RSS-Feed abonnieren
DOI: 10.1055/a-2605-8019
Neutrophil-Mediated Effects on Hemostasis and Thrombosis: Unraveling Their Complex Interaction in Thrombotic Events

Abstract
Neutrophils are astonishing cells involved in nonspecific immunity, especially against bacterial and fungal infections. Their half-life is short, but despite their important role in nonspecific immunity, they defend the host even after their death by providing secondary structures such as neutrophil extracellular traps (NETs). NETs are a network comprising DNA, histones, and proteins, including elastase, cathepsin G, and myeloperoxidase. In this context, in addition to their primary role in hemostasis, they also play a role in thrombosis, an area that has received less attention. Nonetheless, NETs can promote both venous and arterial thrombus formation (immuno-thrombosis), by their effects on primary and secondary hemostasis; their participation in thrombus formation includes the release of microparticles and components of the inflammasome. Neutrophils in interaction with other cells including platelets can further contribute to thrombosis. Activated platelets can capture neutrophil-derived microparticles containing tissue factor (TF), leading to TF accumulation and increased fibrin deposition. Furthermore, neutrophil inflammasomes as a regulator of the generation of IL-1 family proteins have been shown to augment thrombosis formation in response to hypoxia. Overall, understanding the complex and reciprocal effects of neutrophils with other hemostasis-related cells and components provides important insights into hemostatic mechanisms, and this may open avenues in medical research and potential therapeutic interventions.
Declaration of GenAI Use
During the writing process of this paper, the authors used Claude to assist with improving the readability of the text. The authors have reviewed and edited the text and take full responsibility for the content of the article.
Ethical Approval
The study was approved by the Ethics Committee at the Babol University of Medical Sciences (No. IR.MUBABOL.REC.1399.150) and does not contain any studies with human participants or animals performed by any of the authors.
Publikationsverlauf
Eingereicht: 02. März 2025
Angenommen: 11. Mai 2025
Artikel online veröffentlicht:
03. Juni 2025
© 2025. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Gordon S. Phagocytosis: the legacy of Metchnikoff. Cell 2016; 166 (05) 1065-1068
- 2 Ehrlich P, Himmelweit F. Histology, biochemistry and pathology. 1956
- 3 Cavaillon J-M. The historical milestones in the understanding of leukocyte biology initiated by Elie Metchnikoff. J Leukoc Biol 2011; 90 (03) 413-424
- 4 Kapoor S, Opneja A, Nayak L. The role of neutrophils in thrombosis. Thromb Res 2018; 170: 87-96
- 5 Brinkmann V, Reichard U, Goosmann C. et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303 (5663) 1532-1535
- 6 Iba T, Miki T, Hashiguchi N, Tabe Y, Nagaoka I. Is the neutrophil a 'prima donna'in the procoagulant process during sepsis?. Crit Care 2014; 18: 1-8
- 7 Darbousset R, Thomas GM, Mezouar S. et al. Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation. Blood 2012; 120 (10) 2133-2143
- 8 Pfeiler S, Stark K, Massberg S, Engelmann B. Propagation of thrombosis by neutrophils and extracellular nucleosome networks. Haematologica 2017; 102 (02) 206-213
- 9 Gross PL, Furie BC, Merrill-Skoloff G, Chou J, Furie B. Leukocyte-versus microparticle-mediated tissue factor transfer during arteriolar thrombus development. J Leukoc Biol 2005; 78 (06) 1318-1326
- 10 Vorobjeva NV, Chernyak BV. NETosis: molecular mechanisms, role in physiology and pathology. Biochemistry (Mosc) 2020; 85 (10) 1178-1190
- 11 Boon GD. An overview of hemostasis. Toxicol Pathol 1993; 21 (02) 170-179
