T. Levels of tumor necrosis factor \u03b1\/cachectin (TNF\u03b1) in sera from patients with sickle cell disease. Acta Haematol. 1993;90(4):172\u2013176.","journal-title":"Acta Haematol"},{"key":"e_1_3_4_108_2","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.954054","article-title":"Are IL-1 family cytokines important in management of sickle cell disease in Sub-Saharan Africa patients?","volume":"14","author":"Siransy LK","year":"2023","unstructured":"Siransy LK, Dasse RS, Adou H, Kouacou P, Kouamenan S, Sekongo Y, Yeboah R, Memel C, Assi-Sahoin A, Moussa SY, et al. Are IL-1 family cytokines important in management of sickle cell disease in Sub-Saharan Africa patients? Front Immunol. 2023;14: Article 954054.","journal-title":"Front Immunol"},{"issue":"3","key":"e_1_3_4_109_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s11239-020-02318-x","article-title":"COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis","volume":"51","author":"Fan BE","year":"2021","unstructured":"Fan BE, Ng J, Chan SSW, Christopher D, Tso ACY, Ling LM, Young BE, Wong LJL, Sum CLL, Tan HT, et al. COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis. J Thromb Thrombolysis. 2021;51(3):663\u2013674.","journal-title":"J Thromb Thrombolysis"},{"issue":"5","key":"e_1_3_4_110_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4103\/0019-5049.144643","article-title":"Overview of the coagulation system","volume":"58","author":"Palta S","year":"2014","unstructured":"Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth. 2014;58(5):515\u2013523.","journal-title":"Indian J Anaesth"},{"issue":"3","key":"e_1_3_4_111_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00282-996-0279-2","article-title":"Abnormalities of coagulation and fibrinolysis in homozygous sickle cell disease","volume":"38","author":"Nsiri B","year":"1996","unstructured":"Nsiri B, Gritli N, Bayoudh F, Messaoud T, Fattoum S, Machghoul S. Abnormalities of coagulation and fibrinolysis in homozygous sickle cell disease. Hematol Cell Ther. 1996;38(3):279\u2013284.","journal-title":"Hematol Cell Ther"},{"issue":"1","key":"e_1_3_4_112_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4103\/2078-7685.197527","article-title":"Tissue factor, tissue factor pathway inhibitor and factor VII activity in cardiovascular complicated type 2 diabetes mellitus","volume":"1","author":"El-Hagracy RS","year":"2010","unstructured":"El-Hagracy RS, Kamal GM, Sabry IM, Saad AA, Abou NF, Ezz E, Nasr HAR. Tissue factor, tissue factor pathway inhibitor and factor VII activity in cardiovascular complicated type 2 diabetes mellitus. J Diabetol. 2010;1(1):4.","journal-title":"J Diabetol"},{"issue":"9","key":"e_1_3_4_113_2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s40265-018-0922-6","article-title":"Inhibition of tissue factor pathway inhibitor (TFPI) as a treatment for haemophilia: Rationale with focus on concizumab","volume":"78","author":"Chowdary P","year":"2018","unstructured":"Chowdary P. Inhibition of tissue factor pathway inhibitor (TFPI) as a treatment for haemophilia: Rationale with focus on concizumab. Drugs. 2018;78(9):881\u2013890.","journal-title":"Drugs"},{"key":"e_1_3_4_114_2","unstructured":"Diapharma. Antithrombin (ATIII). 2024."},{"issue":"9","key":"e_1_3_4_115_2","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1055\/a-2071-0477","article-title":"Activation of the acute-phase response in hemophilia","volume":"123","author":"Knowles LM","year":"2023","unstructured":"Knowles LM, Wolter C, Menger MD, Laschke MW, Beyer L, Gr\u00fcn U, Eichler H, Pilch J. Activation of the acute-phase response in hemophilia. Thromb Haemost. 2023;123(9):867\u2013879.","journal-title":"Thromb Haemost"},{"key":"e_1_3_4_116_2","doi-asserted-by":"crossref","first-page":"1789886","DOI":"10.3389\/fmed.2026.1789886","article-title":"Establishment of reference intervals for plasma IL-6, IL-8, IL-10, and IL-1 beta in healthy adults from Lianyungang, Jiangsu, China: A single-center flow cytometry analysis","volume":"13","author":"Yang F","year":"2026","unstructured":"Yang F, Cao R, Yang F, Liu Q, Zhu W. Establishment of reference intervals for plasma IL-6, IL-8, IL-10, and IL-1 beta in healthy adults from Lianyungang, Jiangsu, China: A single-center flow cytometry analysis. Front Med. 2026;13:1789886.","journal-title":"Front Med"},{"issue":"1","key":"e_1_3_4_117_2","doi-asserted-by":"crossref","first-page":"6483490","DOI":"10.1155\/2021\/6483490","article-title":"Serum TNF-\u03b1 level as a possible predictor of inhibitor levels in severe hemophilia A","volume":"2021","author":"Susanah S","year":"2021","unstructured":"Susanah S, Raspati H, Sari NM, Rakhmilla LE, Sribudiani Y, Moestopo O, Sinaga P, Idjradinata P, Maskoen AM. Serum TNF-\u03b1 level as a possible predictor of inhibitor levels in severe hemophilia A. Biomed Res Int. 2021;2021(1):6483490.","journal-title":"Biomed Res Int"},{"key":"e_1_3_4_118_2","unstructured":"Mayo Clinic Laboratories. Cytokine panel plasma. Mayo Clinic Laboratories Test Catalog Test ID: CYPAN Unit Code: 610259. 2026. [accessed 11 Jun 2026] https:\/\/www.mayocliniclabs.com\/test-catalog\/Overview\/610259"},{"issue":"2","key":"e_1_3_4_119_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4103\/mamcjms.mamcjms_95_19","article-title":"A cross-sectional study evaluating inflammatory markers in hemophilia and association with chronic complications","volume":"6","author":"Aggarwal S","year":"2020","unstructured":"Aggarwal S, Kumar S, Gupta N, Garg S, Chakravarty A, Ish P, Dhar J. A cross-sectional study evaluating inflammatory markers in hemophilia and association with chronic complications. MAMC J Med Sci. 2020;6(2):107\u2013112.","journal-title":"MAMC J Med Sci"},{"issue":"6","key":"e_1_3_4_120_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/hae.14046","article-title":"WFH guidelines for the management of hemophilia","volume":"26","author":"Srivastava A","year":"2020","unstructured":"Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, Carcao M, Mahlangu J, Ragni MV, Windyga J, et al. WFH guidelines for the management of hemophilia. Haemophilia. 2020;26(Suppl 6):1\u2013158.","journal-title":"Haemophilia"}],"container-title":["Computational and Structural Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/csbj.0180","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/csbj.0180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:02:41Z","timestamp":1785916961000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.34133\/csbj.0180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,1]]},"references-count":119,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,3,1]]}},"alternative-id":["10.34133\/csbj.0180"],"URL":"https:\/\/doi.org\/10.34133\/csbj.0180","relation":{},"ISSN":["2001-0370"],"issn-type":[{"value":"2001-0370","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,1]]},"assertion":[{"value":"2026-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"0180"}}