Platelet‑related parameters as potential biomarkers for the prognosis of sepsis

Zhang,Chao; Shang,Xueyi; Yuan,Yuan; Li,Yan

doi:10.3892/etm.2023.11832

Platelet‑related parameters as potential biomarkers for the prognosis of sepsis

Authors:
- Chao Zhang
- Xueyi Shang
- Yuan Yuan
- Yan Li
View Affiliations

Affiliations: Hebei Key Laboratory of Nerve Injury and Repair, Institute of Basic Medicine, Chengde Medical University, Chengde, Hebei 067000, P.R. China, Department of Critical Care Medicine, The Fifth Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100071, P.R. China, State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, P.R. China
Published online on: February 10, 2023 https://doi.org/10.3892/etm.2023.11832
Article Number: 133
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Early diagnosis and accurate prognosis are key for reducing the fatality rate and medical expenses associated with sepsis. Platelets are involved in the delayed tissue injury that occurs during sepsis. Therefore, the aim of the present study was to investigate the usefulness of platelets and associated parameters as prognostic markers of sepsis. The present study collected patient samples based on The Third International Consensus Definitions for Sepsis and Septic Shock criteria. Platelet‑associated parameters were detected by flow cytometry and their correlation with clinical scores and prognoses was analyzed. Considering the association between endothelial cells and platelet activation, levels of plasma tumor necrosis factor‑like weak inducer of apoptosis (TWEAK) and angiopoietin‑2 (Ang‑2) were analyzed by ELISA. The results showed significant differences in platelet P‑selectin expression and phosphatidylserine exposure, mitochondrial membrane potential (Mmp)‑Index values and plasma levels of TWEAK and Ang‑2 between patients and healthy controls (P<0.05). Except for P‑selectin and TWEAK levels, all parameters were correlated with clinical scores (acute physiology and chronic health evaluation II and sequential/sepsis‑related organ failure assessment). Additionally, platelet Mmp‑Index between admission and the end of therapy was only different in non‑survivors (P<0.001) and platelet phosphatidylserine exposure was significantly lower in survivors (P=0.006). Therefore, of the parameters tested, the dynamic monitoring of phosphatidylserine exposure, platelet Mmp‑Index values and plasma Ang‑2 levels had the most potential for the assessment of disease severity and clinical outcomes.

