Skip to content
naulon
Get started

Corrected on Feb 28, 2018.

Source: the publisher, via Crossref · checked Nov 2, 2026 · Read the notice

Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critical ill patients?

Antoine Dewitte, Sébastien Lepreux, Julien Villeneuve and 4 more

Annals of Intensive Care · 2017 · Review · CC BY-NC-ND

doi:10.1186/s13613-017-0337-7

Abstract

Beyond haemostasis, platelets have emerged as versatile effectors of the immune response. The contribution of platelets in inflammation, tissue integrity and defence against infections has considerably widened the spectrum of their role in health and disease. Here, we propose a narrative review that first describes these new platelet attributes. We then examine their relevance to microcirculatory alterations in multi-organ dysfunction, a major sepsis complication. Rapid progresses that are made on the knowledge of novel platelet functions should improve the understanding of thrombocytopenia, a common condition and a predictor of adverse outcome in sepsis, and may provide potential avenues for management and therapy.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 275

  1. 1.

    Singer M, De Santis V, Vitale D, Jeffcoate W. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet. 2004;364(9433):545-548.

    Not in our library10.1016/s0140-6736(04)16815-3

  2. 2.

    Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369(21):2063.

    Not in our library10.1056/nejmc1312359

  3. 3.

    Deutschman CS, Tracey KJ. Sepsis: current dogma and new perspectives. Immunity. 2014;40(4):463-475.

    Not in our library10.1016/j.immuni.2014.04.001

  4. 4.

    Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013;41(5):1167-1174.

    Not in our library10.1097/ccm.0b013e31827c09f8

  5. 5.

    Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, et al. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016;193(3):259-272.

    Not in our library10.1164/rccm.201504-0781oc

  6. 6.

    Baughman RP, Lower EE, Flessa HC, Tollerud DJ. Thrombocytopenia in the intensive care unit. Chest. 1993;104(4):1243-1247.

    Not in our library10.1378/chest.104.4.1243

  7. 7.

    Drews RE, Weinberger SE. Thrombocytopenic disorders in critically ill patients. Am J Respir Crit Care Med. 2000;162(2 Pt 1):347-351.

    Not in our library10.1164/ajrccm.162.2.ncc3-00

  8. 8.

    Vanderschueren S, De Weerdt A, Malbrain M, Vankersschaever D, Frans E, Wilmer A, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med. 2000;28(6):1871-1876.

    Not in our library10.1097/00003246-200006000-00031

  9. 9.

    Strauss R, Wehler M, Mehler K, Kreutzer D, Koebnick C, Hahn EG. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome. Crit Care Med. 2002;30(8):1765-1771.

    Not in our library10.1097/00003246-200208000-00015

  10. 10.

    Smith-Erichsen N. Serial determinations of platelets, leucocytes and coagulation parameters in surgical septicemia. Scand J Clin Lab Invest Suppl. 1985;178:7-14.

    Not in our library

  11. 11.

    Akca S, Haji-Michael P, de Mendonca A, Suter P, Levi M, Vincent JL. Time course of platelet counts in critically ill patients. Crit Care Med. 2002;30(4):753-756.

    Not in our library10.1097/00003246-200204000-00005

  12. 12.

    Crowther MA, Cook DJ, Meade MO, Griffith LE, Guyatt GH, Arnold DM, et al. Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors. J Crit Care. 2005;20(4):348-353.

    Not in our library10.1016/j.jcrc.2005.09.008

  13. 13.

    Moreau D, Timsit JF, Vesin A, Garrouste-Orgeas M, de Lassence A, Zahar JR, et al. Platelet count decline: an early prognostic marker in critically ill patients with prolonged ICU stays. Chest. 2007;131(6):1735-1741.

    Not in our library10.1378/chest.06-2233

  14. 14.

    Hui P, Cook DJ, Lim W, Fraser GA, Arnold DM. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest. 2011;139(2):271-278.

    Not in our library10.1378/chest.10-2243

  15. 15.
    Thrombocytopenia in adult patients with sepsis: incidence, risk factors, and its association with clinical outcome · 2013
    No notice
  16. 16.

    Semple JW, Freedman J. Platelets and innate immunity. Cell Mol Life Sci. 2010;67(4):499-511.

    Not in our library10.1007/s00018-009-0205-1

  17. 17.

    Semple JW, Italiano JE, Freedman J. Platelets and the immune continuum. Nat Rev Immunol. 2011;11(4):264-274.

    Not in our library10.1038/nri2956

  18. 18.

    Vieira-de-Abreu A, Campbell RA, Weyrich AS, Zimmerman GA. Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum. Semin Immunopathol. 2012;34(1):5-30.

    Not in our library10.1007/s00281-011-0286-4

  19. 19.

    Herter JM, Rossaint J, Zarbock A. Platelets in inflammation and immunity. J Thromb Haemost. 2014;12(11):1764-1775.

    Not in our library10.1111/jth.12730

  20. 20.

    Morrell CN, Aggrey AA, Chapman LM, Modjeski KL. Emerging roles for platelets as immune and inflammatory cells. Blood. 2014;123(18):2759-2767.

    Not in our library10.1182/blood-2013-11-462432

  21. 21.

    Xu XR, Zhang D, Oswald BE, Carrim N, Wang X, Hou Y, et al. Platelets are versatile cells: new discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond. Crit Rev Clin Lab Sci. 2016;53(6):409-430.

    Not in our library10.1080/10408363.2016.1200008

  22. 22.

    Dewitte A, Tanga A, Villeneuve J, Lepreux S, Ouattara A, Desmouliere A, et al. New frontiers for platelet CD154. Exp Hematol Oncol. 2015;4:6.

    Not in our library10.1186/s40164-015-0001-6

  23. 23.

    Thomas MR, Storey RF. The role of platelets in inflammation. Thromb Haemost. 2015;114(3):449-458.

    Not in our library10.1160/th14-12-1067

  24. 24.

    Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801-810.

    Not in our library10.1001/jama.2016.0287

  25. 25.

    Riedemann NC, Guo RF, Ward PA. The enigma of sepsis. J Clin Investig. 2003;112(4):460-467.

    Not in our library10.1172/jci200319523

  26. 26.
    Sepsis biomarkers: a review · 2010
    No notice
  27. 27.

    Aziz M, Jacob A, Yang WL, Matsuda A, Wang P. Current trends in inflammatory and immunomodulatory mediators in sepsis. J Leukoc Biol. 2013;93(3):329-342.

    Not in our library10.1189/jlb.0912437

  28. 28.

    Parlato M, Cavaillon JM. Host response biomarkers in the diagnosis of sepsis: a general overview. Methods Mol Biol. 2015;1237:149-211.

    Not in our library10.1007/978-1-4939-1776-1_15

  29. 29.

    Claushuis TA, van Vught LA, Scicluna BP, Wiewel MA, Klein Klouwenberg PM, Hoogendijk AJ, et al. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients. Blood. 2016;127(24):3062-3072.

    Not in our library10.1182/blood-2015-11-680744

  30. 30.

    Hatherill M, Tibby SM, Turner C, Ratnavel N, Murdoch IA. Procalcitonin and cytokine levels: relationship to organ failure and mortality in pediatric septic shock. Crit Care Med. 2000;28(7):2591-2594.

    Not in our library10.1097/00003246-200007000-00068

  31. 31.

    Marshall JC. Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med. 2001;29(7 Suppl):S99-S106.

    Not in our library10.1097/00003246-200107001-00032

  32. 32.
    Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness. · 2015
    Not checked
  33. 33.

    Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008;8(10):776-787.

    Not in our library10.1038/nri2402

  34. 34.

    Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S, Remick DG. The pathogenesis of sepsis. Annu Rev Pathol. 2011;6:19-48.

    Not in our library10.1146/annurev-pathol-011110-130327

  35. 35.

    Wiersinga WJ, Leopold SJ, Cranendonk DR, van der Poll T. Host innate immune responses to sepsis. Virulence. 2014;5(1):36-44.

    Not in our library10.4161/viru.25436

  36. 36.

