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1
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Yang JY, Li LL, Fu SZ. Association analysis of sepsis progression to sepsis-induced coagulopathy: a study based on the MIMIC-IV database. BMC Infect Dis 2025; 25:573. [PMID: 40259248 PMCID: PMC12013014 DOI: 10.1186/s12879-025-10972-w] [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: 12/20/2024] [Accepted: 04/14/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND Sepsis-induced coagulopathy (SIC) is a severe complication of sepsis, characterized by poor prognosis and high mortality. However, the predictive factors for the development of SIC in sepsis patients remain to be determined. The aim of this study was to develop an easy-to-use and efficient nomogram for predicting the risk of sepsis patients developing SIC in the intensive care unit (ICU), based on common indicators and complications observed at admission. METHODS A total of 12, 455 sepsis patients from the MIMIC database were screened and randomly divided into training and validation cohorts. In the training cohort, LASSO regression was used for variable selection and regularization. The selected variables were then incorporated into a multivariable logistic regression model to construct the nomogram for predicting the risk of sepsis patients developing sepsis-induced coagulopathy (SIC). The model's predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC), and its calibration was assessed through a calibration curve. Additionally, decision curve analysis (DCA) was performed to evaluate the clinical applicability of the model. External validation was conducted using data from the ICU database of Xingtai People's Hospital. RESULTS Among the 12, 455 sepsis patients, 5, 145 (41. 3%) developed SIC. The occurrence of SIC was significantly associated with the SOFA score, red blood cell count, red cell distribution width (RDW), white blood cell count, platelet count, INR, and lactate levels. Additionally, hypertension was identified as a potential protective factor. A nomogram was developed to predict the risk of SIC, which showed an AUC of 0. 81 (95% CI: 0. 79-0. 83) in the training set, 0. 83 (95% CI: 0. 82-0. 84) in the validation set, and 0. 79 (95% CI: 0. 74-0. 84) in the external validation. The calibration curve of the nomogram showed good consistency between the observed and predicted probabilities of SIC. CONCLUSIONS The novel nomogram demonstrates excellent predictive performance for the incidence of SIC in ICU patients with sepsis and holds promise for assisting clinicians in early identification and intervention of SIC. CLINICAL TRIAL Not applicable.
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Affiliation(s)
- Jian-Yue Yang
- Department of Critical Care Medicine, Xingtai People's Hospital, Hebei, 054001, China
| | - Li-Li Li
- Department of Critical Care Medicine, Xingtai People's Hospital, Hebei, 054001, China
| | - Su-Zhen Fu
- Department of Critical Care Medicine, Xingtai People's Hospital, Hebei, 054001, China.
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2
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Coloretti I, Corcione A, De Pascale G, Donati A, Forfori F, Marietta M, Panigada M, Simioni P, Tascini C, Viale P, Girardis M. Protein C in adult patients with sepsis: from pathophysiology to monitoring and supplementation. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2025; 5:21. [PMID: 40229903 PMCID: PMC11998338 DOI: 10.1186/s44158-025-00243-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 04/04/2025] [Indexed: 04/16/2025]
Abstract
Protein C (PC) plays a crucial role in modulating inflammation and coagulation in sepsis. Its anticoagulant and cytoprotective properties are critical in mitigating sepsis-induced coagulopathy, which is associated with high mortality rates. In sepsis, low levels of PC are associated with an elevated risk of multiple organ dysfunction and increased mortality. Routine monitoring of PC levels is not widely implemented but appears relevant in selected populations, such as patients with purpura fulminans, sepsis-induced coagulopathy (SIC), disseminated intravascular coagulopathy (DIC) or hyperinflammatory septic shock phenotypes. Treatment with PC has been limited to PC concentrate approved for paediatric use in congenital PC deficiencies and purpura fulminans, while the efficacy of PC supplementation in sepsis remains a subject of debate. Considering the physiological significance of PC and its role in sepsis pathophysiology, additional studies are necessary to fully elucidate its therapeutic efficacy in specific clinical settings.
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Affiliation(s)
- Irene Coloretti
- Anaesthesiology and Intensive Care Department, University Hospital of Modena, University of Modena, Reggio Emilia, Modena, Italy.
| | - Antonio Corcione
- Department of Critical Care, AORN Ospedali Dei Colli, Naples, Italy
| | - Gennaro De Pascale
- Dipartimento Di Scienze Biotecnologiche Di Base, Cliniche Intensivologiche E Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento Di Scienze Dell'Emergenza, Fondazione Policlinico Universitario A. Gemelli IRCCS, Anestesiologiche E Della Rianimazione, Rome, Italy
| | - Abele Donati
- Department of Biomedical Sciences and Public Health, Università Politecnica Delle Marche, Ancona, Italy
- Anesthesia and Intensive Care, Azienda Ospedaliero Universitaria Delle Marche, Ancona, Italy
| | - Francesco Forfori
- Dipartimento Di Patologia Chirurgica, Medica, Molecolare Ed Area Critica, Università Di Pisa. AOUP, Pisa, Italy
| | - Marco Marietta
- Department of Hematology-Azienda Ospedaliero, Universitaria Di Modena, Modena, Italy
| | - Mauro Panigada
- Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Paolo Simioni
- Clinica Medica 1, Azienda Ospedale Università Di Padova, Padua, Italy
| | - Carlo Tascini
- Department of Medicine (DMED), University of Udine, Udine, Italy
- Infectious Diseases Clinic, ASUFC "Santa Maria Della Misericordia" University Hospital of Udine, Udine, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Massimo Girardis
- Anaesthesiology and Intensive Care Department, University Hospital of Modena, University of Modena, Reggio Emilia, Modena, Italy
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Iba T, Levy JH, Maier CL, Helms J, Umemura Y, Moore H, Othman M, Thachil J, Connors JM, Levi M, Scarlatescu E. Updated definition and scoring of disseminated intravascular coagulation in 2025: communication from the ISTH SSC Subcommittee on Disseminated Intravascular Coagulation. J Thromb Haemost 2025:S1538-7836(25)00220-X. [PMID: 40216223 DOI: 10.1016/j.jtha.2025.03.038] [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: 01/29/2025] [Revised: 03/17/2025] [Accepted: 03/31/2025] [Indexed: 05/02/2025]
Abstract
Compelling evidence supports the need to update the 2001 definition and diagnosis of disseminated intravascular coagulation (DIC) to reflect our current understanding of disease pathophysiology. DIC has been long considered a critical and untreatable sequela of various underlying causes, with resolution only after treatment of the eliciting etiology. Recent views have evolved to appreciate that DIC-associated mortality may be reduced by detection and treatment at an early stage. The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on DIC proposes an updated definition of DIC: "an acquired, life-threatening intravascular disorder characterized by systemic coagulation activation, dysregulated fibrinolysis, and endothelial injury, resulting in microthrombosis. DIC arises from various underlying etiologies and progresses from a potentially asymptomatic early phase to an advanced phase with hemorrhage and/or organ dysfunction." In accordance with this more comprehensive definition, we propose to establish more tailored diagnostic criteria that detect early-phase DIC based on the underlying disease. We also propose a modification to overt DIC diagnostic criteria and scoring for late-phase DIC. These consensus-driven modifications reflect knowledge obtained since the original 2001 definition, which advanced clinical practice and research on DIC. This revised framework is anticipated to foster more precise and earlier diagnoses, improve patient stratification in clinical studies, and facilitate the development of targeted therapies dependent on pathophysiological context.
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Affiliation(s)
- Toshiaki Iba
- Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
| | - Jerrold H Levy
- Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, North Carolina, USA
| | - Cheryl L Maier
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Julie Helms
- Medical Intensive Care Unit-National Health Commission, Strasbourg University Hospital, French National Institute of Health and Medical Research, University Medical Research 1260, Regenerative Nanomedicine, Field Medical Treatment Station, Strasbourg University, Strasbourg, France
| | - Yutaka Umemura
- Division of Trauma and Surgical Critical Care, Osaka General Medical Center, Sumiyoshi, Osaka, Japan
| | - Hunter Moore
- Department of Surgery, AdventHealth Transplant Institution, Porter Hospital, Denver, Colorado, USA
| | - Maha Othman
- Department of Biomedical and Molecular Science, School of Medicine, Queen's University, Kingston, Ontario, Canada; School of Baccalaureate Nursing, St Lawrence College, Kingston, Ontario, Canada; Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Jecko Thachil
- Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom
| | - Jean M Connors
- Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 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
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, University of Medicine and Pharmacy "Carol Davila" Bucharest, Bucharest, Romania
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Yang S, Sun Q, Yuan X, Wang J, Wang H, Hu W, Peng Q, Zhang C, Li X, Huang W, Xie J, Guo F, Liu L, Yang Y, Huang Y. Effect of prone position on ventilation-perfusion matching in patients with moderate to severe ARDS with different clinical phenotypes. Respir Res 2025; 26:70. [PMID: 40022116 PMCID: PMC11871685 DOI: 10.1186/s12931-025-03154-4] [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: 09/18/2024] [Accepted: 02/13/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND ARDS is a heterogeneous syndrome involving different subphenotypes with different clinical features and different responses to treatment strategies. The prone position (PP) is an effective treatment for ARDS; however, whether the effects of prone positioning vary among ARDS patients with different subphenotypes remains unknown. OBJECTIVES To evaluated the impact of PP on ventilation-perfusion matching(VQ matching) by contrast-enhanced Electrical impedance tomography (EIT) in ARDS patients with different subphenotypes. METHODS This was a prospective, observational study at the medical ICU of Zhongda Hospital, Southeast University. ARDS patients undergoing mechanical ventilation were screened and allocated to different subphenotypes based on lung morphology (focal/non-focal) and D-dimer level (low/high D-dimer). EIT was used in the supine position and 3 h, 6 h, and 12 h after the PP during the first PP session. RESULTS From July 1, 2021, to July 1, 2022, 25 patients were included in this study. 10 patients (40%) were focal ARDS, and 15 were non-focal ARDS based on baseline morphology. 12 patients (48%) were high D-dimer ARDS, and 13 were low D-dimer ARDS based on baseline D-dimer levels. PaO2/FiO2 increased significantly 3 h after prone positioning in focal ARDS patients (130.30[109.94-147.30] vs. 213.50[176.00-256.50] mmHg, p < 0.001), while the effect of improved oxygenation was not apparent until 6 h after prone positioning in non-focal ARDS patients (104.60[95.20-127.00] vs. 190.20[160.10-213.20] mm Hg, p < 0.001). VQ matching improved after 3 h in the prone position in the focal ARDS group (69.93 ± 6.69 vs. 78.22 ± 5.07, p = 0.006) but improved after only 6 h in the prone position in the non-focal ARDS group (67.32 ± 4.78 vs. 78.70 ± 5.93, p < 0.001). In ARDS patients with varying levels of D-dimer, increased PaO2/FiO2 (126.60[99.30-146.20] vs. 185.20[112.10-236.00] mmHg, p = 0.013) and improved VQ matching (67.60 ± 4.60 vs. 72.97 ± 6.48, p = 0.023) were observed at 3 h in the PP in patients with low D-dimer ARDS. In contrast, increased PaO2/FiO2(105.20[95.20-124.10] vs. 195.2[183.20-213.20], p < 0.001) and improved VQ matching (67.19 ± 6.70 vs. 72.50 ± 6.37, p < 0.001) were revealed only after 6 h in the prone position in high D-dimer ARDS patients. CONCLUSIONS For moderate to severe ARDS patients, non-focal and high D-dimer ARDS patients need longer PP to improve oxygenation and VQmatching than the focal and low D-dimer patients. CLINICAL TRIAL REGISTRATION This was a prospective, observational study registered in the Chinese Clinical Trial Registry (ChiCTR2200055442, https://www.chictr.org.cn/ ), on June 30, 2021.
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Affiliation(s)
- Shuhe Yang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Qin Sun
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Xueyan Yuan
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Jinlong Wang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Haofei Wang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Wenhan Hu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Qingyun Peng
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Chen Zhang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Xiangquan Li
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Wei Huang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Jianfeng Xie
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Fengmei Guo
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Ling Liu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Yi Yang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Yingzi Huang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
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Curtiaud A, Iba T, Angles-Cano E, Meziani F, Helms J. Biomarkers of sepsis-induced coagulopathy: diagnostic insights and potential therapeutic implications. Ann Intensive Care 2025; 15:12. [PMID: 39821561 PMCID: PMC11739444 DOI: 10.1186/s13613-025-01434-2] [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: 09/10/2024] [Accepted: 01/06/2025] [Indexed: 01/19/2025] Open
Abstract
Diagnosing coagulopathy in septic patients remains challenging in intensive care. Disseminated intravascular coagulation (DIC) indeed presents with complex pathophysiology, complicating timely diagnosis. Epidemiological data indicate a significant prevalence of DIC in septic patients, with mortality rates up to 60%. Despite advances, current biomarker-based diagnostic tools often fail to provide early and accurate detection. This review evaluates the utility and limitations of traditional and emerging biomarkers for diagnosing sepsis-induced coagulopathy (SIC) and DIC. We also assess the effectiveness of anticoagulant therapy guided by biomarker-based diagnostic criteria.
