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Paschke L, Foltan M, Wagner MS, Lubnow M, Gruber M, Krenkel L, Lehle K. Clinical Relevance of Platelet-Leukocyte Aggregates and Platelet P-Selectin Expression During Venovenous Extracorporeal Membrane Oxygenation. ASAIO J 2025:00002480-990000000-00672. [PMID: 40177949 DOI: 10.1097/mat.0000000000002421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2025] Open
Abstract
Thrombosis continues to be a significant complication during venovenous extracorporeal membrane oxygenation (V-V ECMO). Platelet activation markers might serve as indicators of inflammation and thrombogenesis. The aim was to identify these markers in ECMO patients. Blood from 10 ECMO patients (before, during, after ECMO) and 11 healthy volunteers were collected to determine platelet-neutrophil-aggregates (PNAs), platelet-monocyte-aggregates (PMAs), fibrinogen-binding, and P-selectin-expression on platelets by flow cytometry. Critical illness was associated with significantly elevated levels of PNAs and PMAs, increased P-selectin expression, reduced fibrinogen-binding, and restricted activation of platelets. Although PNAs and PMAs decreased significantly within 2 hours after the initiation of ECMO and remained at those levels, ECMO did not affect basal P-selectin expression and fibrinogen-binding. These results correlated with coagulation activation. Platelet markers before ECMO were not indicators for an imminent system exchange and end of therapy. In conclusion, platelet dysfunction during ECMO was mainly attributed to the critical illness. Extracorporeal membrane oxygenation support strengthened the restricted response of platelets to exogenous agonists (P-selectin). Furthermore, a decrease in PNAs/PMAs after ECMO started identified a reduced inflammatory response. There was no correlation of analyzed platelet parameters with the incidence of thrombotic complications.
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Affiliation(s)
- Lukas Paschke
- From the Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Maik Foltan
- From the Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Maria S Wagner
- From the Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Matthias Lubnow
- Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany
| | - Michael Gruber
- Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany
| | - Lars Krenkel
- Regensburg Center of Biomedical Engineering, Ostbayerische Technische Hochschule, Regensburg, Germany
| | - Karla Lehle
- From the Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany
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Li X, Li T, Fu H, Lin F, Li C, Bai Q, Jin Z. C-reactive protein to platelet ratio as an early biomarker in differentiating neonatal late-onset sepsis in neonates with pneumonia. Sci Rep 2025; 15:10760. [PMID: 40155410 PMCID: PMC11953421 DOI: 10.1038/s41598-025-94845-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 03/17/2025] [Indexed: 04/01/2025] Open
Abstract
Neonates with pneumonia (NWP) may experience unidentified life-threatening sepsis, yet distinguishing NWP from neonates with sepsis (NWS) based solely on clinical presentation remains challenging. This study aimed to evaluate the diagnostic utility of the C-reactive protein to platelet ratio (CPR) in distinguishing neonatal late-onset sepsis (LOS) among NWPs. From February 2016 to March 2022, a total of 1385 NWPs aged over 3 days were included. Of these, 174 neonates with confirmed positive blood cultures were categorized into the sepsis cohort, while the remainder formed the pneumonia cohort. All clinical data were retrospectively extracted from electronic medical records. CPR was calculated as the ratio of C-reactive protein levels to platelet count. Independent risk factors (IRFs) for neonatal LOS were identified through multivariate logistic regression. The diagnostic performance of CPR in identifying LOS among NWPs was analyzed using receiver operating characteristic (ROC) curve metrics. Statistical analyses were conducted using SPSS version 24.0 and MedCalc version 15.2.2. Neonates with NWS demonstrated significantly higher CPR compared to those with NWP alone. Further analysis revealed a notably increased incidence of sepsis among neonates exhibiting elevated CPR levels relative to those with lower values. Correlation analysis identified a direct association between CPR and elevated procalcitonin, creatinine, and urea nitrogen levels, as well as prolonged hospitalization. Multiple logistic regression analysis identified CPR as an IRF for late-onset NWS. ROC curve analysis demonstrated that CPR outperformed CRP and platelet count individually in diagnosing NWS, with a diagnostic sensitivity of 54% and specificity of 85%. CPR serves as an effective initial diagnostic marker with superior accuracy in distinguishing delayed NWS from NWP compared to CRP and platelet count alone.
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Affiliation(s)
- Xiaojuan Li
- Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
| | - Tiewei Li
- Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
| | - Hui Fu
- Department of Neonatal Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
| | - Fatao Lin
- Department of Neonatal Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
| | - Ci Li
- Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
| | - Qiongdan Bai
- Department of Neonatal Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
| | - Zhipeng Jin
- Pediatric Intensive Care Unit, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
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Chen S, Wu A, Shen X, Kong J, Huang Y. Disrupting the dangerous alliance: Dual anti-inflammatory and anticoagulant strategy targets platelet-neutrophil crosstalk in sepsis. J Control Release 2025; 379:814-831. [PMID: 39848591 DOI: 10.1016/j.jconrel.2025.01.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 01/13/2025] [Accepted: 01/17/2025] [Indexed: 01/25/2025]
Abstract
Sepsis is a life-threatening disease characterized by excessive systemic inflammation and coagulopathy. Platelets and neutrophils form a "dangerous alliance" through crosstalk, promoting the inflammatory cytokine storm and coagulation disorders during sepsis. Platelet-neutrophil crosstalk leads to the formation of platelet-neutrophil complexes (PNCs), which are the central "protagonists" of this "dangerous alliance." These PNCs further enhance the crosstalk between platelets and neutrophils, amplifying immune and coagulation responses through positive feedback loops. Although some targeted therapies have been reported recently, they primarily focus on inducing neutrophil apoptosis or degrading existing neutrophil extracellular traps (NETs). Limited strategies are available for targeting platelets and suppressing sepsis-associated PNCs. Herein, we propose a two-pronged approach to intercept platelet-neutrophil crosstalk by simultaneously targeting drugs to both platelets and neutrophils of the "dangerous alliance." This strategy not only effectively alleviates inflammation induced by platelet-neutrophil crosstalk but also reduces PNC formation, thereby dismantling the structural scaffold of microthrombi. In a sepsis mouse model, this approach significantly decreased markers of platelet-neutrophil crosstalk, reduced the cytokine storm, and lowered the risk of thrombosis. Moreover, it alleviated organ damage caused by PNC infiltration and prolonged the survival of septic mice. Overall, this work combines anti-inflammatory and anticoagulant therapies to effectively disrupt the "dangerous alliance" between platelets and neutrophils, offering a promising strategy for treating sepsis.
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Affiliation(s)
- Sa Chen
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Aijia Wu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Xinran Shen
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Jinxia Kong
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Yuan Huang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China..
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Li X, Liu S, Xie J, Liu L, Duan C, Yang L, Wang Y, Wu Y, Shan N, Zhang Y, Zhang Y, Zhuang R. Salvianolic acid B improves the microcirculation in a mouse model of sepsis through a mechanism involving the platelet receptor CD226. Br J Pharmacol 2025; 182:988-1004. [PMID: 39443080 DOI: 10.1111/bph.17371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 08/03/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND AND PURPOSE Salvianolic acid B (SalB) demonstrates diverse clinical applications, particularly in cardiovascular and cerebral protection. This study primarily investigated the effects of SalB on sepsis. EXPERIMENTAL APPROACH The model of sepsis via caecal ligation puncture (CLP) was established in male C57BL/6 mice. Therapeutic effects of SalB on hepatic and pulmonary injury, inflammatory responses and microcirculatory disturbances in sepsis were evaluated. Platelet aggregation and adhesion were measured via flow cytometry and an adhesion test. After overexpression of platelet-related activating molecules by 293T cells, the efficient binding of SalB and platelet CD226 molecules was further evaluated. Finally, neutralizing antibody experiments were used to assess the mechanism of SalB in alleviating the progression of sepsis. KEY RESULTS SalB mitigated hepatic and pulmonary impairments, reduced inflammatory cytokine levels and enhanced mesenteric microvascular blood flow in septic mice. SalB enhanced CLP-induced reduction of platelet count and platelet pressure cumulative volume. SalB reduced platelet adhesion to endothelial cells and platelet aggregation to leukocytes. A high binding efficiency was observed between SalB and the platelet adhesion molecule CD226. Ex vivo, interactions between SalB and platelets from CD226-knockout mice were markedly decreased. In vivo administration of CD226 neutralizing antibodies significantly delayed disease progression and enhanced mesenteric microcirculation in septic mice. CONCLUSION AND IMPLICATIONS In our murine model of sepsis, treatment with SalB improved the microcirculatory disturbance and hindered the progression of sepsis by inhibiting platelet CD226 function. Our results suggest SalB is a promising therapeutic approach to the treatment of sepsis.
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Affiliation(s)
- Xuemei Li
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
- College of Life Sciences, Northwest University, Xi'an, Shaanxi, China
| | - Shanshou Liu
- Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Jiangang Xie
- Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Lin Liu
- Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Chujun Duan
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
- Institute of Medical Research, Northwestern Polytechnical University, Xi'an, Shaanxi, China
| | - Lu Yang
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yuling Wang
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yilin Wu
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Niqi Shan
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yun Zhang
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Yuan Zhang
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Ran Zhuang
- Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China
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Kim YH, Lee DH, Seo HS, Eun SH, Lee DS, Choi YK, Lee SH, Kim TY. Genome-based taxonomic identification and safety assessment of an Enterococcus strain isolated from a homemade dairy product. Int Microbiol 2024; 27:1513-1525. [PMID: 38466360 DOI: 10.1007/s10123-024-00496-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/24/2024] [Accepted: 03/05/2024] [Indexed: 03/13/2024]
Abstract
The aim of this study was to explore the taxonomic identification and evaluate the safety of a bacterium, Enterococcus lactis IDCC 2105, isolated from homemade cheese in Korea, using whole genome sequence (WGS) analysis. It sought to identify the species level of this Enterococcus spp., assess its antibiotic resistance, and evaluate its virulence potential. WGS analysis confirmed the bacterial strain IDCC 2105 as E. lactis and identified genes responsible for resistance to erythromycin and clindamycin, specifically msrC, and eatAv, which are chromosomally located, indicating a minimal risk for horizontal gene transfer. The absence of plasmids in E. lactis IDCC 2105 further diminishes the likelihood of resistance gene dissemination. Additionally, our investigation into seven virulence factors, including hemolysis, platelet aggregation, biofilm formation, hyaluronidase, gelatinase, ammonia production, and β-glucuronidase activity, revealed no detectable virulence traits. Although bioinformatic analysis suggested the presence of collagen adhesion genes acm and scm, these were not corroborated by phenotypic virulence assays. Based on these findings, E. lactis IDCC 2105 presents as a safe strain for potential applications, contributing valuable information on its taxonomy, antibiotic resistance profile, and lack of virulence factors, supporting its use in food products.
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Affiliation(s)
- Young-Hoo Kim
- Department of Biological Engineering, College of Engineering, Konkuk University, Seoul, 05029, South Korea
| | | | - Han Sol Seo
- Yunovia Co., Ltd, Hwaseong, 18449, South Korea
| | | | - Do Sup Lee
- Yunovia Co., Ltd, Hwaseong, 18449, South Korea
| | | | - Sang Hyun Lee
- Department of Biological Engineering, College of Engineering, Konkuk University, Seoul, 05029, South Korea
| | - Tae-Yoon Kim
- Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam, 13488, Republic of Korea.
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Tomic J, Jakovac S, Zovko T, Ljevak I, Karabatic S, Mucic M, Pravdic D. Platelet Indices in Patients With Gram-Negative and Gram-Positive Sepsis: A Retrospective Cross-Sectional Study. Cureus 2024; 16:e71601. [PMID: 39417064 PMCID: PMC11481407 DOI: 10.7759/cureus.71601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2024] [Indexed: 10/19/2024] Open
Abstract
OBJECTIVES Different inflammatory processes and sepsis can significantly affect the number of platelets and platelet indices. Therefore, in this study, total platelet count (PLT), thrombocrit (Pct), platelet distribution width (PDW), mean platelet volume (MPV), and platelet-large cell ratio (P-LCR) were analyzed in patients with Gram-negative and Gram-positive bacterial sepsis and in sterile blood cultures. MATERIALS AND METHODS Inclusion criteria were an increased number of inflammatory parameters (elevated values of leukocytes, C-reactive protein (CRP), procalcitonin (PCT), and positive blood culture. Exclusion criteria were patients who did not have elevated values of inflammatory parameters and did not have a positive blood culture. Samples were collected from patients who had sepsis confirmed by blood cultures at the Department of Microbiology and Molecular Diagnostics at University Clinical Hospital Mostar in the period from 2019 to 2022. Three groups were analyzed, patients who had sterile blood cultures, patients with blood cultures with isolated Gram-positive bacteria, and patients with blood cultures with isolated Gram-negative bacteria. Specific infectious agents were identified for each group of patients. In addition to the above, PLT, Pct, MPV, PDW, P-LCR, PCT, CRP, the total number of leukocytes, and the number of neutrophil leukocytes were analyzed in each group. RESULTS The values of PCT, CRP, and the number of neutrophile leukocytes were significantly higher in patients with Gram-negative sepsis as compared to Gram-positive sepsis and to control group. Patients with sepsis have decreased PLT and Ptc and increased values of MPV, PDW, and P-LCR. In sepsis caused by the Gram-negative bacteria, i.e., Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, the values of the same parameters were more changed compared to sepsis caused by Gram-positive bacteria, i.e., Streptococcus pneumoniae, Enterococcus spp., and methicillin-resistant Staphylococcus aureus (MRSA). When comparing Gram-negative negative bacteria, PLT was lowest in sepsis caused by Escherichia coli, the PDW value was highest in sepsis caused by Acinetobacter baumannii, and MPV and P-LCR were the highest in sepsis caused by Klebsiella pneumoniae. CONCLUSION Our study showed that platelet indices are significantly changed in patients with sepsis. Patients with sepsis have decreased values of PLT and Pct and increased values of MPV, PDW, and P-LCR, indicating an increase in thrombocyte production. Moreover, the results were more prominent in sepsis caused by Gram-negative bacteria compared to sepsis caused by Gram-positive bacteria.