- 12 McMichael M. Primary hemostasis. J Vet Emerg Crit Care (San Antonio) 2005; 15 (01) 1-8
- 13 Fekadu J, Modlich U, Bader P, Bakhtiar S. Understanding the role of LFA-1 in leukocyte adhesion deficiency type I (LAD I): moving towards inflammation?. Int J Mol Sci 2022; 23 (07) 3578
- 14 Yang L, Froio RM, Sciuto TE, Dvorak AM, Alon R, Luscinskas FW. ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-α-activated vascular endothelium under flow. Blood 2005; 106 (02) 584-592
- 15 Marcus AJ. Stratton lecture 1989. Thrombosis and inflammation as multicellular processes: pathophysiologic significance of transcellular metabolism. Blood 1990; 76 (10) 1903-1907
- 16 Heestermans M, Salloum-Asfar S, Salvatori D. et al. Role of platelets, neutrophils, and factor XII in spontaneous venous thrombosis in mice. Blood 2016; 127 (21) 2630-2637
- 17 Lisman T. Platelet-neutrophil interactions as drivers of inflammatory and thrombotic disease. Cell Tissue Res 2018; 371 (03) 567-576
- 18 Periayah MH, Halim AS, Mat Saad AZ. Mechanism action of platelets and crucial blood coagulation pathways in hemostasis. Int J Hematol Oncol Stem Cell Res 2017; 11 (04) 319-327
- 19 Lam FW, Vijayan KV, Rumbaut RE. Platelets and their interactions with other immune cells. Compr Physiol 2015; 5 (03) 1265-1280
- 20 Tomaiuolo M, Brass LF, Stalker TJ. Regulation of platelet activation and coagulation and its role in vascular injury and arterial thrombosis. Interv Cardiol Clin 2017; 6 (01) 1-12
- 21 Golebiewska EM, Poole AW. Platelet secretion: From haemostasis to wound healing and beyond. Blood Rev 2015; 29 (03) 153-162
- 22 Zarbock A, Polanowska-Grabowska RK, Ley K. Platelet-neutrophil-interactions: linking hemostasis and inflammation. Blood Rev 2007; 21 (02) 99-111
- 23 Kappelmayer J, Nagy Jr B. The interaction of selectins and PSGL-1 as a key component in thrombus formation and cancer progression. BioMed Res Int 2017; 2017 (01) 6138145
- 24 McEver RP. GMP-140: a receptor for neutrophils and monocytes on activated platelets and endothelium. J Cell Biochem 1991; 45 (02) 156-161
- 25 Bevilacqua MP, Stengelin S, Gimbrone Jr MA, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 1989; 243 (4895) 1160-1165
- 26 Chen J, Fu X, Wang Y. et al. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood 2010; 115 (03) 706-712
- 27 Pillai VG, Bao J, Zander CB. et al. Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP. Blood 2016; 128 (01) 110-119
- 28 Bonnefoy A, Legrand C. Proteolysis of subendothelial adhesive glycoproteins (fibronectin, thrombospondin, and von Willebrand factor) by plasmin, leukocyte cathepsin G, and elastase. Thromb Res 2000; 98 (04) 323-332
- 29 Raife TJ, Cao W, Atkinson BS. et al. Leukocyte proteases cleave von Willebrand factor at or near the ADAMTS13 cleavage site. Blood 2009; 114 (08) 1666-1674
- 30 Burstein SA. Cytokines, platelet production and hemostasis. Platelets 1997; 8 (2–3): 93-104
- 31 Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth 2014; 58 (05) 515-523
- 32 Gillis S, Furie BC, Furie B. Interactions of neutrophils and coagulation proteins. Semin Hematol 1997; 34 (04) 336-342
- 33 Naudin C, Burillo E, Blankenberg S, Butler L, Renné T. Factor XII contact activation. Semin Thromb Hemost 2017; 43 (08) 814-826
- 34 Varjú I, Kolev K. Networks that stop the flow: a fresh look at fibrin and neutrophil extracellular traps. Thromb Res 2019; 182: 1-11
- 35 Kirchhofer D, Riederer MA, Baumgartner HR. Specific accumulation of circulating monocytes and polymorphonuclear leukocytes on platelet thrombi in a vascular injury model. Blood 1997; 89 (04) 1270-1278
- 36 Mukhopadhyay S, Johnson TA, Duru N. et al. Fibrinolysis and inflammation in venous thrombus resolution. Front Immunol 2019; 10: 1348