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Affiliation(s)
- Anaïs Curtiaud
- Faculté de Médecine, Service de Médecine Intensive-Réanimation, Université de Strasbourg (UNISTRA), Hôpitaux universitaires de Strasbourg, Nouvel Hôpital Civil, 1, place de l'Hôpital, Strasbourg, F-67091, cedex, France
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France
| | - Toshiaki Iba
- Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Eduardo Angles-Cano
- Innovative Therapies in Haemostasis, Université Paris Cité - INSERM U-1140, Paris, 75006, France
| | - Ferhat Meziani
- Faculté de Médecine, Service de Médecine Intensive-Réanimation, Université de Strasbourg (UNISTRA), Hôpitaux universitaires de Strasbourg, Nouvel Hôpital Civil, 1, place de l'Hôpital, Strasbourg, F-67091, cedex, France
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France
| | - Julie Helms
- Faculté de Médecine, Service de Médecine Intensive-Réanimation, Université de Strasbourg (UNISTRA), Hôpitaux universitaires de Strasbourg, Nouvel Hôpital Civil, 1, place de l'Hôpital, Strasbourg, F-67091, cedex, France.
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France.
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6
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Bao R, Fan M, Hu M, Li L, Hasichaolu . Risk Factors and Predictive Model for Disseminated Intravascular Coagulation in Patients with Multiple Myeloma. Clin Appl Thromb Hemost 2025; 31:10760296251316873. [PMID: 39930869 PMCID: PMC11811966 DOI: 10.1177/10760296251316873] [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: 11/22/2024] [Revised: 01/03/2025] [Accepted: 01/14/2025] [Indexed: 02/13/2025] Open
Abstract
OBJECTIVES Multiple myeloma (MM) is a hematologic malignancy comprising approximately 10% of all blood cancers. Patients with MM are at risk for disseminated intravascular coagulation (DIC), a serious complication characterized by systemic coagulation activation, leading to microthrombi, organ dysfunction, and severe bleeding. This study aims to investigate the incidence of DIC among MM patients and identify risk factors associated with DIC development. We also sought to develop a predictive formula for assessing DIC risk. METHODS A retrospective analysis was conducted on MM patients. Logistic regression analysis was used to identify factors significantly associated with DIC. The predictive power of the logistic regression model was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS The incidence of DIC among hospitalized MM patients was 16.8%. Significant factors identified by logistic regression analysis included prothrombin time (PT), fibrin degradation products (FDP), and D-dimer levels. ROC curve analysis indicated that the predictive model had strong discriminatory power, with an area under the curve (AUC) of 0.927. A predictive formula for the probability of DIC occurrence was developed based on the logistic regression model. CONCLUSIONS The predictive formula developed in this study offers a tool for early identification of MM patients at high risk of DIC. While the model demonstrates strong predictive capability, further validation and refinement are required to improve its accuracy and clinical application.
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Affiliation(s)
- Rong Bao
- Department of Clinical Laboratory, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Mengtong Fan
- Clinical Laboratory Diagnostics, Shanxi Medical University, Taiyuan, China
| | - Min Hu
- Department of Clinical Laboratory, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Ling Li
- Department of Clinical Laboratory, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Hasichaolu
- Department of Clinical Laboratory, First Hospital of Shanxi Medical University, Taiyuan, China
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7
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Girardis M, David S, Ferrer R, Helms J, Juffermans NP, Martin-Loeches I, Povoa P, Russell L, Shankar-Hari M, Iba T, Coloretti I, Parchim N, Nielsen ND. Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis. Intensive Care Med 2024; 50:1580-1592. [PMID: 39222142 DOI: 10.1007/s00134-024-07586-2] [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: 03/01/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024]
Abstract
The interplay between the immune system, coagulation, and endothelium is critical in regulating the host response to infection. However, in sepsis and other critical illnesses, a dysregulated immune response can lead to excessive alterations in these mechanisms, resulting in coagulopathy, endothelial dysfunction, and multi-organ dysfunction. This review aims to provide a comprehensive analysis of the pathophysiological mechanisms that govern the complex interplay between immune dysfunction, endothelial dysfunction, and coagulation in sepsis. It emphasises clinical significance, evaluation methods, and potential therapeutic interventions. Understanding these mechanisms is essential for developing effective treatments that can modulate the immune response, mitigate thrombosis, restore endothelial function, and ultimately improve patient survival.
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Affiliation(s)
- Massimo Girardis
- Anaesthesiology and Intensive Care Department, University Hospital of Modena, University of Modena, Reggio Emilia, Italy.
| | - Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Ricard Ferrer
- Intensive Care Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Julie Helms
- Université de Strasbourg (UNISTRA), Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Strasbourg, France
| | - Nicole P Juffermans
- Department of Intensive Care and Translational Laboratory of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Ignacio Martin-Loeches
- Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James' Hospital, Dublin, D08 NHY1, Ireland
- Hospital Clinic, Universitat de Barcelona, IDIBAPS, CIBERES, 08180, Barcelona, Spain
| | - Pedro Povoa
- NOVA Medical School, NOVA University of Lisbon, Lisbon, Portugal
- Center for Clinical Epidemiology and Research Unit of Clinical Epidemiology, OUH Odense University Hospital, Odense, Denmark
- Department of Intensive Care, Hospital de São Francisco Xavier, CHLO, Lisbon, Portugal
| | - Lene Russell
- Copenhagen University Hospital Gentofte, Hellerup, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Manu Shankar-Hari
- Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK
- Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK
| | - Toshiaki Iba
- Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Irene Coloretti
- Anaesthesiology and Intensive Care Department, University Hospital of Modena, University of Modena, Reggio Emilia, Italy
| | - Nicholas Parchim
- Division of Pulmonary, Critical Care and Sleep Medicine & Section of Transfusion Medicine and Therapeutic Pathology, University of New Mexico School of Medicine, New Mexico, Mexico
| | - Nathan D Nielsen
- Division of Pulmonary, Critical Care and Sleep Medicine & Section of Transfusion Medicine and Therapeutic Pathology, University of New Mexico School of Medicine, New Mexico, Mexico
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8
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Lou J, Zhang J, Deng Q, Chen X. Neutrophil extracellular traps mediate neuro-immunothrombosis. Neural Regen Res 2024; 19:1734-1740. [PMID: 38103239 PMCID: PMC10960287 DOI: 10.4103/1673-5374.389625] [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: 03/29/2023] [Revised: 07/29/2023] [Accepted: 10/14/2023] [Indexed: 12/18/2023] Open
Abstract
Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammatory reactions. Neutrophil extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation mechanisms. Histones, von Willebrand factor, fibrin, and many other factors participate in the interplay between inflammation and thrombosis. Neuro-immunothrombosis summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases, providing cutting-edge insights into post-neurotrauma thrombotic events. The blood-brain barrier defends the brain and spinal cord against external assaults, and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological diseases. Further research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis, but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis, and identified modulators of neuro-immunothrombosis. However, these neurological diseases occur in blood vessels, and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain injury. This review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.
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Affiliation(s)
- Jianbo Lou
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Jianning Zhang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
| | - Quanjun Deng
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Xin Chen
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Neurological Institute, Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
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9
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Meziani F, Iba T, Levy JH, Helms J. Sepsis-induced coagulopathy: a matter of timeline. Intensive Care Med 2024; 50:1404-1405. [PMID: 38856751 DOI: 10.1007/s00134-024-07507-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/29/2024] [Indexed: 06/11/2024]
Affiliation(s)
- Ferhat Meziani
- Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Université de Strasbourg (UNISTRA), 1, place de l'Hôpital, 67091, Strasbourg Cedex, France.
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France.
| | - Toshiaki Iba
- Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Jerrold H Levy
- Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Julie Helms
- Faculté de Médecine, Hôpitaux Universitaires de Strasbourg, Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Université de Strasbourg (UNISTRA), 1, place de l'Hôpital, 67091, Strasbourg Cedex, France
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France
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10
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Fang J, Huang P, Cui W, Lin Y, Rong D, Li X. COMPREHENSIVE THERAPEUTIC EFFICACY ANALYSIS OF INTRAVENOUS IMMUNOGLOBULIN IN TREATING SEPSIS-INDUCED COAGULOPATHY: A SINGLE-CENTER, RETROSPECTIVE OBSERVATIONAL STUDY. Shock 2024; 62:4-12. [PMID: 38321608 DOI: 10.1097/shk.0000000000002336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
ABSTRACT Objective : The aim of the study is to investigate the efficacy of intravenous immunoglobulin (IVIg) in treating sepsis-induced coagulopathy ( SIC ). Methods : A retrospective controlled analysis was conducted on 230 patients with SIC at Ganzhou People's Hospital from January 2016 to December 2022. All patients were screened using propensity score matching and treated according to the SSC2016 guidelines. Compared with the control group (n = 115), patients in the test group (n = 115) received IVIg (200 mg/kg.d) for 3 consecutive days after admission. The rating scales, coagulation function, survival, and treatment duration were evaluated. Results : On day 3 of treatment, both groups exhibited reduced platelet and thromboelastogram (TEG) maximum amplitude (MA) levels, with the control group showing a more significant decrease ( P < 0.05). By the fifth day, these levels had recovered in both groups. However, the test group experienced a significant increase by day 7 ( P < 0.05). Coagulation factors II and X began to increase on day 3, and normalization was significantly faster in the test group on day 5 ( P < 0.05). The levels of prothrombin time, international normalized ratio, activated partial thromboplastin time, d -dimer, fibrinogen, fibrin degradation products, TEG-R, and TEG-K exhibited a notable decline on day 3 and demonstrated significantly faster recovery on day 5 in the test group ( P < 0.05). In addition, both groups showed a reduction in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, disseminated intravascular coagulation, and lactate (LAC) levels on day 3, but the test group's scores decreased significantly more by day 7 ( P < 0.05). Within the test group, white blood cell count, C-reactive protein, procalcitonin, IL-6, and Tmax levels were lower ( P < 0.05). Furthermore, the test group demonstrated shorter duration for intensive care unit stay, mechanical ventilation, and continuous renal replacement therapy ( P < 0.05). No significant differences were observed in the duration of fever or vasoactive drug use between the groups. However, the log-rank method indicated a higher 28-day survival rate in the test group ( P < 0.05). Conclusion : IVIg can successfully increase platelet count and coagulation factors, correct coagulation disorders, enhance organ function, and reduce 28-day mortality in patients with SIC .
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Affiliation(s)
| | | | - Wanfu Cui
- Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ye Lin
- Department of Gastroenterology, Ganzhou People's Hospital, Ganzhou, China
| | - Dan Rong
- Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, China
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11
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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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12
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Williams B, Zou L, Pittet JF, Chao W. Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesth Analg 2024; 138:696-711. [PMID: 38324297 PMCID: PMC10916756 DOI: 10.1213/ane.0000000000006888] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2023] [Indexed: 02/08/2024]
Abstract
Physiological hemostasis is a balance between pro- and anticoagulant pathways, and in sepsis, this equilibrium is disturbed, resulting in systemic thrombin generation, impaired anticoagulant activity, and suppression of fibrinolysis, a condition termed sepsis-induced coagulopathy (SIC). SIC is a common complication, being present in 24% of patients with sepsis and 66% of patients with septic shock, and is often associated with poor clinical outcomes and high mortality. 1 , 2 Recent preclinical and clinical studies have generated new insights into the molecular pathogenesis of SIC. In this article, we analyze the complex pathophysiology of SIC with a focus on the role of procoagulant innate immune signaling in hemostatic activation--tissue factor production, thrombin generation, endotheliopathy, and impaired antithrombotic functions. We also review clinical presentations of SIC, the diagnostic scoring system and laboratory tests, the current standard of care, and clinical trials evaluating the efficacies of anticoagulant therapies.