View Figures

View References

1	Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, et al: Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study. Lancet. 395:200–211. 2020.PubMed/NCBI View Article : Google Scholar
2	An G and Cockrell RC: Agent-based modeling of systemic inflammation: A pathway toward controlling sepsis. Methods Mol Biol. 2321:231–257. 2021.PubMed/NCBI View Article : Google Scholar
3	Kataria Y and Remick D: Sepsis Biomarkers. Methods Mol Biol. 2321:177–189. 2021.PubMed/NCBI View Article : Google Scholar
4	Cantey JB and Lee JH: Biomarkers for the diagnosis of neonatal sepsis. Clin Perinatol. 48:215–227. 2021.PubMed/NCBI View Article : Google Scholar
5	Odum JD, Wong HR and Stanski NL: A Precision medicine approach to biomarker utilization in pediatric sepsis-associated acute kidney injury. Front Pediatr. 9(632248)2021.PubMed/NCBI View Article : Google Scholar
6	Dewitte A, Lepreux S, Villeneuve J, Rigothier C, Combe C, Ouattara A and Ripoche J: Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critically [corrected] ill patients. Ann Intensive Care. 7(115)2017.PubMed/NCBI View Article : Google Scholar
7	Al Saleh K and Al Qahtani RM: Platelet count patterns and patient outcomes in sepsis at a tertiary care center: Beyond the APACHE score. Medicine (Baltimore). 100(e25013)2021.PubMed/NCBI View Article : Google Scholar
8	Bouglé A and Duranteau J: Pathophysiology of sepsis-induced acute kidney injury: The role of global renal blood flow and renal vascular resistance. Contrib Nephrol. 174:89–97. 2011.PubMed/NCBI View Article : Google Scholar
9	Ge S, Ma Y, Xie M, Qiao T and Zhou J: The role of platelet to mean platelet volume ratio in the identification of adult-onset still's disease from sepsis. Clinics (Sao Paulo). 76(e2307)2021.PubMed/NCBI View Article : Google Scholar
10	You S, Sun X, Zhou Y, Zhong C, Chen J, Zhai W and Cao Y: The prognostic significance of white blood cell and platelet count for inhospital mortality and pneumonia in acute ischemic stroke. Curr Neurovasc Res. 18:427–434. 2021.PubMed/NCBI View Article : Google Scholar
11	Beyan C and Beyan E: Is mean platelet volume and inflammatory activity really correlated in patients with ankylosing spondylitis. Mod Rheumatol. 30(410)2020.PubMed/NCBI View Article : Google Scholar
12	Demir AD: Relationship of the platelet distribution width/platelet count ratio with thyroid antibody levels in patients with Hashimoto's thyroiditis. J Int Med Res. 49(3000605211043241)2021.PubMed/NCBI View Article : Google Scholar
13	Shen G, Li S, Shao Z, Liu L, Liu Q, Yu H, Wang H and Mei Z: Platelet indices in patients with acute appendicitis: A systematic review with meta-analysis. Updates Surg. 73:1327–1341. 2021.PubMed/NCBI View Article : Google Scholar
14	Zhou Y, Wei F and Liu C: Mean platelet volume/platelet count ratio predicts long-term mortality in patients with infective endocarditis. Biomark Med. 14:823–827. 2020.PubMed/NCBI View Article : Google Scholar
15	Li L, Yu J and Zhou Z: Platelet-associated parameters in patients with psoriasis: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 100(e28234)2021.PubMed/NCBI View Article : Google Scholar
16	Jiang SQ, Huang QF, Xie WM, Lv C and Quan XQ: . The association between severe COVID-19 and low platelet count: Evidence from 31 observational studies involving 7613 participants. Br J Haematol. 190:e29–e33. 2020.PubMed/NCBI View Article : Google Scholar
17	Chen Y, Yang Y, Cheng J, Lu J and Hu W: Platelet count and mortality of H7N9 infected patients in Guangdong, China. Platelets. 31:268–271. 2020.PubMed/NCBI View Article : Google Scholar
18	Leli C, Di Matteo L, Gotta F, Vay D, Cavallo V, Mazzeo R, Busso S, Carrabba L and Rocchetti A: Clinical utility of platelet count for screening of malaria. New Microbiol. 43:89–92. 2020.PubMed/NCBI
19	Kirby P, Smith S, Ward L, Hanson J and Currie BJ: Clinical Utility of Platelet Count as a Prognostic Marker for Melioidosis. Am J Trop Med Hyg. 100:1085–1087. 2019.PubMed/NCBI View Article : Google Scholar
20	Shah D, Khataniar M, Sawhney A, Nautiyal M, Desai R and Kakar A: An observational study to see the correlation between trends of platelet counts and immature platelet fraction in dengue infection. Trop Doct. 51:378–381. 2021.PubMed/NCBI View Article : Google Scholar
21	Zhang S, Zheng Y, Chen S, Huang S, Liu K, Lv Q, Jiang Y and Yuan Y: Suilysin-induced platelet-neutrophil complexes formation is triggered by pore formation-dependent calcium Influx. Sci Rep. 6(36787)2016.PubMed/NCBI View Article : Google Scholar
22	Zhang S, Wang J, Chen S, Yin J, Pan Z, Liu K, Li L, Zheng Y, Yuan Y and Jiang Y: Effects of suilysin on streptococcus suis-induced platelet aggregation. Front Cell Infect Microbiol. 6(128)2016.PubMed/NCBI View Article : Google Scholar
23	Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al: The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 315:801–810. 2016.PubMed/NCBI View Article : Google Scholar
24	Wang H, Kang X, Shi Y, Bai ZH, Lv JH, Sun JL and Pei HH: SOFA score is superior to APACHE-II score in predicting the prognosis of critically ill patients with acute kidney injury undergoing continuous renal replacement therapy. Ren Fail. 42:638–645. 2020.PubMed/NCBI View Article : Google Scholar
25	Nagai M, Hirayama K, Ebihara I, Higuchi T, Imaizumi M, Maruyama H, Miyamoto Y, Kakita T, Ogawa Y, Fujita S, et al: Serum TNF-related and weak inducer of apoptosis levels in septic shock patients. Ther Apher Dial. 15:342–348. 2011.PubMed/NCBI View Article : Google Scholar