- 37 Nosaka M, Ishida Y, Kimura A, Kondo T. Time-dependent appearance of intrathrombus neutrophils and macrophages in a stasis-induced deep vein thrombosis model and its application to thrombus age determination. Int J Legal Med 2009; 123 (03) 235-240
- 38 Selak MA, Chignard M, Smith JB. Cathepsin G is a strong platelet agonist released by neutrophils. Biochem J 1988; 251 (01) 293-299
- 39 Kornecki E, Ehrlich YH, Egbring R. et al. Granulocyte-platelet interactions and platelet fibrinogen receptor exposure. Am J Physiol 1988; 255 (3 Pt 2): H651-H658
- 40 Hagberg IA, Roald HE, Lyberg T. Adhesion of leukocytes to growing arterial thrombi. Thromb Haemost 1998; 80 (05) 852-858
- 41 Varma MR, Varga AJ, Knipp BS. et al. Neutropenia impairs venous thrombosis resolution in the rat. J Vasc Surg 2003; 38 (05) 1090-1098
- 42 Obi AT, Andraska E, Kanthi Y. et al. Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia. Thromb Haemost 2017; 117 (02) 339-348
- 43 Longstaff C, Kolev K. Basic mechanisms and regulation of fibrinolysis. J Thromb Haemost 2015; 13 (Suppl. 01) S98-S105
- 44 Marder VJ, Budzynski AZ. Degradation products of fibrinogen and crosslinked fibrin-projected clinical applications. Thromb Diath Haemorrh 1974; 32 (01) 49-56
- 45 Marder VJ, Budzynski AZ, Barlow GH. Comparison of the physicochemical properties of fragment D derivatives of fibrinogen and fragment D-D of cross-linked fibrin. Biochim Biophys Acta 1976; 427 (01) 1-14
- 46 Machovich R, Owen WG. The elastase-mediated pathway of fibrinolysis. Blood Coagul Fibrinolysis 1990; 1 (01) 79-90
- 47 Xue Y, Bodin C, Olsson K. Crystal structure of the native plasminogen reveals an activation-resistant compact conformation. J Thromb Haemost 2012; 10 (07) 1385-1396
- 48 Beatty K, Bieth J, Travis J. Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin. J Biol Chem 1980; 255 (09) 3931-3934
- 49 Reibetanz U, Schönberg M, Rathmann S, Strehlow V, Göse M, Leßig J. Inhibition of human neutrophil elastase by α1-antitrypsin functionalized colloidal microcarriers. ACS Nano 2012; 6 (07) 6325-6336
- 50 Owen CA, Campbell MA, Sannes PL, Boukedes SS, Campbell EJ. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. J Cell Biol 1995; 131 (03) 775-789
- 51 Cruz DBD, Helms J, Aquino LR. et al. DNA-bound elastase of neutrophil extracellular traps degrades plasminogen, reduces plasmin formation, and decreases fibrinolysis: proof of concept in septic shock plasma. FASEB J 2019; 33 (12) 14270-14280
- 52 Ryan TJ, Lai L, Malik AB. Plasmin generation induces neutrophil aggregation: dependence on the catalytic and lysine binding sites. J Cell Physiol 1992; 151 (02) 255-261
- 53 Montrucchio G, Lupia E, De Martino A. et al. Plasmin promotes an endothelium-dependent adhesion of neutrophils. Involvement of platelet activating factor and P-selectin. Circulation 1996; 93 (12) 2152-2160
- 54 Syrovets T, Simmet T. Novel aspects and new roles for the serine protease plasmin. Cell Mol Life Sci 2004; 61 (7-8): 873-885
- 55 D'Alessio S, Blasi F. The urokinase receptor as an entertainer of signal transduction. Front Biosci (Landmark Ed) 2009; 14 (12) 4575-4587
- 56 Collen D, Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78 (12) 3114-3124
- 57 Blasi F. Urokinase and urokinase receptor: a paracrine/autocrine system regulating cell migration and invasiveness. BioEssays 1993; 15 (02) 105-111
- 58 Pluskota E, Soloviev DA, Bdeir K, Cines DB, Plow EF. Integrin alphaMbeta2 orchestrates and accelerates plasminogen activation and fibrinolysis by neutrophils. J Biol Chem 2004; 279 (17) 18063-18072
- 59 Moir E, Robbie LA, Bennett B, Booth NA. Polymorphonuclear leucocytes have two opposing roles in fibrinolysis. Thromb Haemost 2002; 87 (06) 1006-1010
- 60 Plesner T, Ploug M, Ellis V. et al. The receptor for urokinase-type plasminogen activator and urokinase is translocated from two distinct intracellular compartments to the plasma membrane on stimulation of human neutrophils. Blood 1994; 83 (03) 808-815
