May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department?

Elisabetta Segre; Luca Pigozzi; Davide Lison; Emanuele Pivetta; Ornella Bosco; Barbara Vizio; Umberto Suppo; Fabrizio Turvani; Fulvio Morello; Stefania Battista; Corrado Moiraghi; Giuseppe Montrucchio; Enrico Lupia

doi:10.1515/cclm-2014-0219

Article

May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department?

Elisabetta Segre , Luca Pigozzi , Davide Lison , Emanuele Pivetta , Ornella Bosco , Barbara Vizio , Umberto Suppo , Fabrizio Turvani , Fulvio Morello , Stefania Battista , Corrado Moiraghi , Giuseppe Montrucchio and Enrico Lupia

Published/Copyright: May 29, 2014

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 52 Issue 10

Abstract

Background: Thrombopoietin (TPO), a growth factor primarily involved in regulating thrombopoiesis, has been recently implicated in the pathogenesis of sepsis. TPO levels are, indeed, greatly increased in patients with sepsis compared to control subjects, and correlate with sepsis severity. The aim of this study was to evaluate TPO as predictive biomarker of sepsis and of sepsis severity in patients entering the emergency department (ED) with systemic inflammatory response syndrome (SIRS).

Methods: This was a prospective observational study. Ours is a sub-study of the ‘Need-speed trial’, a multi-center observational study involving six Italian centers affiliated to the GREAT Italian Network. TPO was measured by ELISA.

Results: We enrolled 13 patients with SIRS (6 with acute pancreatitis, 3 with acute heart failure, 1 with pulmonary embolism, and 3 with allergic reactions), and 40 patients with sepsis, eight of whom had severe sepsis and three septic shock. TPO was significantly higher in patients with sepsis than with SIRS. In addition, TPO was higher in patients with severe sepsis than with sepsis, and in patients with septic shock than with severe sepsis, although these differences did not reach the statistical significance.

Conclusions: Our preliminary results suggest that TPO may have the potential to be considered a promising early biomarker for both the diagnosis of sepsis and the assessment of sepsis severity in patients with SIRS entering the ED.

Keywords: biomarker; sepsis; systemic inflammatory response syndrome (SIRS); thrombopoietin

Corresponding author: Enrico Lupia, MD, Department of Medical Sciences, University of Turin, Via Genova 3, 10126, Torino, Italy, Phone: +39 011 6705395, Fax: +39 011 6705367, E-mail: enrico.lupia@unito.it

Acknowledgments

This work was supported by Ministero dell’Università e della Ricerca Scientifica e Tecnologica (MURST) ex-60%, and Progetto di Ricerca Sanitaria Finalizzata – Regione Piemonte to GM and EL.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Kaushansky K. Thrombopoietin: a tool for understanding thrombopoiesis. J Thromb Haemost 2003;1:1587–92.10.1046/j.1538-7836.2003.00273.xSearch in Google Scholar

2. Chou FS, Mulloy JC. The thrombopoietin/Mpl pathway in hematopoiesis and leukemogenesis. J Cell Biochem 2011;112:1491–8.10.1002/jcb.23089Search in Google Scholar

3. Bartley TD, Bogenberger J, Hunt P, Li YS, Lu HS, Martin F, et al. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell 1994;77:1117–24.10.1016/0092-8674(94)90450-2Search in Google Scholar

4. de Sauvage FJ, Hass PE, Spencer SD, Malloy BE, Gurney AL, Spencer SA, et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 1994;369: 533–8.10.1038/369533a0Search in Google Scholar

5. Ezumi Y, Takayama H, Okuma M. Thrombopoietin, c-Mpl ligand, induces tyrosine phosphorylation of TYK2, JAK2, and STAT3, and enhances agonists-induced aggregation in platelets in vitro. FEBS Lett 1995;374:48–52.10.1016/0014-5793(95)01072-MSearch in Google Scholar

6. Montrucchio G, Brizzi MF, Calosso G, Marengo S, Pegoraro L, Camussi G. Effects of recombinant human megakaryocyte growth and development factor on platelet activation. Blood 1996;87:2762–8.10.1182/blood.V87.7.2762.bloodjournal8772762Search in Google Scholar

7. Oda A, Miyakawa Y, Druker BJ, Ozaki K, Yabusaki K, Shirasawa Y, et al. Thrombopoietin primes human platelet aggregation induced by shear stress and by multiple agonists. Blood 1996;87:4664–70.10.1182/blood.V87.11.4664.bloodjournal87114664Search in Google Scholar

8. Tibbles HE, Navara CS, Hupke MA, Vassilev AO, Uckun FM. Thrombopoietin induces p-selectin expression on platelets and subsequent platelet/leukocyte interactions. Biochem Biophys Res Commun 2002;292:987–91.10.1006/bbrc.2002.6759Search in Google Scholar PubMed

9. Lupia E, Bosco O, Bergerone S, Dondi AE, Goffi A, Oliaro E, et al. Thrombopoietin contributes to enhanced platelet activation in patients with unstable angina. J Am Coll Cardiol 2006;48: 2195–203.10.1016/j.jacc.2006.04.106Search in Google Scholar PubMed

10. Lupia E, Bosco O, Goffi A, Poletto C, Locatelli S, Spatola T, et al. Thrombopoietin contributes to enhanced platelet activation in cigarette smokers. Atherosclerosis 2010;210:314–9.10.1016/j.atherosclerosis.2009.11.019Search in Google Scholar PubMed