    Raymond SL, Holden DC, Mira JC, Stortz JA, Loftus TJ, Mohr AM, et al. Microbial recognition and danger signals in sepsis and trauma. Biochim Biophys Acta. 2017;1863(10 Pt B):2564-2573.

    Not in our library10.1016/j.bbadis.2017.01.013

  37. 37.

    Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, et al. A genomic storm in critically injured humans. J Exp Med. 2011;208(13):2581-2590.

    Not in our library10.1084/jem.20111354

  38. 38.

    Munford RS, Pugin J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med. 2001;163(2):316-321.

    Not in our library10.1164/ajrccm.163.2.2007102

  39. 39.

    Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138-150.

    Not in our library10.1056/nejmra021333

  40. 40.

    Ward NS, Casserly B, Ayala A. The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med. 2008;29(4):617-625.

    Not in our library10.1016/j.ccm.2008.06.010

  41. 41.

    Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C, et al. Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 2013;93(3):1247-1288.

    Not in our library10.1152/physrev.00037.2012

  42. 42.

    Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862-874.

    Not in our library10.1038/nri3552

  43. 43.

    Delano MJ, Ward PA. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol Rev. 2016;274(1):330-353.

    Not in our library10.1111/imr.12499

  44. 44.

    Machlus KR, Italiano JE. The incredible journey: from megakaryocyte development to platelet formation. J Cell Biol. 2013;201(6):785-796.

    Not in our library10.1083/jcb.201304054

  45. 45.

    Hitchcock IS, Kaushansky K. Thrombopoietin from beginning to end. Br J Haematol. 2014;165(2):259-268.

    Not in our library10.1111/bjh.12772

  46. 46.

    Josefsson EC, Dowling MR, Lebois M, Kile BT, Michelson AD. The regulation of platelet life span. Platelets. 2013;51-66.

    Not in our library

  47. 47.

    Grozovsky R, Giannini S, Falet H, Hoffmeister KM. Regulating billions of blood platelets: glycans and beyond. Blood. 2015;126(16):1877-1884.

    Not in our library10.1182/blood-2015-01-569129

  48. 48.

    Rendu F, Brohard-Bohn B. The platelet release reaction: granules’ constituents, secretion and functions. Platelets. 2001;12(5):261-273.

    Not in our library10.1080/09537100120068170

  49. 49.

    Coppinger JA, Cagney G, Toomey S, Kislinger T, Belton O, McRedmond JP, et al. Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood. 2004;103(6):2096-2104.

    Not in our library10.1182/blood-2003-08-2804

  50. 50.

    Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci. 2008;13:3532-3548.

    Not in our library10.2741/2947

  51. 51.

    Nieuwland R, Sturk A, Michelson AD. Platelet-derived microparticles. Platelets. 2013;403-413.

    Not in our library

  52. 52.

    Melki I, Tessandier N, Zufferey A, Boilard E. Platelet microvesicles in health and disease. Platelets. 2017;28(3):214-221.

    Not in our library10.1080/09537104.2016.1265924

  53. 53.

    Morrell CN, Maggirwar SB. Recently recognized platelet agonists. Curr Opin Hematol. 2011;18(5):309-314.

    Not in our library10.1097/moh.0b013e3283497dfb

  54. 54.

    Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol. 2002;22(9):1381-1389.

    Not in our library10.1161/01.atv.0000031340.68494.34

  55. 55.

    Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost. 2011;105(Suppl 1):S13-S33.

    Not in our library10.1160/ths10-11-0720

  56. 56.

    Garraud O, Hamzeh-Cognasse H, Pozzetto B, Cavaillon JM, Cognasse F. Bench-to-bedside review: platelets and active immune functions-new clues for immunopathology? Crit Care. 2013;17(4):236.

    Not in our library10.1186/cc12716

  57. 57.

    Nurden AT. The biology of the platelet with special reference to inflammation, wound healing and immunity. Front Biosci (Landmark Ed). 2018;01(23):726-751.

    Not in our library10.2741/4613

  58. 58.

    Kapur R, Zufferey A, Boilard E, Semple JW. Nouvelle cuisine: platelets served with inflammation. J Immunol. 2015;194(12):5579-5587.

    Not in our library10.4049/jimmunol.1500259

  59. 59.

    Manne BK, Xiang SC, Rondina MT. Platelet secretion in inflammatory and infectious diseases. Platelets. 2017;28(2):155-164.

    Not in our library10.1080/09537104.2016.1240766

  60. 60.

    Chen J, Lopez JA. Interactions of platelets with subendothelium and endothelium. Microcirculation. 2005;12(3):235-246.

    Not in our library10.1080/10739680590925484

  61. 61.

    Siegel-Axel DI, Gawaz M. Platelets and endothelial cells. Semin Thromb Hemost. 2007;33(2):128-135.

    Not in our library10.1055/s-2007-969025

  62. 62.

    Etulain J, Schattner M. Glycobiology of platelet-endothelial cell interactions. Glycobiology. 2014;24(12):1252-1259.

    Not in our library10.1093/glycob/cwu056

  63. 63.
    Modulation of Endothelial Glycocalyx Structure under Inflammatory Conditions · 2014
    No notice
  64. 64.

    Schmidt EP, Kuebler WM, Lee WL, Downey GP. Adhesion molecules: master controllers of the circulatory system. Compr Physiol. 2016;6(2):945-973.

    Not in our library10.1002/cphy.c150020

  65. 65.

    Page C, Pitchford S. Neutrophil and platelet complexes and their relevance to neutrophil recruitment and activation. Int Immunopharmacol. 2013;17(4):1176-1184.

    Not in our library10.1016/j.intimp.2013.06.004

  66. 66.

    May AE, Seizer P, Gawaz M. Platelets: inflammatory firebugs of vascular walls. Arterioscler Thromb Vasc Biol. 2008;28(3):s5-s10.

    Not in our library10.1161/atvbaha.107.158915

  67. 67.

    Lowenberg EC, Meijers JC, Levi M. Platelet-vessel wall interaction in health and disease. Neth J Med. 2010;68(6):242-251.

    Not in our library

  68. 68.

    Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. J Physiol. 2012;590(Pt 5):1023-1034.

    Not in our library10.1113/jphysiol.2011.225417

  69. 69.

    Rondina MT, Weyrich AS, Zimmerman GA. Platelets as cellular effectors of inflammation in vascular diseases. Circ Res. 2013;112(11):1506-1519.

    Not in our library10.1161/circresaha.113.300512

  70. 70.
    The role of platelets in the recruitment of leukocytes during vascular disease · 2015
    No notice
  71. 71.

    Middleton EA, Weyrich AS, Zimmerman GA. Platelets in pulmonary immune responses and inflammatory lung diseases. Physiol Rev. 2016;96(4):1211-1259.

    Not in our library10.1152/physrev.00038.2015

  72. 72.

    Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, et al. Neutrophils scan for activated platelets to initiate inflammation. Science. 2014;346(6214):1234-1238.

    Not in our library10.1126/science.1256478

  73. 73.
    Platelets Guide Leukocytes to Their Sites of Extravasation · 2016
    No notice
  74. 74.

    Peters MJ, Dixon G, Kotowicz KT, Hatch DJ, Heyderman RS, Klein NJ. Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing. Br J Haematol. 1999;106(2):391-399.

    Not in our library10.1046/j.1365-2141.1999.01553.x

  75. 75.

    Haselmayer P, Grosse-Hovest L, von Landenberg P, Schild H, Radsak MP. TREM-1 ligand expression on platelets enhances neutrophil activation. Blood. 2007;110(3):1029-1035.

    Not in our library10.1182/blood-2007-01-069195

  76. 76.
    Platelets in Inflammation: Regulation of Leukocyte Activities and Vascular Repair · 2015
    No notice
  77. 77.

    Kral JB, Schrottmaier WC, Salzmann M, Assinger A. Platelet interaction with innate immune cells. Transfus Med Hemother. 2016;43(2):78-88.

    Not in our library10.1159/000444807

  78. 78.

