Association of the immature platelet fraction with sepsis diagnosis and severity

Rodolfo Monteiro Enz Hubert, Melina Veiga Rodrigues, Bruna Dolci Andreguetto, Thiago M Santos, Maria de Fátima Pereira Gilberti, Vagner de Castro, Joyce M Annichino-Bizzacchi, Desanka Dragosavac, Marco Antonio Carvalho-Filho, Erich Vinicius De Paula, Rodolfo Monteiro Enz Hubert, Melina Veiga Rodrigues, Bruna Dolci Andreguetto, Thiago M Santos, Maria de Fátima Pereira Gilberti, Vagner de Castro, Joyce M Annichino-Bizzacchi, Desanka Dragosavac, Marco Antonio Carvalho-Filho, Erich Vinicius De Paula

Abstract

Management of Sepsis would greatly benefit from the incorporation of simple and informative new biomarkers in clinical practice. Ideally, a sepsis biomarker should segregate infected from non-infected patients, provide information about prognosis and organ-specific damage, and be accessible to most healthcare services. The immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) are new analytical parameters of the complete blood count, that have been studied as biomarkers of several inflammatory conditions. Recently, a study performed in critically-ill patients suggested that IPF could be a more accurate sepsis biomarker than C-reactive protein (CRP) and procalcitonin. In this retrospective study we evaluated the performance of IPF and IRF as biomarkers of sepsis diagnosis and severity. 41 patients admitted to two intensive care units were evaluated, 12 of which with severe sepsis or septic shock, and 11 with non-complicated sepsis. Significantly higher IPF levels were observed in patients with severe sepsis/septic shock. IPF correlated with sepsis severity scores and presented the highest diagnostic accuracy for the presence of sepsis of all studied clinical and laboratory parameters. No significant differences were observed in IRF levels. Our results suggest that IPF levels could be used as a biomarker of sepsis diagnosis and severity.

Figures

Figure 1. IPF and IRF in sepsis…
Figure 1. IPF and IRF in sepsis and SIRS.
Box-plot showing similar IPF and IRF values in patients with sepsis (n = 23) and SIRS (n = 14). Mann-Whitney test.
Figure 2. IPF and IRF in sepsis…
Figure 2. IPF and IRF in sepsis patients compared to healthy individuals.
Box-plot showing significantly increased values for IPF and IRF in patients with sepsis (n = 23) compared to healthy individuals (n = 178). Mann-Whitney test.
Figure 3. Association of laboratory parameters with…
Figure 3. Association of laboratory parameters with sepsis severity.
Box-plot showing that neither C-reactive protein (a), platelet count (b), nor IRF (d) presented significant differences between patients with severe sepsis or septic shock (“severe sepsis” group; n = 12), compared to non-complicated sepsis (“sepsis” group; n = 11). As expected, lactate levels were higher in the former group (c). All values obtained at the time of ICU admission. Mann-Whitney test.
Figure 4. IPF and sepsis severity.
Figure 4. IPF and sepsis severity.
Box-plots showing higher IPF in patients with severe sepsis compared to non-complicated sepsis (upper panel). Similar values were obtained when patients were stratified by median SOFA score (lower panel). All values obtained at the time of ICU admission. Mann-Whitney test.

