Clin Chem Lab Med 2014; 52(10): 1479–1483 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* May thrombopoietin be a useful marker of sepsis severity assessment in patients with SIRS entering the emergency department? Abstract Background: Thrombopoietin (TPO), a growth factor pri- marily 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 meas- ured by ELISA. Results: We enrolled 13 patients with SIRS (6 with acute pancreatitis, 3 with acute heart failure, 1 with pulmo- nary 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 enter- ing the ED. Keywords: biomarker; sepsis; systemic inflammatory response syndrome (SIRS); thrombopoietin. DOI 10.1515/cclm-2014-0219 Received February 27, 2014; accepted April 15, 2014; previously pub- lished online May 29, 2014 Introduction Thrombopoietin (TPO) is a humoral growth factor mainly characterized for its ability to stimulate the proliferation and differentiation of megakaryocytes [1, 2]. It is consti- tutively produced by the liver and kidneys, and acts by stimulating its receptor, c-Mpl [3, 4]. Upon TPO binding, c-Mpl receptors undergo homodimerization to initiate intracellular signaling, including activation of the JAK2/ signal transducers and activators of transcription (STAT) pathway [5]. Elevated plasma TPO levels have been reported in different clinical conditions, including several hemato- logical diseases usually associated with thrombocytope- nia, where increased circulating TPO may be a response to altered bone marrow hematopoiesis or bone marrow failure [18–20]. In addition to its role in thrombopoiesis, TPO also directly modulates the homeostatic potential of mature platelets. In particular, although unable to induce plate- let aggregation per se, TPO enhances platelet activation and platelet-leukocyte adhesion in response to different agonists [6–8]. This ‘priming’ action exerted by TPO on platelet activation and platelet-leukocyte interaction may have *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 Elisabetta Segre, Luca Pigozzi, Davide Lison, Emanuele Pivetta, Umberto Suppo, Fabrizio Turvani and Enrico Lupia: Department of Medical Sciences, University of Turin, Turin, Italy; and Emergency Medicine Unit, ‘Città della Salute e della Scienza di Torino’ Hospital, Turin, Italy Ornella Bosco, Barbara Vizio and Giuseppe Montrucchio: Department of Medical Sciences, University of Turin, Turin, Italy Fulvio Morello, Stefania Battista and Corrado Moiraghi: Emergency Medicine Unit, ‘Città della Salute e della Scienza di Torino’ Hospital, Turin, Italy Brought to you by | Tokyo Daigaku Authenticated Download Date | 5/21/15 12:18 PM