    Gawaz M, Fateh-Moghadam S, Pilz G, Gurland HJ, Werdan K. Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure. Eur J Clin Investig. 1995;25(11):843-851.

    Not in our library10.1111/j.1365-2362.1995.tb01694.x

  79. 79.

    Russwurm S, Vickers J, Meier-Hellmann A, Spangenberg P, Bredle D, Reinhart K, et al. Platelet and leukocyte activation correlate with the severity of septic organ dysfunction. Shock. 2002;17(4):263-268.

    Not in our library10.1097/00024382-200204000-00004

  80. 80.

    Stohlawetz P, Folman CC, von dem Borne AE, Pernerstorfer T, Eichler HG, Panzer S, et al. Effects of endotoxemia on thrombopoiesis in men. Thromb Haemost. 1999;81(4):613-617.

    Not in our library

  81. 81.

    Michelson AD, Barnard MR, Krueger LA, Valeri CR, Furman MI. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation. 2001;104(13):1533-1537.

    Not in our library10.1161/hc3801.095588

  82. 82.

    Ioannou A, Kannan L, Tsokos GC. Platelets, complement and tissue inflammation. Autoimmunity. 2013;46(1):1-5.

    Not in our library10.3109/08916934.2012.722144

  83. 83.

    Stocker TJ, Ishikawa-Ankerhold H, Massberg S, Schulz C. Small but mighty: platelets as central effectors of host defense. Thromb Haemost. 2017;117(4):651-661.

    Not in our library10.1160/th16-12-0921

  84. 84.

    Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol. 2013;13(1):34-45.

    Not in our library10.1038/nri3345

  85. 85.

    Muller F, Mutch NJ, Schenk WA, Smith SA, Esterl L, Spronk HM, et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell. 2009;139(6):1143-1156.

    Not in our library10.1016/j.cell.2009.11.001

  86. 86.

    Esmon CT. The interactions between inflammation and coagulation. Br J Haematol. 2005;131(4):417-430.

    Not in our library10.1111/j.1365-2141.2005.05753.x

  87. 87.

    Esmon CT. Coagulation inhibitors in inflammation. Biochem Soc Trans. 2005;33(Pt 2):401-405.

    Not in our library10.1042/bst0330401

  88. 88.
    SEPSIS-ASSOCIATED DISSEMINATED INTRAVASCULAR COAGULATION AND THROMBOEMBOLIC DISEASE · 2010
    No notice
  89. 89.

    Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38-44.

    Not in our library10.1016/j.thromres.2016.11.007

  90. 90.

    Simmons J, Pittet JF. The coagulopathy of acute sepsis. Curr Opin Anaesthesiol. 2015;28(2):227-236.

    Not in our library10.1097/aco.0000000000000163

  91. 91.

    Davis RP, Miller-Dorey S, Jenne CN. Platelets and coagulation in infection. Clin Transl Immunol. 2016;5(7):e89.

    Not in our library10.1038/cti.2016.39

  92. 92.

    Ma AC, Kubes P. Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis. J Thromb Haemost. 2008;6(3):415-420.

    Not in our library10.1111/j.1538-7836.2007.02865.x

  93. 93.

    Ghasemzadeh M, Hosseini E. Platelet-leukocyte crosstalk: linking proinflammatory responses to procoagulant state. Thromb Res. 2013;131(3):191-197.

    Not in our library10.1016/j.thromres.2012.11.028

  94. 94.
    Platelets: New Bricks in the Building of Neutrophil Extracellular Traps · 2016
    No notice
  95. 95.

    Swystun LL, Liaw PC. The role of leukocytes in thrombosis. Blood. 2016;128(6):753-762.

    Not in our library10.1182/blood-2016-05-718114

  96. 96.

    McDonald B, Davis RP, Kim SJ, Tse M, Esmon CT, Kolaczkowska E, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017;129(10):1357-1367.

    Not in our library10.1182/blood-2016-09-741298

  97. 97.

    Nieuwland R, Berckmans RJ, McGregor S, Boing AN, Romijn FP, Westendorp RG, et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood. 2000;95(3):930-935.

    Not in our library

  98. 98.

    George FD. Microparticles in vascular diseases. Thromb Res. 2008;122(Suppl 1):S55-S59.

    Not in our library10.1016/s0049-3848(08)70020-3

  99. 99.

    Italiano JE, Mairuhu AT, Flaumenhaft R. Clinical relevance of microparticles from platelets and megakaryocytes. Curr Opin Hematol. 2010;17(6):578-584.

    Not in our library10.1097/moh.0b013e32833e77ee

  100. 100.

    Reid VL, Webster NR. Role of microparticles in sepsis. Br J Anaesth. 2012;109(4):503-513.

    Not in our library10.1093/bja/aes321

  101. 101.

    Tokes-Fuzesi M, Woth G, Ernyey B, Vermes I, Muhl D, Bogar L, et al. Microparticles and acute renal dysfunction in septic patients. J Crit Care. 2013;28(2):141-147.

    Not in our library10.1016/j.jcrc.2012.05.006

  102. 102.

    Souza AC, Yuen PS, Star RA. Microparticles: markers and mediators of sepsis-induced microvascular dysfunction, immunosuppression, and AKI. Kidney Int. 2015;87(6):1100-1108.

    Not in our library10.1038/ki.2015.26

  103. 103.

    Ripoche J. Blood platelets and inflammation: their relationship with liver and digestive diseases. Clin Res Hepatol Gastroenterol. 2011;35(5):353-357.

    Not in our library10.1016/j.clinre.2011.02.012

  104. 104.

    Gawaz M, Vogel S. Platelets in tissue repair: control of apoptosis and interactions with regenerative cells. Blood. 2013;122(15):2550-2554.

    Not in our library10.1182/blood-2013-05-468694

  105. 105.
    Platelet secretion: From haemostasis to wound healing and beyond · 2015
    No notice
  106. 106.

    Nachman RL, Rafii S. Platelets, petechiae, and preservation of the vascular wall. N Engl J Med. 2008;359(12):1261-1270.

    Not in our library10.1056/nejmra0800887

  107. 107.

    Ho-Tin-Noe B, Demers M, Wagner DD. How platelets safeguard vascular integrity. J Thromb Haemost. 2011;9(Suppl 1):56-65.

    Not in our library10.1111/j.1538-7836.2011.04317.x

  108. 108.

    Weyrich AS, Zimmerman GA. Platelets in lung biology. Annu Rev Physiol. 2013;75:569-591.

    Not in our library10.1146/annurev-physiol-030212-183752

  109. 109.

    Kitchens CS, Weiss L. Ultrastructural changes of endothelium associated with thrombocytopenia. Blood. 1975;46(4):567-578.

    Not in our library

  110. 110.

    Broos K, Feys HB, De Meyer SF, Vanhoorelbeke K, Deckmyn H. Platelets at work in primary hemostasis. Blood Rev. 2011;25(4):155-167.

    Not in our library10.1016/j.blre.2011.03.002

  111. 111.

    Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev. 2013;93(1):327-358.

    Not in our library10.1152/physrev.00016.2011

  112. 112.

    Goerge T, Ho-Tin-Noe B, Carbo C, Benarafa C, Remold-O’Donnell E, Zhao BQ, et al. Inflammation induces hemorrhage in thrombocytopenia. Blood. 2008;111(10):4958-4964.

    Not in our library10.1182/blood-2007-11-123620

  113. 113.

    Mazzucco L, Borzini P, Gope R. Platelet-derived factors involved in tissue repair-from signal to function. Transfus Med Rev. 2010;24(3):218-234.

    Not in our library10.1016/j.tmrv.2010.03.004

  114. 114.

    Rafii S, Cao Z, Lis R, Siempos II, Chavez D, Shido K, et al. Platelet-derived SDF-1 primes the pulmonary capillary vascular niche to drive lung alveolar regeneration. Nat Cell Biol. 2015;17(2):123-136.

    Not in our library10.1038/ncb3096

  115. 115.

    Morel O, Toti F, Morel N, Freyssinet JM. Microparticles in endothelial cell and vascular homeostasis: are they really noxious? Haematologica. 2009;94(3):313-317.