- 61 Heiple JM, Ossowski L. Human neutrophil plasminogen activator is localized in specific granules and is translocated to the cell surface by exocytosis. J Exp Med 1986; 164 (03) 826-840
- 62 Ploug M, Plesner T, Rønne E. et al. The receptor for urokinase-type plasminogen activator is deficient on peripheral blood leukocytes in patients with paroxysmal nocturnal hemoglobinuria. Blood 1992; 79 (06) 1447-1455
- 63 Gyetko MR, Sud S, Chen G-H, Fuller JA, Chensue SW, Toews GB. Urokinase-type plasminogen activator is required for the generation of a type 1 immune response to pulmonary Cryptococcus neoformans infection. J Immunol 2002; 168 (02) 801-809
- 64 Grøndahl-Hansen J, Kirkeby LT, Ralfkiaer E, Kristensen P, Lund LR, Danø K. Urokinase-type plasminogen activator in endothelial cells during acute inflammation of the appendix. Am J Pathol 1989; 135 (04) 631-636
- 65 Lacroix R, Plawinski L, Robert S. et al. Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis. Haematologica 2012; 97 (12) 1864-1872
- 66 Helms J, Clere-Jehl R, Bianchini E. et al. Thrombomodulin favors leukocyte microvesicle fibrinolytic activity, reduces NETosis and prevents septic shock-induced coagulopathy in rats. Ann Intensive Care 2017; 7 (01) 118
- 67 Abraham E, Gyetko MR, Kuhn K. et al. Urokinase-type plasminogen activator potentiates lipopolysaccharide-induced neutrophil activation. J Immunol 2003; 170 (11) 5644-5651
- 68 Cao D, Mizukami IF, Garni-Wagner BA. et al. Human urokinase-type plasminogen activator primes neutrophils for superoxide anion release. Possible roles of complement receptor type 3 and calcium. J Immunol 1995; 154 (04) 1817-1829
- 69 Boyle MD, Chiodo VA, Lawman MJ, Gee AP, Young M. Urokinase: a chemotactic factor for polymorphonuclear leukocytes in vivo. J Immunol 1987; 139 (01) 169-174
- 70 Odekon LE, Gilboa N, Del Vecchio P, Gudewicz PW. Urokinase in conditioned medium from phorbol ester-pretreated endothelial cells promotes polymorphonuclear leukocyte migration. Circ Shock 1992; 37 (02) 169-175
- 71 Gyetko MR, Sitrin RG, Fuller JA, Todd III RF, Petty H, Standiford TJ. Function of the urokinase receptor (CD87) in neutrophil chemotaxis. J Leukoc Biol 1995; 58 (05) 533-538
- 72 May AE, Kanse SM, Lund LR, Gisler RH, Imhof BA, Preissner KT. Urokinase receptor (CD87) regulates leukocyte recruitment via β 2 integrins in vivo. J Exp Med 1998; 188 (06) 1029-1037
- 73 Mondino A, Blasi F. uPA and uPAR in fibrinolysis, immunity and pathology. Trends Immunol 2004; 25 (08) 450-455
- 74 Gyetko MR, Chen GH, McDonald RA. et al. Urokinase is required for the pulmonary inflammatory response to Cryptococcus neoformans. A murine transgenic model. J Clin Invest 1996; 97 (08) 1818-1826
- 75 Gyetko MR, Sud S, Kendall T, Fuller JA, Newstead MW, Standiford TJ. Urokinase receptor-deficient mice have impaired neutrophil recruitment in response to pulmonary Pseudomonas aeruginosa infection. J Immunol 2000; 165 (03) 1513-1519
- 76 Blasi F. uPA, uPAR, PAI-1: key intersection of proteolytic, adhesive and chemotactic highways?. Immunol Today 1997; 18 (09) 415-417
- 77 Vaday GG, Lider O. Extracellular matrix moieties, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol 2000; 67 (02) 149-159
- 78 Plesner T, Behrendt N, Ploug M. Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR. Stem Cells 1997; 15 (06) 398-408
- 79 Ouk T, Potey C, Maestrini I. et al. Neutrophils in tPA-induced hemorrhagic transformations: main culprit, accomplice or innocent bystander?. Pharmacol Ther 2019; 194: 73-83
- 80 Roever L, Levine SR. Cerebral hemorrhage following thrombolytic therapy for stroke: are neutrophils really neutral?. Neurology 2015; 85 (16) 1360-1361