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Affiliation(s)
- Brittney Williams
- From the Division of Cardiothoracic Anesthesia, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland
- Translational Research Program, Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, Maryland
| | - Lin Zou
- Translational Research Program, Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, Maryland
| | - Jean-Francois Pittet
- Division of Critical Care, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Wei Chao
- Translational Research Program, Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, Baltimore, Maryland
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13
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Kutlutürk I, Tokuç EÖ, Karabaş L, Rückert R, Kaya M, Karagöz A, Munk MR. How the immune response to the structural proteins of SARS-CoV-2 affects the retinal vascular endothelial cells: an immune thrombotic and/or endotheliopathy process with in silico modeling. Immunol Res 2024; 72:50-71. [PMID: 37642808 DOI: 10.1007/s12026-023-09412-1] [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: 04/14/2023] [Accepted: 07/28/2023] [Indexed: 08/31/2023]
Abstract
Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins.
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Affiliation(s)
- Işıl Kutlutürk
- Division of Ophthalmology, Ümraniye Trn. And Rch. Hospital, Istanbul, Turkey.
| | - Ecem Önder Tokuç
- Ophthalmology Department, University of Health Science, Derince Training and Research Hospital, Izmit-Kocaeli, Turkey
| | - Levent Karabaş
- Ophthalmology Department, Kocaeli University School of Medicine, Izmit-Kocaeli, Turkey
| | | | | | - Ali Karagöz
- Koşuyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Marion R Munk
- Inselspital, University Hospital Bern, Bern, Switzerland
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Augenarzt-Praxisgemeinschaft Gutblick AG, Bern, Switzerland
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14
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Helms J, Merdji H, Loewert S, Severac F, Monnier A, Kaurin J, Curtiaud A, Meziani F, Demiselle J. Disseminated intravascular coagulation is strongly associated with severe acute kidney injury in patients with septic shock. Ann Intensive Care 2023; 13:119. [PMID: 38038826 PMCID: PMC10692023 DOI: 10.1186/s13613-023-01216-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 11/17/2023] [Indexed: 12/02/2023] Open
Abstract
BACKGROUND Disseminated intravascular coagulation (DIC) worsens the prognosis of septic shock and contributes to multiple organ failure. To date, no data linking DIC and acute kidney injury (AKI) occurrence, severity, and evolution in this setting are available. We aimed at analyzing the association between AKI occurrence, severity and evolution in patients with septic shock-induced DIC. In a prospective monocentric cohort study, consecutive patients, 18 years and older, admitted in the ICU of Strasbourg University Hospital in the setting of systemic hypotension requiring vasopressor related to an infection, without history of terminal chronic kidney disease were eligible. AKI was defined according to the KDIGO classification. DIC diagnosis was based on the International Society on Thrombosis and Haemostasis (ISTH) score. Evolution of AKI was evaluated through the composite endpoint of major adverse kidney events. Only patients with DIC that occurred before or at the time of AKI diagnosis were considered. Univariate and multivariate analysis were performed to determine factors associated with renal outcomes. RESULTS 350 patients were included, of whom 129 experienced DIC. Patients with DIC were more seriously ill (median SAPS II 64 vs. 56, p < 0.001), and had higher 28-day mortality (43.3% vs. 26.2%, p < 0.001). AKI was more frequent in patients with DIC (86.8% vs. 74.2%, p < 0.005), particularly for the more severe stage of AKI [KDIGO 3 in 58.1% of patients with DIC vs. 30.8% of patients without DIC, p < 0.001, AKI requiring renal replacement therapy (RRT) in 47.3% of patients with DIC vs. 21.3% of patients without DIC, p < 0.001]. After adjustment for confounding factors, DIC occurrence remained associated with the risk of having the more severe stage of AKI with an odds ratio (OR) of 2.74 [IC 95% (1.53-4.91), p < 0.001], and with the risk of requiring RRT during the ICU stay [OR 2.82 (1.53-5.2), p < 0.001]. CONCLUSION DIC appears to be strongly associated with the risk of developing the more severe form of AKI (stage 3 of the KDIGO classification, RRT requirement), even after adjustment for severity and other relevant factors.
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Affiliation(s)
- Julie Helms
- Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
- UMR 1260, Regenerative Nanomedicine (RNM), FMTS, INSERM (French National Institute of Health and Medical Research), Strasbourg, France
| | - Hamid Merdji
- Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
- UMR 1260, Regenerative Nanomedicine (RNM), FMTS, INSERM (French National Institute of Health and Medical Research), Strasbourg, France
| | - Sébastien Loewert
- Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
| | - François Severac
- Groupe Méthodes en Recherche Clinique (GMRC), Hôpital Civil, Hôpitaux universitaires de Strasbourg, Strasbourg, France
| | - Alexandra Monnier
- Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
| | - Julian Kaurin
- Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
| | - Anaïs Curtiaud
- Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
| | - Ferhat Meziani
- Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France
- UMR 1260, Regenerative Nanomedicine (RNM), FMTS, INSERM (French National Institute of Health and Medical Research), Strasbourg, France
| | - Julien Demiselle
- Service de Médecine Intensive-Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France.
- UMR 1260, Regenerative Nanomedicine (RNM), FMTS, INSERM (French National Institute of Health and Medical Research), Strasbourg, France.
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15
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Gigante B, Levy JH, van Gorp E, Bartoloni A, Bochaton-Piallat ML, Bäck M, Ten Cate H, Christersson C, Ferreiro JL, Geisler T, Lutgens E, Schulman S, Storey RF, Thachil J, Vilahur G, Liaw PC, Rocca B. Management of patients on antithrombotic therapy with severe infections: a joint clinical consensus statement of the ESC Working Group on Thrombosis, the ESC Working Group on Atherosclerosis and Vascular Biology, and the International Society on Thrombosis and Haemostasis. Eur Heart J 2023; 44:3040-3058. [PMID: 37439553 DOI: 10.1093/eurheartj/ehad388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 05/01/2023] [Accepted: 05/29/2023] [Indexed: 07/14/2023] Open
Abstract
Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs. Bacterial and viral pathogens constitute an increasing threat to global public health, especially for patients with ongoing antithrombotic treatment who have a high risk of thrombotic recurrences and high susceptibility to severe infections with increased morbidity and mortality. Similarly, sepsis survivors are at increased risk for major vascular events. Coagulopathy, which often complicates severe infections, is associated with a high mortality and obligates clinicians to adjust antithrombotic drug type and dosing to avoid bleeding while preventing thrombotic complications. This clinical consensus statement reviews the best available evidence to provide expert opinion and statements on the management of patients hospitalized for severe bacterial or viral infections with a pre-existing indication for antithrombotic therapy (single or combined), in whom sepsis-induced coagulopathy is often observed. Balancing the risk of thrombosis and bleeding in these patients and preventing infections with vaccines, if available, are crucial to prevent events or improve outcomes and prognosis.
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Affiliation(s)
- Bruna Gigante
- Division of Cardiovascular Medicine, Department of Medicine, Karolinska Institutet, Solnavägen 30. 17164 and Department of Cardiology, Danderyds Hospital, Entrévägen 2, 182 88, Stockholm, Sweden
| | - Jerrold H Levy
- Departments of Anesthesiology, Critical Care, and Surgery (Cardiothoracic), Duke University School of Medicine, Durham, United States; 2301 Erwin Road, Durham, NC 27710, USA
| | - Eric van Gorp
- Department of Viroscience, Erasmus MC, Rotterdam, PO box 2040 [Room Ee1726], 3000 CA Rotterdam, The Netherlands
| | - Alessandro Bartoloni
- Department of Experimental and Clinical Medicine, Infectious Diseases Unit, University of Florence, Largo Brambilla 3, 50100 Florence, Italy
| | - Marie-Luce Bochaton-Piallat
- Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1 rue Michel-Servet 1, CH-1211 Genève, Switzerland
| | - Magnus Bäck
- Department of Translational Cardiology, Karolinska Institutet and Karolinska University Hospital, CMM L8:01, 171 76 Stockholm, Sweden
- INSERM U1116, University of Lorraine, Nancy University Hospital, 2 rue Jean Lamour, 54505 Vandoeuvre les Nancy Cedex, France
| | - Hugo Ten Cate
- Department of Internal medicine, Thrombosis Expertise Center, Maastricht University Medical Center and CARIM school for cardiovascular diseases, Universiteitsingel 50, PO Box 616, 6200 MD Maastricht, The Netherlands
- Center for Thrombosis and Haemostasis, Gutenberg University Medical Center, Langenbeckstr. 1, Bldg. 403, 55131 Mainz, Germany
| | - Christina Christersson
- Department of Medical Sciences, Cardiology, Uppsala University, Akademiska Sjukhuset, 75185, Uppsala, Sweden
| | - José Luis Ferreiro
- Department of Cardiology and Bio-Heart Cardiovascular Diseases Research Group; Bellvitge University Hospital - Bellvitge Biomedical Research Institute (IDIBELL); CIBERCV; L'Hospitalet de Llobregat, Hospital Duran i Reynals - Edifici Terapèutic - 2a planta Gran Via de l'Hospitalet, 199, 08908 Hospitalet de Llobregat Barcelona -Spain
| | - Tobias Geisler
- Department of Cardiology and Angiology, University Hospital Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany
| | - Esther Lutgens
- Cardiovascular Medicine, Experimental CardioVascular Immunology Laboratory, Mayo Clinic, 200 First St SW, 55905, Rochester, MN, USA
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians Universität, München, Germany & German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Pettenkoferstrasse 9, 80336, Munich, Germany
| | - Sam Schulman
- Department of Medicine and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada HHS - General Hospital 237, Barton Street East, Hamilton, ON, L8L 2X2, Canada
- Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Bol'shaya Pirogovskaya Ulitsa, 2, стр. 4, Moscow 119435, Russia
| | - Robert F Storey
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Pegasus House, 463a Glossop Road, Sheffield, S10 2QD, UK
| | - Jecko Thachil
- Department of Haematology, Manchester University Hospitals, Oxford road, Manchester, M13 9WL, UK
| | - Gemma Vilahur
- Institut de Recerca Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, CIBERCV, Avda. Sant Antoni Maria Claret 167, 08025 Barcelona, Spain
| | - Patricia C Liaw
- Department of Medicine, Thrombosis & Atherosclerosis Research Institute (TaARI), McMaster University, 237 Barton Street East Hamilton, Ontario L8L 2X2, Canada
| | - Bianca Rocca
- Department of Safety and Bioethics, Section on Pharmacology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy
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16
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Jang JH, Shin KH, Lee HR, Son E, Lee SE, Seol HY, Yoon SH, Kim T, Cho WH, Jeon D, Kim YS, Yeo HJ. Initial Tumor Necrosis Factor-Alpha and Endothelial Activation Are Associated with Hemorrhagic Complications during Extracorporeal Membrane Oxygenation. J Clin Med 2023; 12:4520. [PMID: 37445555 DOI: 10.3390/jcm12134520] [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: 05/12/2023] [Revised: 06/22/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
Studies on inflammatory markers, endothelial activation, and bleeding during extracorporeal membrane oxygenation (ECMO) are lacking. Blood samples were prospectively collected after ECMO initiation from 150 adult patients who underwent ECMO for respiratory failure between 2018 and 2021. After excluding patients who died early (within 48 h), 132 patients were finally included. Their tumor necrosis factor-alpha (TNF-α), tissue factor (TF), soluble thrombomodulin (sTM), and E-selectin levels were measured. A Cox proportional hazards regression model was used to estimate the hazard ratio for hemorrhagic complications during ECMO. The 132 patients were divided into hemorrhagic (n = 23, H group) and non-complication (n = 109, N group) groups. The sequential organ failure assessment score, hemoglobin level, and ECMO type were included as covariates in all Cox models to exclude the effects of clinical factors. After adjusting for these factors, initial TNF-α, TF, sTM, E-selectin, and activated protein C levels were significantly associated with hemorrhagic complications (all p < 0.001). TNF-α, TF, and E-selectin better predicted hemorrhagic complications than the model that included only the aforementioned clinical factors (clinical factors only (area under the curve [AUC]: 0.804), reference; TNF-α (AUC: 0.914); TF (AUC: 0.915); E-selectin (AUC: 0.869)). Conclusions: TNF-α levels were significantly predictive of hemorrhagic complications during ECMO.
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Affiliation(s)
- Jin Ho Jang
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
| | - Kyung-Hwa Shin
- Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Hye Rin Lee
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
| | - Eunjeong Son
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
| | - Seung Eun Lee
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Hee Yun Seol
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Seong Hoon Yoon
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
| | - Taehwa Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
| | - Woo Hyun Cho
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Doosoo Jeon
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Yun Seong Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Hye Ju Yeo
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Transplantation Research Center and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
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Fiedler L, Motloch LJ, Dieplinger AM, Jirak P, Davtyan P, Gareeva D, Badykova E, Badykov M, Lakman I, Agapitov A, Sadikova L, Pavlov V, Föttinger F, Mirna M, Kopp K, Hoppe UC, Pistulli R, Cai B, Yang B, Zagidullin N. Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors. Front Pharmacol 2023; 14:1093396. [PMID: 37324463 PMCID: PMC10266094 DOI: 10.3389/fphar.2023.1093396] [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: 11/10/2022] [Accepted: 05/18/2023] [Indexed: 06/17/2023] Open
Abstract
Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ 2-statistics = 6.45, p = 0.013 and SCD: χ 2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.