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Affiliation(s)
- Josipa Tomic
- Department of Microbiology and Molecular Diagnostics, University Clinical Hospital Mostar, Mostar, BIH
| | - Sanja Jakovac
- Department of Microbiology and Molecular Diagnostics, University Clinical Hospital Mostar, Mostar, BIH
| | - Tanja Zovko
- Department of Pulmonary Diseases and Tuberculosis, University Clinical Hospital Mostar, Mostar, BIH
| | - Ivona Ljevak
- Department of Microbiology and Molecular Diagnostics, University Clinical Hospital Mostar, Mostar, BIH
| | - Sandra Karabatic
- Clinic for Pulmonary Diseases, University Hospital Centre Zagreb, Zagreb, HRV
| | - Marjana Mucic
- Faculty of Health Studies, University Clinical Hospital Mostar, Mostar, BIH
| | - Danijel Pravdic
- Clinic for Internal Diseases, University Clinical Hospital Mostar, Mostar, BIH
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Scarlatescu F, Scarlatescu E, Tomescu DR, Bartos D. The Correlation of Hemostatic Parameters with the Development of Early Sepsis-Associated Encephalopathy. A Retrospective Observational Study. J Crit Care Med (Targu Mures) 2024; 10:329-336. [PMID: 39829725 PMCID: PMC11740703 DOI: 10.2478/jccm-2024-0040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 09/28/2024] [Indexed: 01/22/2025] Open
Abstract
Introduction Sepsis-associated encephalopathy (SAE) is one of the most common complications seen both in early and late stages of sepsis, with a wide spectrum of clinical manifestations ranging from mild neurological dysfunction to delirium and coma. The pathophysiology of SAE is still not completely understood, and the diagnosis can be challenging especially in early stages of sepsis and in patients with subtle symptoms. Aim of the study The objective of this study was to assess the coagulation profile in patients with early SAE and to compare the hemostatic parameters between septic patients with and without SAE in the first 24 hours from sepsis diagnosis. Material and methods This retrospective observational study included 280 patients with sepsis in the first 24 hours after sepsis diagnosis. A complete blood count was available in all patients; a complex hemostatic assessment including standard coagulation tests, plasmatic levels of coagulation factors, inhibitors, D-dimers, and Rotation thromboelastometry (ROTEM, Instrumentation Laboratory) was performed in a subgroup of patients. Results Early SAE was diagnosed in 184 patients (65.7%) and was correlated with a higher platelet count, after adjusting for age and leucocyte count. Compared to patients without neurological dysfunction, patients with early SAE presented a more active coagulation system revealed by faster propagation phase, increased clot firmness and elasticity with a higher platelet contribution to clot strength. The initiation of coagulation and clot lysis were not different between the groups. Conclusion In the early stages of sepsis, the development of SAE is correlated with increased systemic clotting activity where platelets seem to have an important role. More research is needed to investigate the role of platelets and the coagulation system in relation to the development of early SAE.
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Affiliation(s)
| | - Ecaterina Scarlatescu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Fundeni Clinical Institute, Bucharest, Romania
| | - Dana Rodica Tomescu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Fundeni Clinical Institute, Bucharest, Romania
| | - Daniela Bartos
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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Bakowski W, Smiechowicz J, Dragan B, Goździk W, Adamik B. Platelet Aggregation Alterations in Patients with Severe Viral Infection Treated at the Intensive Care Unit: Implications for Mortality Risk. Pathogens 2024; 13:778. [PMID: 39338970 PMCID: PMC11435101 DOI: 10.3390/pathogens13090778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/26/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Severe viral infections often result in abnormal platelet function, affecting various stages of hemostasis. Activated platelets are often considered prothrombotic and more susceptible to further stimulation. However, emerging evidence suggests that initial hyperactivation is followed by platelet exhaustion and hypo-responsiveness, affecting platelet degranulation, activation, and aggregation. We examined early alterations in platelet aggregation among patients (N = 28) with acute respiratory distress syndrome and SARS-CoV-2 infection who were receiving mechanical ventilation and venovenous extracorporeal membrane oxygenation support. Blood samples were stimulated with four different activators: arachidonic acid, adenosine diphosphate, thrombin receptor-activating protein 6, and ristocetin. Our observations revealed that platelet aggregation was reduced in most patients upon admission (ranging from 61 to 89%, depending on the agonist used), and this trend intensified during the 5-day observation period. Concurrently, other coagulation parameters remained within normal ranges, except for elevated d-dimer and fibrinogen levels. Importantly, we found a significant association between platelet aggregation and patient mortality. Impaired platelet aggregation was more severe in patients who ultimately died, and reduced aggregation was associated with a significantly lower probability of survival, as confirmed by Kaplan-Meier analysis (p = 0.028). These findings underscore the potential of aggregometry as an early detection tool for identifying patients at higher risk of mortality within this specific cohort.
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Affiliation(s)
| | | | | | | | - Barbara Adamik
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (W.B.); (J.S.); (B.D.); (W.G.)
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Wang Q, Zhang G. Platelet count as a prognostic marker for acute respiratory distress syndrome. BMC Pulm Med 2024; 24:396. [PMID: 39153980 PMCID: PMC11330071 DOI: 10.1186/s12890-024-03204-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 08/07/2024] [Indexed: 08/19/2024] Open
Abstract
BACKGROUND This study aimed to evaluate the role of platelet count (PLT) in the prognosis of patients with acute respiratory distress syndrome (ARDS). METHODS The data were extracted from the Medical Information Mart for Intensive Care database (version 2.2). Patients diagnosed with ARDS according to criteria from Berlin Definition and had the platelet count (PLT) measured within the first day after intensive care unit admission were analyzed. Based on PLT, ARDS patients were divided into four groups: PLT ≤ 100 × 109/L, PLT 101-200 × 109/L, PLT 201-300 × 109/L, and PLT > 300 × 109/L. The primary outcome was 28-day mortality. Survival probabilities were analyzed using Kaplan-Meier. Furthermore, the association between PLT and mortality in ARDS patients was assessed using a univariate and multivariable Cox proportional hazards model. RESULTS Overall, the final analysis included 3,207 eligible participants with ARDS. According to the Kaplan-Meier curves for 28-day mortality of PLT, PLT ≤ 100 × 109/L was associated with a higher incidence of mortality (P = 0.001), the same trends were observed in the 60-day (P = 0.001) and 90-day mortality (P = 0.001). In the multivariate model adjusted for the potential factors, the adjusted hazard ratio at PLT 101-200 × 109/L group, PLT 201-300 × 109/L, and PLT > 300 × 109/L was 0.681 [95% confidence interval (CI): 0.576-0.805, P < 0.001], 0.733 (95% CI: 0.604-0.889, P = 0.002), and 0.787 (95% CI: 0.624-0.994, P = 0.044) compared to the reference group (PLT ≤ 100 × 109/L), respectively. Similar relationships between the PLT ≤ 100 × 109/L group and 28-day mortality were obtained in most subgroups. CONCLUSION PLT appeared to be an independent predictor of mortality in critically ill patients with ARDS.
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Affiliation(s)
- Qianwen Wang
- Department of Intensive care unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hang Zhou, Zhe Jiang, 310000, China, No 3 East Road Qingchun
| | - Ge Zhang
- Department of Intensive care unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hang Zhou, Zhe Jiang, 310000, China, No 3 East Road Qingchun.
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10
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Isdahl M, Katz L, Johnson M, Leverson G, Al-Adra D, Thibeault S. Predictors for postoperative dysphagia in liver transplant recipients. FRONTIERS IN TRANSPLANTATION 2024; 3:1415141. [PMID: 39221171 PMCID: PMC11363258 DOI: 10.3389/frtra.2024.1415141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 07/23/2024] [Indexed: 09/04/2024]
Abstract
Introduction Liver transplant recipients are at a heightened risk for oropharyngeal dysphagia; identification of those who are at high risk for postoperative dysphagia could reduce hospital costs and length of stay. We sought to identify predictors of dysphagia, in a large cohort of patients who underwent liver transplantation. Methods Electronic medical records were queried for patients undergoing liver transplantation, who underwent instrumental swallowing evaluations. Demographics, functional outcomes, and interventions were collected. Logistic regression analyses were performed to identify predictors of dysphagia. Results Seven hundred and ninety-five patients met inclusionary criteria. Multivariate analyses found ethnic group (p = .0191), MELD Score (p < 0001), cold ischemia time (p = .0123), and length of intubation (p < .0001) to be predictors of post-operative development of dysphagia. Pre-transplant dialysis (p < .0001), dysphagia related to end stage liver disease (p < .0001), Karnofsky Performance Status Scale (p < .0001), wait time to transplant (p = 0.0173), surgery time (p = 0.0095), tracheostomy (p < 0.0001), and transfusion of intraoperative RBC (p < .0001), intraoperative platelets (p = 0.0018), intraoperative FFP (p = 0.0495), perioperative FFP (p = 0.0002), perioperative platelets (p = 0.0151) and perioperative RBC (p = 0.0002) were variables of significance associated with the development of postoperative dysphagia from univariate analysis. Conclusions Our results propose a set of predictors that should be considered when identifying post-operative critically ill patients at risk for dysphagia.
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Affiliation(s)
- Marian Isdahl
- Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, University of Wisconsin, Madison, WI, United States
| | - Lily Katz
- Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, University of Wisconsin, Madison, WI, United States
| | - Michaela Johnson
- Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, University of Wisconsin, Madison, WI, United States
- Department of Brain and Spine, University of Tennessee Medical Center, Knoxville, TN, United States
| | - Glen Leverson
- Department of Surgery, University of Wisconsin Madison, Madison, WI, United States
| | - David Al-Adra
- Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Susan Thibeault
- Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, University of Wisconsin, Madison, WI, United States
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Lee YY, Kim SD, Park JK, Lee WJ, Han JE, Seo MS, Seo MG, Bae S, Kwak D, Saba E, Rhee MH. Red ginseng extract inhibits lipopolysaccharide-induced platelet-leukocyte aggregates in mice. J Ginseng Res 2024; 48:428-434. [PMID: 39036730 PMCID: PMC11258389 DOI: 10.1016/j.jgr.2024.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 03/27/2024] [Accepted: 03/29/2024] [Indexed: 07/23/2024] Open
Abstract
Background Platelet-leukocyte aggregates (PLAs) play important roles in cardiovascular disease and sepsis. Red ginseng extract (RGE) has been well-studied for its antiplatelet and anti-inflammatory activities. However, the potential inhibitory effects of RGE on PLA have not been investigated. Methods Six-week-old ICR mice were given oral gavage of RGE for 7 days, followed by an intraperitoneal injection of 15 mg/kg of lipopolysaccharide. Mice were euthanized 24 h later, and blood samples were collected for further analysis. Flow cytometry was utilized to sort populations of PLAs and platelet-neutrophil aggregates (PNAs). By using confocal microscopy, PNAs were validated. Morphological changes in platelets and leukocytes were visualized with scanning electron microscopy. Expressions of tissue factor (TF) and platelet factor 4 (PF4) were investigated using enzyme-linked immunosorbent assay. Results Populations of activated platelets, PLAs and PNAs, were significantly increased with LPS-induction. Treatment with 200 and 400 mg/kg of RGE decreased platelet activation. Moreover, the populations of PLAs and PNAs were reduced. PNAs were visible in the blood of septic mice, and this was attenuated by treatment with 400 mg/kg of RGE. Morphologically, sepsisinduced platelet activation and fibrin formation in the blood. This was reduced with RGE treatment. Sepsis-induced increase in the plasma levels of TF and PF4 was also reduced with RGE treatment. Conclusion This study shows that RGE is a potential therapeutic that reduces the activation of platelets and targets PLA and PNA formation. Detailed inhibitory mechanisms of RGE should be studied.