    Not in our library10.3324/haematol.2008.003657

  116. 116.

    Yeaman MR. Platelets: at the nexus of antimicrobial defence. Nat Rev Microbiol. 2014;12(6):426-437.

    Not in our library10.1038/nrmicro3269

  117. 117.

    Cox D, Kerrigan SW, Watson SP. Platelets and the innate immune system: mechanisms of bacterial-induced platelet activation. J Thromb Haemost. 2011;9(6):1097-1107.

    Not in our library10.1111/j.1538-7836.2011.04264.x

  118. 118.

    Kerrigan SW. The expanding field of platelet-bacterial interconnections. Platelets. 2015;26(4):293-301.

    Not in our library10.3109/09537104.2014.997690

  119. 119.

    de Stoppelaar SF, Claushuis TA, Schaap MC, Hou B, van der Poll T, Nieuwland R, et al. Toll-like receptor signalling is not involved in platelet response to streptococcus pneumoniae in vitro or in vivo. PLoS ONE. 2016;11(6):e0156977.

    Not in our library10.1371/journal.pone.0156977

  120. 120.
    Platelets and Infections – Complex Interactions with Bacteria · 2015
    No notice
  121. 121.

    Fitzgerald JR, Foster TJ, Cox D. The interaction of bacterial pathogens with platelets. Nat Rev Microbiol. 2006;4(6):445-457.

    Not in our library10.1038/nrmicro1425

  122. 122.

    Chan JK, Roth J, Oppenheim JJ, Tracey KJ, Vogl T, Feldmann M, et al. Alarmins: awaiting a clinical response. J Clin Investig. 2012;122(8):2711-2719.

    Not in our library10.1172/jci62423

  123. 123.

    Semeraro F, Ammollo CT, Morrissey JH, Dale GL, Friese P, Esmon NL, et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood. 2011;118(7):1952-1961.

    Not in our library10.1182/blood-2011-03-343061

  124. 124.

    de Stoppelaar SF, van ‘t Veer C, van der Poll T. The role of platelets in sepsis. Thromb Haemost. 2014;112(4):666-677.

    Not in our library10.1160/th14-02-0126

  125. 125.

    Elzey BD, Sprague DL, Ratliff TL. The emerging role of platelets in adaptive immunity. Cell Immunol. 2005;238(1):1-9.

    Not in our library10.1016/j.cellimm.2005.12.005

  126. 126.

    Middleton E, Rondina MT. Platelets in infectious disease. Hematol Am Soc Hematol Educ Program. 2016;2016(1):256-261.

    Not in our library10.1182/asheducation-2016.1.256

  127. 127.

    Dankert J, van der Werff J, Zaat SA, Joldersma W, Klein D, Hess J. Involvement of bactericidal factors from thrombin-stimulated platelets in clearance of adherent viridans streptococci in experimental infective endocarditis. Infect Immun. 1995;63(2):663-671.

    Not in our library10.1128/iai.63.2.663-671.1995

  128. 128.

    McMorran BJ, Marshall VM, de Graaf C, Drysdale KE, Shabbar M, Smyth GK, et al. Platelets kill intraerythrocytic malarial parasites and mediate survival to infection. Science. 2009;323(5915):797-800.

    Not in our library10.1126/science.1166296

  129. 129.

    de Stoppelaar SF, van ‘t Veer C, Claushuis TA, Albersen BJ, Roelofs JJ, van der Poll T. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice. Blood. 2014;124(25):3781-3790.

    Not in our library10.1182/blood-2014-05-573915

  130. 130.

    Kahn F, Hurley S, Shannon O. Platelets promote bacterial dissemination in a mouse model of streptococcal sepsis. Microbes Infect. 2013;15(10–11):669-676.

    Not in our library10.1016/j.micinf.2013.05.003

  131. 131.

    Rittirsch D, Hoesel LM, Ward PA. The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol. 2007;81(1):137-143.

    Not in our library10.1189/jlb.0806542

  132. 132.

    Doi K, Leelahavanichkul A, Yuen PS, Star RA. Animal models of sepsis and sepsis-induced kidney injury. J Clin Investig. 2009;119(10):2868-2878.

    Not in our library10.1172/jci39421

  133. 133.

    Ward PA. New approaches to the study of sepsis. EMBO Mol Med. 2012;4(12):1234-1243.

    Not in our library10.1002/emmm.201201375

  134. 134.

    Fink MP. Animal models of sepsis. Virulence. 2014;5(1):143-153.

    Not in our library10.4161/viru.26083

  135. 135.

    Vincent JL. Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology. Crit Care. 2001;5(2):S1-S5.

    Not in our library10.1186/cc1332

  136. 136.

    Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood. 2003;101(10):3765-3777.

    Not in our library10.1182/blood-2002-06-1887

  137. 137.

    Bateman RM, Sharpe MD, Ellis CG. Bench-to-bedside review: microvascular dysfunction in sepsis–hemodynamics, oxygen transport, and nitric oxide. Crit Care. 2003;7(5):359-373.

    Not in our library10.1186/cc2353

  138. 138.

    Peters K, Unger RE, Brunner J, Kirkpatrick CJ. Molecular basis of endothelial dysfunction in sepsis. Cardiovasc Res. 2003;60(1):49-57.

    Not in our library10.1016/s0008-6363(03)00397-3

  139. 139.

    Warkentin TE, Aird WC, Rand JH. Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome. Hematol Am Soc Hematol Educ Program. 2003;2003:497-519.

    Not in our library10.1182/asheducation-2003.1.497

  140. 140.

    Matsuda N, Hattori Y. Vascular biology in sepsis: pathophysiological and therapeutic significance of vascular dysfunction. J Smooth Muscle Res. 2007;43(4):117-137.

    Not in our library10.1540/jsmr.43.117

  141. 141.

    Schouten M, Wiersinga WJ, Levi M, van der Poll T. Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol. 2008;83(3):536-545.

    Not in our library10.1189/jlb.0607373

  142. 142.

    Gando S. Microvascular thrombosis and multiple organ dysfunction syndrome. Crit Care Med. 2010;38(2 Suppl):S35-S42.

    Not in our library10.1097/ccm.0b013e3181c9e31d

  143. 143.

    Goldenberg NM, Steinberg BE, Slutsky AS, Lee WL. Broken barriers: a new take on sepsis pathogenesis. Sci Transl Med. 2011;3(88):88ps25.

    Not in our library10.1126/scitranslmed.3002011

  144. 144.

    Tyml K. Critical role for oxidative stress, platelets, and coagulation in capillary blood flow impairment in sepsis. Microcirculation. 2011;18(2):152-162.

    Not in our library10.1111/j.1549-8719.2010.00080.x

  145. 145.

    Boisrame-Helms J, Kremer H, Schini-Kerth V, Meziani F. Endothelial dysfunction in sepsis. Curr Vasc Pharmacol. 2013;11(2):150-160.

    Not in our library

  146. 146.

    De Backer D, Orbegozo Cortes D, Donadello K, Vincent JL. Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock. Virulence. 2014;5(1):73-79.

    Not in our library10.4161/viru.26482

  147. 147.

    Opal SM, van der Poll T. Endothelial barrier dysfunction in septic shock. J Int Med. 2015;277(3):277-293.

    Not in our library10.1111/joim.12331

  148. 148.

    Ince C, Mayeux PR, Nguyen T, Gomez H, Kellum JA, Ospina-Tascon GA, et al. The endothelium in sepsis. Shock. 2016;45(3):259-270.

    Not in our library10.1097/shk.0000000000000473

  149. 149.

    Xing K, Murthy S, Liles WC, Singh JM. Clinical utility of biomarkers of endothelial activation in sepsis–a systematic review. Crit Care. 2012;16(1):R7.

    Not in our library10.1186/cc11145

  150. 150.

    Ait-Oufella H, Maury E, Lehoux S, Guidet B, Offenstadt G. The endothelium: physiological functions and role in microcirculatory failure during severe sepsis. Intensive Care Med. 2010;36(8):1286-1298.