26	Michels M, van der Ven AJ, Djamiatun K, Fijnheer R, de Groot PG, Griffioen AW, Sebastian S, Faradz SM and de Mast Q: Imbalance of angiopoietin-1 and angiopoetin-2 in severe dengue and relationship with thrombocytopenia, endothelial activation, and vascular stability. Am J Trop Med Hyg. 87:943–946. 2012.PubMed/NCBI View Article : Google Scholar
27	Karabulut B and Alatas SO: Diagnostic Value of neutrophil to lymphocyte ratio and mean platelet volume on early onset neonatal sepsis on term neonate. J Pediatr Intensive Care. 10:143–147. 2021.PubMed/NCBI View Article : Google Scholar
28	McDonald B and Dunbar M: Platelets and Intravascular Immunity: Guardians of the vascular space during bloodstream infections and sepsis. Front Immunol. 10(2400)2019.PubMed/NCBI View Article : Google Scholar
29	Mangalesh S, Dudani S and Malik A: Platelet Indices and their kinetics predict mortality in patients of sepsis. Indian J Hematol Blood Transfus. 24:1–9. 2021.PubMed/NCBI View Article : Google Scholar
30	Tunjungputri RN, van de Heijden W, Urbanus RT, de Groot PG, van der Ven A and de Mast Q: Higher platelet reactivity and platelet-monocyte complex formation in Gram-positive sepsis compared to Gram-negative sepsis. Platelets. 28:595–601. 2017.PubMed/NCBI View Article : Google Scholar
31	Gründler K, Angstwurm M, Hilge R, Baumann P, Annecke T, Crispin A, Sohn HY, Massberg S and Kraemer BF: Platelet mitochondrial membrane depolarization reflects disease severity in patients with sepsis and correlates with clinical outcome. Crit Care. 18(R31)2014.PubMed/NCBI View Article : Google Scholar
32	Kümpers P, van Meurs M, David S, Molema G, Bijzet J, Lukasz A, Biertz F, Haller H and Zijlstra JG: Time course of angiopoietin-2 release during experimental human endotoxemia and sepsis. Crit Care. 13(R64)2009.PubMed/NCBI View Article : Google Scholar
33	Yamakawa K, Ogura H, Koh T, Ogawa Y, Matsumoto N, Kuwagata Y and Shimazu T: Platelet mitochondrial membrane potential correlates with severity in patients with systemic inflammatory response syndrome. J Trauma Acute Care Surg. 74:411–417. 2013.PubMed/NCBI View Article : Google Scholar
34	Abós B, Pérez-Fernández E, Morel E, Perdiguero P and Tafalla C: Pro-Inflammatory and B Cell Regulating Capacities of TWEAK in Rainbow Trout (Oncorhynchus mykiss). Front Immunol. 12(748836)2021.PubMed/NCBI View Article : Google Scholar
35	Manu V, Chakrabarty BK and Singh S: Analysis of platelet-activating factors in severe sepsis by flow cytometry and its correlation with clinical sepsis scoring system: A pilot study. Med J Armed Forces India. 75:429–36. 2019.PubMed/NCBI View Article : Google Scholar
36	Lhermusier T, Chap H and Payrastre B: Platelet membrane phospholipid asymmetry: From the characterization of a scramblase activity to the identification of an essential protein mutated in Scott syndrome. J Thromb Haemost. 9:1883–1891. 2011.PubMed/NCBI View Article : Google Scholar
37	Vinholt PJ: The role of platelets in bleeding in patients with thrombocytopenia and hematological disease. Clin Chem Lab Med. 57:1808–1817. 2019.PubMed/NCBI View Article : Google Scholar
38	Hanafi MMM, Afzan A, Yaakob H, Aziz R, Sarmidi MR, Wolfender JL and Prieto JM: In Vitro Pro-apoptotic and anti-migratory effects of Ficus deltoidea L. plant extracts on the human prostate cancer cell lines PC3. Front Pharmacol. 8(895)2017.PubMed/NCBI View Article : Google Scholar
39	Cao Y, Ma W, Liu Z, Pei Y, Zhu Y, Chen F, Zou L, Jiang Y, Liu X, Huang J, et al: Early predictive value of platelet function for clinical outcome in sepsis. J Infect. 84:628–636. 2022.PubMed/NCBI View Article : Google Scholar
40	Roderburg C, Benz F, Schüller F, Pombeiro I, Hippe HJ, Frey N, Trautwein C, Luedde T, Koch A, Tacke F and Luedde M: Serum levels of TNF receptor ligands are dysregulated in sepsis and predict mortality in Critically Ill patients. PLoS One. 11(e0153765)2016.PubMed/NCBI View Article : Google Scholar
41	Melendez E, Whitney JE, Norton JS, Silverman M, Harju-Baker S, Mikacenic C, Wurfel MM and Liles WC: Systemic Angiopoietin-1/2 dysregulation in pediatric sepsis and septic shock. Int J Med Sci. 16:318–323. 2019.PubMed/NCBI View Article : Google Scholar
42	Hussain RM, Neiweem AE, Kansara V, Harris A and Ciulla TA: Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease. Expert Opin Investig Drugs. 28:861–869. 2019.PubMed/NCBI View Article : Google Scholar
43	Khan M, Aziz AA, Shafi NA, Abbas T and Khanani AM: Targeting Angiopoietin in Retinal Vascular Diseases: A Literature review and summary of clinical trials involving faricimab. Cells. 9(1869)2020.PubMed/NCBI View Article : Google Scholar
44	Wright JK, Hayford K, Tran V, Al Kibria GM, Baqui A, Manajjir A, Mahmud A, Begum N, Siddiquee M, Kain KC and Farzin A: Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: A matched case-control study. BMC Pediatr. 18(118)2018.PubMed/NCBI View Article : Google Scholar
45	Fang Y, Li C, Shao R, Yu H, Zhang Q and Zhao L: Prognostic significance of the angiopoietin-2/angiopoietin-1 and angiopoietin-1/Tie-2 ratios for early sepsis in an emergency department. Crit Care. 19(367)2015.PubMed/NCBI View Article : Google Scholar
46	Liu Y, Hou JH, Li Q, Chen KJ, Wang SN and Wang JM: Biomarkers for diagnosis of sepsis in patients with systemic inflammatory response syndrome: A systematic review and meta-analysis. Springerplus. 5(2091)2016.PubMed/NCBI View Article : Google Scholar
47	Matowicka-Karna J: Markers of inflammation, activation of blood platelets and coagulation disorders in inflammatory bowel diseases. Postepy Hig Med Dosw. 70:305–312. 2016.PubMed/NCBI View Article : Google Scholar