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Affiliation(s)
- Yuan Yee Lee
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
- Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States
| | - Sung Dae Kim
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jin-Kyu Park
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Won-Jae Lee
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jee Eun Han
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Min-Soo Seo
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Min-Goo Seo
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Seulgi Bae
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Dongmi Kwak
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Evelyn Saba
- Department of Veterinary Biomedical Sciences, Faculty of Veterinary and Animal Sciences, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan
| | - Man Hee Rhee
- Department of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
- Institute for Veterinary Biomedical Science, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea
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12
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Li BR, Zhuo Y, Jiang YY, Zhang SY. Random forest differentiation of Escherichia coli in elderly sepsis using biomarkers and infectious sites. Sci Rep 2024; 14:12973. [PMID: 38839818 PMCID: PMC11153632 DOI: 10.1038/s41598-024-63944-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 06/03/2024] [Indexed: 06/07/2024] Open
Abstract
This study addresses the challenge of accurately diagnosing sepsis subtypes in elderly patients, particularly distinguishing between Escherichia coli (E. coli) and non-E. coli infections. Utilizing machine learning, we conducted a retrospective analysis of 119 elderly sepsis patients, employing a random forest model to evaluate clinical biomarkers and infection sites. The model demonstrated high diagnostic accuracy, with an overall accuracy of 87.5%, and impressive precision and recall rates of 93.3% and 87.5%, respectively. It identified infection sites, platelet distribution width, reduced platelet count, and procalcitonin levels as key predictors. The model achieved an F1 Score of 90.3% and an area under the receiver operating characteristic curve of 88.0%, effectively differentiating between sepsis subtypes. Similarly, logistic regression and least absolute shrinkage and selection operator analysis underscored the significance of infectious sites. This methodology shows promise for enhancing elderly sepsis diagnosis and contributing to the advancement of precision medicine in the field of infectious diseases.
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Affiliation(s)
- Bu-Ren Li
- Department of Clinical Laboratory, Fuding Hospital, Fujian University of Traditional Chinese Medicine, 120 South Road of Old City, Fuding, 355200, Fujian, China
| | - Ying Zhuo
- Department of Clinical Laboratory, Fuding Hospital, Fujian University of Traditional Chinese Medicine, 120 South Road of Old City, Fuding, 355200, Fujian, China
| | - Ying-Ying Jiang
- Department of Clinical Laboratory, Fuding Hospital, Fujian University of Traditional Chinese Medicine, 120 South Road of Old City, Fuding, 355200, Fujian, China
| | - Shi-Yan Zhang
- Department of Clinical Laboratory, Fuding Hospital, Fujian University of Traditional Chinese Medicine, 120 South Road of Old City, Fuding, 355200, Fujian, China.
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13
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Iba T, Helms J, Maier CL, Levi M, Scarlatescu E, Levy JH. The role of thromboinflammation in acute kidney injury among patients with septic coagulopathy. J Thromb Haemost 2024; 22:1530-1540. [PMID: 38382739 DOI: 10.1016/j.jtha.2024.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/22/2024] [Accepted: 02/07/2024] [Indexed: 02/23/2024]
Abstract
Inflammation and coagulation are critical self-defense mechanisms for mitigating infection that can nonetheless induce tissue injury and organ dysfunction. In severe cases, like sepsis, a dysregulated thromboinflammatory response may result in multiorgan dysfunction. Sepsis-associated acute kidney injury (AKI) is a significant contributor to patient morbidity and mortality. The connection between AKI and thromboinflammation is largely due to unique aspects of the renal vasculature. Specifically, the interaction between blood cells with the endothelial, glomerular, and peritubular capillary systems during thromboinflammation reduces oxygen supply to tubular epithelial cells. Previous studies have focused on tubular epithelial cell damage due to hypoxia, oxidative stress, and nephrotoxins. Although these factors are pivotal in acute tubular injury or necrosis, recent studies have demonstrated that AKI in sepsis encompasses a mixture of tubular and glomerular damage subtypes. In cases of sepsis-induced coagulopathy, thromboinflammation within the glomerulus and peritubular capillaries is an important pathogenic mechanism for AKI. Unfortunately, and despite the use of renal replacement therapy, the development of AKI in sepsis continues to be associated with high morbidity, mortality, and clinical challenges requiring alternative approaches. This review introduces the important role of thromboinflammation in AKI pathogenesis and details innovative vascular-targeting therapeutic strategies.
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Affiliation(s)
- Toshiaki Iba
- Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Julie Helms
- French National Institute of Health and Medical Research, United Medical Resources 1260, Regenerative Nanomedicine, Federation de Medicine Translationnelle de Strasbourg, Strasbourg University Hospital, Medical Intensive Care Unit - NHC, Strasbourg University, Strasbourg, France
| | - Cheryl L Maier
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Marcel Levi
- Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands; Department of Medicine, University College London Hospitals National Health Service Foundation Trust, Cardio-metabolic Programme-National Institute for Health and Care Research University College London Hospitals/University College London Biomedical Research Centre, London, United Kingdom
| | - Ecaterina Scarlatescu
- University of Medicine and Pharmacy "Carol Davila," Bucharest, Romania; Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, Bucharest, Romania
| | - Jerrold H Levy
- Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, North Carolina, USA
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14
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Aggarwal S, Sangle AL, Siddiqui MS, Haseeb M, Engade MB. An Observational Study on C-Reactive Protein to Platelet Ratio in Neonatal Sepsis. Cureus 2024; 16:e62230. [PMID: 39006693 PMCID: PMC11241635 DOI: 10.7759/cureus.62230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/12/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND Neonatal sepsis is a serious medical condition affecting many individuals in the developing world. C-reactive protein (CRP) level in serum and platelet counts have been reported to have role in diagnosis of neonatal sepsis. OBJECTIVE To evaluate the CRP to Platelet ratio (CPR) in relation to time and blood culture reports in neonatal sepsis patients from a tertiary care centre in the Marathwada region of Maharashtra. METHODS The present observational study was conducted at the level III Neonatal Intensive Care Unit of a tertiary care centre in Aurangabad city of Marathwada region in Maharashtra from September 2022 to July 2023. The study included 120 neonates (delivered after completion of 28-42 weeks of gestation) with clinical/culture-positive sepsis. The newborns of seropositive mothers, neonates delivered in other hospitals, babies with congenital dysmorphic features, and babies requiring surgical procedures were excluded from the study. Blood samples for complete blood count (CBC) and CRP were collected on days 1, 3 and 5. Blood cultures were sent on day 1 of illness. Repeated measures ANOVA was used to compare the parameters of CPR, CRP, and platelet count in blood culture-positive and blood culture-negative neonatal sepsis patients on days 1, 3 and 5. RESULTS Blood culture was positive in 37 (30.8%) cases. A repeated measures ANOVA showed a significant overall difference in the CPR across days 1, 3, and 5 (p = 0.006). The CPR was significantly higher in culture-positive neonates compared to culture-negative neonates (p = 0.042). CONCLUSION Higher CPR in blood culture-positive neonates compared to blood culture-negative neonates supports the role of CPR in the diagnosis and management of neonatal sepsis.
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Affiliation(s)
- Shreya Aggarwal
- Pediatrics, Mahatma Gandhi Mission Medical College and Hospital, Aurangabad, IND
| | - Avinash L Sangle
- Pediatrics, Mahatma Gandhi Mission Medical College and Hospital, Aurangabad, IND
| | - Mohd Saeed Siddiqui
- Pediatrics, Mahatma Gandhi Mission Medical College and Hospital, Aurangabad, IND
| | - Mohammad Haseeb
- Pediatrics, Mahatma Gandhi Mission Medical College and Hospital, Aurangabad, IND
| | - Madhuri B Engade
- Pediatrics, Mahatma Gandhi Mission Medical College and Hospital, Aurangabad, IND
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15
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Mizuno T, Nagano F, Takahashi K, Yamada S, Fruhashi K, Maruyama S, Tsuboi N. Macrophage-1 antigen exacerbates histone-induced acute lung injury and promotes neutrophil extracellular trap formation. FEBS Open Bio 2024; 14:574-583. [PMID: 38360057 PMCID: PMC10988669 DOI: 10.1002/2211-5463.13779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 01/17/2024] [Accepted: 02/06/2024] [Indexed: 02/17/2024] Open
Abstract
Acute lung injury (ALI), which occurs in association with sepsis, trauma, and coronavirus disease 2019 (COVID-19), is a serious clinical condition with high mortality. Excessive platelet-leukocyte aggregate (PLA) formation promotes neutrophil extracellular trap (NET) release and thrombosis, which are involved in various diseases, including ALI. Macrophage-1 antigen (Mac-1, CD11b/CD18), which is expressed on the surface of leukocytes, is known to promote NET formation. This study aimed to elucidate the role of Mac-1 in extracellular histone-induced ALI. Exogenous histones were administered to Mac-1-deficient mice and wild-type (WT) mice with or without neutrophil or platelet depletion, and several parameters were investigated 1 h after histone injection. Depletion of neutrophils or platelets improved survival time and macroscopic and microscopic properties of lung tissues, and decreased platelet-leukocyte formation and plasma myeloperoxidase levels. These improvements were also observed in Mac-1-/- mice. NET formation in Mac-1-/- bone marrow neutrophils (BMNs) was significantly lower than that in WT BMNs. In conclusion, our findings suggest that Mac-1 is associated with exacerbation of histone-induced ALI and the promotion of NET formation in the presence of activated platelets.
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Affiliation(s)
- Tomohiro Mizuno
- Department of Pharmacotherapeutics and InformaticsFujita Health University School of MedicineToyoakeJapan
| | - Fumihiko Nagano
- Department of NephrologyNagoya University School of MedicineJapan
| | - Kazuo Takahashi
- Department of Biomedical Molecular SciencesFujita Health University School of MedicineToyoakeJapan
| | - Shigeki Yamada
- Department of Pharmacotherapeutics and InformaticsFujita Health University School of MedicineToyoakeJapan
| | | | - Shoichi Maruyama
- Department of NephrologyNagoya University School of MedicineJapan
| | - Naotake Tsuboi
- Department of NephrologyFujita Health University School of MedicineToyoakeJapan
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16
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Effah CY, Ding X, Drokow EK, Li X, Tong R, Sun T. Bacteria-derived extracellular vesicles: endogenous roles, therapeutic potentials and their biomimetics for the treatment and prevention of sepsis. Front Immunol 2024; 15:1296061. [PMID: 38420121 PMCID: PMC10899385 DOI: 10.3389/fimmu.2024.1296061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 01/24/2024] [Indexed: 03/02/2024] Open
Abstract
Sepsis is one of the medical conditions with a high mortality rate and lacks specific treatment despite several years of extensive research. Bacterial extracellular vesicles (bEVs) are emerging as a focal target in the pathophysiology and treatment of sepsis. Extracellular vesicles (EVs) derived from pathogenic microorganisms carry pathogenic factors such as carbohydrates, proteins, lipids, nucleic acids, and virulence factors and are regarded as "long-range weapons" to trigger an inflammatory response. In particular, the small size of bEVs can cross the blood-brain and placental barriers that are difficult for pathogens to cross, deliver pathogenic agents to host cells, activate the host immune system, and possibly accelerate the bacterial infection process and subsequent sepsis. Over the years, research into host-derived EVs has increased, leading to breakthroughs in cancer and sepsis treatments. However, related approaches to the role and use of bacterial-derived EVs are still rare in the treatment of sepsis. Herein, this review looked at the dual nature of bEVs in sepsis by highlighting their inherent functions and emphasizing their therapeutic characteristics and potential. Various biomimetics of bEVs for the treatment and prevention of sepsis have also been reviewed. Finally, the latest progress and various obstacles in the clinical application of bEVs have been highlighted.
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Affiliation(s)
- Clement Yaw Effah
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Zhengzhou Key Laboratory of Sepsis, Henan Sepsis Diagnosis and Treatment Center, Henan Key Laboratory of Sepsis in Health Commission, Zhengzhou, China
| | - Xianfei Ding
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Zhengzhou Key Laboratory of Sepsis, Henan Sepsis Diagnosis and Treatment Center, Henan Key Laboratory of Sepsis in Health Commission, Zhengzhou, China
| | - Emmanuel Kwateng Drokow
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Department of Epidemiology and Biostatistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
| | - Xiang Li
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Zhengzhou Key Laboratory of Sepsis, Henan Sepsis Diagnosis and Treatment Center, Henan Key Laboratory of Sepsis in Health Commission, Zhengzhou, China
| | - Ran Tong
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Zhengzhou Key Laboratory of Sepsis, Henan Sepsis Diagnosis and Treatment Center, Henan Key Laboratory of Sepsis in Health Commission, Zhengzhou, China
| | - Tongwen Sun
- Department of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Critical Care Medicine, Henan Key Laboratory of Critical Care Medicine, Zhengzhou, China
- Zhengzhou Key Laboratory of Sepsis, Henan Sepsis Diagnosis and Treatment Center, Henan Key Laboratory of Sepsis in Health Commission, Zhengzhou, China
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17
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Han X, Song X, Xiao Z, Zhu G, Gao R, Ni B, Li J. Study on the mechanism of MDSC-platelets and their role in the breast cancer microenvironment. Front Cell Dev Biol 2024; 12:1310442. [PMID: 38404689 PMCID: PMC10884319 DOI: 10.3389/fcell.2024.1310442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 01/29/2024] [Indexed: 02/27/2024] Open
Abstract
Myeloid-derived suppressor cells (MDSCs) are key immunosuppressive cells in the tumor microenvironment (TME) that play critical roles in promoting tumor growth and metastasis. Tumor-associated platelets (TAPs) help cancer cells evade the immune system and promote metastasis. In this paper, we describe the interaction between MDSCs and TAPs, including their generation, secretion, activation, and recruitment, as well as the effects of MDSCs and platelets on the generation and changes in the immune, metabolic, and angiogenic breast cancer (BC) microenvironments. In addition, we summarize preclinical and clinical studies, traditional Chinese medicine (TCM) therapeutic approaches, and new technologies related to targeting and preventing MDSCs from interacting with TAPs to modulate the BC TME, discuss the potential mechanisms, and provide perspectives for future development. The therapeutic strategies discussed in this review may have implications in promoting the normalization of the BC TME, reducing primary tumor growth and distant lung metastasis, and improving the efficiency of anti-tumor therapy, thereby improving the overall survival (OS) and progression-free survival (PFS) of patients. However, despite the significant advances in understanding these mechanisms and therapeutic strategies, the complexity and heterogeneity of MDSCs and side effects of antiplatelet agents remain challenging. This requires further investigation in future prospective cohort studies.
