Download PDF
Semin Thromb Hemost 2020; 46(03): 320-327
DOI: 10.1055/s-0039-3400256
Review Article

Immature Platelets As a Predictor of Disease Severity and Mortality in Sepsis and Septic Shock: A Systematic Review

Christian Velling Thorup
1   Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
2   Department of Emergency, Randers Regional Hospital, Randers, Denmark
,
Steffen Christensen
3   Department of Anesthesia and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark
,
Anne-Mette Hvas
1   Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
› Author Affiliations Funding No funding was provided for this study.
› Further Information
    Permissions and Reprints

Abstract

Sepsis is associated with high morbidity and mortality, and short-term mortality remains above 30% despite relevant supportive and antibiotic treatments. The aim of this systematic review was to summarize and discuss the current evidence of the association of an increased number of circulating immature platelets with disease severity and mortality in patients with sepsis or septic shock. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered at the PROSPERO database (registration number: CRD42018104326). A systematic literature search was performed in PubMed, Web of Science, Scopus, and Embase on June 20, 2018, without time restrictions. The included studies were quality-assessed by the National Institutes of Health's Quality Assessment Tools. In total, 14 studies were included. The parameters used for the determination of platelet maturity were mean platelet volume, immature platelets fraction, reticulated platelet percentage, and absolute immature platelets count. Nine studies reported significantly increased immature platelet markers in nonsurvivors of septic shock compared with survivors, as well as in patients with severe sepsis or septic shock compared with patients without severe sepsis and septic shock. Six of these nine studies demonstrated that increased immature platelet markers were predictors of mortality and/or disease severity (area under the receiver operating curve: 0.599–0.886). This review suggests that an increased number of circulating immature platelets is associated with increased disease severity and mortality in patients with sepsis and septic shock. Larger studies are needed to confirm whether immature platelets should be routinely monitored to support the prediction of disease severity and mortality in septic patients.

Keywords

immature platelets - immature platelet fraction - mean platelet volume - mortality - biomarkers - septic shock - sepsis

Supplementary Material



Publication History

Publication Date:
13 December 2019 (online)