    Not in our library10.1007/s00134-010-1893-6

  151. 151.

    Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2013;369(18):1726-1734.

    Not in our library10.1056/nejmra1208943

  152. 152.

    Gawaz M, Dickfeld T, Bogner C, Fateh-Moghadam S, Neumann FJ. Platelet function in septic multiple organ dysfunction syndrome. Intensive Care Med. 1997;23(4):379-385.

    Not in our library10.1007/s001340050344

  153. 153.

    Hurley SM, Lutay N, Holmqvist B, Shannon O. The dynamics of platelet activation during the progression of streptococcal sepsis. PLoS ONE. 2016;11(9):e0163531.

    Not in our library10.1371/journal.pone.0163531

  154. 154.

    Levi M. Platelets in critical illness. Semin Thromb Hemost. 2016;42(3):252-257.

    Not in our library10.1055/s-0035-1570080

  155. 155.

    Heffner JE, Sahn SA, Repine JE. The role of platelets in the adult respiratory distress syndrome. Culprits or bystanders? Am Rev Respir Dis. 1987;135(2):482-492.

    Not in our library10.1164/arrd.1987.135.2.482

  156. 156.

    Bozza FA, Shah AM, Weyrich AS, Zimmerman GA. Amicus or adversary: platelets in lung biology, acute injury, and inflammation. Am J Respir Cell Mol Biol. 2009;40(2):123-134.

    Not in our library10.1165/rcmb.2008-0241tr

  157. 157.

    Reilly JP, Christie JD. Linking genetics to ARDS pathogenesis: the role of the platelet. Chest. 2015;147(3):585-586.

    Not in our library10.1378/chest.14-2701

  158. 158.

    Yadav H, Kor DJ. Platelets in the pathogenesis of acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol. 2015;28:ajplung 00266.

    Not in our library10.1152/ajplung.00266.2015

  159. 159.

    Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1334-1349.

    Not in our library10.1056/nejm200005043421806

  160. 160.

    Bhattacharya J, Matthay MA. Regulation and repair of the alveolar-capillary barrier in acute lung injury. Annu Rev Physiol. 2013;75:593-615.

    Not in our library10.1146/annurev-physiol-030212-183756

  161. 161.

    Kiefmann R, Heckel K, Schenkat S, Dorger M, Wesierska-Gadek J, Goetz AE. Platelet-endothelial cell interaction in pulmonary micro-circulation: the role of PARS. Thromb Haemost. 2004;91(4):761-770.

    Not in our library10.1160/th03-11-0685

  162. 162.

    Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Investig. 2006;116(12):3211-3219.

    Not in our library10.1172/jci29499

  163. 163.

    Looney MR, Nguyen JX, Hu Y, Van Ziffle JA, Lowell CA, Matthay MA. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. J Clin Investig. 2009;119(11):3450-3461.

    Not in our library10.1172/jci38432

  164. 164.

    Ortiz-Munoz G, Mallavia B, Bins A, Headley M, Krummel MF, Looney MR. Aspirin-triggered 15-epi-lipoxin A4 regulates neutrophil-platelet aggregation and attenuates acute lung injury in mice. Blood. 2014;124(17):2625-2634.

    Not in our library10.1182/blood-2014-03-562876

  165. 165.

    Katz JN, Kolappa KP, Becker RC. Beyond thrombosis: the versatile platelet in critical illness. Chest. 2011;139(3):658-668.

    Not in our library10.1378/chest.10-1971

  166. 166.

    Sharron M, Hoptay CE, Wiles AA, Garvin LM, Geha M, Benton AS, et al. Platelets induce apoptosis during sepsis in a contact-dependent manner that is inhibited by GPIIb/IIIa blockade. PLoS ONE. 2012;7(7):e41549.

    Not in our library10.1371/journal.pone.0041549

  167. 167.

    Brown KA, Brain SD, Pearson JD, Edgeworth JD, Lewis SM, Treacher DF. Neutrophils in development of multiple organ failure in sepsis. Lancet. 2006;368(9530):157-169.

    Not in our library10.1016/s0140-6736(06)69005-3

  168. 168.

    Zarbock A, Ley K. The role of platelets in acute lung injury (ALI). Front Biosci (Landmark Ed). 2009;01(14):150-158.

    Not in our library10.2741/3236

  169. 169.

    Idell S. Coagulation, fibrinolysis, and fibrin deposition in acute lung injury. Crit Care Med. 2003;31(4 Suppl):S213-S220.

    Not in our library10.1097/01.ccm.0000057846.21303.ab

  170. 170.

    Caudrillier A, Kessenbrock K, Gilliss BM, Nguyen JX, Marques MB, Monestier M, et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Investig. 2012;122(7):2661-2671.

    Not in our library10.1172/jci61303

  171. 171.

    McVey M, Tabuchi A, Kuebler WM. Microparticles and acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2012;303(5):L364-L381.

    Not in our library10.1152/ajplung.00354.2011

  172. 172.

    Asaduzzaman M, Lavasani S, Rahman M, Zhang S, Braun OO, Jeppsson B, et al. Platelets support pulmonary recruitment of neutrophils in abdominal sepsis. Crit Care Med. 2009;37(4):1389-1396.

    Not in our library10.1097/ccm.0b013e31819ceb71

  173. 173.

    Cloutier N, Pare A, Farndale RW, Schumacher HR, Nigrovic PA, Lacroix S, et al. Platelets can enhance vascular permeability. Blood. 2012;120(6):1334-1343.

    Not in our library10.1182/blood-2012-02-413047

  174. 174.

    Reddy AJ, Kleeberger SR. Genetic polymorphisms associated with acute lung injury. Pharmacogenomics. 2009;10(9):1527-1539.

    Not in our library10.2217/pgs.09.89

  175. 175.

    Wei Y, Wang Z, Su L, Chen F, Tejera P, Bajwa EK, et al. Platelet count mediates the contribution of a genetic variant in LRRC16A to ARDS risk. Chest. 2015;147(3):607-617.

    Not in our library10.1378/chest.14-1246

  176. 176.

    De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166(1):98-104.

    Not in our library10.1164/rccm.200109-016oc

  177. 177.

    Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004;351(2):159-169.

    Not in our library10.1056/nejmra032401

  178. 178.

    Langenberg C, Wan L, Egi M, May CN, Bellomo R. Renal blood flow in experimental septic acute renal failure. Kidney Int. 2006;69(11):1996-2002.

    Not in our library10.1038/sj.ki.5000440

  179. 179.

    Shum HP, Yan WW, Chan TM. Recent knowledge on the pathophysiology of septic acute kidney injury: a narrative review. J Crit Care. 2016;31(1):82-89.

    Not in our library10.1016/j.jcrc.2015.09.017

  180. 180.

    Post EH, Kellum JA, Bellomo R, Vincent JL. Renal perfusion in sepsis: from macro- to microcirculation. Kidney Int. 2017;91(1):45-60.

    Not in our library10.1016/j.kint.2016.07.032

  181. 181.

    Wan L, Bagshaw SM, Langenberg C, Saotome T, May C, Bellomo R. Pathophysiology of septic acute kidney injury: what do we really know? Crit Care Med. 2008;36(4 Suppl):S198-S203.

    Not in our library10.1097/ccm.0b013e318168ccd5

  182. 182.

    Lerolle N, Nochy D, Guerot E, Bruneval P, Fagon JY, Diehl JL, et al. Histopathology of septic shock induced acute kidney injury: apoptosis and leukocytic infiltration. Intensive Care Med. 2010;36(3):471-478.

    Not in our library10.1007/s00134-009-1723-x

  183. 183.

    Jacobs R, Honore PM, Joannes-Boyau O, Boer W, De Regt J, De Waele E, et al. Septic acute kidney injury: the culprit is inflammatory apoptosis rather than ischemic necrosis. Blood Purif. 2011;32(4):262-265.

    Not in our library10.1159/000330244

  184. 184.