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Affiliation(s)
- Xinpu Han
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Hematology-Oncology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaotong Song
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhigang Xiao
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guanghui Zhu
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ruike Gao
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Baoyi Ni
- Department of Oncology, First Hospital of Heilongjiang University of Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jie Li
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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18
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Jeong SH, Park JY, Ryu YB, Kim WS, Lee IC, Kim JH, Kim D, Ha JH, Lee BW, Nam J, Cho KO, Kwon HJ. Myristica fragrans Extract Inhibits Platelet Desialylation and Activation to Ameliorate Sepsis-Associated Thrombocytopenia in a Murine CLP-Induced Sepsis Model. Int J Mol Sci 2023; 24:ijms24108863. [PMID: 37240208 DOI: 10.3390/ijms24108863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/11/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
Sepsis, characterized by an uncontrolled host inflammatory response to infections, remains a leading cause of death in critically ill patients worldwide. Sepsis-associated thrombocytopenia (SAT), a common disease in patients with sepsis, is an indicator of disease severity. Therefore, alleviating SAT is an important aspect of sepsis treatment; however, platelet transfusion is the only available treatment strategy for SAT. The pathogenesis of SAT involves increased platelet desialylation and activation. In this study, we investigated the effects of Myristica fragrans ethanol extract (MF) on sepsis and SAT. Desialylation and activation of platelets treated with sialidase and adenosine diphosphate (platelet agonist) were assessed using flow cytometry. The extract inhibited platelet desialylation and activation via inhibiting bacterial sialidase activity in washed platelets. Moreover, MF improved survival and reduced organ damage and inflammation in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. It also prevented platelet desialylation and activation via inhibiting circulating sialidase activity, while maintaining platelet count. Inhibition of platelet desialylation reduces hepatic Ashwell-Morell receptor-mediated platelet clearance, thereby reducing hepatic JAK2/STAT3 phosphorylation and thrombopoietin mRNA expression. This study lays a foundation for the development of plant-derived therapeutics for sepsis and SAT and provides insights into sialidase-inhibition-based sepsis treatment strategies.
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Affiliation(s)
- Seong-Hun Jeong
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
- Laboratory of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Ji-Young Park
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
- Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup 53212, Republic of Korea
| | - Young Bae Ryu
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
| | - Woo Sik Kim
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
| | - In-Chul Lee
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
- Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup 53212, Republic of Korea
| | - Ju-Hong Kim
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
| | - Dohoon Kim
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
| | - Ji-Hye Ha
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
| | - Ba-Wool Lee
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
| | - Jiyoung Nam
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
| | - Kyoung-Oh Cho
- Laboratory of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea
| | - Hyung-Jun Kwon
- Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea
- Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup 53212, Republic of Korea
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19
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Mendelson AA, Erickson D, Villar R. The role of the microcirculation and integrative cardiovascular physiology in the pathogenesis of ICU-acquired weakness. Front Physiol 2023; 14:1170429. [PMID: 37234410 PMCID: PMC10206327 DOI: 10.3389/fphys.2023.1170429] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 04/28/2023] [Indexed: 05/28/2023] Open
Abstract
Skeletal muscle dysfunction after critical illness, defined as ICU-acquired weakness (ICU-AW), is a complex and multifactorial syndrome that contributes significantly to long-term morbidity and reduced quality of life for ICU survivors and caregivers. Historically, research in this field has focused on pathological changes within the muscle itself, without much consideration for their in vivo physiological environment. Skeletal muscle has the widest range of oxygen metabolism of any organ, and regulation of oxygen supply with tissue demand is a fundamental requirement for locomotion and muscle function. During exercise, this process is exquisitely controlled and coordinated by the cardiovascular, respiratory, and autonomic systems, and also within the skeletal muscle microcirculation and mitochondria as the terminal site of oxygen exchange and utilization. This review highlights the potential contribution of the microcirculation and integrative cardiovascular physiology to the pathogenesis of ICU-AW. An overview of skeletal muscle microvascular structure and function is provided, as well as our understanding of microvascular dysfunction during the acute phase of critical illness; whether microvascular dysfunction persists after ICU discharge is currently not known. Molecular mechanisms that regulate crosstalk between endothelial cells and myocytes are discussed, including the role of the microcirculation in skeletal muscle atrophy, oxidative stress, and satellite cell biology. The concept of integrated control of oxygen delivery and utilization during exercise is introduced, with evidence of physiological dysfunction throughout the oxygen delivery pathway - from mouth to mitochondria - causing reduced exercise capacity in patients with chronic disease (e.g., heart failure, COPD). We suggest that objective and perceived weakness after critical illness represents a physiological failure of oxygen supply-demand matching - both globally throughout the body and locally within skeletal muscle. Lastly, we highlight the value of standardized cardiopulmonary exercise testing protocols for evaluating fitness in ICU survivors, and the application of near-infrared spectroscopy for directly measuring skeletal muscle oxygenation, representing potential advancements in ICU-AW research and rehabilitation.
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Affiliation(s)
- Asher A. Mendelson
- Section of Critical Care Medicine, Department of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Dustin Erickson
- Section of Critical Care Medicine, Department of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Rodrigo Villar
- Faculty of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, MB, Canada
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20
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Yang M, Jiang H, Ding C, Zhang L, Ding N, Li G, Zhang F, Wang J, Deng L, Liu J, Xu Y. STING activation in platelets aggravates septic thrombosis by enhancing platelet activation and granule secretion. Immunity 2023; 56:1013-1026.e6. [PMID: 36944334 DOI: 10.1016/j.immuni.2023.02.015] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 11/09/2022] [Accepted: 02/22/2023] [Indexed: 03/23/2023]
Abstract
Sepsis is a dysregulated inflammatory consequence of systemic infection. As a result, excessive platelet activation leads to thrombosis and coagulopathy, but we currently lack sufficient understanding of these processes. Here, using the cecal ligation and puncture (CLP) model of sepsis, we observed septic thrombosis and neutrophil extracellular trap formation (NETosis) within the mouse vasculature by intravital microscopy. STING activation in platelets was a critical driver of sepsis-induced pathology. Platelet-specific STING deficiency suppressed platelet activation and granule secretion, which alleviated sepsis-induced intravascular thrombosis and NETosis in mice. Mechanistically, sepsis-derived cGAMP promoted the binding of STING to STXBP2, the assembly of SNARE complex, granule secretion, and subsequent septic thrombosis, which probably depended on the palmitoylation of STING. We generated a peptide, C-ST5, to block STING binding to STXBP2. Septic mice treated with C-ST5 showed reduced thrombosis. Overall, platelet activation via STING reveals a potential strategy for limiting life-threatening sepsis-mediated coagulopathy.
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Affiliation(s)
- Mina Yang
- Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Haojie Jiang
- Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Chen Ding
- Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Lin Zhang
- Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Nan Ding
- Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Guoming Li
- Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Fei Zhang
- Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jing Wang
- Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Liufu Deng
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Junling Liu
- Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
| | - Yanyan Xu
- Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
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21
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Liu X, Yin W, Li Y, Qin Y, Zou T. Association between minimal decrease in platelet counts and outcomes in septic patients: a retrospective observational study. BMJ Open 2023; 13:e069027. [PMID: 37185200 PMCID: PMC10151909 DOI: 10.1136/bmjopen-2022-069027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/17/2023] Open
Abstract
OBJECTIVES Although platelets have been linked to inflammatory development in sepsis, knowledge on their role as an indicator in sepsis treatment is scarce. Here, we investigated the association between time-dependent changes in platelet counts with mortality rates to reveal the role of platelets in sepsis therapy. DESIGN A retrospective cohort study. SETTING We screened the Medical Information Mart for Intensive Care (MIMIC-IV), a public database comprising data from critical care subjects at the Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts, USA. PARTICIPANTS A total of 7981 patients, who were admitted to the BIDMC between 2008 and 2019, were analysed based on Sepsis-3 criteria from MIMIC-IV. PRIMARY AND SECONDARY OUTCOME MEASURES Primary and secondary outcomes included 30-day mortality after admission and length of intensive care unit (ICU) stay and hospitalisation, respectively. RESULTS Patients with ≤10% reduction in proportion of platelet counts were associated with significantly lower 30-day mortality (14.1% vs 23.5%, p<0.001, Kaplan-Meier analysis, p<0.0001). Multivariable analysis revealed that decreased platelet-count percentage ≤10% on day 4 after ICU admission was associated with lower probability of 30-day non-survival (OR=0.73, 95% CI 0.64 to 0.82, p＜0.001). Patients in the ≤10% group had significantly shorter ICU stays than those in the >10% group (6.8 vs 7.5, p＜0.001). Restricted cubic spline curves revealed that mortality rates decreased with increase in proportion of platelet counts. CONCLUSIONS A ≤10% decrease in platelet-count percentage among sepsis patients after treatments is independently associated with decreased 30-day mortality, suggesting that changes in proportion of platelet counts after treatments could be an indicator for assessing the therapeutic effects of sepsis.
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Affiliation(s)
- Xing Liu
- Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Wanhong Yin
- Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Yi Li
- Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Yiwei Qin
- Department of Intensive Medicine, Chengdu Medical College, The First Affiliated Hospital, Chengdu, Sichuan, China
| | - Tongjuan Zou
- Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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22
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Russo I, Barale C, Melchionda E, Penna C, Pagliaro P. Platelets and Cardioprotection: The Role of Nitric Oxide and Carbon Oxide. Int J Mol Sci 2023; 24:ijms24076107. [PMID: 37047079 PMCID: PMC10094148 DOI: 10.3390/ijms24076107] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/16/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Nitric oxide (NO) and carbon monoxide (CO) represent a pair of biologically active gases with an increasingly well-defined range of effects on circulating platelets. These gases interact with platelets and cells in the vessels and heart and exert fundamentally similar biological effects, albeit through different mechanisms and with some peculiarity. Within the cardiovascular system, for example, the gases are predominantly vasodilators and exert antiaggregatory effects, and are protective against damage in myocardial ischemia-reperfusion injury. Indeed, NO is an important vasodilator acting on vascular smooth muscle and is able to inhibit platelet activation. NO reacts with superoxide anion (O2(-•)) to form peroxynitrite (ONOO(-)), a nitrosating agent capable of inducing oxidative/nitrative signaling and stress both at cardiovascular, platelet, and plasma levels. CO reduces platelet reactivity, therefore it is an anticoagulant, but it also has some cardioprotective and procoagulant properties. This review article summarizes current knowledge on the platelets and roles of gas mediators (NO, and CO) in cardioprotection. In particular, we aim to examine the link and interactions between platelets, NO, and CO and cardioprotective pathways.
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Affiliation(s)
- Isabella Russo
- Department of Clinical and Biological Sciences of Turin University, Orbassano, I-10043 Turin, Italy
| | - Cristina Barale
- Department of Clinical and Biological Sciences of Turin University, Orbassano, I-10043 Turin, Italy
| | - Elena Melchionda
- Department of Clinical and Biological Sciences of Turin University, Orbassano, I-10043 Turin, Italy
| | - Claudia Penna
- Department of Clinical and Biological Sciences of Turin University, Orbassano, I-10043 Turin, Italy
| | - Pasquale Pagliaro
- Department of Clinical and Biological Sciences of Turin University, Orbassano, I-10043 Turin, Italy
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23
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Liu HT, Lai CY, Liao JJ, Chen YJ, Cheng SB, Wu CC. Immediate postoperative parenteral anticoagulant therapy in patients with mesenteric ischemia after intestinal resection: a retrospective cohort study at a single institute. BMC Gastroenterol 2023; 23:56. [PMID: 36890480 PMCID: PMC9996985 DOI: 10.1186/s12876-023-02691-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 02/22/2023] [Indexed: 03/10/2023] Open
Abstract
BACKGROUND Bowel gangrene represents a major fatal event in acute mesenteric ischemia. Intestinal resection is inevitable in patients with peritonitis and bowel gangrene. This retrospective study aimed to elucidate the benefit of postoperative parenteral anticoagulation in patients with intestinal resection. METHODS Patients with acute mesenteric ischemia and bowel gangrene were recruited retrospectively between January 2007 and December 2019. All patients underwent bowel resection. They were categorized into two groups: patients without immediate parenteral anticoagulant therapy (Group A) and those with immediate parenteral anticoagulant therapy (Group B). Thirty-day mortality and survival were analyzed. RESULTS A total of 85 patients were included, with 29 patients in Group A and 56 patients in Group B. Patients in Group B had lower 30-day mortality (16.1%) and a higher 2-year survival rate (45.4%) than patients in Group A (30-day mortality: 51.7%, p = 0.001; 2-year survival rate: 19.0%, p = 0.001). In the 30-day mortality multivariate analysis, patients in Group B had a better outcome (odds ratio = 0.080, 95% confidence interval between 0.011 and 0.605, p = 0.014). Patients in Group B also had a better outcome in the survival multivariate analysis (hazard ratio: 0.435, 95% confidence interval between 0.213 and 0.887, p = 0.022). CONCLUSIONS Immediate postoperative parenteral anticoagulant therapy improves prognosis in patients with acute mesenteric ischemia treated by intestinal resection. Trial registration This research was retrospectively approved by the Institutional Review Board (IRB) I&II of Taichung Veterans General Hospital (TCVGH-IRB No.CE21256B) on July 28th, 2021. The informed consent waiver was also approved by IRB I&II of Taichung Veterans General Hospital. The Declaration of Helsinki and ICH-GCP guidelines were followed during this study.