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Affiliation(s)
- Lukas Fiedler
- University Department of Internal Medicine II, Cardiology and Internal Intensive Care Medicine, Paracelsus Medical University, Salzburg, Austria
- Department of Internal Medicine, Nephrology and Intensive Care Medicine, Hospital Wiener Neustadt, Wiener Neustadt, Austria
| | - Lukas J. Motloch
- University Department of Internal Medicine II, Cardiology and Internal Intensive Care Medicine, Paracelsus Medical University, Salzburg, Austria
| | - Anna-Maria Dieplinger
- Nursing Science Program, Institute for Nursing Science and Practice, Paracelsus Medical University, Salzburg, Austria
- Medical Faculty, Johannes Kepler University Linz, Linz, Austria
| | - Peter Jirak
- University Department of Internal Medicine II, Cardiology and Internal Intensive Care Medicine, Paracelsus Medical University, Salzburg, Austria
| | - Paruir Davtyan
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Diana Gareeva
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Elena Badykova
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Marat Badykov
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
| | - Irina Lakman
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
- Scientific Laboratory for the Socio-Economic Region Problems Investigation, Ufa University of Science and Technology, Ufa, Russia
| | - Aleksandr Agapitov
- Scientific Laboratory for the Socio-Economic Region Problems Investigation, Ufa University of Science and Technology, Ufa, Russia
| | - Liana Sadikova
- Scientific Laboratory for the Socio-Economic Region Problems Investigation, Ufa University of Science and Technology, Ufa, Russia
| | - Valentin Pavlov
- Department of Urology, Bashkir State Medical University, Ufa, Russia
| | - Fabian Föttinger
- University Department of Internal Medicine II, Cardiology and Internal Intensive Care Medicine, Paracelsus Medical University, Salzburg, Austria
| | - Moritz Mirna
- University Department of Internal Medicine II, Cardiology and Internal Intensive Care Medicine, Paracelsus Medical University, Salzburg, Austria
| | - Kristen Kopp
- University Department of Internal Medicine II, Cardiology and Internal Intensive Care Medicine, Paracelsus Medical University, Salzburg, Austria
| | - Uta C. Hoppe
- University Department of Internal Medicine II, Cardiology and Internal Intensive Care Medicine, Paracelsus Medical University, Salzburg, Austria
| | - Rudin Pistulli
- Department of Cardiology I, Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, Muenster, Germany
| | - Benzhi Cai
- Department of Pharmacology (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China
| | - Baofeng Yang
- Department of Pharmacology (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China
| | - Naufal Zagidullin
- Department of Internal Diseases, Bashkir State Medical University, Ufa, Russia
- Department of Biomedical Engineering, Ufa University of Science and Technology, Ufa, Russia
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18
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Huang B, Yan J, Li C, Jin F, Ma R, Cao G, Chen Y, Liu K, Ning X. Red blood cell distribution width is a risk factor for multiple organ dysfunction syndrome in elderly patients with infection: a case control study. Aging Clin Exp Res 2023:10.1007/s40520-023-02431-w. [PMID: 37233902 DOI: 10.1007/s40520-023-02431-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/30/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Infection is the leading cause of multiple organ dysfunction syndrome (MODS) in the elderly. Red blood cell distribution width (RDW) was considered to be associated with many diseases. We aimed to explore whether RDW was associated with MODS in elderly infected patients. METHODS We retrospectively collected data from elderly patients (≥ 65 years old) with infection. In this study, we conducted a 1:3 case-control match based on age and gender and utilized binary Logistic regression to investigate the impact of variables such as RDW on MODS. RESULTS A total of 576 eligible patients were included in this study. RDW in the case group was significantly higher than that in control group (p < 0.001). Multivariate analysis found that RDW was an independent risk factor for MODS in elderly infected patients (OR = 1.397, 95% CI: 1.166-1.674, p < 0.001). CONCLUSIONS RDW was an independent risk factor for MODS in elderly patients with infection.
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Affiliation(s)
- Boyong Huang
- Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
- Special Service Department, No. 989 Hospital of the PLA Joint Logistic Support Force, Pingdingshan, 467000, China
| | - Jipeng Yan
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Cui Li
- Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Fengzhong Jin
- Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Rui Ma
- Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Guihua Cao
- Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Yang Chen
- Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China
| | - Kun Liu
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi'an, 710032, China.
| | - Xiaoxuan Ning
- Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
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Merdji H, Levy B, Jung C, Ince C, Siegemund M, Meziani F. Microcirculatory dysfunction in cardiogenic shock. Ann Intensive Care 2023; 13:38. [PMID: 37148451 PMCID: PMC10164225 DOI: 10.1186/s13613-023-01130-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/13/2023] [Indexed: 05/08/2023] Open
Abstract
Cardiogenic shock is usually defined as primary cardiac dysfunction with low cardiac output leading to critical organ hypoperfusion, and tissue hypoxia, resulting in high mortality rate between 40% and 50% despite recent advances. Many studies have now evidenced that cardiogenic shock not only involves systemic macrocirculation, such as blood pressure, left ventricular ejection fraction, or cardiac output, but also involves significant systemic microcirculatory abnormalities which seem strongly associated with the outcome. Although microcirculation has been widely studied in the context of septic shock showing heterogeneous alterations with clear evidence of macro and microcirculation uncoupling, there is now a growing body of literature focusing on cardiogenic shock states. Even if there is currently no consensus regarding the treatment of microcirculatory disturbances in cardiogenic shock, some treatments seem to show a benefit. Furthermore, a better understanding of the underlying pathophysiology may provide hypotheses for future studies aiming to improve cardiogenic shock prognosis.
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Affiliation(s)
- Hamid Merdji
- Intensive Care Unit, Department of Acute Medicine, University Hospital, Basel, Switzerland
- Department of Clinical Research, University of Basel, Basel, Switzerland
| | - Bruno Levy
- Institut Lorrain du Cœur et des Vaisseaux, Medical Intensive Care Unit Brabois, Université de Lorraine, CHRU de Nancy, INSERM U1116, Nancy, France
| | - Christian Jung
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, 40225, Düsseldorf, Germany
| | - Can Ince
- Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Martin Siegemund
- Intensive Care Unit, Department of Acute Medicine, University Hospital, Basel, Switzerland
- Department of Clinical Research, University of Basel, Basel, Switzerland
| | - Ferhat Meziani
- Faculté de Médecine, Université de Strasbourg (UNISTRA), Strasbourg, France.
- Service de Médecine Intensive-Réanimation, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, 1, Place de L'Hôpital, 67091, Strasbourg Cedex, France.
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Strasbourg, France.
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20
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Gazzaniga G, Tavecchia GA, Bravi F, Scavelli F, Travi G, Campo G, Vandenbriele C, Tritschler T, Sterne JAC, Murthy S, Morici N. The effect of antithrombotic treatment on mortality in patients with acute infection: A meta-analysis of randomized clinical trials. Int J Cardiol 2023:S0167-5273(23)00646-0. [PMID: 37149006 DOI: 10.1016/j.ijcard.2023.04.057] [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] [Received: 01/14/2023] [Revised: 04/26/2023] [Accepted: 04/30/2023] [Indexed: 05/08/2023]
Abstract
BACKGROUND AND AIMS Acute infections cause relevant activation of innate immunity and inflammatory cascade. An excessive response against pathogens has been proved to trigger the pathophysiological process of thrombo-inflammation. Nevertheless, an association between the use of antithrombotic agents and the outcome of critically ill patients with infectious diseases is lacking. The aim of this meta-analysis is to determine the impact of antithrombotic treatment on survival of patients with acute infective disease. METHODS MEDLINE, Embase, Cinahl, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched from inception to March 2021. We included randomized controlled trials (RCTs) that evaluated any antithrombotic agent in patients with infectious diseases other than COVID-19. Two authors independently performed study selection, data extraction and risk of bias evaluation. The primary outcome was all-cause mortality. Summary estimates for mortality were calculated using the inverse-variance random-effects method. RESULTS A total of 16,588 patients participating in 18 RCTs were included, of whom 2141 died. Four trials evaluated therapeutic-dose anticoagulation, 1 trial prophylactic-dose anticoagulation, 4 trials aspirin, and 9 trials other antithrombotic agents. Overall, the use of antithrombotic agents was not associated with all-cause mortality (relative risk 0.96; 95% confidence interval, 0.90-1.03). CONCLUSIONS The use of antithrombotics is not associated with all-cause mortality in patients with infectious disease other than COVID-19. Complex pathophysiological interplays between inflammatory and thrombotic pathways may explain these results and need further investigation. REGISTRATION PROSPERO, CRD42021241182.
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Affiliation(s)
- Gianluca Gazzaniga
- Department of Medical Biotechnology and Translational Medicine, Postgraduate School of Clinical Pharmacology and Toxicology, Università degli Studi di Milano, Milan, Italy
| | - Giovanni Amedeo Tavecchia
- Cardiology Department and De Gasperis Cardio Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Postgraduate School of Cardiovascular Diseases, University of Milano Bicocca, Milan, Italy
| | - Francesca Bravi
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Francesca Scavelli
- Cardiology Department and De Gasperis Cardio Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giovanna Travi
- Infectious Diseases Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Gianluca Campo
- Cardiovascular Institute, Azienda Ospedaliera Universitaria di Ferrara, Cona, Italy
| | | | - Tobias Tritschler
- Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Jonathan A C Sterne
- Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Srinivas Murthy
- BC Children's Hospital, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Nuccia Morici
- IRCCS S. Maria Nascente - Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy.
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21
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How to manage coagulopathies in critically ill patients. Intensive Care Med 2023; 49:273-290. [PMID: 36808215 DOI: 10.1007/s00134-023-06980-6] [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: 11/08/2022] [Accepted: 01/06/2023] [Indexed: 02/19/2023]
Abstract
Coagulopathy is a severe and frequent complication in critically ill patients, for which the pathogenesis and presentation may be variable depending on the underlying disease. Based on the dominant clinical phenotype, the current review differentiates between hemorrhagic coagulopathies, characterized by a hypocoagulable and hyperfibrinolysis state, and thrombotic coagulopathies with a systemic prothrombotic and antifibrinolytic phenotype. We discuss the differences in pathogenesis and treatment of the common coagulopathies.
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22
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Zhu C, Hou Z, Zhu R, Zhou B, Sun Y, Li Z, Li X, Ding R, Luan Z, Liang Y, Wang L, Ma X. Comparisons of coagulation characteristics between elderly and non-elderly patients with sepsis: A prospective study. Surgery 2023; 173:1303-1310. [PMID: 36774318 DOI: 10.1016/j.surg.2023.01.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 12/11/2022] [Accepted: 01/06/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND A blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. METHODS Adult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18-64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. RESULTS Of the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. CONCLUSION Elderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.
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Affiliation(s)
- Chengrui Zhu
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhenzhen Hou
- Department of Surgical Intensive Care Unit, Beijing Chaoyang Hospital Affiliated to Capital Medical University, China
| | - Ran Zhu
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Baosen Zhou
- Department of Clinical Epidemiology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yini Sun
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhiliang Li
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Xu Li
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Renyu Ding
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhenggang Luan
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yingjian Liang
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Liang Wang
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Xiaochun Ma
- Department of Critical Care Medicine, The First Hospital of China Medical University, Shenyang, Liaoning Province, China.
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23
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Corda F, Ballocco I, Corda A, Mollica A, Cilano A, Polinas M, Pinna Parpaglia ML. Coagulation Abnormalities in Dogs with Parvoviral Enteritis. Vet Sci 2023; 10:vetsci10010041. [PMID: 36669042 PMCID: PMC9861196 DOI: 10.3390/vetsci10010041] [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: 11/30/2022] [Revised: 12/29/2022] [Accepted: 01/02/2023] [Indexed: 01/09/2023] Open
Abstract
Hemostatic alterations have been documented in dogs with canine parvoviral enteritis. This study's aims were to measure the standard coagulation parameters, and to assess the relationship between them and the clinical variables in dogs with canine parvoviral enteritis. Nine client-owned dogs with a canine parvoviral infection were included in a prospective, observational clinical study. Clinical score and coagulation status were assessed at admission. All nine dogs showed alterations of three or more standard coagulation variables. A correlation analysis evidenced a significantly high positive correlation between the activated partial thromboplastin time and clinical score. The present study concurs that dogs with canine parvoviral enteritis have coagulation disorders that are detectable by measuring the standard coagulation parameters.