- 81 del Zoppo GJ. Inflammation and the neurovascular unit in the setting of focal cerebral ischemia. Neuroscience 2009; 158 (03) 972-982
- 82 Uhl B, Zuchtriegel G, Puhr-Westerheide D. et al. Tissue plasminogen activator promotes postischemic neutrophil recruitment via its proteolytic and nonproteolytic properties. Arterioscler Thromb Vasc Biol 2014; 34 (07) 1495-1504
- 83 Carbone F, Vuilleumier N, Bertolotto M. et al. Treatment with recombinant tissue plasminogen activator (r-TPA) induces neutrophil degranulation in vitro via defined pathways. Vascul Pharmacol 2015; 64: 16-27
- 84 Lenglet S, Montecucco F, Mach F, Schaller K, Gasche Y, Copin JC. Analysis of the expression of nine secreted matrix metalloproteinases and their endogenous inhibitors in the brain of mice subjected to ischaemic stroke. Thromb Haemost 2014; 112 (02) 363-378
- 85 Rijken DC, Lijnen HR. New insights into the molecular mechanisms of the fibrinolytic system. J Thromb Haemost 2009; 7 (01) 4-13
- 86 Wu K, Urano T, Ihara H. et al. The cleavage and inactivation of plasminogen activator inhibitor type 1 by neutrophil elastase: the evaluation of its physiologic relevance in fibrinolysis. Blood 1995; 86 (03) 1056-1061
- 87 Brower MS, Harpel PC. Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase. J Biol Chem 1982; 257 (16) 9849-9854
- 88 Gramse M, Egbring R, Havemann K. Alpha 2-plasmin inhibitor inactivation by human granulocyte elastase. Hoppe Seylers Z Physiol Chem 1984; 365 (01) 19-26
- 89 Marshall LJ, Ramdin LS, Brooks T, DPhil PC, Shute JK. Plasminogen activator inhibitor-1 supports IL-8-mediated neutrophil transendothelial migration by inhibition of the constitutive shedding of endothelial IL-8/heparan sulfate/syndecan-1 complexes. J Immunol 2003; 171 (04) 2057-2065
- 90 Roelofs JJ, Teske GJ, Bonta PI. et al. Plasminogen activator inhibitor-1 regulates neutrophil influx during acute pyelonephritis. Kidney Int 2009; 75 (01) 52-59
- 91 Praetner M, Zuchtriegel G, Holzer M. et al. Plasminogen activator inhibitor-1 promotes neutrophil infiltration and tissue injury on ischemia–reperfusion. Arterioscler Thromb Vasc Biol 2018; 38 (04) 829-842
- 92 Schofield ZV, Woodruff TM, Halai R, Wu MC-L, Cooper MA. Neutrophils–a key component of ischemia-reperfusion injury. Shock 2013; 40 (06) 463-470
- 93 Boffa MB, Koschinsky ML. Curiouser and curiouser: recent advances in measurement of thrombin-activatable fibrinolysis inhibitor (TAFI) and in understanding its molecular genetics, gene regulation, and biological roles. Clin Biochem 2007; 40 (07) 431-442
- 94 Kawamura T, Okada N, Okada H. Elastase from activated human neutrophils activates procarboxypeptidase R. Microbiol Immunol 2002; 46 (03) 225-230
- 95 Ammollo CT, Semeraro F, Xu J, Esmon NL, Esmon CT. Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation. J Thromb Haemost 2011; 9 (09) 1795-1803
- 96 Metzemaekers M, Gouwy M, Proost P. Neutrophil chemoattractant receptors in health and disease: double-edged swords. Cell Mol Immunol 2020; 17 (05) 433-450
- 97 Myles T, Nishimura T, Yun TH. et al. Thrombin activatable fibrinolysis inhibitor, a potential regulator of vascular inflammation. J Biol Chem 2003; 278 (51) 51059-51067
- 98 Renckens R, Roelofs JJ, ter Horst SA. et al. Absence of thrombin-activatable fibrinolysis inhibitor protects against sepsis-induced liver injury in mice. J Immunol 2005; 175 (10) 6764-6771
- 99 Owczarek D, Undas A, Foley JH, Nesheim ME, Jabłonski K, Mach T. Activated thrombin activatable fibrinolysis inhibitor (TAFIa) is associated with inflammatory markers in inflammatory bowel diseases TAFIa level in patients with IBD. J Crohns Colitis 2012; 6 (01) 13-20
- 100 Hayakawa M, Sawamura A, Gando S, Jesmin S, Naito S, Ieko M. A low TAFI activity and insufficient activation of fibrinolysis by both plasmin and neutrophil elastase promote organ dysfunction in disseminated intravascular coagulation associated with sepsis. Thromb Res 2012; 130 (06) 906-913