    Takasu O, Gaut JP, Watanabe E, To K, Fagley RE, Sato B, et al. Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med. 2013;187(5):509-517.

    Not in our library10.1164/rccm.201211-1983oc

  185. 185.
    Renal blood flow in sepsis · 2005
    No notice
  186. 186.

    Prowle JR, Ishikawa K, May CN, Bellomo R. Renal blood flow during acute renal failure in man. Blood Purif. 2009;28(3):216-225.

    Not in our library10.1159/000230813

  187. 187.

    Chvojka J, Sykora R, Karvunidis T, Radej J, Krouzecky A, Novak I, et al. New developments in septic acute kidney injury. Physiol Res. 2010;59(6):859-869.

    Not in our library10.33549/physiolres.931936

  188. 188.

    Murugan R, Karajala-Subramanyam V, Lee M, Yende S, Kong L, Carter M, et al. Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival. Kidney Int. 2010;77(6):527-535.

    Not in our library10.1038/ki.2009.502

  189. 189.

    Kellum JA. Impaired renal blood flow and the ‘spicy food’ hypothesis of acute kidney injury. Crit Care Med. 2011;39(4):901-903.

    Not in our library10.1097/ccm.0b013e31820f70bb

  190. 190.

    Zarjou A, Agarwal A. Sepsis and acute kidney injury. J Am Soc Nephrol. 2011;22(6):999-1006.

    Not in our library10.1681/asn.2010050484

  191. 191.

    Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol. 2012;2(2):1303-1353.

    Not in our library10.1002/cphy.c110041

  192. 192.

    Gomez H, Ince C, De Backer D, Pickkers P, Payen D, Hotchkiss J, et al. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock. 2014;41(1):3-11.

    Not in our library10.1097/shk.0000000000000052

  193. 193.

    Umbro I, Gentile G, Tinti F, Muiesan P, Mitterhofer AP. Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury. J Infect. 2015;72:131-142.

    Not in our library10.1016/j.jinf.2015.11.008

  194. 194.

    Gomez H, Kellum JA. Sepsis-induced acute kidney injury. Curr Opin Crit Care. 2016;22(6):546-553.

    Not in our library10.1097/mcc.0000000000000356

  195. 195.

    Bellomo R, Kellum JA, Ronco C, Wald R, Martensson J, Maiden M, et al. Acute kidney injury in sepsis. Intensive Care Med. 2017;43(6):816-828.

    Not in our library10.1007/s00134-017-4755-7

  196. 196.

    Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Investig. 2011;121(11):4210-4221.

    Not in our library10.1172/jci45161

  197. 197.

    Zarbock A, Gomez H, Kellum JA. Sepsis-induced acute kidney injury revisited: pathophysiology, prevention and future therapies. Curr Opin Crit Care. 2014;20(6):588-595.

    Not in our library10.1097/mcc.0000000000000153

  198. 198.

    Glodowski SD, Wagener G. New insights into the mechanisms of acute kidney injury in the intensive care unit. J Clin Anesth. 2015;27(2):175-180.

    Not in our library10.1016/j.jclinane.2014.09.011

  199. 199.

    Schwarzenberger C, Sradnick J, Lerea KM, Goligorsky MS, Nieswandt B, Hugo CP, et al. Platelets are relevant mediators of renal injury induced by primary endothelial lesions. Am J Physiol Renal Physiol. 2015;308(11):F1238-F1246.

    Not in our library10.1152/ajprenal.00535.2014

  200. 200.
    Nanomechanics of the Endothelial Glycocalyx in Experimental Sepsis · 2013
    No notice
  201. 201.

    Becker BF, Jacob M, Leipert S, Salmon AH, Chappell D. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol. 2015;80(3):389-402.

    Not in our library10.1111/bcp.12629

  202. 202.
    Glycocalyx and sepsis-induced alterations in vascular permeability · 2015
    No notice
  203. 203.

    Martin L, Koczera P, Zechendorf E, Schuerholz T. The endothelial glycocalyx: new diagnostic and therapeutic approaches in sepsis. Biomed Res Int. 2016;2016:3758278.

    Not in our library10.1155/2016/3758278

  204. 204.

    Zuk A, Bonventre JV. Acute kidney injury. Annu Rev Med. 2016;14(67):293-307.

    Not in our library10.1146/annurev-med-050214-013407

  205. 205.

    Doi K, Rabb H. Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets. Kidney Int. 2016;89(3):555-564.

    Not in our library10.1016/j.kint.2015.11.019

  206. 206.

    Lapchak PH, Kannan L, Ioannou A, Rani P, Karian P, Dalle Lucca JJ, et al. Platelets orchestrate remote tissue damage after mesenteric ischemia-reperfusion. Am J Physiol Gastrointest Liver Physiol. 2012;302(8):G888-G897.

    Not in our library10.1152/ajpgi.00499.2011

  207. 207.

    Singbartl K, Bishop JV, Wen X, Murugan R, Chandra S, Filippi MD, et al. Differential effects of kidney-lung cross-talk during acute kidney injury and bacterial pneumonia. Kidney Int. 2011;80(6):633-644.

    Not in our library10.1038/ki.2011.201

  208. 208.

    Lapchak PH, Ioannou A, Kannan L, Rani P, Dalle Lucca JJ, Tsokos GC. Platelet-associated CD40/CD154 mediates remote tissue damage after mesenteric ischemia/reperfusion injury. PLoS ONE. 2012;7(2):e32260.

    Not in our library10.1371/journal.pone.0032260

  209. 209.

    Lapchak PH, Ioannou A, Rani P, Lieberman LA, Yoshiya K, Kannan L, et al. The role of platelet factor 4 in local and remote tissue damage in a mouse model of mesenteric ischemia/reperfusion injury. PLoS ONE. 2012;7(7):e39934.

    Not in our library10.1371/journal.pone.0039934

  210. 210.

    Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature. 1998;391(6667):591-594.

    Not in our library10.1038/35393

  211. 211.

    Frossard JL, Kwak B, Chanson M, Morel P, Hadengue A, Mach F. Cd40 ligand-deficient mice are protected against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury. Gastroenterology. 2001;121(1):184-194.

    Not in our library10.1053/gast.2001.25483

  212. 212.

    Hashimoto N, Kawabe T, Imaizumi K, Hara T, Okamoto M, Kojima K, et al. CD40 plays a crucial role in lipopolysaccharide-induced acute lung injury. Am J Respir Cell Mol Biol. 2004;30(6):808-815.

    Not in our library10.1165/rcmb.2003-0197oc

  213. 213.

    Rahman M, Zhang S, Chew M, Ersson A, Jeppsson B, Thorlacius H. Platelet-derived CD40L (CD154) mediates neutrophil upregulation of Mac-1 and recruitment in septic lung injury. Ann Surg. 2009;250(5):783-790.

    Not in our library10.1097/sla.0b013e3181bd95b7

  214. 214.

    Stephan F, Hollande J, Richard O, Cheffi A, Maier-Redelsperger M, Flahault A. Thrombocytopenia in a surgical ICU. Chest. 1999;115(5):1363-1370.

    Not in our library10.1378/chest.115.5.1363

  215. 215.

    Mavrommatis AC, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S. Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med. 2000;28(2):451-457.

    Not in our library10.1097/00003246-200002000-00027

  216. 216.

    Nijsten MW, ten Duis HJ, Zijlstra JG, Porte RJ, Zwaveling JH, Paling JC, et al. Blunted rise in platelet count in critically ill patients is associated with worse outcome. Crit Care Med. 2000;28(12):3843-3846.

    Not in our library10.1097/00003246-200012000-00017

  217. 217.

    Sharma B, Sharma M, Majumder M, Steier W, Sangal A, Kalawar M. Thrombocytopenia in septic shock patients–a prospective observational study of incidence, risk factors and correlation with clinical outcome. Anaesth Intensive Care. 2007;35(6):874-880.

    Not in our library10.1177/0310057x0703500604

  218. 218.