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Affiliation(s)
- Hsiao-Tien Liu
- Department of Surgery, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan, ROC. .,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
| | - Chia-Yu Lai
- Organ Transplantation Center, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Jian-Jhou Liao
- Department of Surgery, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan, ROC
| | - Yi-Ju Chen
- Department of Surgery, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan, ROC
| | - Shao-Bin Cheng
- Organ Transplantation Center, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Cheng-Chung Wu
- Department of Surgery, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan, ROC.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan
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24
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Frydman GH, Ellett F, Jorgensen J, Marand AL, Zukerberg L, Selig MK, Tessier SN, Wong KHK, Olaleye D, Vanderburg CR, Fox JG, Tompkins RG, Irimia D. Megakaryocytes respond during sepsis and display innate immune cell behaviors. Front Immunol 2023; 14:1083339. [PMID: 36936945 PMCID: PMC10019826 DOI: 10.3389/fimmu.2023.1083339] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 02/07/2023] [Indexed: 03/06/2023] Open
Abstract
Megakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the peripheral circulation. However, while platelets are known to participate in immune responses and play significant functions during infections, the role of MKs within the immune system remains largely unexplored. Histological studies of sepsis patients identified increased nucleated CD61+ cells (MKs) in the lungs, and CD61+ staining (likely platelets within microthrombi) in the kidneys, which correlated with the development of organ dysfunction. Detailed imaging cytometry of peripheral blood from patients with sepsis found significantly higher MK counts, which we predict would likely be misclassified by automated hematology analyzers as leukocytes. Utilizing in vitro techniques, we show that both stem cell derived MKs (SC MKs) and cells from the human megakaryoblastic leukemia cell line, Meg-01, undergo chemotaxis, interact with bacteria, and are capable of releasing chromatin webs in response to various pathogenic stimuli. Together, our observations suggest that MK cells display some basic innate immune cell behaviors and may actively respond and play functional roles in the pathophysiology of sepsis.
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Affiliation(s)
- Galit H. Frydman
- Division of Comparative Medicine and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States
- BioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - Felix Ellett
- BioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - Julianne Jorgensen
- BioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - Anika L. Marand
- BioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - Lawrence Zukerberg
- Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
| | - Martin K. Selig
- Department of Pathology, Massachusetts General Hospital, Boston, MA, United States
| | - Shannon N. Tessier
- BioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - Keith H. K. Wong
- BioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - David Olaleye
- Division of Comparative Medicine and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States
| | | | - James G. Fox
- Division of Comparative Medicine and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Ronald G. Tompkins
- BioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
| | - Daniel Irimia
- BioMEMS Resource Center and Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
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25
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Coagulation Disorders in Sepsis and COVID-19-Two Sides of the Same Coin? A Review of Inflammation-Coagulation Crosstalk in Bacterial Sepsis and COVID-19. J Clin Med 2023; 12:jcm12020601. [PMID: 36675530 PMCID: PMC9866352 DOI: 10.3390/jcm12020601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/27/2022] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
Sepsis is a major cause of morbidity and mortality worldwide. Sepsis-associated coagulation disorders are involved in the pathogenesis of multiorgan failure and lead to a subsequently worsening prognosis. Alongside the global impact of the COVID-19 pandemic, a great number of research papers have focused on SARS-CoV-2 pathogenesis and treatment. Significant progress has been made in this regard and coagulation disturbances were once again found to underlie some of the most serious adverse outcomes of SARS-CoV-2 infection, such as acute lung injury and multiorgan dysfunction. In the attempt of untangling the mechanisms behind COVID-19-associated coagulopathy (CAC), a series of similarities with sepsis-induced coagulopathy (SIC) became apparent. Whether they are, in fact, the same disease has not been established yet. The clinical picture of CAC shows the unique feature of an initial phase of intravascular coagulation confined to the respiratory system. Only later on, patients can develop a clinically significant form of systemic coagulopathy, possibly with a consumptive pattern, but, unlike SIC, it is not a key feature. Deepening our understanding of CAC pathogenesis has to remain a major goal for the research community, in order to design and validate accurate definitions and classification criteria.
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26
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Tian C, Wang K, Zhao M, Cong S, Di X, Li R. Extracellular vesicles participate in the pathogenesis of sepsis. Front Cell Infect Microbiol 2022; 12:1018692. [PMID: 36579343 PMCID: PMC9791067 DOI: 10.3389/fcimb.2022.1018692] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 11/23/2022] [Indexed: 12/14/2022] Open
Abstract
Sepsis is one of the leading causes of mortality worldwide and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The early diagnosis and effective treatment of sepsis still face challenges due to its rapid progression, dynamic changes, and strong heterogeneity among different individuals. To develop novel strategies to control sepsis, a better understanding of the complex mechanisms of sepsis is vital. Extracellular vesicles (EVs) are membrane vesicles released from cells through different mechanisms. In the disease state, the number of EVs produced by activated or apoptotic cells and the cargoes they carry were altered. They regulated the function of local or distant host cells in autocrine or paracrine ways. Current studies have found that EVs are involved in the occurrence and development of sepsis through multiple pathways. In this review, we focus on changes in the cargoes of EVs in sepsis, the regulatory roles of EVs derived from host cells and bacteria, and how EVs are involved in multiple pathological processes and organ dysfunction in sepsis. Overall, EVs have great application prospects in sepsis, such as early diagnosis of sepsis, dynamic monitoring of disease, precise therapeutic targets, and prevention of sepsis as a vaccine platform.
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Affiliation(s)
- Chang Tian
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Ke Wang
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Min Zhao
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Shan Cong
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Xin Di
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Ranwei Li
- Department of Urinary Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China,*Correspondence: Ranwei Li,
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27
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Williams B, Zhu J, Zou L, Chao W. Innate immune TLR7 signaling mediates platelet activation and platelet-leukocyte aggregate formation in murine bacterial sepsis. Platelets 2022; 33:1251-1259. [PMID: 35920588 PMCID: PMC9833650 DOI: 10.1080/09537104.2022.2107627] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Thrombocytopenia is a common complication in sepsis and is associated with higher mortality. Activated platelets express CD62P, which facilitates platelet-leukocyte aggregate (PLA) formation and contributes to thrombocytopenia in sepsis. We have reported that thrombocytopenia in murine sepsis is partly attributable to TLR7 signaling, but the underlying mechanism is unclear. In the current study, we tested the hypothesis that TLR7 mediates platelet activation and PLA formation during sepsis. In vitro, whole blood from WT mice treated with loxoribine, a TLR7 agonist, exhibited a dose-dependent increase in activated platelets compared to the control (PBS with 0.05% DMSO) or loxoribine-treated TLR7-/- whole blood. In a murine model of sepsis, there was a significant increase in platelet activation and PLA formation 24 hours after cecal ligation and puncture (CLP) as evidenced by double positive expression of CD41+/CD62P+ and CD45+/CD62P+, respectively. The sepsis-induced PLA formation was significantly attenuated in TLR7-/- mice. Finally, in ex-vivo experiments, plasma isolated from septic mice induced WT platelet activation, but such effect was significantly attenuated in platelets deficient of TLR7. These findings demonstrate a pivotal role of TLR7 signaling in platelet activation and PLA formation during bacterial sepsis.
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28
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Ultraporous Polyquaternium-Carboxylated Chitosan Composite Hydrogel Spheres with Anticoagulant, Antibacterial, and Rapid Endotoxin Removal Profiles for Sepsis Treatment. Biomacromolecules 2022; 23:3728-3742. [PMID: 35926229 DOI: 10.1021/acs.biomac.2c00583] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hemoperfusion is an important method to remove endotoxins and save the lives of patients with sepsis. However, the current adsorbents for hemoperfusion have disadvantages of insufficient endotoxin adsorption capacity, poor blood compatibility, and so on. Herein, we proposed a novel emulsion templating (ET) method to prepare ultraporous and double-network carboxylated chitosan (CCS)-poly(diallyl dimethylammonium chloride) (PDDA) hydrogel spheres (ET-CCSPD), bearing both negative and positive charges. CCS was introduced to balance the strong positive charges of PDDA to improve hemocompatibility, and emulsion templates endowed the adsorbent with an ultraporous structure for enhanced adsorption efficacy. The ET-CCSPDs neither damaged blood cells nor activated complement responses. In addition, the activated partial thromboplastin time (APTT) was prolonged to 8.5 times, which was beneficial for reducing the injection of anticoagulant in patients. The ET-CCSPDs had excellent scavenging performance against bacteria and endotoxin, with removal ratios of 96.7% for E. coli and 99.8% for S. aureus, respectively, and the static removal ratio of endotoxin in plasma was as high as 99.1% (C0 = 5.50 EU/mL, critical illness level). An adsorption cartridge filled with the ET-CCSPDs could remove 84.7% of endotoxin within 1 h (C0 = 100 EU/mL in PBS). Interestingly, the ET-CCSPDs had a good inhibitory effect on the cytokines produced by endotoxin-mediated septic blood. By developing the ET method to prepare ultraporous and double-network adsorbents, the problems of low adsorption efficiency and poor blood compatibility of traditional endotoxin adsorbents have been solved, thus opening a new route to fabricate absorbents for blood purification.
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29
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Greve F, Aulbach I, Mair O, Biberthaler P, Hanschen M. The Clinical Impact of Platelets on Post-Injury Serum Creatinine Concentration in Multiple Trauma Patients: A Retrospective Cohort Study. Medicina (B Aires) 2022; 58:medicina58070901. [PMID: 35888620 PMCID: PMC9317692 DOI: 10.3390/medicina58070901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 07/01/2022] [Accepted: 07/04/2022] [Indexed: 11/16/2022] Open
Abstract
Background and objective: Platelets contribute to the immunological response after multiple trauma. To determine the clinical impact, this study analyzes the association between platelets and creatinine concentration as an indicator of kidney function in polytraumatized patients. Methods: We investigated all patients presenting an Injury Severity Score (ISS) ≥16 for a 2-year period at our trauma center. Platelet counts and creatinine concentrations were analyzed, and correlation analysis was performed within 10 days after multiple trauma. Results: 83 patients with a median ISS of 22 were included. Platelet count was decreased on day 3 (p ≤ 0.001) and increased on day 10 (p ≤ 0.001). Platelet count was elevated on day 10 in younger patients and diminished in severely injured patients (ISS ≥35) on day 1 (p = 0.012) and day 3 (p = 0.011). Creatinine concentration was decreased on day 1 (p = 0.003) and day 10 (p ≤ 0.001) in female patients. Age (p = 0.01), male sex (p = 0.004), and injury severity (p = 0.014) were identified as factors for increased creatinine concentration on day 1, whereas platelets (p = 0.046) were associated with decreased creatinine concentrations on day 5 after multiple trauma. Conclusions: Kinetics of platelet count and creatinine concentration are influenced by age, gender, and trauma severity. There was no clear correlation between platelet counts and creatinine concentration. However, platelets seem to have a modulating effect on creatinine concentrations in the vulnerable phase after trauma.
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Affiliation(s)
- Frederik Greve
- Department of Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (I.A.); (O.M.); (P.B.); (M.H.)
- Correspondence: ; Tel.: +49-89-4140-2126
| | - Ina Aulbach
- Department of Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (I.A.); (O.M.); (P.B.); (M.H.)
- Department of Traumatology and Reconstructive Surgery, Charité-Universitätsmedizin Berlin, 12203 Berlin, Germany
| | - Olivia Mair
- Department of Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (I.A.); (O.M.); (P.B.); (M.H.)
| | - Peter Biberthaler
- Department of Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (I.A.); (O.M.); (P.B.); (M.H.)
| | - Marc Hanschen
- Department of Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, Germany; (I.A.); (O.M.); (P.B.); (M.H.)
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30
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Marchetti M, Gomez-Rosas P, Russo L, Gamba S, Sanga E, Verzeroli C, Ambaglio C, Schieppati F, Restuccia F, Bonanomi E, Rizzi M, Fagiuoli S, D’Alessio A, Gerotziafas GT, Lorini L, Falanga A. Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients. Front Cardiovasc Med 2022; 9:896362. [PMID: 35757331 PMCID: PMC9226333 DOI: 10.3389/fcvm.2022.896362] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 05/09/2022] [Indexed: 12/12/2022] Open
Abstract
Introduction In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization. Materials and Methods Intensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed. Results Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding. Conclusion This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.