References

    1. Gaieski D. F., Edwards J. M., Kallan M. J. & Carr B. G. Benchmarking the incidence and mortality of severe sepsis in the United States. Critical care medicine 41, 1167–1174, 10.1097/CCM.0b013e31827c09f8 (2013).
    1. Dellinger R. P. et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Critical care medicine 41, 580–637, 10.1097/CCM.0b013e31827e83af (2013).
    1. Opal S. M., Dellinger R. P., Vincent J. L., Masur H. & Angus D. C. The Next Generation of Sepsis Clinical Trial Designs: What Is Next After the Demise of Recombinant Human Activated Protein C? Critical care medicine, 10.1097/CCM.0000000000000325 (2014).
    1. Di Somma S. et al. Opinion paper on innovative approach of biomarkers for infectious diseases and sepsis management in the emergency department. Clinical chemistry and laboratory medicine: CCLM/FESCC 51, 1167–1175, 10.1515/cclm-2012-0795 (2013).
    1. Magrini L. et al. Comparison between white blood cell count, procalcitonin and C reactive protein as diagnostic and prognostic biomarkers of infection or sepsis in patients presenting to emergency department. Clinical chemistry and laboratory medicine: CCLM/FESCC, 10.1515/cclm-2014-0210 (2014).
    1. Fiotti N. et al. Procalcitonin in early rule-in/rule-out of sepsis in SIRS patients admitted to a medical ward. Clinical chemistry and laboratory medicine: CCLM/FESCC, 10.1515/cclm-2014-0196 (2014).
    1. Hui P., Cook D. J., Lim W., Fraser G. A. & Arnold D. M. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest 139, 271–278, 10.1378/chest.10-2243 (2011).
    1. Morrell C. N., Aggrey A. A., Chapman L. M. & Modjeski K. L. Emerging roles for platelets as immune and inflammatory cells. Blood 123, 2759–2767, 10.1182/blood-2013-11-462432 (2014).
    1. Wiersinga W. J., Leopold S. J., Cranendonk D. R. & van der Poll T. Host innate immune responses to sepsis. Virulence 5, 36–44, 10.4161/viru.25436 (2014).
    1. Hoffmann J. J. Reticulated platelets: analytical aspects and clinical utility. Clinical chemistry and laboratory medicine: CCLM/FESCC, 10.1515/cclm-2014-0165 (2014).
    1. Briggs C., Kunka S., Hart D., Oguni S. & Machin S. J. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. British journal of haematology 126, 93–99, 10.1111/j.1365-2141.2004.04987.x (2004).
    1. Buttarello M. & Plebani M. Automated blood cell counts: state of the art. American journal of clinical pathology 130, 104–116, 10.1309/EK3C7CTDKNVPXVTN (2008).
    1. Lee E. Y., Kim S. J., Song Y. J., Choi S. J. & Song J. Immature platelet fraction in diabetes mellitus and metabolic syndrome. Thrombosis research 132, 692–695, 10.1016/j.thromres.2013.09.035 (2013).
    1. Larsen S. B., Grove E. L., Hvas A. M. & Kristensen S. D. Platelet turnover in stable coronary artery disease - influence of thrombopoietin and low-grade inflammation. PloS one 9, e85566, 10.1371/journal.pone.0085566 (2014).
    1. De Blasi R. A. et al. Immature platelet fraction in predicting sepsis in critically ill patients. Intensive care medicine 39, 636–643, 10.1007/s00134-012-2725-7 (2013).
    1. Kumar A. et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical care medicine 34, 1589–1596, 10.1097/01.CCM.0000217961.75225.E9 (2006).
    1. Clerico A. & Plebani M. Biomarkers for sepsis: an unfinished journey. Clinical chemistry and laboratory medicine: CCLM/FESCC 51, 1135–1138, 10.1515/cclm-2013-0003 (2013).
    1. Di Mario A. et al. Immature platelet fraction (IPF) in hospitalized patients with neutrophilia and suspected bacterial infection. The Journal of infection 59, 201–206, 10.1016/j.jinf.2009.07.007 (2009).
    1. Meintker L., Haimerl M., Ringwald J. & Krause S. W. Measurement of immature platelets with Abbott CD-Sapphire and Sysmex XE-5000 in haematology and oncology patients. Clinical chemistry and laboratory medicine: CCLM/FESCC 51, 2125–2131, 10.1515/cclm-2013-0252 (2013).
    1. Kemna E., Pickkers P., Nemeth E., van der Hoeven H. & Swinkels D. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood 106, 1864–1866, 10.1182/blood-2005-03-1159 (2005).
    1. van Eijk L. T. et al. Inflammation-induced hepcidin-25 is associated with the development of anemia in septic patients: an observational study. Crit Care 15, R9, 10.1186/cc9408 (2011).
    1. Caudrillier A. et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. The Journal of clinical investigation 122, 2661–2671, 10.1172/JCI61303 (2012).
    1. McDonald B., Urrutia R., Yipp B. G., Jenne C. N. & Kubes P. Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis. Cell host & microbe 12, 324–333, 10.1016/j.chom.2012.06.011 (2012).
    1. Hong K. H. et al. Prognostic value of immature platelet fraction and plasma thrombopoietin in disseminated intravascular coagulation. Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 20, 409–414, 10.1097/MBC.0b013e32832b1866 (2009).
    1. Lesko L. J. & Atkinson A. J. Jr Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annual review of pharmacology and toxicology 41, 347–366, 10.1146/annurev.pharmtox.41.1.347 (2001).
    1. Frank R. & Hargreaves R. Clinical biomarkers in drug discovery and development. Nature reviews. Drug discovery 2, 566–580, 10.1038/nrd1130 (2003).
    1. Sackett D. L. & Haynes R. B. The architecture of diagnostic research. BMJ 324, 539–541 (2002).
    1. Luz Fiusa M. M. et al. A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia. Crit Care 17, R169, 10.1186/cc12848 (2013).
    1. Alves B. E. et al. Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study. Journal of translational medicine 9, 23, 10.1186/1479-5876-9-23 (2011).
    1. Bone R. C. et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101, 1644–1655 (1992).
    1. Vincent J. L. et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive care medicine 22, 707–710 (1996).
    1. Knaus W. A., Draper E. A., Wagner D. P. & Zimmerman J. E. APACHE II: a severity of disease classification system. Critical care medicine 13, 818–829 (1985).

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