    Thiolliere F, Serre-Sapin AF, Reignier J, Benedit M, Constantin JM, Lebert C, et al. Epidemiology and outcome of thrombocytopenic patients in the intensive care unit: results of a prospective multicenter study. Intensive Care Med. 2013;39(8):1460-1468.

    Not in our library10.1007/s00134-013-2963-3

  219. 219.

    Williamson DR, Lesur O, Tetrault JP, Nault V, Pilon D. Thrombocytopenia in the critically ill: prevalence, incidence, risk factors, and clinical outcomes. Can J Anaesth. 2013;60(7):641-651.

    Not in our library10.1007/s12630-013-9933-7

  220. 220.

    Aydemir H, Piskin N, Akduman D, Kokturk F, Aktas E. Platelet and mean platelet volume kinetics in adult patients with sepsis. Platelets. 2015;26(4):331-335.

    Not in our library10.3109/09537104.2012.701027

  221. 221.

    Thiery-Antier N, Binquet C, Vinault S, Meziani F, Boisrame-Helms J, Quenot JP. Is thrombocytopenia an early prognostic marker in septic shock? Crit Care Med. 2016;44(4):764-772.

    Not in our library10.1097/ccm.0000000000001520

  222. 222.

    Greinacher A, Selleng K. Thrombocytopenia in the intensive care unit patient. Hematol Am Soc Hematol Educ Program. 2010;2010:135-143.

    Not in our library10.1182/asheducation-2010.1.135

  223. 223.

    Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, et al. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. 1995;274(12):968-974.

    Not in our library10.1001/jama.1995.03530120060042

  224. 224.

    Martin CM, Priestap F, Fisher H, Fowler RA, Heyland DK, Keenan SP, et al. A prospective, observational registry of patients with severe sepsis: the Canadian Sepsis Treatment and Response Registry. Crit Care Med. 2009;37(1):81-88.

    Not in our library10.1097/ccm.0b013e31819285f0

  225. 225.

    Selleng S, Malowsky B, Strobel U, Wessel A, Ittermann T, Wollert HG, et al. Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positive. J Thromb Haemost. 2010;8(1):30-36.

    Not in our library10.1111/j.1538-7836.2009.03626.x

  226. 226.

    Vandijck DM, Blot SI, De Waele JJ, Hoste EA, Vandewoude KH, Decruyenaere JM. Thrombocytopenia and outcome in critically ill patients with bloodstream infection. Heart Lung. 2010;39(1):21-26.

    Not in our library10.1016/j.hrtlng.2009.07.005

  227. 227.

    Lim SY, Jeon EJ, Kim HJ, Jeon K, Um SW, Koh WJ, et al. The incidence, causes, and prognostic significance of new-onset thrombocytopenia in intensive care units: a prospective cohort study in a Korean hospital. J Korean Med Sci. 2012;27(11):1418-1423.

    Not in our library10.3346/jkms.2012.27.11.1418

  228. 228.

    Lieberman L, Bercovitz RS, Sholapur NS, Heddle NM, Stanworth SJ, Arnold DM. Platelet transfusions for critically ill patients with thrombocytopenia. Blood. 2014;123(8):1146-1151.

    Not in our library10.1182/blood-2013-02-435693

  229. 229.

    Pene F, Benoit DD. Thrombocytopenia in the critically ill: considering pathophysiology rather than looking for a magic threshold. Intensive Care Med. 2013;39(9):1656-1659.

    Not in our library10.1007/s00134-013-3022-9

  230. 230.

    Greinacher A, Selleng S. How I evaluate and treat thrombocytopenia in the intensive care unit patient. Blood. 2016;128(26):3032-3042.

    Not in our library10.1182/blood-2016-09-693655

  231. 231.

    Ning S, Barty R, Liu Y, Heddle NM, Rochwerg B, Arnold DM. Platelet transfusion practices in the icu: data from a large transfusion registry. Chest. 2016;150(3):516-523.

    Not in our library10.1016/j.chest.2016.04.004

  232. 232.

    Antier N, Quenot JP, Doise JM, Noel R, Demaistre E, Devilliers H. Mechanisms and etiologies of thrombocytopenia in the intensive care unit: impact of extensive investigations. Ann Intensive Care. 2014;4:24.

    Not in our library10.1186/s13613-014-0024-x

  233. 233.

    Larkin CM, Santos-Martinez MJ, Ryan T, Radomski MW. Sepsis-associated thrombocytopenia. Thromb Res. 2016;141:11-16.

    Not in our library10.1016/j.thromres.2016.02.022

  234. 234.

    Pigozzi L, Aron JP, Ball J, Cecconi M. Understanding platelet dysfunction in sepsis. Intensive Care Med. 2016;42(4):583-586.

    Not in our library10.1007/s00134-015-4012-x

  235. 235.

    De Blasi RA, Cardelli P, Costante A, Sandri M, Mercieri M, Arcioni R. Immature platelet fraction in predicting sepsis in critically ill patients. Intensive Care Med. 2013;39(4):636-643.

    Not in our library10.1007/s00134-012-2725-7

  236. 236.

    Levi M. Platelets at a crossroad of pathogenic pathways in sepsis. J Thromb Haemost. 2004;2(12):2094-2095.

    Not in our library10.1111/j.1538-7836.2004.01004.x

  237. 237.

    Yaguchi A, Lobo FL, Vincent JL, Pradier O. Platelet function in sepsis. J Thromb Haemost. 2004;2(12):2096-2102.

    Not in our library10.1111/j.1538-7836.2004.01009.x

  238. 238.

    Goyette RE, Key NS, Ely EW. Hematologic changes in sepsis and their therapeutic implications. Semin Respir Crit Care Med. 2004;25(6):645-659.

    Not in our library10.1055/s-2004-860979

  239. 239.

    Arnold DM, Lim W. A rational approach to the diagnosis and management of thrombocytopenia in the hospitalized patient. Semin Hematol. 2011;48(4):251-258.

    Not in our library10.1053/j.seminhematol.2011.08.002

  240. 240.

    Thiele T, Selleng K, Selleng S, Greinacher A, Bakchoul T. Thrombocytopenia in the intensive care unit-diagnostic approach and management. Semin Hematol. 2013;50(3):239-250.

    Not in our library10.1053/j.seminhematol.2013.06.008

  241. 241.

    Smock KJ, Perkins SL. Thrombocytopenia: an update. Int J Lab Hematol. 2014;36(3):269-278.

    Not in our library10.1111/ijlh.12214

  242. 242.

    Thachil J, Warkentin TE. How do we approach thrombocytopenia in critically ill patients? Br J Haematol. 2017;177(1):27-38.

    Not in our library10.1111/bjh.14482

  243. 243.

    Remick DG. Cytokine therapeutics for the treatment of sepsis: why has nothing worked? Curr Pharm Des. 2003;9(1):75-82.

    Not in our library10.2174/1381612033392567

  244. 244.

    Thomas MR, Outteridge SN, Ajjan RA, Phoenix F, Sangha GK, Faulkner RE, et al. Platelet P2Y12 inhibitors reduce systemic inflammation and its prothrombotic effects in an experimental human model. Arterioscler Thromb Vasc Biol. 2015;35(12):2562-2570.

    Not in our library10.1161/atvbaha.115.306528

  245. 245.

    Winning J, Neumann J, Kohl M, Claus RA, Reinhart K, Bauer M, et al. Antiplatelet drugs and outcome in mixed admissions to an intensive care unit. Crit Care Med. 2010;38(1):32-37.

    Not in our library10.1097/ccm.0b013e3181b4275c

  246. 246.

    Erlich JM, Talmor DS, Cartin-Ceba R, Gajic O, Kor DJ. Prehospitalization antiplatelet therapy is associated with a reduced incidence of acute lung injury: a population-based cohort study. Chest. 2011;139(2):289-295.

    Not in our library10.1378/chest.10-0891

  247. 247.

    Losche W, Boettel J, Kabisch B, Winning J, Claus RA, Bauer M. Do aspirin and other antiplatelet drugs reduce the mortality in critically ill patients? Thrombosis. 2012;2012:720254.

    Not in our library10.1155/2012/720254

  248. 248.

