Thrombocytes in sepsis

Authors: Karvunidis Thomas 1;  Chvojka Jiří 1;  Lysák Daniel 2;  Kroužecký Aleš 1;  Raděj Jaroslav 1;  Novák Ivan 1;  Matějovič Martin 1
Authors‘ workplace: I. interní klinika, Jednotka intenzivní péče, Univerzita Karlova v Praze, Lékařská fakulta v Plzni a Fakultní nemocnice Plzeň 1;  Hematologicko-onkologické oddělení, Fakultní nemocnice Plzeň 2
Published in: Anest. intenziv. Med., 21, 2010, č. 6, s. 342-350
Category: Intensive Care Medicine - Review Article


Sepsis and septic shock are the most frequent causes of death in intensive care units. Thrombocytopenia and/or platelet function impairment are common parts of the multiple organ dysfunction syndrome. However, thrombocytes are not mere bystanders as documented in the present literature. Platelets, primary actors in haemostasis and thrombin generation during endothelial integrity disruption, similarly to leukocytes, maintain important functions of innate defense mechanisms of the host. These cellular fragments express and secrete numbers of adhesive and pro-inflammatory molecules that serve to initiate and modulate the primary immune response. Such haemostatic and especially non-haemostatic functions of platelets and their role in the pathogenesis of systemic inflammation will be discussed in this review.

platelets – sepsis – innate immunity – intercellular interaction


1. Martin, G. S., Mannino, D. M., Eaton, S. et al. The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med., 2003, 348, p. 1546–1554.

2. Annane, D., Bellissant, E., Cavaillon, J. M. Septic shock. Lancet, 2005, 365, p. 63–78.

3. Folman, C. C., Linthorst, G. E., van, M. J. et al. Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis? Thromb. Haemost., 2000, 83, p. 923–930.

4. Stohlawetz, P., Folman, C. C., von dem Borne, A. E. et al. Effects of endotoxemia on thrombopoiesis in men. Thromb. Haemost., 1999, 81, p. 613–617.

5. Kaushansky, K. Thrombopoietin. N. Engl. J. Med., 1998, 339, p. 746–754.

6. Jurk, K., Kehrel, B. E. Platelets: physiology and biochemistry. Semin. Thromb. Hemost., 2005, 31, p. 381–392.

7. Smyth, S. S., McEver, R. P., Weyrich, A. S. et al. Platelet functions beyond hemostasis. J. Thromb. Haemost., 2009, 7, p. 1759–1766.

8. Levi, M. Platelets. Crit. Care Med., 2005, 33, p. S523–S525.

9. Levi, M. Platelets at a crossroad of pathogenic pathways in sepsis. J. Thromb. Haemost., 2004, 2, p. 2094–2095.

10. Vincent, J. L., Yagushi, A., Pradier, O. Platelet function in sepsis. Crit. Care Med., 2002, 30, p. S313–S317.

11. Vanderschueren, S., De, W. A., Malbrain, M. et al. Thrombocytopenia and prognosis in intensive care. Crit. Care Med., 2000, 28, p. 1871–1876.

12. Strauss, R., Wehler, M., Mehler, K. et al. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome. Crit. Care Med., 2002, 30, p. 1765–1771.

13. Akca, S., Haji-Michael, P., de, M. A. et al. Time course of platelet counts in critically ill patients. Crit. Care Med., 2002, 30, p. 753–756.

14. Francois, B., Trimoreau, F., Vignon, P. et al. Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor. Am. J. Med., 1997, 103, p. 114–120.

15. Zimmerman, G. A., McIntyre, T. M., Prescott, S. M. et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit. Care Med., 2002, 30, p. S294–S301.

16. Weyrich, A. S., Zimmerman, G. A. Platelets: signaling cells in the immune continuum. Trends Immunol., 2004, 25, p. 489–495.

17. Levi, M., Lowenberg, E. C. Thrombocytopenia in critically ill patients. Semin. Thromb. Hemost., 2008, 34, p. 417–424.