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med 2014; 42 (03) 625-631
    Google Scholar
  • 2 Liu VX, Fielding-Singh V, Greene JD. et al. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 2017; 196 (07) 856-863
    Google Scholar
  • 3 Ferrer R, Martin-Loeches I, Phillips G. et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 2014; 42 (08) 1749-1755
    Google Scholar
  • 4 Kim HI, Park S. Sepsis: early recognition and optimized treatment. Tuberc Respir Dis (Seoul) 2019; 82 (01) 6-14
    Google Scholar
  • 5 Dellinger RP, Carlet JM, Masur H. et al; Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32 (03) 858-873
    Google Scholar
  • 6 Singer M, Deutschman CS, Seymour CW. et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016; 315 (08) 801-810
    Google Scholar
  • 7 Kumar S, Tripathy S, Jyoti A, Singh SG. Recent advances in biosensors for diagnosis and detection of sepsis: a comprehensive review. Biosens Bioelectron 2019; 124-125: 205-215
    Google Scholar
  • 8 Giannakopoulos K, Hoffmann U, Ansari U. et al. The use of biomarkers in sepsis: a systematic review. Curr Pharm Biotechnol 2017; 18 (06) 499-507
    Google Scholar
  • 9 Li Z, Yang F, Dunn S, Gross AK, Smyth SS. Platelets as immune mediators: their role in host defense responses and sepsis. Thromb Res 2011; 127 (03) 184-188
    Google Scholar
  • 10 Levi M, Sivapalaratnam S. Disseminated intravascular coagulation: an update on pathogenesis and diagnosis. Expert Rev Hematol 2018; 11 (08) 663-672
    Google Scholar
  • 11 Thiery-Antier N, Binquet C, Vinault S, Meziani F, Boisramé-Helms J, Quenot JP. EPIdemiology of Septic Shock Group. Is thrombocytopenia an early prognostic marker in septic shock?. Crit Care Med 2016; 44 (04) 764-772
    Google Scholar
  • 12 Greco E, Lupia E, Bosco O, Vizio B, Montrucchio G. Platelets and multi-organ failure in sepsis. Int J Mol Sci 2017; 18 (10) 2200
    Google Scholar
  • 13 de Stoppelaar SF, van 't Veer C, van der Poll T. The role of platelets in sepsis. Thromb Haemost 2014; 112 (04) 666-677
    Google Scholar
  • 14 Salvagno GL, Montagnana M, Degan M. et al. Evaluation of platelet turnover by flow cytometry. Platelets 2006; 17 (03) 170-177
    Google Scholar
  • 15 Meintker L, Haimerl M, Ringwald J, Krause SW. Measurement of immature platelets with Abbott CD-Sapphire and Sysmex XE-5000 in haematology and oncology patients. Clin Chem Lab Med 2013; 51 (11) 2125-2131
    Google Scholar
  • 16 Xu K, Chan NC, Hirsh J. et al. Quantifying immature platelets as markers of increased platelet production after coronary artery bypass grafting surgery. Eur J Haematol 2018; 101 (03) 362-367
    Google Scholar
  • 17 Hong H, Xiao W, Maitta RW. Steady increment of immature platelet fraction is suppressed by irradiation in single-donor platelet components during storage. PLoS One 2014; 9 (01) e85465
    Google Scholar
  • 18 Hoffmann JJ. Reticulated platelets: analytical aspects and clinical utility. Clin Chem Lab Med 2014; 52 (08) 1107-1117
    Google Scholar
  • 19 Sachdev R, Tiwari AK, Goel S, Raina V, Sethi M. Establishing biological reference intervals for novel platelet parameters (immature platelet fraction, high immature platelet fraction, platelet distribution width, platelet large cell ratio, platelet-X, plateletcrit, and platelet distribution width) and their correlations among each other. Indian J Pathol Microbiol 2014; 57 (02) 231-235
    Google Scholar
  • 20 Pons I, Monteagudo M, Lucchetti G. et al. Correlation between immature platelet fraction and reticulated platelets. Usefulness in the etiology diagnosis of thrombocytopenia. Eur J Haematol 2010; 85 (02) 158-163
    Google Scholar
  • 21 de Wit N, Oosting J, Hoffmann J, Krockenberger M, van Dun L. Comparative evaluation of the Abbott CELL-DYN Sapphire reticulated platelets fraction and the Sysmex Xe-2100 IPF. Int J Lab Hematol 2009; 31 (Suppl. 01) 98
    Google Scholar
  • 22 Choi SW, Kim BB, Choi DH. et al. Stroke or left atrial thrombus prediction using antithrombin III and mean platelet volume in patients with nonvalvular atrial fibrillation. Clin Cardiol 2017; 40 (11) 1013-1019
    Google Scholar
  • 23 Kovács S, Csiki Z, Zsóri KS, Bereczky Z, Shemirani AH. Characteristics of platelet count and size and diagnostic accuracy of mean platelet volume in patients with venous thromboembolism. A systematic review and meta-analysis. Platelets 2019; 30 (02) 139-147
    Google Scholar
  • 24 Balli M, Taşolar H, Çetin M. et al. Relationship of platelet indices with acute stent thrombosis in patients with acute coronary syndrome. Postepy Kardiol Interwencyjnej 2015; 11 (03) 224-229