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24
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Chen Y, Chen W, Ba F, Zheng Y, Zhou Y, Shi W, Li J, Yang Z, Mao E, Chen E, Chen Y. Prognostic Accuracy of the Different Scoring Systems for Assessing Coagulopathy in Sepsis: A Retrospective Study. Clin Appl Thromb Hemost 2023; 29:10760296231207630. [PMID: 37920943 PMCID: PMC10623916 DOI: 10.1177/10760296231207630] [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: 08/28/2023] [Revised: 09/26/2023] [Accepted: 09/27/2023] [Indexed: 11/04/2023] Open
Abstract
There is no gold standard for the diagnosis of coagulation dysfunction in sepsis, and the use of the current scoring systems is still controversial. The purpose of this study was to assess the performance of sepsis-induced coagulopathy (SIC), the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC), and the International Society on Thrombosis and Haemostasis overt DIC (ISTH overt-DIC). The relationship between each scoring system and 28-day all-cause mortality was examined. Among 452 patients (mean age, 65 [48,76] years), 306 [66.7%] were men, the median SOFA score was 6 [4,9], and the median APACHE II score was 15 [11,22]. A total of 132 patients (29.2%) died within 28 days. Both the diagnosis of SIC (AUROC, 0.779 [95% CI, 0.728-0.830], P < 0.001) and ISTH overt-DIC (AUROC, 0.782 [95% CI, 0.732-0.833], P < 0.001) performed equally well in the discrimination of 28-day all-cause mortality (between-group difference: SIC versus ISTH overt-DIC, -0.003 [95% CI, -0.025-0.018], P = 0.766). However, the SIC demonstrated greater calibration for 28-day all-cause mortality than ISTH overt-DIC (the coincidence of the calibration curve of the former is higher than that of the latter). The diagnosis of JAAM DIC was not independently associated with 28-day all-cause mortality in sepsis (RR, 1.115, [95% CI 0.660-1.182], P = 0.684). The SIC scoring system demonstrated superior prognostic prediction ability in comparison with the others and is the most appropriate standard for diagnosing coagulopathy in sepsis.
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Affiliation(s)
- Yuwei Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Emergency, the First Hospital of Handan, Handan, China
| | - Weiwei Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fuhua Ba
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanjun Zheng
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Zhou
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen Shi
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian Li
- Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhitao Yang
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Enqiang Mao
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Erzhen Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying Chen
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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25
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Lemiale V, Mabrouki A, Miry L, Mokart D, Pène F, Kouatchet A, Mayaux J, Bruneel F, Perez P, Meert AP, Moreau AS, Benoit D, Darmon M, Zafrani L, Clere-Jehl R. Sepsis-associated coagulopathy in onco-hematology patients presenting with thrombocytopenia: a multicentric observational study. Leuk Lymphoma 2023; 64:197-204. [PMID: 36305707 DOI: 10.1080/10428194.2022.2136971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Coagulation disorders increase mortality rate during septic shock, but the impact of concomitant hematological malignancies remains unknown. The study assessed coagulation disorders in onco-hematological patients with thrombocytopenia (<100 G/L) admitted to ICU for septic shock. Among 146 included patients, 50 patients had lymphoma and 49 patients had acute leukemia. ICU mortality rate was 43.8% (n = 64). Median increase in prothrombin time (PT) at day(d) 1 was 4.7 s (IQR 3.2-7.9) in ICU survivors vs. 6.4 s (IQR 4.5-13.7; p < 0.01) in non-survivors. Fibrinogen kinetics (increase in fibrinogen levels between d1 and d2) was +0.55 (-0.22-1.55) vs. +0.10 g/L (-0.40-0.50; p = 0.03) in surviving and non-surviving patients, respectively. PT increase ≥6 s at d1 (OR 5.5; 95% CI 1.1-6.0; p = 0.03) and mechanical ventilation (OR 7.4; 95% CI 3.3-17.7; p < 0.001) were independently associated with ICU mortality. This study provides information and new ways to identify hematological patients with high-risk mortality.
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Affiliation(s)
- Virginie Lemiale
- Department of Medical Intensive Care Unit, Saint-Louis Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Asma Mabrouki
- Department of Medical Intensive Care Unit, Saint-Louis Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Loïc Miry
- Neuro-Intensive Care Unit, Rothschild Foundation Hospital, France
| | - Djamel Mokart
- Medical and Surgical Intensive Care Unit, Institut Paoli-Calmettes, Marseille, France
| | - Frédéric Pène
- Service de Médecine Intensive-réanimation, Hôpital Cochin, AP-HP, Centre & Université Paris Cité, Paris, France
| | - Achille Kouatchet
- Medical Intensive Care Unit, Angers University Hospital, Angers, France
| | - Julien Mayaux
- Service de Médecine Intensive et Réanimation (Département R3S), AP-HP, Groupe Hospitalier Universitaire-Sorbonne Université, site Pitié-Salpêtrière, Paris, France
| | - Fabrice Bruneel
- Department of Critical Care, Versailles Hospital, Le Chesnay, France
| | - Pierre Perez
- Medical Intensive Care Unit, Hôpital Brabois, Vandoeuvre Les Nancy, France
| | - Anne-Pascale Meert
- Soins intensifs et urgences oncologiques, Service de Médecine interne, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Bruxelles, Belgique
| | - Anne-Sophie Moreau
- Pôle de médecine intensive réanimation, Hôpital Roger Salengro, CHU Lille, Lille cedex, France
| | - Dominique Benoit
- Medical Unit, Department of Intensive Care, Ghent University Hospitalc, Ghent, Belgium
| | - Michael Darmon
- Department of Medical Intensive Care Unit, Saint-Louis Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Lara Zafrani
- Department of Medical Intensive Care Unit, Saint-Louis Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.,INSERM U976, Human Immunology, Pathophysiology and Immunotherapy, Saint-Louis Teaching Hospital, Paris University, Paris, France
| | - Raphaël Clere-Jehl
- Department of Medical Intensive Care Unit, Saint-Louis Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.,Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM (French National Institute of Health and Medical Research), UMR_S1109, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg Cedex, France
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Lian H, Zhang H, Ding X, Wang X. The importance of a sepsis layered early warning system for critical patients. Am J Transl Res 2022; 14:5229-5242. [PMID: 36105025 PMCID: PMC9452367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/12/2022] [Indexed: 06/15/2023]
Abstract
Critical illness, particularly sepsis, is associated with high mortality, so prevention is more important than effective therapy. Advances in medical science have provided more opportunities for early warning and early intervention to avoid the development of critical illness. Existing early warning systems (EWS) have the advantages of high efficiency and convenience. However, with the development of medical technology, they do not completely meet clinical needs. EWS should contain elements that meet many dimensions of clinical requirements, including risk warning, response warning, injury warning, critical warning, and death warning. By summarizing previous studies, we outlined a layered EWS that follows RISK bundles. RISK represents different warning sign categories: R: host response, I: organ injury, S: changes in vital signs, and K: gradual appearance of "killed" organs. We plan to construct a complete layered EWS to guide clinical activities and subsequent clinical studies in the near future.
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Affiliation(s)
- Hui Lian
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, P. R. China
| | - Hongmin Zhang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, P. R. China
| | - Xin Ding
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, P. R. China
| | - Xiaoting Wang
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, P. R. China
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, P. R. China
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Dimiati H, Widasari N. COVID-19 and Thrombosis Complication in Children. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Since it was discovered in Wuhan in December 2019, most studies on COVID-19 have been centered on symptomatic adults. An expanded pro-inflammatory cytokine reaction, abnormal clot formation, overactive platelets, and hypercoagulable state are among the well-known clinical characteristics of endothelial dysfunction that may arise in patients with COVID-19. These conditions can lead to venous thromboembolism, arterial thrombosis, and pulmonary embolism. To date, the predominance of thromboembolic complications in children infected with severe acute respiratory syndrome coronavirus 2 has not been fully documented, and there is no explicit recommendation for the prevention of thrombosis in children.
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Vasudeva Rao U, Wasim MD, Rajeev P, Rai S, Pradeep Kumar K. Acute limb ischaemia: not an uncommon complication of COVID-19 infection. Ann R Coll Surg Engl 2022; 104:e211-e215. [PMID: 35446698 PMCID: PMC9246543 DOI: 10.1308/rcsann.2021.0342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
A new variant of coronavirus (2019-nCoV) causing acute respiratory distress in humans was identified for the first time in 2019, in Wuhan, China. One of the many complications of infection with this coronavirus is hypercoagulopathy, resulting in acute thrombosis; often leading to acute limb ischaemia. Herein, we report 20 cases of COVID-19 with peripheral arterial thrombosis involving either upper or lower limbs. Some patients underwent vascular procedures and most had to undergo amputation at some level. All the cases (n=20) were referred to us during the 8-month period June 2020 to March 2021. The most common age group was between 51 and 60 years, of whom 80% were males; all the patients had diabetes. The right lower limb was most affected (50%); 15 patients underwent embolectomy. Twenty-five per cent of patients presented with wet gangrene. One patient with upper limb thrombosis recovered after embolectomy and did not require any amputation. Eighty-five per cent of patients underwent some form of amputation and the mortality rate was 10%. Arterial thrombosis is one complication patients may develop during COVID-19 illness, which may affect the outcome. Patients with comorbid conditions like diabetes are at higher risk of developing arterial thrombosis during COVID-19 infection. Susceptibility to coagulopathy may continue even after patient discharge and it is important that both patients and treating physicians are aware of this limb-threatening complication and seek early medical attention.
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Affiliation(s)
| | - MD Wasim
- Sri Krishnasevasharama Hospital, Bangalore, India
| | - P Rajeev
- Sri Krishnasevasharama Hospital, Bangalore, India
| | - S Rai
- Sri Krishnasevasharama Hospital, Bangalore, India
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29
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Chiscano-Camón L, Plata-Menchaca E, Ruiz-Rodríguez JC, Ferrer R. Fisiopatología del shock séptico. Med Intensiva 2022. [DOI: 10.1016/j.medin.2022.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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30
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The OpenSAFELY Collaborative, Tazare J, Walker AJ, Tomlinson LA, Hickman G, Rentsch CT, Williamson EJ, Bhaskaran K, Evans D, Wing K, Mathur R, Wong AYS, Schultze A, Bacon S, Bates C, Morton CE, Curtis HJ, Nightingale E, McDonald HI, Mehrkar A, Inglesby P, Davy S, MacKenna B, Cockburn J, Hulme WJ, Warren-Gash C, Bhate K, Nitsch D, Powell E, Mulick A, Forbes H, Minassian C, Croker R, Parry J, Hester F, Harper S, Eggo RM, Evans SJW, Smeeth L, Douglas IJ, Goldacre B. Rates of serious clinical outcomes in survivors of hospitalisation with COVID-19 in England: a descriptive cohort study within the OpenSAFELY platform. Wellcome Open Res 2022; 7:142. [PMID: 37362009 PMCID: PMC10285340 DOI: 10.12688/wellcomeopenres.17735.1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2022] [Indexed: 03/07/2024] Open
Abstract
Background: Patients surviving hospitalisation for COVID-19 are thought to be at high risk of cardiometabolic and pulmonary complications, but quantification of that risk is limited. We aimed to describe the overall burden of these complications in people after discharge from hospital with COVID-19. Methods: Working on behalf of NHS England, we used linked primary care records, death certificate and hospital data from the OpenSAFELY platform. We constructed three cohorts: patients discharged following hospitalisation with COVID-19, patients discharged following pre-pandemic hospitalisation with pneumonia, and a frequency-matched cohort from the general population in 2019. We studied seven outcomes: deep vein thrombosis (DVT), pulmonary embolism (PE), ischaemic stroke, myocardial infarction (MI), heart failure, AKI and new type 2 diabetes mellitus (T2DM) diagnosis. Absolute rates were measured in each cohort and Fine and Gray models were used to estimate age/sex adjusted subdistribution hazard ratios comparing outcome risk between discharged COVID-19 patients and the two comparator cohorts. Results: Amongst the population of 77,347 patients discharged following hospitalisation with COVID-19, rates for the majority of outcomes peaked in the first month post-discharge, then declined over the following four months. Patients in the COVID-19 population had markedly higher risk of all outcomes compared to matched controls from the 2019 general population. Across the whole study period, the risk of outcomes was more similar when comparing patients discharged with COVID-19 to those discharged with pneumonia in 2019, although COVID-19 patients had higher risk of T2DM (15.2 versus 37.2 [rate per 1,000-person-years for COVID-19 versus pneumonia, respectively]; SHR, 1.46 [95% CI: 1.31 - 1.63]). Conclusions: Risk of cardiometabolic and pulmonary adverse outcomes is markedly raised following discharge from hospitalisation with COVID-19 compared to the general population. However, excess risks were similar to those seen following discharge post-pneumonia. Overall, this suggests a large additional burden on healthcare resources.