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Affiliation(s)
- Marina Marchetti
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
- *Correspondence: Marina Marchetti,
| | - Patricia Gomez-Rosas
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
- Hematology Service, Hospital General Regional Tecamac Instituto Mexicano del Seguro Social (IMSS), Mexico, Mexico
| | - Laura Russo
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Sara Gamba
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Eleonora Sanga
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Cristina Verzeroli
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Chiara Ambaglio
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Francesca Schieppati
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Francesco Restuccia
- Department of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Ezio Bonanomi
- Department of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Marco Rizzi
- Unit of Infectious Diseases, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Stefano Fagiuoli
- Department of Internal Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Andrea D’Alessio
- Medical Oncology and Internal Medicine, Policlinico San Marco – Gruppo San Donato, Bergamo, Italy
| | - Grigorios T. Gerotziafas
- Sorbonne Université, INSERM UMR_S938, Research Group “Cancer-Hemostasis-Angiogenesis”, Centre de Recherche Saint-Antoine, Institut Universitaire de Cancérologie, Paris, France
| | - Luca Lorini
- Department of Anesthesiology and Critical Care Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Anna Falanga
- Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
- School of Medicine and Surgery, University of Milano Bicocca, Milan, Italy
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Raia L, Zafrani L. Endothelial Activation and Microcirculatory Disorders in Sepsis. Front Med (Lausanne) 2022; 9:907992. [PMID: 35721048 PMCID: PMC9204048 DOI: 10.3389/fmed.2022.907992] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/16/2022] [Indexed: 11/19/2022] Open
Abstract
The vascular endothelium is crucial for the maintenance of vascular homeostasis. Moreover, in sepsis, endothelial cells can acquire new properties and actively participate in the host's response. If endothelial activation is mostly necessary and efficient in eliminating a pathogen, an exaggerated and maladaptive reaction leads to severe microcirculatory damage. The microcirculatory disorders in sepsis are well known to be associated with poor outcome. Better recognition of microcirculatory alteration is therefore essential to identify patients with the worse outcomes and to guide therapeutic interventions. In this review, we will discuss the main features of endothelial activation and dysfunction in sepsis, its assessment at the bedside, and the main advances in microcirculatory resuscitation.
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Affiliation(s)
- Lisa Raia
- Medical Intensive Care Unit, Hôpital Saint-Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
| | - Lara Zafrani
- Medical Intensive Care Unit, Hôpital Saint-Louis, Assistance Publique des Hôpitaux de Paris, Paris, France
- INSERM UMR 976, University of Paris Cité, Paris, France
- *Correspondence: Lara Zafrani
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32
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Changes in Platelet Function in Preterm Newborns with Prematurity Related Morbidities. CHILDREN 2022; 9:children9060791. [PMID: 35740728 PMCID: PMC9221979 DOI: 10.3390/children9060791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/19/2022] [Accepted: 05/23/2022] [Indexed: 11/17/2022]
Abstract
Platelet indices represent useful biomarkers to express the thromboembolic status, inflammatory response, and oxidative stress in preterm newborns. Our study presented platelet count and function changes in prematurity-related morbidities such as respiratory distress syndrome, intraventricular bleeding, and anemia of prematurity in preterm newborn cases reported to healthy full-term newborns by flow cytometry and hematological methods. The platelet volume represents the average size of platelets in the blood samples, showing the significantly increased values in preterm newborns compared with healthy full-term newborns due to increasing activated platelet production. Flow cytometric analysis of immature platelet fractions (IPF) made using thiazole orange staining to detect their mRNA content and a glycoprotein (anti-GPIIIa) antibody for platelet gating. CD61-TO expression from premature newborns was significantly lower compared to healthy full-term neonates. Preterm newborn cases with respiratory distress syndrome and a need for respiratory support (RDS+) were characterized by a significantly increased platelet volume and a decreased immature platelet fraction reported in RDS− cases. Evaluating the platelet function in the newborn is difficult because the laboratory methodologies work with small quantities of newborn blood samples. The immature platelet fractions and platelet volume promise to be diagnostic biomarkers for diseases.
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Miao J, Ren Z, Zhong Z, Xu F, Wang J, Yang J. The Correlation of Antibacterial Peptides Concentration in Umbilical Cord Blood and Early Onset Sepsis in Preterm Infants. Front Pediatr 2022; 10:903319. [PMID: 35664882 PMCID: PMC9160713 DOI: 10.3389/fped.2022.903319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 04/20/2022] [Indexed: 11/25/2022] Open
Abstract
Umbilical cord blood from singleton preterm infants was collected during delivery, and the concentration of LL37 was measured. C-reactive protein (CRP), white blood cell count (WBC), platelets (PLT), and mean platelet volume (MPV) were determined within 3 days after birth. The differences in LL37, CRP, WBC, PLT, and MPV levels between the two groups were compared. Pearson correlation method was used to analyze the correlation between these factors. The early individual value of each detected index for early onset sepsis was analyzed by ROC curve. The level of LL37 in umbilical cord blood of sepsis group was significantly higher than those in the control group (383.85 ± 46.71 vs. 252.37 ± 83.30 ng/ml). Meanwhile, the levels of CRP, WBC, and MPV in the sepsis group were significantly higher than those in the control group (CRP:5.73 ± 4.19 vs. 2.50 ± 2.77 mg/L; WBC: 13.47 ± 12.35 vs. 6.83 ± 3.55 × 109/L; MPV: 11.20 ± 1.11 vs. 8.90 ± 0.68 fL), the level of PLT was significantly lower than those in the control group (PLT: 161.00 ± 38.51 vs. 241.50 ± 49.85 × 109/L) (P < 0.05). Pearson correlation analysis showed that the expression of LL37 was negatively correlated with PLT level (r = -0.9347, P < 0.0001), and positively correlated with MPV level (r = 0.9463, P < 0.0001). ROC curve analysis showed that the area under curve of LL37 for diagnosis of early onset sepsis was 0.875, the prediction probability was 0.7, the sensitivity was 90.0% and the specificity was 80.0%.
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Affiliation(s)
- Jiayu Miao
- Department of Pediatrics, Guangdong Women and Children Hospital, Guangzhou, China
| | - Zhuxiao Ren
- Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Zhicheng Zhong
- Department of Prenatal Diagnosis, Guangdong Women and Children Hospital, Guangzhou, China
| | - Fang Xu
- Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Jianlan Wang
- Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou, China
| | - Jie Yang
- Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou, China
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34
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Gonzalez DA, Kumar R, Asif S, Bali A, Dang AK. Sepsis and Thrombocytopenia: A Nowadays Problem. Cureus 2022; 14:e25421. [PMID: 35774677 PMCID: PMC9236694 DOI: 10.7759/cureus.25421] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/27/2022] [Indexed: 12/11/2022] Open
Abstract
Sepsis is a life-threatening organ failure produced by a dysregulated host response to infection that involves 15.6% of hospital mortality. The most common signs and symptoms of sepsis are hypotension, tachypnea, fever, and leukocytosis, whether suspected or confirmed. Including a major one, thrombocytopenia is a sign that is an independent predictor of poor outcomes in patients with sepsis, increasing their mortality rate and their length of stay in the intensive care unit (ICU). So far, the ongoing treatment for this problem is securing the airway, treating hypoxemia, and providing vascular access for hydration, antibiotic delivery, and vasopressors, if needed. This article has reviewed the different possible mechanisms found for sepsis-associated thrombocytopenia, going from the most acknowledged one as decreased platelet production to the potential aftermath of sepsis itself as disseminated intravascular coagulation (DIC). This article has also discussed the future treatment for patients suffering from thrombocytopenia and sepsis, going from phase I and II trials as GI antagonists to the well-known drug aspirin as a possible treatment for this problem.
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Affiliation(s)
- Daniel A Gonzalez
- Medicine, Universidad Catolica Santiago de Guayaquil, Guayaquil, ECU
| | - Rajeswar Kumar
- Medicine, Rajah Muthaiah Medical College and Hospital, Chidambaram, IND
| | - Saba Asif
- Internal Medicine, Apollo Hospitals, Hyderabad, IND
| | - Anoushka Bali
- Research, Acharya Shri Chander College of Medical Sciences and Hospital, Jammu, IND
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35
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Kobayashi M, Kudo D, Ohbe H, Kushimoto S. Antiplatelet pretreatment and mortality in patients with severe sepsis: A secondary analysis from a multicenter, prospective survey of severe sepsis in Japan. J Crit Care 2022; 69:154015. [PMID: 35344826 DOI: 10.1016/j.jcrc.2022.154015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 11/29/2021] [Accepted: 02/16/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE Antiplatelet agents may attenuate inflammatory and coagulation responses in patients with sepsis. This study aimed to examine the association between pre-sepsis antiplatelet therapy and survival outcomes in patients with sepsis. MATERIALS AND METHODS This was a secondary analysis of a Japanese multicenter registry dataset. Participants aged >16 years who were admitted to intensive care units for the treatment of severe sepsis (Sepsis 2 criteria) were dichotomized, according to their pretreatment status with antiplatelet agents. The primary outcome was in-hospital mortality. The data were analyzed using inverse probability of treatment weighting (IPTW) with a propensity score for pre-existing treatment using antiplatelet medication after multiple imputation. RESULTS Data from a total of 1184 eligible patients (2016-2017) were analyzed. A total of 175 patients were pretreated with antiplatelet medication. After IPTW, the patients' characteristics were well balanced between the groups. The in-hospital mortality rate among patients pretreated with antiplatelet medication was significantly lower than that among patients pretreated without antiplatelet medication (18.15% vs. 25.31%, difference: -7.86%, 95% confidence interval [CI]: -14.3 to -1.4, p = 0.016). CONCLUSIONS In this study, pretreatment with antiplatelet medication before the onset of sepsis was associated with decreased in-hospital mortality rates.
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Affiliation(s)
- Masakazu Kobayashi
- Department of Emergency and Critical Care Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
| | - Daisuke Kudo
- Department of Emergency and Critical Care Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan; Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
| | - Hiroyuki Ohbe
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan
| | - Shigeki Kushimoto
- Department of Emergency and Critical Care Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan; Division of Emergency and Critical Care Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
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36
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Theuerkauf K, Obach-Schröck C, Staszyk C, Moritz A, Roscher KA. Activated platelets and platelet-leukocyte aggregates in the equine systemic inflammatory response syndrome. J Vet Diagn Invest 2022; 34:448-457. [PMID: 35168432 PMCID: PMC9066687 DOI: 10.1177/10406387221077969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
In humans, activated platelets contribute to sepsis complications and to multiple organ failure. In our prospective analytical study of cases of the equine systemic inflammatory response syndrome (SIRS), we adapted a standard human protocol for the measurement of activated platelets and platelet-leukocyte aggregates (PLAs) in equine platelet-leukocyte-rich plasma (PLRP) by flow cytometry, and we investigated the hypothesis that activated platelets and PLAs are increased in clinical cases of SIRS. We included 17 adult horses and ponies fulfilling at least 2 SIRS criteria, and 10 healthy equids as controls. Activation of platelets was determined by increased expression of CD62P on platelets. Activated platelets and PLAs were measured before and after in vitro activation of platelets with collagen. Median expression of CD62P on platelets was significantly increased after activation in the control group: 1.45% (interquartile range [IQR]: 1.08-1.99%) initially versus 8.78% (IQR: 6.79-14.78%, p = 0.002) after activation. The equids with SIRS had significantly more activated platelets and PLAs in native PLRP than controls: CD62P 4.92% (median, IQR: 2.21-12.41%) versus 1.45% in controls (median, IQR: 1.08-1.99%, p = 0.0007), and PLAs 4.16% (median, IQR: 2.50-8.58%) versus 2.95% in controls (median, IQR: 1.57-3.22%, p = 0.048). To our knowledge, increased platelet activation and PLAs have not been demonstrated previously with flow cytometry in clinical cases of equine SIRS.