18. Oppenheim-Eden, A., Glantz, L., Eidelman, L. A. et al. Spontaneous intracerebral hemorrhage in critically ill patients: incidence over six years and associated factors. Intensive Care Med., 1999, 25, p. 63–67.

19. Russwurm, S., Vickers, J., Meier-Hellmann, A. et al. Platelet and leukocyte activation correlate with the severity of septic organ dysfunction. Shock, 2002, 17, p. 263–268.

20. Levi, M. Platelets in sepsis. Hematology., 2005, 10 Suppl 1, p. 129–131.

21. Levi, M. Platelets. Crit. Care Med., 2005, 33, p. S523–S525.

22. Zarbock, A., Polanowska-Grabowska, R. K., Ley, K. Platelet-neutrophil-interactions: linking hemostasis and inflammation. Blood Rev., 2007, 21, p. 99–111.

23. von, H. P., Weber, C. Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ. Res., 2007, 100, p. 27–40.

24. Semple, J. W., Freedman, J. Platelets and innate immunity. Cell Mol. Life Sci., 2010, 67, p. 499–511.

25. Fox, J. E. The platelet cytoskeleton. Thromb. Haemost., 1993, 70, p. 884–893.

26. Puccetti, L., Pasqui, A. L., Pastorelli, M. et al. Platelet hyperactivity after statin treatment discontinuation. Thromb. Haemost., 2003, 90, p. 476–482.

27. Yaguchi, A., Lobo, F. L., Vincent, J. L. et al. Platelet function in sepsis. J. Thromb. Haemost., 2004, 2, p. 2096–2102.

28. Weyrich, A. S., Schwertz, H., Kraiss, L. W. et al. Protein synthesis by platelets: historical and new perspectives. J. Thromb. Haemost., 2009, 7, p. 241–246.

29. van der, F. M., van Leeuwen, H. J., van Kessel, K. P. et al. Plasma vascular endothelial growth factor in severe sepsis. Shock, 2005, 23, p. 35–38.

30. Yano, K., Liaw, P. C., Mullington, J. M. et al. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. J. Exp. Med., 2006, 203, p. 1447–1458.

31. Annane, D., Bellissant, E., Cavaillon, J. M. Septic shock. Lancet, 2005, 365, p. 63–78.

32. Tsiotou, A. G., Sakorafas, G. H., Anagnostopoulos, G. et al. Septic shock; current pathogenetic concepts from a clinical perspective. Med. Sci. Monit., 2005, 11, p. RA76–RA85.

33. Brown, K. A., Brain, S. D., Pearson, J. D. et al. Neutrophils in development of multiple organ failure in sepsis. Lancet, 2006, 368, p. 157–169.

34. Elzey, B. D., Tian, J., Jensen, R. J. et al. Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments. Immunity, 2003, 19, p. 9–19.

35. Annane, D., Bellissant, E., Cavaillon, J. M. Septic shock. Lancet, 2005, 365, p. 63–78.

36. Matsuda, N., Hattori, Y. Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy. J. Pharmacol. Sci., 2006, 101, p. 189–198.

37. McGettrick, A. F., O’Neill, L. A. Toll-like receptors: key activators of leucocytes and regulator of haematopoiesis. Br. J. Haematol., 2007, 139, p. 185–193.

38. Shiraki, R., Inoue, N., Kawasaki, S. et al. Expression of Toll--like receptors on human platelets. Thromb. Res., 2004, 113, p. 379–385.

39. Andonegui, G., Kerfoot, S. M., McNagny, K. et al. Platelets express functional Toll-like receptor-4. Blood, 2005, 106, p. 2417–2423.

40. Beaulieu, L. M., Freedman, J. E. The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes. Thromb. Res., 2010, 125, p. 205–209.

41. Ishii, K. J., Akira, S. Toll-like Receptors and Sepsis. Curr. Infect. Dis. Rep., 2004, 6, p. 361–366.

42. Aslam, R., Speck, E. R., Kim, M. et al. Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo. Blood, 2006, 107, p. 637–641.