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Affiliation(s)
- The OpenSAFELY Collaborative
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
- TPP, TPP House, 129 Low Lane, Horsforth, Leeds, LS18 5PX, UK
- NIHR Health Protection Research Unit (HPRU) in Immunisation, London, UK
| | - John Tazare
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Alex J. Walker
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | | | - George Hickman
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | | | | | | | - David Evans
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | - Kevin Wing
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Rohini Mathur
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Angel YS. Wong
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Anna Schultze
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Seb Bacon
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | - Chris Bates
- TPP, TPP House, 129 Low Lane, Horsforth, Leeds, LS18 5PX, UK
| | | | - Helen J. Curtis
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
- NIHR Health Protection Research Unit (HPRU) in Immunisation, London, UK
| | | | | | - Amir Mehrkar
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | - Peter Inglesby
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | - Simon Davy
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | - Brian MacKenna
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | | | - William J. Hulme
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | | | - Ketaki Bhate
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Dorothea Nitsch
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Emma Powell
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Amy Mulick
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Harriet Forbes
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | | | - Richard Croker
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
| | - John Parry
- TPP, TPP House, 129 Low Lane, Horsforth, Leeds, LS18 5PX, UK
| | - Frank Hester
- TPP, TPP House, 129 Low Lane, Horsforth, Leeds, LS18 5PX, UK
| | - Sam Harper
- TPP, TPP House, 129 Low Lane, Horsforth, Leeds, LS18 5PX, UK
| | - Rosalind M. Eggo
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | | | - Liam Smeeth
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Ian J Douglas
- London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
| | - Ben Goldacre
- The DataLab, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX26GG, UK
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The Role of Excessive Anticoagulation and Missing Hyperinflammation in ECMO-Associated Bleeding. J Clin Med 2022; 11:jcm11092314. [PMID: 35566439 PMCID: PMC9102211 DOI: 10.3390/jcm11092314] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 02/26/2022] [Accepted: 04/19/2022] [Indexed: 12/30/2022] Open
Abstract
Extracorporeal membrane oxygenation (ECMO) is increasingly used in carefully selected patients with cardiac or respiratory failure. However, complications are common and can be associated with worse outcomes, while data on risk factors and outcomes are inconsistent and sparse. Therefore, we sought to investigate potential risk factors and predictors of haemorrhage and adverse events during ECMO and its influence on mortality. We retrospectively reviewed all patients on ECMO support admitted to intensive care units of a tertiary university centre in Austria. In a period of ten years, ECMO support was used in 613 patients, with 321 patients meeting the inclusion criteria of this study. Haemorrhage, occurring in more than one third of the included patients (123, 38%), represented the most common and serious ECMO complication, being associated with an increased one year mortality (51% vs. 35%, p = 0.005). The main risk factors for haemorrhage were severity of the disease (hazard ratio (HR) = 1.01, p = 0.047), a prolonged activated partial thromboplastin time (HR = 1.01, p = 0.007), and lower values of C-reactive protein (HR = 0.96, p = 0.005) and procalcitonin (HR = 0.99, p = 0.029). In summary, haemorrhage remained the main ECMO complication with increased mortality. Moreover, we reported a possible association of lower inflammation and bleeding during ECMO support for the first time. This generated a new hypothesis that warrants further research. Finally, we recommend stricter monitoring of anticoagulation especially in patients without hyperinflammation.
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Zhou W, Fan C, He S, Chen Y, Xie C. Impact of Platelet Transfusion Thresholds on Outcomes of Patients With Sepsis: Analysis of the MIMIC-IV Database. Shock 2022; 57:486-493. [PMID: 34966069 PMCID: PMC8906242 DOI: 10.1097/shk.0000000000001898] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/15/2021] [Accepted: 11/30/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND The benefits of platelet thresholds for transfusion remain unclear. This study assessed the effect of two transfusion thresholds on the survival outcomes of patients with sepsis and thrombocytopenia. METHODS In this retrospective cohort study, data of patients with sepsis admitted to an intensive care unit (ICU) and who had received platelet transfusion were extracted from the Medical Information Mart for Intensive Care IV database. Patients were classified into the lower-threshold group (below 20,000/μL) and higher-threshold group (20,000-50,000/μL), based on thresholds calculated from their pretransfusion platelet count. The endpoints included 28- and 90-day mortality, red blood cell (RBC) transfusion, ICU-free days, and hospital-free days. RESULTS There were 76 and 217 patients in the lower-threshold and higher-threshold groups, respectively. The higher-threshold group had a higher rate of surgical ICU admission (35.0% vs. 9.2%) and lower quick Sequential Organ Failure Assessment (qSOFA) score than the lower-threshold group. In the higher-threshold group, 94 (43.3%) and 132 (60.8%) patients died within 28 and 90 days, compared to 51 (67.1%) and 63 (82.9%) patients in the lower-threshold group (adjusted odds ratio, 1.96; 95% confidence interval, 1.16 to 3.03; P = 0.012; adjusted odds ratio, 2.04; 95% confidence interval, 1.16 to 3.57; P = 0.012, respectively). After stratification by mortality risk, the subgroup analysis showed a consistent trend favoring higher-threshold transfusion but reached statistical significance only in the low-risk group. There were no differences in red blood cell transfusion, ICU-free days, and hospital-free days between the groups. The E-value analysis suggested robustness to unmeasured confounding. CONCLUSIONS In patients with sepsis and thrombocytopenia, platelet transfusion at a higher threshold was associated with a greater reduction in the 28- and 90-day mortalities than that at a lower threshold.
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Affiliation(s)
- Wei Zhou
- Department of Emergency, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Chiscano-Camón L, Plata-Menchaca E, Ruiz-Rodríguez JC, Ferrer R. [Pathophysiology of septic shock]. Med Intensiva 2022; 46 Suppl 1:1-13. [PMID: 38341256 DOI: 10.1016/j.medine.2022.03.010] [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: 02/01/2022] [Accepted: 03/20/2022] [Indexed: 02/12/2024]
Abstract
Sepsis and septic shock result from an inadequate host response to an infection, which causes organ dysfunction. The progression of this condition is manifested by the occurrence of successive clinical stages, resulting from the systemic inflammatory response secondary to the activation of different inflammatory mediators, leading to organ dysfunction. There is a high burden of evidence on the role of endotoxin in the pathogenesis of sepsis and its crucial role in triggering the inflammatory response in sepsis caused by gram-negative bacteria. The coagulation cascade activation in sepsis patients is part of the host's adaptive immune response to infection. The endothelium is the main target in sepsis, which is metabolically active and can.
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Affiliation(s)
- Luis Chiscano-Camón
- Servicio de Medicina Intensiva, Hospital Universitario Vall d'Hebron, Barcelona, España; Grupo de Investigación Sepsis Organ Dysfunction and Resuscitation (SODIR), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, España; Departament de Medicina. Universitat Autònoma de Barcelona. Barcelona. España
| | - Erika Plata-Menchaca
- Servicio de Medicina Intensiva, Hospital Universitario Vall d'Hebron, Barcelona, España; Grupo de Investigación Sepsis Organ Dysfunction and Resuscitation (SODIR), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, España
| | - Juan Carlos Ruiz-Rodríguez
- Servicio de Medicina Intensiva, Hospital Universitario Vall d'Hebron, Barcelona, España; Grupo de Investigación Sepsis Organ Dysfunction and Resuscitation (SODIR), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, España; Departament de Medicina. Universitat Autònoma de Barcelona. Barcelona. España
| | - Ricard Ferrer
- Servicio de Medicina Intensiva, Hospital Universitario Vall d'Hebron, Barcelona, España; Grupo de Investigación Sepsis Organ Dysfunction and Resuscitation (SODIR), Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, España; Departament de Medicina. Universitat Autònoma de Barcelona. Barcelona. España.
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Rieder M, Gauchel N, Kaier K, Jakob C, Borgmann S, Classen AY, Schneider J, Eberwein L, Lablans M, Rüthrich M, Dolff S, Wille K, Haselberger M, Heuzeroth H, Bode C, von Zur Mühlen C, Rieg S, Duerschmied D. Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities. Clin Res Cardiol 2022; 111:322-332. [PMID: 34546427 PMCID: PMC8453472 DOI: 10.1007/s00392-021-01939-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 09/06/2021] [Indexed: 12/15/2022]
Abstract
AIMS Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients. METHODS AND RESULTS We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056). CONCLUSIONS Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.
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Affiliation(s)
- Marina Rieder
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
| | - Nadine Gauchel
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany.
| | - Klaus Kaier
- Institute of Medical Biometry and Statistics, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
| | - Carolin Jakob
- Department I for Internal Medicine, Faculty of Medicine, University of Cologne, University Hospital Cologne, Cologne, Germany
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Stefan Borgmann
- Department of Infectious Diseases and Infection Control, Ingolstadt Hospital, Ingolstadt, Germany
| | - Annika Y Classen
- Department I for Internal Medicine, Faculty of Medicine, University of Cologne, University Hospital Cologne, Cologne, Germany
- German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Jochen Schneider
- School of Medicine, Technical University of Munich, University Hospital Rechts der Isar, Munich, Germany
| | - Lukas Eberwein
- 4Th Department of Internal Medicine, Klinikum Leverkusen, Leverkusen, Germany
| | - Martin Lablans
- Federated Information Systems, German Cancer Research Center, Heidelberg, Germany
- University Medical Center Mannheim, Mannheim, Germany
| | - Maria Rüthrich
- Department for Internal Medicine II, Hematology and Medical Oncology, University Hospital Jena, Jena, Germany
- Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute, Jena, Germany
| | - Sebastian Dolff
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany
| | - Kai Wille
- University Clinic for Haematology, Oncology, Haemostaseology and Palliative Care, Johannes Wesling Medical Center Minden, University of Bochum, Bochum, Germany
| | | | - Hanno Heuzeroth
- Department of Emergency and Intensive Care Medicine, Klinikum Ernst-Von-Bergmann, Potsdam, Germany
| | - Christoph Bode
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
| | - Constantin von Zur Mühlen
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
| | - Siegbert Rieg
- Division of Infectious Diseases, Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Daniel Duerschmied
- Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
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Rabouël Y, Magnenat S, Lefebvre F, Delabranche X, Gachet C, Hechler B. Transfusion of fresh washed platelets does not prevent experimental polymicrobial-induced septic shock in mice. J Thromb Haemost 2022; 20:449-460. [PMID: 34752015 DOI: 10.1111/jth.15583] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 11/05/2021] [Accepted: 11/08/2021] [Indexed: 11/29/2022]
Abstract
INTRODUCTION The specific role of platelets during sepsis is not yet fully understood, probably related to the paradox of platelets being potentially beneficial but also deleterious via their thrombotic functions. OBJECTIVE To evaluate the impact of thrombocytopenia on septic shock in mice and to investigate whether transfusion of fresh washed platelets, either fully functional or with impaired hemostatic properties, might have beneficial effects. METHODS Septic shock was induced by cecal ligation and puncture (CLP). Experimental depletion of circulating platelets was induced with a rat anti-mouse GPIbα monoclonal antibody. Transfusion of either wild-type washed platelets, platelets treated with the antiplatelet drugs acetylsalicylic acid (ASA) and clopidogrel, or GPIIbIIIa-deficient washed platelets treated with ASA and clopidogrel was performed 4 h after CLP surgery. RESULTS Depletion of circulating platelets negatively affected septic shock, worsening systemic inflammation, coagulopathy, organ damage, and mortality, raising the question of whether a higher platelet count could be protective. Transfusion of fully functional platelets or platelets with combined treatment with ASA and clopidogrel, with or without additional GPIIbIIIa deficiency, afforded an immediate return of circulating platelet counts to their initial values before surgery. However, transfusion of each of the three types of platelets did not prevent arterial hypotension, inflammatory response, coagulopathy, and organ damage during septic shock. CONCLUSION Depletion of circulating platelets negatively affects septic shock, while transfusion of washed platelets has no significant beneficial effect in mice.