- 101 Seitz R, Lerch L, Immel A, Egbring R. D-dimer tests detect both plasmin and neutrophil elastase derived split products. Ann Clin Biochem 1995; 32 (Pt 2): 193-195
- 102 Plow EF. The contribution of leukocyte proteases to fibrinolysis. Blut 1986; 53 (01) 1-9
- 103 Riddle JM, Barnhart MI. Ultrastructural study of fibrin dissolution via emigrated polymorphonuclear neutrophils. Am J Pathol 1964; 45 (05) 805-823
- 104 Barnhart MI. Importance of neutrophilic leukocytes in the resolution of fibrin. Fed Proc 1965; 24 (04) 846-853
- 105 Fuchs TA, Abed U, Goosmann C. et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 2007; 176 (02) 231-241
- 106 Kolev K, Komorowicz E, Owen WG, Machovich R. Quantitative comparison of fibrin degradation with plasmin, miniplasmin, neurophil leukocyte elastase and cathepsin G. Thromb Haemost 1996; 75 (01) 140-146
- 107 Francis CW, Marder VJ. Degradation of cross-linked fibrin by human leukocyte proteases. J Lab Clin Med 1986; 107 (04) 342-352
- 108 Plow EF. The major fibrinolytic proteases of human leukocytes. Biochim Biophys Acta 1980; 630 (01) 47-56
- 109 Kohno I, Inuzuka K, Itoh Y. et al. A monoclonal antibody specific to the granulocyte-derived elastase-fragment D species of human fibrinogen and fibrin: its application to the measurement of granulocyte-derived elastase digests in plasma. Blood 2000; 95 (05) 1721-1728
- 110 Kamikura Y, Wada H, Nobori T. et al. Elevated plasma levels of fibrin degradation products by granulocyte-derived elastase in patients with deep vein thrombosis. Thromb Res 2005; 115 (1-2): 53-57
- 111 Matsumoto T, Wada H, Nobori T. et al. Elevated plasma levels of fibrin degradation products by granulocyte-derived elastase in patients with disseminated intravascular coagulation. Clin Appl Thromb Hemost 2005; 11 (04) 391-400
- 112 Zeng B, Bruce D, Kril J, Ploplis V, Freedman B, Brieger D. Influence of plasminogen deficiency on the contribution of polymorphonuclear leucocytes to fibrin/ogenolysis: studies in plasminogen knock-out mice. Thromb Haemost 2002; 88 (05) 805-810
- 113 Hayakawa M, Sawamura A, Gando S. et al. Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase. Surgery 2011; 149 (02) 221-230
- 114 Gando S, Hayakawa M, Sawamura A. et al. The activation of neutrophil elastase-mediated fibrinolysis is not sufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation associated with systemic inflammation. Thromb Res 2007; 121 (01) 67-73
- 115 Skogen WF, Senior RM, Griffin GL, Wilner GD. Fibrinogen-derived peptide B beta 1-42 is a multidomained neutrophil chemoattractant. Blood 1988; 71 (05) 1475-1479
- 116 Senior RM, Skogen WF, Griffin GL, Wilner GD. Effects of fibrinogen derivatives upon the inflammatory response. Studies with human fibrinopeptide B. J Clin Invest 1986; 77 (03) 1014-1019
- 117 Wright SD, Weitz JI, Huang AJ, Levin SM, Silverstein SC, Loike JD. Complement receptor type three (CD11b/CD18) of human polymorphonuclear leukocytes recognizes fibrinogen. Proc Natl Acad Sci U S A 1988; 85 (20) 7734-7738
- 118 Altieri DC, Agbanyo FR, Plescia J, Ginsberg MH, Edgington TS, Plow EF. A unique recognition site mediates the interaction of fibrinogen with the leukocyte integrin Mac-1 (CD11b/CD18). J Biol Chem 1990; 265 (21) 12119-12122
- 119 Leavell KJ, Peterson MW, Gross TJ. The role of fibrin degradation products in neutrophil recruitment to the lung. Am J Respir Cell Mol Biol 1996; 14 (01) 53-60
- 120 Gross TJ, Leavell KJ, Peterson MW. CD11b/CD18 mediates the neutrophil chemotactic activity of fibrin degradation product D domain. Thromb Haemost 1997; 77 (05) 894-900
- 121 Mesa MA, Vasquez G. NETosis. Autoimmune Dis 2013; 2013 (01) 651497