11. Lupia E, Goffi A, Bosco O, Montrucchio G. Thrombopoietin as biomarker and mediator of cardiovascular damage in critical diseases. Mediators Inflamm 2012;2012:390892.10.1155/2012/390892Search in Google Scholar PubMed PubMed Central

12. Zakynthinos SG, Papanikolaou S, Theodoridis T, Zakynthinos EG, Christopoulou-Kokkinou V, et al. Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients. Crit Care Med 2004;32:1004–10.10.1097/01.CCM.0000121433.61546.A0Search in Google Scholar PubMed

13. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2012;41:580–637.10.1097/CCM.0b013e31827e83afSearch in Google Scholar PubMed

14. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:840–51.10.1056/NEJMra1208623Search in Google Scholar PubMed

15. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368–77.10.1056/NEJMoa010307Search in Google Scholar PubMed

16. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2012;39:165–228.10.1007/s00134-012-2769-8Search in Google Scholar PubMed PubMed Central

17. Levy MM, Macias WL, Vincent JL, Russell JA, Silva E, Trzaskoma B, et al. Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med 2005;33:2194–201.10.1097/01.CCM.0000182798.39709.84Search in Google Scholar PubMed

18. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589–96.10.1097/01.CCM.0000217961.75225.E9Search in Google Scholar PubMed

19. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546–54.10.1056/NEJMoa022139Search in Google Scholar PubMed

20. Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current epidemiology of septic shock: the CUB-Rea network. Am J Respir Crit Care Med 2003;168:165–72.10.1164/rccm.2201087Search in Google Scholar PubMed

21. Ventetuolo CE, Levy MM. Biomarkers: diagnosis and risk assessment in sepsis. Clin Chest Med 2008;29:591–603, vii.10.1016/j.ccm.2008.07.001Search in Google Scholar PubMed

22. Vincent JL, Beumier M. Diagnostic and prognostic markers in sepsis. Expert Rev Anti Infect Ther 2013;11:265–75.10.1586/eri.13.9Search in Google Scholar PubMed

23. Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci 2013; 50:23–36.10.3109/10408363.2013.764490Search in Google Scholar PubMed PubMed Central

24. Chan T, Gu F. Early diagnosis of sepsis using serum biomarkers. Expert Rev Mol Diagn 2011;11:487–96.10.1586/erm.11.26Search in Google Scholar PubMed

25. 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;81:613–7.10.1055/s-0037-1614534Search in Google Scholar

26. Ishiguro A, Suzuki Y, Mito M, Shimbo T, Matsubara K, Kato T, et al. Elevation of serum thrombopoietin precedes thrombocytosis in acute infections. Br J Haematol 2002;116:612–8.10.1046/j.0007-1048.2001.03304.xSearch in Google Scholar PubMed

27. Colarizi P, Fiorucci P, Caradonna A, Ficuccilli F, Mancuso M, Papoff P. Circulating thrombopoietin levels in neonates with infection. Acta Paediatr 1999;88:332–7.10.1111/j.1651-2227.1999.tb01107.xSearch in Google Scholar

28. Bjerre A, Ovstebo R, Kierulf P, Halvorsen S, Brandtzaeg P. Fulminant meningococcal septicemia: dissociation between plasma thrombopoietin levels and platelet counts. Clin Infect Dis 2000;30:643–7.10.1086/313754Search in Google Scholar PubMed

29. Reinhold A, Zhang J, Gessner R, Felderhoff-Mueser U, Obladen M, Dame C. High thrombopoietin concentrations in the cerebrospinal fluid of neonates with sepsis and intraventricular hemorrhage may contribute to brain damage. J Interferon Cytokine Res 2007;27:137–45.10.1089/jir.2006.0096Search in Google Scholar PubMed

30. Oygur N, Tunga M, Mumcu Y, Yesilipek A, Gura A, Coskun M, et al. Thrombopoietin levels of thrombocytopenic term and preterm newborns with infection. Am J Perinatol 2001;18: 279–86.10.1055/s-2001-16990Search in Google Scholar PubMed

31. Folman CC, Linthorst GE, van Mourik J, van Willigen G, de Jonge E, Levi M, et al. Platelets release thrombopoietin (TPO) upon activation: another regulatory loop in thrombocytopoiesis? Thromb Haemost 2000;83:923–30.10.1055/s-0037-1613944Search in Google Scholar

32. Lupia E, Bosco O, Mariano F, Dondi AE, Goffi A, Spatola T, et al. Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation. J Thromb Haemost 2009;7:1000–8.10.1111/j.1538-7836.2009.03348.xSearch in Google Scholar PubMed

33. Lupia E, Spatola T, Cuccurullo A, Bosco O, Mariano F, Pucci A, et al. Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum. Basic Res Cardiol 2010;105:609–20.10.1007/s00395-010-0103-6Search in Google Scholar PubMed

Received: 2014-2-27

Accepted: 2014-4-15

Published Online: 2014-5-29

Published in Print: 2014-10-1

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Articles in the same Issue

https://doi.org/10.1515/cclm-2014-0219

Keywords for this article

biomarker; sepsis; systemic inflammatory response syndrome (SIRS); thrombopoietin