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Affiliation(s)
| | - Carmen Obach-Schröck
- Equine Clinic, Internal Medicine, Department of Veterinary Clinical Science (Theuerkauf, Roscher), Institute of Veterinary-Anatomy, -Histology and -Embryology (Obach-Schröck, Staszyk), Clinical Pathophysiology and Veterinary Clinical Pathology, Department of Veterinary Clinical Science (Moritz), Justus-Liebig-University, Giessen, Germany
| | - Carsten Staszyk
- Equine Clinic, Internal Medicine, Department of Veterinary Clinical Science (Theuerkauf, Roscher), Institute of Veterinary-Anatomy, -Histology and -Embryology (Obach-Schröck, Staszyk), Clinical Pathophysiology and Veterinary Clinical Pathology, Department of Veterinary Clinical Science (Moritz), Justus-Liebig-University, Giessen, Germany
| | - Andreas Moritz
- Equine Clinic, Internal Medicine, Department of Veterinary Clinical Science (Theuerkauf, Roscher), Institute of Veterinary-Anatomy, -Histology and -Embryology (Obach-Schröck, Staszyk), Clinical Pathophysiology and Veterinary Clinical Pathology, Department of Veterinary Clinical Science (Moritz), Justus-Liebig-University, Giessen, Germany
| | - Katja A Roscher
- Equine Clinic, Internal Medicine, Department of Veterinary Clinical Science (Theuerkauf, Roscher), Institute of Veterinary-Anatomy, -Histology and -Embryology (Obach-Schröck, Staszyk), Clinical Pathophysiology and Veterinary Clinical Pathology, Department of Veterinary Clinical Science (Moritz), Justus-Liebig-University, Giessen, Germany
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Prediction of Bacteremia Based on 12-Year Medical Data Using a Machine Learning Approach: Effect of Medical Data by Extraction Time. Diagnostics (Basel) 2022; 12:diagnostics12010102. [PMID: 35054269 PMCID: PMC8774637 DOI: 10.3390/diagnostics12010102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 12/29/2021] [Accepted: 12/31/2021] [Indexed: 12/12/2022] Open
Abstract
Early detection of bacteremia is important to prevent antibiotic abuse. Therefore, we aimed to develop a clinically applicable bacteremia prediction model using machine learning technology. Data from two tertiary medical centers’ electronic medical records during a 12-year-period were extracted. Multi-layer perceptron (MLP), random forest, and gradient boosting algorithms were applied for machine learning analysis. Clinical data within 12 and 24 hours of blood culture were analyzed and compared. Out of 622,771 blood cultures, 38,752 episodes of bacteremia were identified. In MLP with 128 hidden layer nodes, the area under the receiver operating characteristic curve (AUROC) of the prediction performance in 12- and 24-h data models was 0.762 (95% confidence interval (CI); 0.7617–0.7623) and 0.753 (95% CI; 0.7520–0.7529), respectively. AUROC of causative-pathogen subgroup analysis predictive value for Acinetobacter baumannii bacteremia was the highest at 0.839 (95% CI; 0.8388–0.8394). Compared to primary bacteremia, AUROC of sepsis caused by pneumonia was highest. Predictive performance of bacteremia was superior in younger age groups. Bacteremia prediction using machine learning technology appeared possible for acute infectious diseases. This model was more suitable especially to pneumonia caused by Acinetobacter baumannii. From the 24-h blood culture data, bacteremia was predictable by substituting only the continuously variable values.
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38
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Bock M, Bergmann CB, Jung S, Biberthaler P, Heimann L, Hanschen M. Platelets differentially modulate CD4 + Treg activation via GPIIa/IIIb-, fibrinogen-, and PAR4-dependent pathways. Immunol Res 2021; 70:185-196. [PMID: 34932195 PMCID: PMC8917040 DOI: 10.1007/s12026-021-09258-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 12/06/2021] [Indexed: 01/20/2023]
Abstract
CD4+FoxP3+ regulatory T cells (CD4+ Tregs) are known to dampen inflammation following severe trauma. Platelets were shown to augment their posttraumatic activation in burn injury, but the exact mechanisms remain unclear. We hypothesized that platelet activation mechanisms via GPIIb/IIIa, fibrinogen, and PAR4 have an immunological effect and modulate CD4+ Treg activation early after trauma. Therefore, C57Bl/6 N mice were injected with tirofiban (GPIIb/IIIa inhibition), ancrod (fibrinogen splitting enzyme), or tcY-NH2 (selective PAR4 antagonist peptide) before inducing a third-degree burn injury of 25% of the total body surface area. Changes in coagulation, and local and systemic CD4+ Treg activity were assessed via rotational thromboelastometry (ROTEM®) and phospho-flow cytometry 1 h post intervention. The inhibition of GPIIb/IIIa and fibrinogen locally led to a higher basic activity of CD4+ Tregs compared to non-inhibited animals. In contrast, PAR4 disruption on platelets locally led to an increased posttraumatic activation of CD4+ Tregs. Fibrinogen led to complete elimination of coagulation, whereas GPIIb/IIIa or PAR4 inhibition did not. GPIIb/IIIa receptor and fibrinogen inhibition increase CD4+ Tregs activity independently of trauma. Both are crucial for thrombus formation. We suggest platelets trapped in thrombi are unable to interact with CD4+ Tregs but augment their activity when circulating freely. In contrast, PAR4 seems to reduce CD4+ Treg activation following trauma. In summary, GPIIb/IIIa-, PAR4-, and fibrinogen-dependent pathways in platelets modulate CD4+ Treg baseline activity, independently from their hemostatic functionality. PAR4-dependent pathways modulate the posttraumatic interplay of platelets and CD4+ Tregs.
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Affiliation(s)
- Matthias Bock
- Experimental Trauma Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany.,Department of Cardiology, School of Medicine, German Heart Centre Munich, Technical University of Munich, Lazarettstr. 36, 80636, Munich, Germany
| | - Christian B Bergmann
- Experimental Trauma Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany.,Department of Trauma Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany.,Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA
| | - Sonja Jung
- Experimental Trauma Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany
| | - Peter Biberthaler
- Department of Trauma Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany
| | - Laura Heimann
- Experimental Trauma Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany
| | - Marc Hanschen
- Experimental Trauma Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany. .,Department of Trauma Surgery, Klinikum Rechts Der Isar, School of Medicine, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany.
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39
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Barale C, Melchionda E, Morotti A, Russo I. Prothrombotic Phenotype in COVID-19: Focus on Platelets. Int J Mol Sci 2021; 22:ijms222413638. [PMID: 34948438 PMCID: PMC8705811 DOI: 10.3390/ijms222413638] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 12/16/2021] [Accepted: 12/17/2021] [Indexed: 12/15/2022] Open
Abstract
COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients.
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Affiliation(s)
| | | | | | - Isabella Russo
- Correspondence: ; Tel.: +39-011-6705447; Fax: +39-011-9038639
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40
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Risk factors for bleeding in patients with acute necrotizing pancreatitis undergoing endoscopic necrosectomy. HPB (Oxford) 2021; 23:1856-1864. [PMID: 34023211 DOI: 10.1016/j.hpb.2021.04.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/09/2021] [Accepted: 04/27/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND This study investigated risk factors for bleeding in patients with acute necrotizing pancreatitis (ANP) undergoing endoscopic necrosectomy (EN) and the effect of endoscopic haemostasis. METHODS 145 patients with ANP who underwent EN were recruited from January 2014 to December 2018. Patients with and without bleeding were allocated to the bleeding and nonbleeding groups, respectively. Multivariable logistic regression models were used to assess independent risk factors for bleeding. RESULTS 39 patients (26.9%) experienced bleeding. The body mass index and culture-confirmed infectious pancreatic necrosis (IPN), renal failure and continuous renal replacement therapy rates were significantly higher in the bleeding group (all P < 0.01). In addition, the number of debridement procedures was significantly higher in the bleeding group (P = 0.004), accompanied by a higher mortality rate and greater hospitalization costs (all P < 0.05). Most cases of bleeding during EN were successfully stopped by endoscopic haemostasis (94.1%), but this was difficult to achieve after EN. Multivariate analysis revealed that renal failure (odds ratio [OR]: 3.77, P = 0.02), culture-confirmed IPN (OR: 3.19, P = 0.02), and ≥3 debridement procedures (OR: 12.92, P = 0.001) were associated with an increased bleeding risk. CONCLUSION Renal failure, culture-confirmed IPN, and multiple debridement procedures were independent risk factors for bleeding in patients with ANP who underwent EN.
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41
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Detection of Sepsis in Platelets Using MicroRNAs and Membrane Antigens. Genes (Basel) 2021; 12:genes12121877. [PMID: 34946826 PMCID: PMC8701354 DOI: 10.3390/genes12121877] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/22/2021] [Accepted: 11/22/2021] [Indexed: 01/03/2023] Open
Abstract
The present study proposes to legitimize in sepsis a characteristic found in platelets that suffer storage lesions in blood banks, which is the increased expression of miRNA miR-320a in relation to miR-127. Under physiologically normal conditions, an inverse relationship is observed. The aim of this study was to verify whether the analysis of miR-320a and miR-127 expression in platelets could detect a decrease in their viability and function due to the presence of pathogens in the blood of patients hospitalized in the Intensive Care Unit. We also investigated the expression of membrane antigens sensitive to platelet activation. Of the 200 patients analyzed, only those who developed sepsis (140) were found to have a higher relative quantity of miR-320a than that of miR-127. This characteristic and the increased expression of membrane antigens P2Y12, CD62P, CD41, and CD61 showed a significant association (p < 0.01) with all types of sepsis evaluated in this study. Additionally, 40% of patients hospitalized for sepsis had negative results for the first cultures. We conclude that analysis of miR-127 and miR-320a expression combined with membrane antigens evaluation, in association with the available clinical and diagnostic parameters, are important tools to detect the onset of sepsis.
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42
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Wang D, Li J, Sun Y, Ding X, Zhang X, Liu S, Han B, Wang H, Duan X, Sun T. A Machine Learning Model for Accurate Prediction of Sepsis in ICU Patients. Front Public Health 2021; 9:754348. [PMID: 34722452 PMCID: PMC8553999 DOI: 10.3389/fpubh.2021.754348] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 09/20/2021] [Indexed: 12/23/2022] Open
Abstract
Background: Although numerous studies are conducted every year on how to reduce the fatality rate associated with sepsis, it is still a major challenge faced by patients, clinicians, and medical systems worldwide. Early identification and prediction of patients at risk of sepsis and adverse outcomes associated with sepsis are critical. We aimed to develop an artificial intelligence algorithm that can predict sepsis early. Methods: This was a secondary analysis of an observational cohort study from the Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University. A total of 4,449 infected patients were randomly assigned to the development and validation data set at a ratio of 4:1. After extracting electronic medical record data, a set of 55 features (variables) was calculated and passed to the random forest algorithm to predict the onset of sepsis. Results: The pre-procedure clinical variables were used to build a prediction model from the training data set using the random forest machine learning method; a 5-fold cross-validation was used to evaluate the prediction accuracy of the model. Finally, we tested the model using the validation data set. The area obtained by the model under the receiver operating characteristic (ROC) curve (AUC) was 0.91, the sensitivity was 87%, and the specificity was 89%. Conclusions: This newly established machine learning-based model has shown good predictive ability in Chinese sepsis patients. External validation studies are necessary to confirm the universality of our method in the population and treatment practice.
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Affiliation(s)
- Dong Wang
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
| | - Jinbo Li
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Department of Electrical and Computer Engineering, University of Alberta, Edmonton, AB, Canada
| | - Yali Sun
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
| | - Xianfei Ding
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
| | - Xiaojuan Zhang
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
| | - Shaohua Liu
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
| | - Bing Han
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
| | - Haixu Wang
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
| | - Xiaoguang Duan
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
| | - Tongwen Sun
- General Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory for Critical Care Medicine of Henan Province, Zhengzhou, China.,Key Laboratory for Sepsis of Zhengzhou, Zhengzhou, China
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Li X, Li T, Wang J, Feng Y, Ren C, Xu Z, Yang J, Zhang Q, An C. Clinical Value of C-Reactive Protein/Platelet Ratio in Neonatal Sepsis: A Cross-Sectional Study. J Inflamm Res 2021; 14:5123-5129. [PMID: 34675592 PMCID: PMC8502539 DOI: 10.2147/jir.s334642] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 09/29/2021] [Indexed: 01/08/2023] Open
Abstract
Purpose C-reactive protein (CRP) level and platelet (PLT) count have been demonstrated to be independent risk factor for neonatal sepsis. However, no data is currently available in regarding the association between CRP-to-PLT ratio (CPR) and neonatal sepsis. Methods A total of 1048 neonates with suspected sepsis were enrolled in this study. Complete clinical and laboratory data were collected. CPR was calculated as CRP (mg/L)/PLT (107 cells/L). Multivariate logistic regression analysis was performed to identify the potential independent risk factors of neonatal sepsis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of CPR in predicting neonatal sepsis. Results Neonates with sepsis had a higher CPR. CPR also showed a gradual increase in the infection, mild sepsis and severe sepsis groups. Multivariate analysis revealed that CPR was a significant independent predictor of the presence of neonatal sepsis (odds ratio [OR], 1.015; 95% confidence interval [CI], 1.008-1.022, P < 0.001) and severe sepsis (OR, 1.002; 95% CI, 1.000-1.003, P = 0.007). ROC curve revealed showed that CPR had a well-discriminatory power in predicting sepsis (area under curve [AUC], 0.68; 95% CI, 0.65-0.72, P < 0.001) and severe sepsis (AUC, 0.68; 95% CI, 0.65-0.72, P < 0.001). Conclusion The present study demonstrated that a higher CPR is an independent predictor of the presence and severity of neonatal sepsis.