- 122 Lu Y, Tian Y, Liu X. et al. NETs exacerbate placental inflammation and injury through high mobility group protein B1 during preeclampsia. Placenta 2025; 159: 131-139
- 123 Longstaff C, Varjú I, Sótonyi P. et al. Mechanical stability and fibrinolytic resistance of clots containing fibrin, DNA, and histones. J Biol Chem 2013; 288 (10) 6946-6956
- 124 Varjú I, Longstaff C, Szabó L. et al. DNA, histones and neutrophil extracellular traps exert anti-fibrinolytic effects in a plasma environment. Thromb Haemost 2015; 113 (06) 1289-1298
- 125 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
- 126 Das R, Burke T, Plow EF. Histone H2B as a functionally important plasminogen receptor on macrophages. Blood 2007; 110 (10) 3763-3772
- 127 Komissarov AA, Florova G, Idell S. Effects of extracellular DNA on plasminogen activation and fibrinolysis. J Biol Chem 2011; 286 (49) 41949-41962
- 128 Gould TJ, Vu TT, Stafford AR. et al. Cell-free DNA modulates clot structure and impairs fibrinolysis in sepsis. Arterioscler Thromb Vasc Biol 2015; 35 (12) 2544-2553
- 129 Mangold A, Alias S, Scherz T. et al. Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size. Circ Res 2015; 116 (07) 1182-1192
- 130 Ducroux C, Di Meglio L, Loyau S. et al. Thrombus neutrophil extracellular traps content impair tPA-induced thrombolysis in acute ischemic stroke. Stroke 2018; 49 (03) 754-757
- 131 Lim CH, Adav SS, Sze SK, Choong YK, Saravanan R, Schmidtchen A. Thrombin and plasmin alter the proteome of neutrophil extracellular traps. Front Immunol 2018; 9: 1554
- 132 Lengfelder E, Hofmann WK, Nowak D. Impact of arsenic trioxide in the treatment of acute promyelocytic leukemia. Leukemia 2012; 26 (03) 433-442
- 133 Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med 1999; 340 (13) 994-1004
- 134 Liu Y, Wang Z, Jiang M. et al. The expression of annexin II and its role in the fibrinolytic activity in acute promyelocytic leukemia. Leuk Res 2011; 35 (07) 879-884
- 135 O'Connell PA, Madureira PA, Berman JN, Liwski RS, Waisman DM. Regulation of S100A10 by the PML-RAR-α oncoprotein. Blood 2011; 117 (15) 4095-4105
- 136 Arbuthnot C, Wilde JT. Haemostatic problems in acute promyelocytic leukaemia. Blood Rev 2006; 20 (06) 289-297
- 137 Oudijk E-JD, Nieuwenhuis HK, Bos R, Fijnheer R. Elastase mediated fibrinolysis in acute promyelocytic leukemia. Thromb Haemost 2000; 83 (06) 906-908
- 138 MacLeod TJ, Kwon M, Filipenko NR, Waisman DM. Phospholipid-associated annexin A2-S100A10 heterotetramer and its subunits: characterization of the interaction with tissue plasminogen activator, plasminogen, and plasmin. J Biol Chem 2003; 278 (28) 25577-25584
- 139 Bennett B, Booth NA, Croll A, Dawson AA. The bleeding disorder in acute promyelocytic leukaemia: fibrinolysis due to u-PA rather than defibrination. Br J Haematol 1989; 71 (04) 511-517
- 140 Avvisati G, ten Cate JW, Sturk A, Lamping R, Petti MG, Mandelli F. Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia. Br J Haematol 1988; 70 (01) 43-48
- 141 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
- 142 Sakata Y, Murakami T, Noro A, Mori K, Matsuda M. The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia. Blood 1991; 77 (09) 1949-1957
- 143 Wang P, Zhang Y, Yang H. et al. Characteristics of fibrinolytic disorders in acute promyelocytic leukemia. Hematology 2018; 23 (10) 756-764
- 144 Meijers JC, Oudijk EJD, Mosnier LO. et al. Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia. Br J Haematol 2000; 108 (03) 518-523
- 145 Cao M, Li T, He Z. et al. Promyelocytic extracellular chromatin exacerbates coagulation and fibrinolysis in acute promyelocytic leukemia. Blood 2017; 129 (13) 1855-1864
- 146 Kwaan HC, Rego EM. Role of microparticles in the hemostatic dysfunction in acute promyelocytic leukemia. In: Semin Thromb Hemost. Thieme Medical Publishers; 2010: 917-924