    Eisen DP, Reid D, McBryde ES. Acetyl salicylic acid usage and mortality in critically ill patients with the systemic inflammatory response syndrome and sepsis. Crit Care Med. 2012;40(6):1761-1767.

    Not in our library10.1097/ccm.0b013e318246b9df

  249. 249.

    Valerio-Rojas JC, Jaffer IJ, Kor DJ, Gajic O, Cartin-Ceba R. Outcomes of severe sepsis and septic shock patients on chronic antiplatelet treatment: a historical cohort study. Crit Care Res Pract. 2013;2013:782573.

    Not in our library10.1155/2013/782573

  250. 250.

    Sossdorf M, Otto GP, Boettel J, Winning J, Losche W. Benefit of low-dose aspirin and non-steroidal anti-inflammatory drugs in septic patients. Crit Care. 2013;17(1):402.

    Not in our library10.1186/cc11886

  251. 251.

    Otto GP, Sossdorf M, Boettel J, Kabisch B, Breuel H, Winning J, et al. Effects of low-dose acetylsalicylic acid and atherosclerotic vascular diseases on the outcome in patients with severe sepsis or septic shock. Platelets. 2013;24(6):480-485.

    Not in our library10.3109/09537104.2012.724482

  252. 252.

    Akinosoglou K, Alexopoulos D. Use of antiplatelet agents in sepsis: a glimpse into the future. Thromb Res. 2014;133(2):131-138.

    Not in our library10.1016/j.thromres.2013.07.002

  253. 253.

    Chen W, Janz DR, Bastarache JA, May AK, O’Neal HR, Bernard GR, et al. Prehospital aspirin use is associated with reduced risk of acute respiratory distress syndrome in critically ill patients: a propensity-adjusted analysis. Crit Care Med. 2015;43(4):801-807.

    Not in our library10.1097/ccm.0000000000000789

  254. 254.

    Toner P, McAuley DF, Shyamsundar M. Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome. Crit Care. 2015;19:374.

    Not in our library10.1186/s13054-015-1091-6

  255. 255.

    Tsai MJ, Ou SM, Shih CJ, Chao PW, Wang LF, Shih YN, et al. Association of prior antiplatelet agents with mortality in sepsis patients: a nationwide population-based cohort study. Intensive Care Med. 2015;41(5):806-813.

    Not in our library10.1007/s00134-015-3760-y

  256. 256.

    Kor DJ, Erlich J, Gong MN, Malinchoc M, Carter RE, Gajic O, et al. Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients. Crit Care Med. 2011;39(11):2393-2400.

    Not in our library10.1097/ccm.0b013e318225757f

  257. 257.

    Gum PA, Kottke-Marchant K, Poggio ED, Gurm H, Welsh PA, Brooks L, et al. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol. 2001;88(3):230-235.

    Not in our library10.1016/s0002-9149(01)01631-9

  258. 258.

    Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol. 2005;45(8):1157-1164.

    Not in our library10.1016/j.jacc.2005.01.034

  259. 259.

    Macchi L, Sorel N, Christiaens L. Aspirin resistance: definitions, mechanisms, prevalence, and clinical significance. Curr Pharm Des. 2006;12(2):251-258.

    Not in our library10.2174/138161206775193064

  260. 260.

    Wiewel MA, de Stoppelaar SF, van Vught LA, Frencken JF, Hoogendijk AJ, Klein Klouwenberg PM, et al. Chronic antiplatelet therapy is not associated with alterations in the presentation, outcome, or host response biomarkers during sepsis: a propensity-matched analysis. Intensive Care Med. 2016;42(3):352-360.

    Not in our library10.1007/s00134-015-4171-9

  261. 261.

    Muhlestein JB. Effect of antiplatelet therapy on inflammatory markers in atherothrombotic patients. Thromb Haemost. 2010;103(1):71-82.

    Not in our library10.1160/th09-03-0177

  262. 262.

    Zakynthinos SG, Papanikolaou S, Theodoridis T, Zakynthinos EG, Christopoulou-Kokkinou V, Katsaris G, et al. Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients. Crit Care Med. 2004;32(4):1004-1010.

    Not in our library10.1097/01.ccm.0000121433.61546.a0

  263. 263.

    Lupia E, Goffi A, Bosco O, Montrucchio G. Thrombopoietin as biomarker and mediator of cardiovascular damage in critical diseases. Mediat Inflamm. 2012;2012:390892.

    Not in our library10.1155/2012/390892

  264. 264.

    Cuccurullo A, Greco E, Lupia E, De Giuli P, Bosco O, Martin-Conte E, et al. Blockade of thrombopoietin reduces organ damage in experimental endotoxemia and polymicrobial sepsis. PLoS ONE. 2016;11(3):e0151088.

    Not in our library10.1371/journal.pone.0151088

  265. 265.

    Wu Q, Ren J, Wu X, Wang G, Gu G, Liu S, et al. Recombinant human thrombopoietin improves platelet counts and reduces platelet transfusion possibility among patients with severe sepsis and thrombocytopenia: a prospective study. J Crit Care. 2014;29(3):362-366.

    Not in our library10.1016/j.jcrc.2013.11.023

  266. 266.

    Van Deuren M, Neeleman C, Van ‘t Hek LG, Van der Meer JW. A normal platelet count at admission in acute meningococcal disease does not exclude a fulminant course. Intensive Care Med. 1998;24(2):157-161.

    Not in our library10.1007/s001340050538

  267. 267.

    Agrawal S, Sachdev A, Gupta D, Chugh K. Platelet counts and outcome in the pediatric intensive care unit. Indian J Crit Care Med. 2008;12(3):102-108.

    Not in our library10.4103/0972-5229.43678

  268. 268.

    Wang L, Li H, Gu X, Wang Z, Liu S, Chen L. Effect of antiplatelet therapy on acute respiratory distress syndrome and mortality in critically ill patients: a meta-analysis. PLoS ONE. 2016;11(5):e0154754.

    Not in our library10.1371/journal.pone.0154754

  269. 269.

    Kor DJ, Carter RE, Park PK, Festic E, Banner-Goodspeed VM, Hinds R, et al. Effect of aspirin on development of ARDS in at-risk patients presenting to the emergency department: the LIPS-A randomized clinical trial. JAMA. 2016;315(22):2406-2414.

    Not in our library10.1001/jama.2016.6330

  270. 270.

    Osthoff M, Sidler JA, Lakatos B, Frei R, Dangel M, Weisser M, et al. Low-dose acetylsalicylic acid treatment and impact on short-term mortality in Staphylococcus aureus bloodstream infection: a propensity score-matched cohort study. Crit Care Med. 2016;44(4):773-781.

    Not in our library10.1097/ccm.0000000000001554

  271. 271.

    Boyle AJ, Di Gangi S, Hamid UI, Mottram LJ, McNamee L, White G, et al. Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis. Crit Care. 2015;19:109.

    Not in our library10.1186/s13054-015-0846-4

  272. 272.

    O’Neal HR, Koyama T, Koehler EA, Siew E, Curtis BR, Fremont RD, et al. Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome. Crit Care Med. 2011;39(6):1343-1350.

    Not in our library10.1097/ccm.0b013e3182120992

  273. 273.

    Storey RF, James SK, Siegbahn A, Varenhorst C, Held C, Ycas J, et al. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study. Platelets. 2014;25(7):517-525.

    Not in our library10.3109/09537104.2013.842965

  274. 274.

    Winning J, Reichel J, Eisenhut Y, Hamacher J, Kohl M, Deigner HP, et al. Anti-platelet drugs and outcome in severe infection: clinical impact and underlying mechanisms. Platelets. 2009;20(1):50-57.

    Not in our library10.1080/09537100802503368

  275. 275.

    Gross AK, Dunn SP, Feola DJ, Martin CA, Charnigo R, Li Z, et al. Clopidogrel treatment and the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness. J Thromb Thrombolysis. 2013;35(2):147-154.

    Not in our library10.1007/s11239-012-0833-4

Cited by papers we hold 2

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.