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Affiliation(s)
- Yannick Rabouël
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS) Grand Est, BPPS UMR_S1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France
| | - Stéphanie Magnenat
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS) Grand Est, BPPS UMR_S1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France
| | - Floryna Lefebvre
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS) Grand Est, BPPS UMR_S1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France
| | - Xavier Delabranche
- Hôpitaux Universitaires de Strasbourg, Anesthésie, Réanimation et Médecine périopératoire, Nouvel Hôpital Civil, Strasbourg, France
| | - Christian Gachet
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS) Grand Est, BPPS UMR_S1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France
| | - Beatrice Hechler
- Université de Strasbourg, INSERM, Etablissement Français du Sang (EFS) Grand Est, BPPS UMR_S1255, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France
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36
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Park S, Gu JY, Kim HK. Contact system activation in disseminated intravascular coagulation: activities of prekallikrein and high-molecular-weight kininogen are significant risk factors. J Thromb Thrombolysis 2022; 54:11-14. [PMID: 34993714 DOI: 10.1007/s11239-021-02598-x] [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] [Accepted: 10/25/2021] [Indexed: 11/25/2022]
Abstract
The contact system activation can play a role in microthrombus formation of disseminated intravascular coagulation (DIC). This study investigated whether the activity of prekallikrein and high-molecular-weight kininogen (HMWK) correlated DIC progression. Contact system factors (prekallikrein, HMWK, activated factor XII), coagulation factors (IX, XI, XII) and tissue factor were measured in 140 patients who clinically suspected of having DIC. Prekallikrein and HMWK activity levels showed significant linear relationships with DIC score and antithrombin level, whereas prekallikrein and HMWK antigen levels did not. The activated factor XII, factor XII, factor XI and tissue factor were significant risk factors of overt-DIC. This finding suggests that consumption of prekallikrein and HMWK contributes to microvascular thrombosis in DIC. Measurements of prekallikrein and HMWK activity could be used as potential diagnostic markers for overt-DIC.
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Affiliation(s)
- Sooyong Park
- Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Ja-Yoon Gu
- Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyun Kyung Kim
- Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. .,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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37
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Celikkol A, Dogan M, Guzel EC, Erdal B, Yilmaz A. A novel combined index of D-dimer, fibrinogen, albumin, and platelet (FDAPR) as mortality predictor of COVID-19. Niger J Clin Pract 2022; 25:1418-1423. [DOI: 10.4103/njcp.njcp_1633_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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38
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Mori K, Tsujita Y, Yamane T, Eguchi Y. Decreasing Plasma Fibrinogen Levels in the Intensive Care Unit Are Associated with High Mortality Rates In Patients With Sepsis-Induced Coagulopathy. Clin Appl Thromb Hemost 2022; 28:10760296221101386. [PMID: 35549920 PMCID: PMC9112680 DOI: 10.1177/10760296221101386] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Plasma fibrinogen levels increase in response to infection, but they could also decrease due to degradation as in severe coagulopathy. We evaluated 60 septic patients with their CRP levels over 5.00 mg/dL. The patients were classified into three groups based on the ratio of the maximum or minimum fibrinogen concentration within day 3 to the initial concentration on day 0: down-, flat, and uptrend groups (n = 15, 30, and 15, respectively). Both down- and flat trend groups showed reduced inflammatory markers on day 3, and the degree of platelet loss (103/μL) and the mortality rate (%) were more remarkable in the downtrend group ( - 108 vs - 42 [p = 0.026] and 46.7 vs 10.0 [p = 0.027]). On day 0, in total 12 and 9 patients were diagnosed with non-overt DIC in the down- and uptrend groups, of which 5 (41.7%) and 1 (11.1%) died within 28 days after admission. In conclusion, decreasing fibrinogen levels in the ICU are associated with high mortality in patients with sepsis followed by decreasing platelet counts, even when they are diagnosed with non-overt DIC.
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Affiliation(s)
- Keisuke Mori
- School of Medicine, 13051Shiga University of Medical Science, Otsu, Shiga, Japan
| | - Yasuyuki Tsujita
- Emergency and Intensive Care Unit, 469340Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Tetsunobu Yamane
- Emergency and Intensive Care Unit, 469340Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Yutaka Eguchi
- Department of Critical and Intensive Care Medicine, 13051Shiga University of Medical Science, Otsu, Shiga, Japan
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39
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Gauchel N, Krauel K, Hamad MA, Bode C, Duerschmied D. Thromboinflammation as a Driver of Venous Thromboembolism. Hamostaseologie 2021; 41:428-432. [PMID: 34942655 DOI: 10.1055/a-1661-0257] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Thrombus formation has been identified as an integral part in innate immunity, termed immunothrombosis. Activation of host defense systems is known to result in a procoagulant environment. In this system, cellular players as well as soluble mediators interact with each other and their dysregulation can lead to the pathological process of thromboinflammation. These mechanisms have been under intensified investigation during the COVID-19 pandemic. In this review, we focus on the underlying mechanisms leading to thromboinflammation as one trigger of venous thromboembolism.
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Affiliation(s)
- Nadine Gauchel
- Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Krystin Krauel
- Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Muataz Ali Hamad
- Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Christoph Bode
- Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Daniel Duerschmied
- Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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40
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Sarkar M, Madabhavi IV, Quy PN, Govindagoudar MB. COVID-19 and coagulopathy. THE CLINICAL RESPIRATORY JOURNAL 2021; 15:1259-1274. [PMID: 34399021 PMCID: PMC8444678 DOI: 10.1111/crj.13438] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 06/22/2021] [Accepted: 08/10/2021] [Indexed: 02/07/2023]
Abstract
The SARS-CoV-2 is a new coronavirus responsible for the COVID-19 disease and has caused the pandemic worldwide. A large number of cases have overwhelmed the healthcare system worldwide. The COVID-19 infection has been associated with a heightened risk of thromboembolic complications. Various mechanisms are leading to the high thrombotic risk in COVID-19 patients such as inflammation, endotheliitis, hyperviscosity, and hypercoagulability. We searched PubMed, EMBASE, and CINAHL from January 2020 to December 2020. We used the following search terms: COVID-19, coagulopathy, and thrombosis. We reviewed the epidemiology, clinical features, mechanisms, and treatment of COVID-19-associated coagulopathy.
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Affiliation(s)
- Malay Sarkar
- Department of pulmonary medicineIndira Gandhi Medical CollegeShimlaHimachal PradeshIndia
| | - Irappa V. Madabhavi
- Department of Medical and Pediatric OncologyKerudi Cancer HospitalBagalkotKarnatakaIndia
- Department of Medical OncologyJ N Medical CollegeBelagaviKarnatakaIndia
- Department of Medical OncologyNanjappa HospitalShimogaKarnatakaIndia
| | - Pham Nguyen Quy
- Department of Medical OncologyKyoto Miniren Central HospitalKyotoJapan
| | - Manjunath B. Govindagoudar
- Department of Pulmonary and Critical CarePt B D Sharma Postgraduate Institute of Medical SciencesRohtakHaryanaIndia
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41
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Merdji H, Schini-Kerth V, Meziani F, Toti F. Long-term cardiovascular complications following sepsis: is senescence the missing link? Ann Intensive Care 2021; 11:166. [PMID: 34851467 PMCID: PMC8636544 DOI: 10.1186/s13613-021-00937-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 10/08/2021] [Indexed: 12/14/2022] Open
Abstract
Among the long-term consequences of sepsis (also termed “post-sepsis syndrome”) the increased risk of unexplained cardiovascular complications, such as myocardial infarction, acute heart failure or stroke, is one of the emerging specific health concerns. The vascular accelerated ageing also named premature senescence is a potential mechanism contributing to atherothrombosis, consequently leading to cardiovascular events. Indeed, vascular senescence-associated major adverse cardiovascular events (MACE) are a potential feature in sepsis survivors and of the elderly at cardiovascular risk. In these patients, accelerated vascular senescence could be one of the potential facilitating mechanisms. This review will focus on premature senescence in sepsis regardless of age. It will highlight and refine the potential relationships between sepsis and accelerated vascular senescence. In particular, key cellular mechanisms contributing to cardiovascular events in post-sepsis syndrome will be highlighted, and potential therapeutic strategies to reduce the cardiovascular risk will be further discussed.
With improved management of patients, sepsis survivors are increasing each year. Early cardiovascular complications, of yet undeciphered mechanisms, are an emerging health issue in post-sepsis syndrome. Premature senescence of endothelium and vascular tissue is proven an accelerated process of atherogenesis in young septic rats. An increasing body of clinical evidence point at endothelial senescence in the initiation and development of atherosclerosis. Prevention of premature senescence by senotherapy and cardiological follow-up could improve long-term septic patients’ outcomes.
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Affiliation(s)
- Hamid Merdji
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), CRBS (Centre de Recherche en Biomédecine de Strasbourg), FMTS (Fédération de Médecine Translationnelle de Strasbourg), University of Strasbourg, Strasbourg, France.,Department of Intensive Care (Service de Médecine Intensive-Réanimation), Nouvel Hôpital Civil, Hôpital Universitaire de Strasbourg, 1, place de l'Hôpital, 67091, Strasbourg Cedex, France
| | - Valérie Schini-Kerth
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), CRBS (Centre de Recherche en Biomédecine de Strasbourg), FMTS (Fédération de Médecine Translationnelle de Strasbourg), University of Strasbourg, Strasbourg, France.,Faculté de Pharmacie, Université de Strasbourg, Strasbourg, France
| | - Ferhat Meziani
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), CRBS (Centre de Recherche en Biomédecine de Strasbourg), FMTS (Fédération de Médecine Translationnelle de Strasbourg), University of Strasbourg, Strasbourg, France. .,Department of Intensive Care (Service de Médecine Intensive-Réanimation), Nouvel Hôpital Civil, Hôpital Universitaire de Strasbourg, 1, place de l'Hôpital, 67091, Strasbourg Cedex, France.
| | - Florence Toti
- INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), CRBS (Centre de Recherche en Biomédecine de Strasbourg), FMTS (Fédération de Médecine Translationnelle de Strasbourg), University of Strasbourg, Strasbourg, France.,Faculté de Pharmacie, Université de Strasbourg, Strasbourg, France
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42
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NEUT-SFL in Patients with COVID-ARDS: A Novel Biomarker for Thrombotic Events? DISEASE MARKERS 2021; 2021:4361844. [PMID: 34840629 PMCID: PMC8612800 DOI: 10.1155/2021/4361844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 09/24/2021] [Accepted: 10/23/2021] [Indexed: 11/25/2022]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA virus first identified in December 2019 in Wuhan, China, and responsible for coronavirus disease 2019 (COVID-19). The ongoing COVID-19 pandemic is impacting healthcare worldwide. Patients who develop coagulopathy have worse outcomes. The pathophysiology of COVID-19 suggests a strong interplay between hemostasis and immune cells, especially neutrophils. Our purpose was to assess neutrophil fluorescence as a potential biomarker of deep vein thrombosis (DVT) in patients with COVID-acute respiratory distress syndrome (COVID-ARDS). Sixty-one patients with COVID-ARDS admitted to the four intensive care units (ICUs) of a French general hospital were included in this prospective study. Neutrophil activation was assessed by measuring neutrophil fluorescence (NEUT-Side Fluorescence Light, NEUT-SFL) with a specific fluorescent dye staining analyzed by a routine automated flow cytometer Sysmex XN-3000™ (Sysmex, Kobe, Japan). DVT was diagnosed by complete duplex ultrasound (CDU). We found that NEUT-SFL was elevated on admission in patients with COVID-ARDS (49.76 AU, reference value 46.40 AU, p < 0.001), but did not differ between patients with DVT (49.99 AU) and those without (49.52 AU, p = 0.555). NEUT-SFL is elevated in patients with COVID-ARDS, reflecting neutrophil activation, but cannot be used as a marker of thrombosis. Because neutrophils are at interface between immune response and hemostasis through release of neutrophil extracellular traps, monitoring their activation could be an interesting approach to improve our management of coagulopathy during COVID-ARDS. Further research is needed to better understand the pathophysiology of COVID-19 and identify high-performance biomarkers.