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Affiliation(s)
- Xiaojuan Li
- Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, People's Republic of China
| | - Tiewei Li
- Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, People's Republic of China
| | - Jingjing Wang
- Department of Neonatology, Ordos Central Hospital, Ordos, 01700, People's Republic of China
| | - Yichuan Feng
- Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, People's Republic of China
| | - Chong Ren
- Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, People's Republic of China
| | - Zhe Xu
- Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, People's Republic of China
| | - Junmei Yang
- Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, People's Republic of China
| | - Qian Zhang
- The Center for New Drug Safety Evaluation and Research, Inner Mongolia Medical University, Hohhot, People's Republic of China
| | - Caiyan An
- Clinical Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, People's Republic of China
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Ling J, Liao T, Wu Y, Wang Z, Jin H, Lu F, Fang M. Predictive value of red blood cell distribution width in septic shock patients with thrombocytopenia: A retrospective study using machine learning. J Clin Lab Anal 2021; 35:e24053. [PMID: 34674393 PMCID: PMC8649348 DOI: 10.1002/jcla.24053] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 09/27/2021] [Accepted: 09/28/2021] [Indexed: 12/30/2022] Open
Abstract
Background Sepsis‐associated thrombocytopenia (SAT) is common in critical patients and results in the elevation of mortality. Red cell distribution width (RDW) can reflect body response to inflammation and oxidative stress. We try to investigate the relationship between the RDW and the prognosis of patients with SAT through machine learning. Methods 809 patients were retrospectively analyzed from the Medical Information Mart for Intensive Care III (MIMIC‐III) database. The eXtreme Gradient Boosting (XGBoost) and SHapley Additive exPlanations (SHAP) were used to analyze the impact of each feature. Logistic regression analysis, propensity score matching (PSM), receiver‐operating characteristics (ROC) curve analysis, and the Kaplan‐Meier method were used for data processing. Results The patients with thrombocytopenia had higher 28‐day mortality (48.2%). Machine learning indicated that RDW was the second most important in predicting 28‐day mortality. The RDW was significantly increased in non‐survivors by logistic regression and PSM. ROC curve shows that RDW has moderate predictive power for 28‐day mortality. The patients with RDW>16.05 exhibited higher mortality through Kaplan‐Meier analysis. Conclusions Interpretable machine learning can be applied in clinical research. Elevated RDW is not only common in patients with SAT but is also associated with a poor prognosis.
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Affiliation(s)
- Jianmin Ling
- Department of Emergency and Intensive Care Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tongzhou Liao
- Services Computing Technology and System Lab, Cluster and Grid Computing Lab, National Engineering Research Center for Big Data Technology and System, School of Computer Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Yanqing Wu
- Department of Neurology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhaohua Wang
- Department of Emergency and Intensive Care Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hai Jin
- Services Computing Technology and System Lab, Cluster and Grid Computing Lab, National Engineering Research Center for Big Data Technology and System, School of Computer Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Lu
- Services Computing Technology and System Lab, Cluster and Grid Computing Lab, National Engineering Research Center for Big Data Technology and System, School of Computer Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Minghao Fang
- Department of Emergency and Intensive Care Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Platelet Inhibition Prevents NLRP3 Inflammasome Activation and Sepsis-Induced Kidney Injury. Int J Mol Sci 2021; 22:ijms221910330. [PMID: 34638670 PMCID: PMC8508664 DOI: 10.3390/ijms221910330] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 09/20/2021] [Accepted: 09/23/2021] [Indexed: 01/20/2023] Open
Abstract
Platelets, cellular mediators of thrombosis, are activated during sepsis and are increasingly recognized as mediators of the immune response. Platelet activation is significantly increased in sepsis patients compared to ICU control patients. Despite this correlation, the role of activated platelets in contributing to sepsis pathophysiology remains unclear. We previously demonstrated NOD-like receptor protein 3 inflammasome (NLRP3) inflammasome activation in sepsis-induced platelets from cecal-ligation puncture (CLP) rats. Activated platelets were associated with increased pulmonary edema and glomerular injury in CLP vs. SHAM controls. In this study, we investigated whether inhibition of platelet activation would attenuate NLRP3 activation and renal and pulmonary injury in response to CLP. CLP was performed in male and female Sprague Dawley (SD) rats (n = 10/group) to induce abdominal sepsis and SHAM rats served as controls. A subset of CLP animals was treated with Clopidogrel (10 mg/kg/day, CLP + CLOP) to inhibit platelet activation. At 72 h post-CLP, platelet activation and NLRP3 inflammasome assembly were evaluated, IL-1β and IL-18 were measured in plasma, and tissues, renal and pulmonary pathology, and renal function were assessed. Activated platelets were 7.8 ± 3.6% in Sham, 22 ± 6% in CLP and significantly decreased to 14.5 ± 0.6% in CLP + CLOP (n = 8–10/group, p < 0.05). NLRP3 inflammasome assembly was inhibited in platelets of CLP + CLOP animals vs. CLP. Significant increases in plasma and kidney IL-1β and IL-18 in response to CLP were decreased with Clopidogrel treatment. Renal injury, but not lung histology or renal function was improved in CLP + CLOP vs. CLP. These data provide evidence that activated platelets may contribute to sepsis-induced renal injury, possibly via NLRP3 activation in platelets. Platelets may be a therapeutic target to decrease renal injury in septic patients.
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GÜNEYSU F, DURMUŞ E. Pre-hospital antithrombotic drug use status of died COVID-19 patients. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2021. [DOI: 10.32322/jhsm.971453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Makatsariya AD, Slukhanchuk EV, Bitsadze VO, Khizroeva JK, Tretyakova MV, Shkoda AS, Elalamy I, Di Renzo GC, Rizzo G, Pyatigorskaya NV, Solopova AG, Grigoreva KN, Nakaidze IA, Mitryuk DV. The Effect of Various Types of Anticoagulant Therapy on the Reduction of Mortality in COVID-19. ANNALS OF THE RUSSIAN ACADEMY OF MEDICAL SCIENCES 2021; 76:268-278. [DOI: 10.15690/vramn1551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is a viral infection that, in severe course, leads to the development of a cytokine storm, systemic inflammatory response and coagulopathy. Unlike other sepsis-associated disseminated intravascular coagulopathy, COVID-19 induced coagulopathy is realized mainly in thrombosis. Researchers around the world are currently developing adequate diagnostic, monitoring and anticoagulant therapy approaches to safely and effectively manage patients with severe COVID-19. The need to develop laboratory monitoring is due to the fact that 20% of patients have changes in hemostasis indicators, while in patients with a severe form of the disease, they are present in 100% of cases. In case of deaths from COVID-19, there is an increase in the concentration of D-dimer and fibrinogen degradation products. Thus, the severity of hemostasis disorders has an important prognostic value. Anticoagulant therapy is included in the list of all recommendations as an effective means of reducing mortality from COVID-19. The questions of the recommended groups and doses of anticoagulant drugs are still open. The approach to the choice of an anticoagulant should be based not only on risk factors, characteristics of the course of the disease, anamnesis, but also on the wishes of the patient during long-term therapy at the post-hospital stage.
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Rabouel Y, Magnenat S, Delabranche X, Gachet C, Hechler B. Platelet P2Y 12 Receptor Deletion or Pharmacological Inhibition does not Protect Mice from Sepsis or Septic Shock. TH OPEN 2021; 5:e343-e352. [PMID: 34447900 PMCID: PMC8384481 DOI: 10.1055/s-0041-1733857] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 07/06/2021] [Indexed: 12/27/2022] Open
Abstract
Introduction
Platelets are increasingly appreciated as key effectors during sepsis, raising the question of the usefulness of antiplatelet drugs to treat patients with sepsis.
Objective
Evaluate the potential contribution of the platelet P2Y
12
receptor in the pathogenesis of polymicrobial-induced sepsis and septic shock in mice.
Methods
The effects of P2Y
12
inhibition using clopidogrel treatment and of platelet-specific deletion of the P2Y
12
receptor in mice were examined in two severity grades of cecal ligation and puncture (CLP) leading to mild sepsis or septic shock.
Results
Twenty hours after induction of the high grade CLP, clopidogrel- and vehicle-treated mice displayed a similar 30% decrease in mean arterial blood pressure (MAP) characteristic of shock. Septic shock-induced thrombocytopenia was not modified by clopidogrel treatment. Plasma concentrations of inflammatory cytokines and myeloperoxidase (MPO) were similarly increased in clopidogrel- and vehicle-treated mice, indicating comparable increase in systemic inflammation. Thrombin-antithrombin (TAT) complexes and the extent of organ damage were also similar. In mild-grade CLP, clopidogrel- and vehicle-treated mice did not display a significant decrease in MAP, while thrombocytopenia and plasma concentrations of TNFα, IL6, IL10, MPO, TAT and organ damage reached similar levels in both groups, although lower than those reached in the high grade CLP. Similarly, mice with platelet-specific deletion of the P2Y
12
receptor were not protected from CLP-induced sepsis or septic shock.
Conclusion
The platelet P2Y
12
receptor does not contribute to the pathogenesis of sepsis or septic shock in mice, suggesting that P2Y
12
receptor antagonists may not be beneficial in patients with sepsis or septic shock.
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Affiliation(s)
- Yannick Rabouel
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS)-Grand Est, BPPS UMR_S 1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), F-67000 Strasbourg, France
| | - Stéphanie Magnenat
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS)-Grand Est, BPPS UMR_S 1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), F-67000 Strasbourg, France
| | - Xavier Delabranche
- Hôpitaux Universitaires de Strasbourg, Anesthésie, Réanimation et Médecine périopératoire, Nouvel Hôpital Civil, F-67000 Strasbourg, France
| | - Christian Gachet
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS)-Grand Est, BPPS UMR_S 1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), F-67000 Strasbourg, France
| | - Beatrice Hechler
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS)-Grand Est, BPPS UMR_S 1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), F-67000 Strasbourg, France
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Luo Y, Li Z, Ge P, Guo H, Li L, Zhang G, Xu C, Chen H. Comprehensive Mechanism, Novel Markers and Multidisciplinary Treatment of Severe Acute Pancreatitis-Associated Cardiac Injury - A Narrative Review. J Inflamm Res 2021; 14:3145-3169. [PMID: 34285540 PMCID: PMC8286248 DOI: 10.2147/jir.s310990] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 06/15/2021] [Indexed: 12/12/2022] Open
Abstract
Acute pancreatitis (AP) is one of the common acute abdominal inflammatory diseases in clinic with acute onset and rapid progress. About 20% of the patients will eventually develop into severe acute pancreatitis (SAP) characterized by a large number of inflammatory cells infiltration, gland flocculus flaky necrosis and hemorrhage, finally inducing systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Pancreatic enzyme activation, intestinal endotoxemia (IETM), cytokine activation, microcirculation disturbance, autonomic nerve dysfunction and autophagy dysregulation all play an essential role in the occurrence and progression of SAP. Organ dysfunction is the main cause of early death in SAP. Acute kidney injury (AKI) and acute lung injury (ALI) are common, while cardiac injury (CI) is not, but the case fatality risk is high. Many basic studies have observed obvious ultrastructure change of heart in SAP, including myocardial edema, cardiac hypertrophy, myocardial interstitial collagen deposition. Moreover, in clinical practice, patients with SAP often presented various abnormal electrocardiogram (ECG) and cardiac function. Cases complicated with acute myocardial infarction and pericardial tamponade have also been reported and even result in stress cardiomyopathy. Due to the molecular mechanisms underlying SAP-associated cardiac injury (SACI) remain poorly understood, and there is no complete, unified treatment and sovereign remedy at present, this article reviews reports referring to the pathogenesis, potential markers and treatment methods of SACI in recent years, in order to improve the understanding of cardiac injury in severe pancreatitis.
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Affiliation(s)
- YaLan Luo
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - ZhaoXia Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Peng Ge
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - HaoYa Guo
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Lei Li
- Department of Vascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - GuiXin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - CaiMing Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - HaiLong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
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Giustozzi M, Ehrlinder H, Bongiovanni D, Borovac JA, Guerreiro RA, Gąsecka A, Papakonstantinou PE, Parker WAE. Coagulopathy and sepsis: Pathophysiology, clinical manifestations and treatment. Blood Rev 2021; 50:100864. [PMID: 34217531 DOI: 10.1016/j.blre.2021.100864] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 05/31/2021] [Accepted: 06/22/2021] [Indexed: 12/13/2022]
Abstract
Sepsis is a complex syndrome with a high incidence, increasing by 8.7% annually over the last 20 years. Coagulopathy is a leading factor associated with mortality in patients with sepsis and range from slight thrombocytopenia to fatal disorders, such as disseminated intravascular coagulation (DIC). Platelet reactivity increases during sepsis but prospective trials of antiplatelet therapy during sepsis have been disappointing. Thrombocytopenia is a known predictor of worse prognosis during sepsis. The mechanisms underlying thrombocytopenia in sepsis have yet to be fully understood but likely involves decreased platelet production, platelet sequestration and increased consumption. DIC is an acquired thrombohemorrhagic syndrome, resulting in intravascular fibrin formation, microangiopathic thrombosis, and subsequent depletion of coagulation factors and platelets. DIC can be resolved with treatment of the underlying disorder, which is considered the cornerstone in the management of this syndrome. This review presents the current knowledge on the pathophysiology, diagnosis, and treatment of sepsis-associated coagulopathies.
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Affiliation(s)
- Michela Giustozzi
- Internal Vascular and Emergency Medicine and Stroke Unit, University of Perugia, Perugia, Italy.
| | - Hanne Ehrlinder
- Department of Clinical Sciences, Division of Cardiovascular Medicine, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Dario Bongiovanni
- Technical University of Munich, School of Medicine, University hospital rechts der Isar, Department of Internal Medicine I, Munich, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Germany; Department of Cardiovascular Medicine, Humanitas Clinical and Research Center IRCCS and Humanitas University, Rozzano, Milan, Italy
| | - Josip A Borovac
- Department of Pathophysiology, University of Split School of Medicine, Split, Croatia; Clinic for Cardiovascular Diseases, University Hospital of Split (KBC Split), Split, Croatia
| | | | - Aleksandra Gąsecka
- 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
| | - Panteleimon E Papakonstantinou
- Second Cardiology Department, Evangelismos Hospital, Athens, Greece; Hypertension Unit "ESH Excellence Centre", First Cardiology Clinic, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece
| | - William A E Parker
- Cardiovascular Research Unit, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
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