43. Alves-Filho, J. C. Toll-like receptors on platelets: the key for disseminated intravascular coagulation in sepsis? Thromb. Res., 2005, 115, p. 537–538.

44. Jayachandran, M., Brunn, G. J., Karnicki, K. et al. In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: implications for thrombotic risk. J. Appl. Physiol., 2007, 102, p. 429–433.

45. Lewis, J. C., Maldonado, J. E., Mann, K. G. Phagocytosis in human platelets: localization of acid phosphatase-positive phagosomes following latex uptake. Blood, 1976, 47, p. 833–840.

46. White, J. G. Platelets are covercytes, not phagocytes: uptake of bacteria involves channels of the open canalicular system. Platelets., 2005, 16, p. 121–131.

47. Diacovo, T. G., deFougerolles, A. R., Bainton, D. F. et al. A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2. J. Clin. Invest, 1994, 94, p. 1243–1251.

48. Peters, M. J., Heyderman, R. S., Hatch, D. J. et al. Investigation of platelet-neutrophil interactions in whole blood by flow cytometry. J. Immunol. Methods, 1997, 209, p. 125–135.

49. Clark, S. R., Ma, A. C., Tavener, S. A. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat. Med., 2007, 13, p. 463–469.

50. Brinkmann, V., Reichard, U., Goosmann, C. et al. Neutrophil extracellular traps kill bacteria. Science, 2004, 303, p. 1532–1535.

51. Ma, A. C., Kubes, P. Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis. J. Thromb. Haemost., 2008, 6, p. 415–420.

52. Inwald, D. P., McDowall, A., Peters, M. J. et al. CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation. Circ. Res., 2003, 92, p. 1041–1048.

53. Henn, V., Slupsky, J. R., Grafe, M. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature, 1998, 391, p. 591–594.

54. Pignatelli, P., Sanguigni, V., Lenti, L. et al. gp91phox-dependent expression of platelet CD40 ligand. Circulation, 2004, 110, p. 1326–1329.

55. Danese, S., de la, M. C., Reyes, B. M. et al. Cutting edge: T cells trigger CD40-dependent platelet activation and granular RANTES release: a novel pathway for immune response amplification. J. Immunol., 2004, 172, p. 2011–2015.

56. Elzey, B. D., Tian, J., Jensen, R. J. et al. Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments. Immunity., 2003, 19, p. 9–19.

57. Henn, V., Steinbach, S., Buchner, K. et al. The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40. Blood, 2001, 98, p. 1047–1054.

58. Clemetson, K. J. Platelets and pathogens. Cell Mol. Life Sci., 2010, 67, p. 495–498.

59. Yeaman, M. R. Platelets in defense against bacterial pathogens. Cell Mol. Life Sci., 2010, 67, p. 525–544.

60. Yeaman, M. R. Bacterial-platelet interactions: virulence meets host defense. Future. Microbiol., 2010, 5, p. 471–506.

61. Kerrigan, S. W., Cox, D. Platelet-bacterial interactions. Cell Mol. Life Sci., 2010, 67, p. 513–523.

62. Peng, J., Gygi, S. P. Proteomics: the move to mixtures. J. Mass Spectrom., 2001, 36, p. 1083–1091.

63. Karvunidis, T., Mares, J., Thongboonkerd, V. et al. Recent progress of proteomics in critical illness. Shock, 2009, 31, p. 545–552.

64. Garcia, A., Watson, S. P., Dwek, R. A. et al. Applying proteomics technology to platelet research. Mass Spectrom. Rev., 2005, 24, p. 918–930.

65. Kor, D. J., Gajic, O. Blood product transfusion in the critical care setting. Curr. Opin. Crit. Care, 2010, 16, p. 309–316.

Anaesthesiology, Resuscitation and Inten Intensive Care Medicine
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account