    Google Scholar
  • 25 Bath PM, Butterworth RJ. Platelet size: measurement, physiology and vascular disease. Blood Coagul Fibrinolysis 1996; 7 (02) 157-161
    Google Scholar
  • 26 Thompson CB, Jakubowski JA, Quinn PG, Deykin D, Valeri CR. Platelet size as a determinant of platelet function. J Lab Clin Med 1983; 101 (02) 205-213
    Google Scholar
  • 27 Oh GH, Chung SP, Park YS. et al. Mean platelet volume to platelet count ratio as a promising predictor of early mortality in severe sepsis. Shock 2017; 47 (03) 323-330
    Google Scholar
  • 28 Muronoi T, Koyama K, Nunomiya S. et al. Immature platelet fraction predicts coagulopathy-related platelet consumption and mortality in patients with sepsis. Thromb Res 2016; 144: 169-175
    Google Scholar
  • 29 Liberati A, Altman DG, Tetzlaff J. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009; 62 (10) e1-e34
    Google Scholar
  • 30 National Institutes of Health. National Heart, Lung, and Blood Institute. Study Quality Assessment Tools. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools . Accessed November 8, 2018
    Google Scholar
  • 31 Becchi C, Al Malyan M, Fabbri LP, Marsili M, Boddi V, Boncinelli S. Mean platelet volume trend in sepsis: is it a useful parameter?. Minerva Anestesiol 2006; 72 (09) 749-756
    Google Scholar
  • 32 Acikgoz S, Akduman D, Eskici Z. et al. Thrombocyte and erythrocyte indices in sepsis and disseminated intravascular coagulation. J Med Biochem 2012; 31 (01) 60-64
    Google Scholar
  • 33 Guclu E, Durmaz Y, Karabay O. Effect of severe sepsis on platelet count and their indices. Afr Health Sci 2013; 13 (02) 333-338
    Google Scholar
  • 34 Sadaka F, Donnelly P, Griffin M, O'Brien J, Lakshmanan R. Mean platelet volume is not a useful predictor of mortality in septic shock. J Blood Disord Transfus 2014; 5 (02) 194
    Google Scholar
  • 35 Gao Y, Li Y, Yu X. et al. The impact of various platelet indices as prognostic markers of septic shock. PLoS One 2014; 9 (08) e103761
    Google Scholar
  • 36 Kim CH, Kim SJ, Lee MJ. et al. An increase in mean platelet volume from baseline is associated with mortality in patients with severe sepsis or septic shock. PLoS One 2015; 10 (03) e0119437
    Google Scholar
  • 37 Orak M, Karakoç Y, Ustundag M, Yildirim Y, Celen MK, Güloglu C. An investigation of the effects of the mean platelet volume, platelet distribution width, platelet/lymphocyte ratio, and platelet counts on mortality in patents with sepsis who applied to the emergency department. Niger J Clin Pract 2018; 21 (05) 667-671
    Google Scholar
  • 38 Montero-Chacón LB, Padilla-Cuadra JI, Chiou SH, Torrealba-Acosta G. High-density lipoprotein, mean platelet volume, and uric acid as biomarkers for outcomes in patients with sepsis: an observational study. J Intensive Care Med 2018; (e-pub ahead of print) DOI: 10.1177/0885066618772825.
    Google Scholar
  • 39 Enz Hubert RM, Rodrigues MV, Andreguetto BD. et al. Association of the immature platelet fraction with sepsis diagnosis and severity. Sci Rep 2015; 5: 8019
    Google Scholar
  • 40 Park SH, Ha SO, Cho YU, Park CJ, Jang S, Hong SB. Immature platelet fraction in septic patients: clinical relevance of immature platelet fraction is limited to the sensitive and accurate discrimination of septic patients from non-septic patients, not to the discrimination of sepsis severity. Ann Lab Med 2016; 36 (01) 1-8
    Google Scholar
  • 41 Koyama K, Katayama S, Muronoi T. et al. Time course of immature platelet count and its relation to thrombocytopenia and mortality in patients with sepsis. PLoS One 2018; 13 (01) e0192064
    Google Scholar
  • 42 Liu QH, Song MY, Yang BX, Xia RX. Clinical significance of measuring reticulated platelets in infectious diseases. Medicine (Baltimore) 2017; 96 (52) e9424
    Google Scholar
  • 43 Tajarernmuang P, Phrommintikul A, Limsukon A, Pothirat C, Chittawatanarat K. The role of mean platelet volume as a predictor of mortality in critically ill patients: a systematic review and meta-analysis. Crit Care Res Pract 2016; 2016 (16) 4370834
    Google Scholar
  • 44 World Health Organization. Improving the Prevention, Diagnosis and Clinical Management of Sepsis. http://apps.who.int/gb/ebwha/pdf_files/WHA70/A70_13-en.pdf . Accessed April 13, 2018
    Google Scholar
  • 45 GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385 (9963): 117-171
    Google Scholar
  • 46 Freund Y, Lemachatti N, Krastinova E. et al; French Society of Emergency Medicine Collaborators Group. Prognostic accuracy of sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department. JAMA 2017; 317 (03) 301-308
    Google Scholar