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Effect of neutrophil extracellular traps (NET) on thrombosis: A literature review


Neutrophils are used by the innate immune system to form thrombi during many types of thrombosis. The inactivation of endogenous anticoagulants results in increased intravascular coagulation by increasing factor XII activation, decreasing plasmin production, or boosting the tissue factor-dependent extrinsic pathway. The creation of neutrophil extracellular traps (NET) by the externalization of decondensed nucleosomes and granule proteins supports neutrophil-dependent prothrombotic processes. Experimental thrombosis has been demonstrated to be caused by these traps, whether intact or fragmented, since they provide the means to enhance microvascular thrombosis. The von Willebrand factor increases platelet adhesion when neutrophils and activated platelets combine to form NET. Thus, neutrophils and externalized nucleosomes promote intravascular blood coagulation and thrombosis during infections and during conditions resulting from blood vessel damage.


  1. Barret KE, Barman SM, Boitano S, Brooks HL. Ganong’s review of medical physiology, 23rd Edition. United States of America: McGraw Hill Companies. 2010.
  2. Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscaizo J. Harrison’s principle of internal medicine, 18th Edition. United States of America: McGraw Hill Companies. 2012.
  3. Hall J. Guyton and Hall textbook of medical physiology, 12th Edition. Philadelphia: Sauders Elsevier. 2010.
  4. Razak NBA, Jones G, Bhandari M, Berndt MC, Metharom P. Cancer-associated thrombosis: an overview of mechanism, risk factors, and treatment. Cancers. 2018; 10(380): 1-21.
  5. Fernandes CJ, Morinaga LTK, Alver Jr JL, Castro MA, Calderaro D, Jardim CVP, et al. Cancer-associated thrombosis: the when, how and why. Eur Respir Rev. 2019; 28: 180119.
  6. Khorana AA. Cancer-associated thrombosis: updates and controversies. American Society of Hematology. 2012; 626-630.
  7. Elyamani G, Alzahrani AM, Bukhary E. Cancer-Associated Thrombosis: an overview. Clinical Medicine Insights: Oncology. 2014; 8: 129-137.
  8. Meikle CKS, Kelly CA, Garg P, Wuescher LM, Ali RA, Worth RG. Cancer and thrombosis: the platelet perspective. Frontiers in Cells and Developmental Biology. 2017; 4(147): 1-10.
  9. Oppelt P, Betbadal A, Nayak L. Approach to chemotherapy-associated thrombosis. Vasc Med. 2015; 20(2): 153-161.
  10. Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011; 11(8):519-531.
  11. Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol. 2013; 13(1):34-45.
  12. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13 (3):159-175.
  13. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004; 303(5663):1532-1535.
  14. Urban CF, Ermert D, Schmid M, et al. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans. PLoS Pathog. 2009; 5(10):e1000639.
  15. Brinkmann V, Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol. 2007; 5(8):577–582.
  16. Wang Y, Li M, Stadler S, et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol. 2009; 184(2):205-213.
  17. Wang Y, Wysocka J, Sayegh J, et al. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science. 2004; 306(5694):279-283.
  18. Leshner M, Wang S, Lewis C, Zheng H, Chen XA, Santy L, Wang Y. PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures. Front Immunol. 2012; 3:307.
  19. Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007; 176(2): 231-241.
  20. von Kockritz-Blickwede M, Chow OA, Ghochani M, Nizet V. Visualization and functional evaluation of phagocyte extracellular traps. In: Kabelitz D, Kaufman SHE, eds. Methods in Microbiology. Volume 37. London (United Kingdom): Elsevier; 2010. p.139–160.
  21. Li P, Li M, Lindberg MR, et al. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010; 207(9):1853–1862.
  22. Papayannopoulos V, Metzler KD, Hakkim A, et al. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extra- cellular traps. J Cell Biol. 2010; 191(3):677–691.
  23. Brinkmann V, Zychlinsky A. Neutrophil extracellular traps: is immunity the second function of chromatin? J Cell Biol. 2012; 198(5):773-783.
  24. Saitoh T, Komano J, Saitoh Y, et al. Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe. 2012; 12(1):109-116.
  25. Buchanan JT, Simpson AJ, Aziz RK, Liu GY, Kristian SA, Kotb M, Feramisco J, Nizet V. DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps. Curr Biol. 2006; 16:396–400.
  26. Beiter K, Wartha F, Albiger B, Normark S, Zychlinsky A, Henriques- Normark B. An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps. Curr Biol. 2006; 16:401–407.
  27. Yipp BG, Kubes P: NETosis: how vital is it. Blood. 2013; 122(16):2784– 2794.
  28. Yipp BG, Petri B, Salina D, et al. Infection- induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med. 2012; 18(9):1386-1393.

How to Cite

Dewi, N. M. R. P., Prabawa, I. P. Y. ., & Gede Wara Samsarga. (2023). Effect of neutrophil extracellular traps (NET) on thrombosis: A literature review. Intisari Sains Medis, 14(3), 1092–1095.




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Ni Made Ratih Purnama Dewi
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I Putu Yuda Prabawa
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Gede Wara Samsarga
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