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Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality

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Abstract

Purpose

Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis.

Methods

This study is based on a prospective trial regarding the impact of glycemic control on coagulation in sepsis. Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed. At enrollment, we recorded sepsis signs, disease severity, coagulation activation [prothrombin fragments 1 + 2 (F1+2)] and fibrinolysis inhibition [plasminogen activator inhibitor-1 (PAI-1)]. We measured plasma PTX3 levels at enrollment, everyday until day 7, then at days 9, 11, 13, 18, 23 and 28. Mortality was recorded at day 90.

Results

Although not different on day 1, PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days (p = 0.002 by general linear model). On day 1, PTX3 levels were higher in septic shock than in severely septic patients (p = 0.029). Day 1 PTX3 was significantly correlated with platelet count (p < 0.001), SAPS II score (p = 0.006) and SOFA score (p < 0.001). Day 1 PTX3 was correlated with F1+2 concentration and with PAI-1 activity and concentration (p < 0.05 for all).

Conclusions

Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.

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Acknowledgments

The study was funded by a liberal grant for clinical research from Eli Lilly (F1K0020); by funding from the Italian Ministry for University and Scientific Research (MIUR, project FIRB and 2004060419); by the Italian Health Ministry; by the European Commission (Contract 2008-202156 “TOLERAGE”, LSHG-CT-2005-005203 “MUGEN”, LSHP-CT-2003-503240 “MUVAPRED”, SP5B-CT-2006-044161 “FLUINNATE”); by Telethon (grant no. GGP05095); and by the CARIPLO foundation (Project Nobel). We thank all patients who participated in this study and their families. We thank all the staff of our ICUs for their constant efforts to assure the best possible care to all our patients.

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Authors and Affiliations

  1. Dipartimento di Medicina Perioperatoria e Terapie Intensive, Azienda Ospedaliera San Gerardo di Monza, Via Pergolesi 33, 20052, Monza, Italy

    Tommaso Mauri, Giacomo Bellani, Nicolo’ Patroniti, Andrea Coppadoro & Antonio Pesenti

  2. Laboratorio di Ricerca in Immunologia ed Infiammazione, Istituto Clinico Humanitas, Rozzano (MI), Italy

    Giuseppe Peri, Ivan Cuccovillo & Alberto Mantovani

  3. Dipartimento di Medicina Interna, Università degli Studi di Milano, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena, Milan, Italy

    Massimo Cugno

  4. Anestesia e Rianimazione, Azienda Ospedaliera Polo Universitario San Paolo, Milan, Italy

    Gaetano Iapichino

  5. Istituto di Anestesiologia e Rianimazione, Università degli Studi di Milano, Milan, Italy

    Gaetano Iapichino & Luciano Gattinoni

  6. Dipartimento di Anestesia, Rianimazione (Intensiva e Subintensiva) e Terapia del Dolore, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena di Milano, Milan, Italy

    Luciano Gattinoni

  7. Istituto di Patologia Generale, Università degli Studi di Milano, Milan, Italy

    Alberto Mantovani

  8. Dipartimento di Medicina Sperimentale, Università degli Studi Milano-Bicocca, Milan, Italy

    Tommaso Mauri, Giacomo Bellani, Nicolo’ Patroniti, Andrea Coppadoro & Antonio Pesenti

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  1. Tommaso Mauri
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  2. Giacomo Bellani
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  3. Nicolo’ Patroniti
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  4. Andrea Coppadoro
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  6. Ivan Cuccovillo
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  7. Massimo Cugno
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  8. Gaetano Iapichino
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  10. Antonio Pesenti
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  11. Alberto Mantovani
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Corresponding author

Correspondence to Antonio Pesenti.

Additional information

A. Pesenti and A. Mantovani contributed equally to this work.

This article is discussed in the editorial available at: doi:10.1007/s00134-010-1758-z.

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Mauri, T., Bellani, G., Patroniti, N. et al. Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality. Intensive Care Med 36, 621–629 (2010). https://doi.org/10.1007/s00134-010-1752-5

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