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43
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Lonomia obliqua Envenoming and Innovative Research. Toxins (Basel) 2021; 13:toxins13120832. [PMID: 34941670 PMCID: PMC8706654 DOI: 10.3390/toxins13120832] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 11/08/2021] [Accepted: 11/09/2021] [Indexed: 01/21/2023] Open
Abstract
As a tribute to Butantan Institute in its 120th anniversary, this review describes some of the scientific research efforts carried out in the study of Lonomia envenoming in Brazil, a country where accidents with caterpillars reach over 42,000 individuals per year (especially in South and Southeast Brazil). Thus, the promising data regarding the studies with Lonomia’s toxins contributed to the creation of new research centers specialized in toxinology based at Butantan Institute, as well as to the production of the antilonomic serum (ALS), actions which are in line with the Butantan Institute mission “to research, develop, manufacture, and provide products and services for the health of the population”. In addition, the study of the components of the Lonomia obliqua bristle extract led to the discovery of new molecules with peculiar properties, opening a field of knowledge that could lead to the development and innovation of new drugs aimed at cell regeneration and inflammatory diseases.
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44
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The versatile role of the contact system in cardiovascular disease, inflammation, sepsis and cancer. Biomed Pharmacother 2021; 145:112429. [PMID: 34801854 DOI: 10.1016/j.biopha.2021.112429] [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: 10/15/2021] [Revised: 11/09/2021] [Accepted: 11/12/2021] [Indexed: 11/24/2022] Open
Abstract
The human contact system consists of plasma proteins, which - after contact to foreign surfaces - are bound to them, thereby activating the zymogens of the system into enzymes. This activation mechanism gave the system its name - contact system. It is considered as a procoagulant and proinflammatory response mechanism, as activation finally leads to the generation of fibrin and bradykinin. To date, no physiological processes have been described that are mediated by contact activation. However, contact system factors play a pathophysiological role in numerous diseases, such as cardiovascular diseases, arthritis, colitis, sepsis, and cancer. Contact system factors are therefore an interesting target for new therapeutic options in different clinical conditions.
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45
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Mao JY, Zhang JH, Cheng W, Chen JW, Cui N. Effects of Neutrophil Extracellular Traps in Patients With Septic Coagulopathy and Their Interaction With Autophagy. Front Immunol 2021; 12:757041. [PMID: 34707618 PMCID: PMC8542927 DOI: 10.3389/fimmu.2021.757041] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 09/21/2021] [Indexed: 12/01/2022] Open
Abstract
Introduction Neutrophil extracellular traps (NETs) act as a critical trigger of inflammation and coagulation. We hypothesized that NETs are associated with septic hypercoagulability. Materials and Methods In total, 82 patients admitted with sepsis in the Department of Critical Care Medicine of Peking Union Medical College Hospital were enrolled between February 2017 and April 2018. Clinical and hematological parameters and thrombotic or hemorrhagic events were recorded. Blood samples were obtained to assess biomarkers of NET formation, including neutrophil elastase 2 (ELA2) and citrullinated histone H3, and endothelial-derived biomarker syndecan-1. Autophagy levels and their regulation pathway were also examined to explore their interaction with NETs. Result Sepsis patients with disseminated intravascular coagulation (DIC) showed significantly higher levels of NET formation [ELA2, 1,247 (86–625) vs. 2,039 (1,544–2,534), p < 0.0001; H3, 140 (47–233) vs. 307 (199–415), p < 0.0001]. NET formation was independently associated with DIC risk [ELA2, OR 1.0028, 95% CI, 1.0010–1.0045; H3, OR 1.0104, 95% CI, 1.0032–1.0176] and mortality [ELA2, HR 1.0014, 95% CI, 1.0004–1.0024; H3, HR 1.0056, 95% CI, 1.0008–1.0115]. The area under the curve value for ELA2 in predicting DIC occurrence was 0.902 (95% CI, 0.816–0.957), and that of H3 was 0.870 (95% CI, 0.778–0.934). Furthermore, biomarkers of NET formation, endothelial cells, and autophagy exhibited a significant correlation [ELA2 and Syn (r = 0.5985, p < 0.0001), LC3B (r = −0.4224, p < 0.0001); H3 and Syn (r = 0.6383, p < 0.0001), LC3B (r = −0.3005, p = 0.0061)]. Conclusion Increased NET formation is significantly associated with sepsis-induced DIC incidence and mortality in sepsis patients, revealing a significant relationship with the autophagy pathway. Clinical Trial Registration chictr.org.cn, identifier ChiCTR-ROC-17010750.
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Affiliation(s)
- Jia-Yu Mao
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jia-Hui Zhang
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Wei Cheng
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jian-Wei Chen
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Na Cui
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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Cellular and molecular mechanisms in COVID-19 coagulopathy: role of inflammation and endotheliopathy. J Thromb Thrombolysis 2021; 53:282-290. [PMID: 34687400 PMCID: PMC8536904 DOI: 10.1007/s11239-021-02583-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/03/2021] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Coronavirus 2 (CoV-2) infection or coronavirus disease 2019 (COVID-19) is frequently associated with microvascular thrombosis.The microthrombosis in COVID-19 is the result of the interplay between inflammation and endotheliopathy. Elevated interleukin-6 (IL-6) characterizes COVID-19 inflammation resulting in endotheliopathy and coagulopathy marked by elevated D-dimer (DD). Aim of this study is to identify and to describe the coagulation changes in 100 moderate COVID-19 patients having lung involvement and to determine the association of coagulopathy with the severity and prognosis. METHODS Inflammation, endothelial and coagulation molecules were measured in moderate and mild disease. RESULTS IL-6 and tumor necrosis factor-α (TNF-α) and tissue factor (TF), von Willebrand factor (VWF), and tissue factor pathway inhibitor (TFPI) significantly increased in moderate disease as well as D-dimer, thrombin antithrombin complex (TAT), Fibrinogen (Fib), platelet factor-4 (PF4), β-thromboglobulin (β-TG), P-selectin, and platelet adhesion. Shortened clotting time (CT) and clot formation time (CFT), high maximum clot firmness (MCF) and low LY at 30 min were present in 100% of moderate COVID-19 patients compared with mild COVID-19 patients. CONCLUSIONS These findings demonstrate that moderate COVID-19 has a profound inflammation associated with severee ndotheliopathy and intense coagulation activation uncontrolled by TFPI. Attention should be paid to coagulopathy in COVID-19. Closely monitoring of coagulation and application of appropriate anticoagulation may improve the prognosis of moderate COVID-19 and to prevent the progression to severe COVID-19 disease.
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Makatsariya AD, Slukhanchuk EV, Bitsadze VO, Khizroeva JK, Tretyakova MV, Makatsariya NA, Akinshina SV, Shkoda AS, Pankratyeva LL, Di Renzo GC, Rizzo G, Grigorieva KN, Tsibizova VI, Gris JC, Elalamy I. Neutrophil extracellular traps: a role in inflammation and dysregulated hemostasis as well as in patients with COVID-19 and severe obstetric pathology. OBSTETRICS, GYNECOLOGY AND REPRODUCTION 2021; 15:335-350. [DOI: 10.17749/2313-7347/ob.gyn.rep.2021.238] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Numerous studies have proven a close relationship between inflammatory diseases and the state of hypercoagulability. In fact, thromboembolic complications represent one of the main causes of disability and mortality in acute and chronic inflammatory diseases, cancer and obstetric complications. Despite this, the processes of hemostasis and immune responses have long been considered separately; currently, work is underway to identify the molecular basis for a relationship between such systems. It has been identified that various pro-inflammatory stimuli are capable of triggering a coagulation cascade, which in turn modulates inflammatory responses. Neutrophil extracellular traps (NETs) are the networks of histones of extracellular DNA generated by neutrophils in response to inflammatory stimuli. The hemostasis is activated against infection in order to minimize the spread of infection and, if possible, inactivate the infectious agent. Another molecular network is based on fibrin. Over the last 10 years, there has been accumulated a whole body of evidence that NETs and fibrin are able to form a united network within a thrombus, stabilizing each other. Similarities and molecular cross-reactions are also present in the processes of fibrinolysis and lysis of NETs. Both NETs and von Willebrand factor (vWF) are involved in thrombosis as well as inflammation. During the development of these conditions, a series of events occurs in the microvascular network, including endothelial activation, NETs formation, vWF secretion, adhesion, aggregation, and activation of blood cells. The activity of vWF multimers is regulated by the specific metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Studies have shown that interactions between NETs and vWF can lead to arterial and venous thrombosis and inflammation. In addition, the contents released from activated neutrophils or NETs result in decreased ADAMTS-13 activity, which can occur in both thrombotic microangiopathies and acute ischemic stroke. Recently, NETs have been envisioned as a cause of endothelial damage and immunothrombosis in COVID-19. In addition, vWF and ADAMTS-13 levels predict COVID-19 mortality. In this review, we summarize the biological characteristics and interactions of NETs, vWF, and ADAMTS-13, the effect of NETs on hemostasis regulation and discuss their role in thrombotic conditions, sepsis, COVID-19, and obstetric complications.
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Affiliation(s)
| | | | | | | | | | | | | | - A. S. Shkoda
- Vorokhobov City Clinical Hospital № 67, Moscow Healthcare Department
| | - L. L. Pankratyeva
- Vorokhobov City Clinical Hospital № 67, Moscow Healthcare Department; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Health Ministry of Russian Federation
| | - G. C. Di Renzo
- Sechenov University; Center for Prenatal and Reproductive Medicine, University of Perugia
| | - G. Rizzo
- Sechenov University; University of Rome Tor Vergata
| | | | - V. I. Tsibizova
- Almazov National Medical Research Centre, Health Ministry of Russian Federation
| | - J.-C. Gris
- Sechenov University; University of Montpellier
| | - I. Elalamy
- Sechenov University; Medicine Sorbonne University; Hospital Tenon
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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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Coagulopathy in Acute Puumala Hantavirus Infection. Viruses 2021; 13:v13081553. [PMID: 34452419 PMCID: PMC8402851 DOI: 10.3390/v13081553] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/27/2021] [Accepted: 08/02/2021] [Indexed: 12/26/2022] Open
Abstract
Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS), also called nephropathia epidemica (NE), which is mainly endemic in Europe and Russia. The clinical features include a low platelet count, altered coagulation, endothelial activation, and acute kidney injury (AKI). Multiple connections between coagulation pathways and inflammatory mediators, as well as complement and kallikrein–kinin systems, have been reported. The bleeding symptoms are usually mild. PUUV-infected patients also have an increased risk for disseminated intravascular coagulation (DIC) and thrombosis.
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50
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Che Mohd Nassir CMN, Hashim S, Wong KK, Abdul Halim S, Idris NS, Jayabalan N, Guo D, Mustapha M. COVID-19 Infection and Circulating Microparticles-Reviewing Evidence as Microthrombogenic Risk Factor for Cerebral Small Vessel Disease. Mol Neurobiol 2021; 58:4188-4215. [PMID: 34176095 PMCID: PMC8235918 DOI: 10.1007/s12035-021-02457-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 06/16/2021] [Indexed: 02/08/2023]
Abstract
Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) due to novel coronavirus disease 2019 (COVID-19) has affected the global society in numerous unprecedented ways, with considerable morbidity and mortality. Both direct and indirect consequences from COVID-19 infection are recognized to give rise to cardio- and cerebrovascular complications. Despite current limited knowledge on COVID-19 pathogenesis, inflammation, endothelial dysfunction, and coagulopathy appear to play critical roles in COVID-19-associated cerebrovascular disease (CVD). One of the major subtypes of CVD is cerebral small vessel disease (CSVD) which represents a spectrum of pathological processes of various etiologies affecting the brain microcirculation that can trigger subsequent neuroinflammation and neurodegeneration. Prevalent with aging, CSVD is a recognized risk factor for stroke, vascular dementia, and Alzheimer's disease. In the background of COVID-19 infection, the heightened cellular activations from inflammations and oxidative stress may result in elevated levels of microthrombogenic extracellular-derived circulating microparticles (MPs). Consequently, MPs could act as pro-coagulant risk factor that may serve as microthrombi for the vulnerable microcirculation in the brain leading to CSVD manifestations. This review aims to appraise the accumulating body of evidence on the plausible impact of COVID-19 infection on the formation of microthrombogenic MPs that could lead to microthrombosis in CSVD manifestations, including occult CSVD which may last well beyond the pandemic era.
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Affiliation(s)
- Che Mohd Nasril Che Mohd Nassir
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Sabarisah Hashim
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
- Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Kah Keng Wong
- Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Sanihah Abdul Halim
- Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
- Department of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Nur Suhaila Idris
- Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
- Department of Family Medicine, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Nanthini Jayabalan
- Translational Neuroscience Lab, UQ Centre for Clinical Research, the University of Queensland, Herston, Brisbane, 4029, Australia
| | - Dazhi Guo
- Department of Hyperbaric Oxygen, The Sixth Medical Center of PLA General Hospital, 6 Fucheng Rd, Beijing, 100048, China
| | - Muzaimi Mustapha
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia.
- Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
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