- 147 Ma G, Liu F, Lv L, Gao Y, Su Y. Increased promyelocytic-derived microparticles: a novel potential factor for coagulopathy in acute promyelocytic leukemia. Ann Hematol 2013; 92 (05) 645-652
- 148 Bennett M, Parker AC, Ludlam CA. Platelet and fibrinogen survival in acute promyelocytic leukaemia. BMJ 1976; 2 (6035) 565
- 149 von Brühl M-L, Stark K, Steinhart A. et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209 (04) 819-835
- 150 Wohner N, Keresztes Z, Sótonyi P. et al. Neutrophil granulocyte-dependent proteolysis enhances platelet adhesion to the arterial wall under high-shear flow. J Thromb Haemost 2010; 8 (07) 1624-1631
- 151 Franchini M, Veneri D, Lippi G. Inflammation and hemostasis: a bidirectional interaction. Clin Lab 2007; 53 (1-2): 63-67
- 152 Jenne CN, Urrutia R, Kubes P. Platelets: bridging hemostasis, inflammation, and immunity. Int J Lab Hematol 2013; 35 (03) 254-261
- 153 Gupta AK, Joshi MB, Philippova M. et al. Activated endothelial cells induce neutrophil extracellular traps and are susceptible to NETosis-mediated cell death. FEBS Lett 2010; 584 (14) 3193-3197
- 154 Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol 2010; 191 (03) 677-691
- 155 Martinod K, Demers M, Fuchs TA. et al. Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci U S A 2013; 110 (21) 8674-8679
- 156 Ordóñez A, Martínez-Martínez I, Corrales FJ. et al. Effect of citrullination on the function and conformation of antithrombin. FEBS J 2009; 276 (22) 6763-6772
- 157 Nakayama-Hamada M, Suzuki A, Furukawa H, Yamada R, Yamamoto K. Citrullinated fibrinogen inhibits thrombin-catalysed fibrin polymerization. J Biochem 2008; 144 (03) 393-398
- 158 Wang Y, Li M, Stadler S. et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol 2009; 184 (02) 205-213
- 159 Yousefi S, Mihalache C, Kozlowski E, Schmid I, Simon H-U. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ 2009; 16 (11) 1438-1444
- 160 Ward CM, Tetaz TJ, Andrews RK, Berndt MC. Binding of the von Willebrand factor A1 domain to histone. Thromb Res 1997; 86 (06) 469-477
- 161 Brill A, Fuchs TA, Savchenko AS. et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost 2012; 10 (01) 136-144
- 162 Stavrou EX, Fang C, Bane KL. et al. Factor XII and uPAR upregulate neutrophil functions to influence wound healing. J Clin Invest 2018; 128 (03) 944-959
- 163 Massberg S, Grahl L, von Bruehl M-L. et al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 2010; 16 (08) 887-896
- 164 Drechsler M, Megens RT, van Zandvoort M, Weber C, Soehnlein O. Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation 2010; 122 (18) 1837-1845
- 165 Borissoff JI, Joosen IA, Versteylen MO. et al. Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler Thromb Vasc Biol 2013; 33 (08) 2032-2040
- 166 Vallés J, Lago A, Santos MT. et al. Neutrophil extracellular traps are increased in patients with acute ischemic stroke: prognostic significance. Thromb Haemost 2017; 117 (10) 1919-1929
- 167 Laridan E, Denorme F, Desender L. et al. Neutrophil extracellular traps in ischemic stroke thrombi. Ann Neurol 2017; 82 (02) 223-232
- 168 Daniel L, Fakhouri F, Joly D. et al. Increase of circulating neutrophil and platelet microparticles during acute vasculitis and hemodialysis. Kidney Int 2006; 69 (08) 1416-1423
- 169 Pitanga TN, de Aragão França L, Rocha VCJ. et al. Neutrophil-derived microparticles induce myeloperoxidase-mediated damage of vascular endothelial cells. BMC Cell Biol 2014; 15: 21
- 170 Pluskota E, Woody NM, Szpak D. et al. Expression, activation, and function of integrin alphaMbeta2 (Mac-1) on neutrophil-derived microparticles. Blood 2008; 112 (06) 2327-2335
- 171 Gupta N, Sahu A, Prabhakar A. et al. Activation of NLRP3 inflammasome complex potentiates venous thrombosis in response to hypoxia. Proc Natl Acad Sci U S A 2017; 114 (18) 4763-4768