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Bezati S, Ventoulis I, Verras C, Boultadakis A, Bistola V, Sbyrakis N, Fraidakis O, Papadamou G, Fyntanidou B, Parissis J, Polyzogopoulou E. Major Bleeding in the Emergency Department: A Practical Guide for Optimal Management. J Clin Med 2025; 14:784. [PMID: 39941455 PMCID: PMC11818891 DOI: 10.3390/jcm14030784] [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: 12/16/2024] [Revised: 01/15/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
Major bleeding is a life-threatening condition with high morbidity and mortality. Trauma, gastrointestinal bleeding, haemoptysis, intracranial haemorrhage or other causes of bleeding represent major concerns in the Emergency Department (ED), especially when complicated by haemodynamic instability. Severity and source of bleeding, comorbidities, and prior use of anticoagulants are pivotal factors affecting both the clinical status and the patients' differential response to haemorrhage. Thus, risk stratification is fundamental in the initial assessment of patients with bleeding. Aggressive resuscitation is the principal step for achieving haemodynamic stabilization of the patient, which will further allow appropriate interventions to be made for the definite control of bleeding. Overall management of major bleeding in the ED should follow a holistic individualized approach which includes haemodynamic stabilization, repletion of volume and blood loss, and reversal of coagulopathy and identification of the source of bleeding. The aim of the present practical guide is to provide an update on recent epidemiological data about the most common etiologies of bleeding and summarize the latest evidence regarding the bundles of care for the management of patients with major bleeding of traumatic or non-traumatic etiology in the ED.
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Affiliation(s)
- Sofia Bezati
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, 50200 Ptolemaida, Greece;
| | - Christos Verras
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
| | - Antonios Boultadakis
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
| | - Vasiliki Bistola
- Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Nikolaos Sbyrakis
- Department of Emergency Medicine, University Hospital of Heraklion, 71500 Crete, Greece;
| | - Othon Fraidakis
- Department of Emergency Medicine, Venizelion Hospital of Heraklion, 71409 Crete, Greece;
| | - Georgia Papadamou
- Department of Emergency Medicine, University Hospital of Larissa, 41334 Larissa, Greece;
| | - Barbara Fyntanidou
- Department of Emergency Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece;
| | - John Parissis
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
| | - Effie Polyzogopoulou
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (C.V.); (A.B.); (J.P.); (E.P.)
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Barrett L, Curry N. Transfusion in trauma: empiric or guided therapy? Res Pract Thromb Haemost 2025; 9:102663. [PMID: 39882556 PMCID: PMC11774821 DOI: 10.1016/j.rpth.2024.102663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 10/31/2024] [Accepted: 10/31/2024] [Indexed: 01/31/2025] Open
Abstract
A state of the art lecture titled "Transfusion therapy in trauma-what to give? Empiric vs guided" was presented at the International Society on Thrombosis and Haemostasis Congress in 2024. Uncontrolled bleeding is the commonest preventable cause of death after traumatic injury. Hemostatic resuscitation is the foundation of contemporary transfusion practice for traumatic bleeding and has 2 main aims: to immediately support the circulating blood volume and to treat/prevent the associated trauma-induced coagulopathy. There are 2 broad types of hemostatic resuscitation strategy: empiric ratio-based therapy, often using red blood cells and fresh frozen plasma in a 1:1 ratio, and targeted therapy where the use of platelets, plasma, or fibrinogen is guided by laboratory or viscoelastic hemostatic tests. There are benefits, and limitations, to each strategy and neither approach has yet been shown to improve outcomes across all patient groups. Questions remain, and future directions for improving transfusion therapy are likely to require novel approaches that have greater flexibility to evaluate and treat heterogeneous trauma cohorts. Such approaches may include the integration of machine learning technologies in clinical systems, with real-time linkage of clinical and laboratory data, to aid early recognition of patients at the greatest risk of bleeding and to direct and individualize transfusion therapies. Greater mechanistic understanding of the underlying pathobiology of trauma-induced coagulopathy and the direct effects of common treatments on this process will be of equal importance to the development of new treatments. Finally, we summarize relevant new data on this topic presented at the 2024 ISTH Congress.
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Affiliation(s)
- Liam Barrett
- Oxford Haemophilia and Thrombosis Centre, Department of Haematology, Oxford University Hospitals National Health Service Foundation Trust, Nuffield Orthopaedic Centre, Oxford, UK
- Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK
| | - Nicola Curry
- Oxford Haemophilia and Thrombosis Centre, Department of Haematology, Oxford University Hospitals National Health Service Foundation Trust, Nuffield Orthopaedic Centre, Oxford, UK
- Radcliffe Department of Medicine, Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK
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Jamali B, Nouri S, Amidi S. Local and Systemic Hemostatic Agents: A Comprehensive Review. Cureus 2024; 16:e72312. [PMID: 39583426 PMCID: PMC11585330 DOI: 10.7759/cureus.72312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/23/2024] [Indexed: 11/26/2024] Open
Abstract
Traumatic hemorrhage is the leading preventable cause of death worldwide. Systemic administration of hemostatic agents requires trained personnel and preparation, limiting their use in combat environments and prehospital settings. However, local administration of hemostatic agents may ameliorate these challenges. Currently available hemostatic products are limited by risk of infection, immunogenicity, tissue damage, limited usage and efficacy, high costs, short shelf life, and storage requirements under specific conditions. Future studies should be considered to overcome these limitations and develop effective, multifunctional hemostatic materials for widespread usage. In this review, we will provide an overview of the most commonly used systemic and local hemostatic agents in hemorrhage control.
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Affiliation(s)
- Bardia Jamali
- Research Center for Health Management in Mass Gathering, Red Crescent Society of the Islamic Republic of Iran, Tehran, IRN
- Research Center for Emergency and Disaster Resilience, Red Crescent Society of Islamic Republic of Iran, Tehran, IRN
| | - Saeed Nouri
- Research Center for Health Management in Mass Gathering, Red Crescent Society of the Islamic Republic of Iran, Tehran, IRN
- Research Center for Emergency and Disaster Resilience, Red Crescent Society of Islamic Republic of Iran, Tehran, IRN
| | - Salimeh Amidi
- Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IRN
- Research Center for Emergency and Disaster Resilience, Red Crescent Society of Islamic Republic of Iran, Tehran, IRN
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Zhang J, Jin Z, Tang B, Huang X, Wang Z, Chen Q, He J. Enhancing Trauma Care: A Machine Learning Approach with XGBoost for Predicting Urgent Hemorrhage Interventions Using NTDB Data. Bioengineering (Basel) 2024; 11:768. [PMID: 39199726 PMCID: PMC11352089 DOI: 10.3390/bioengineering11080768] [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: 07/02/2024] [Revised: 07/21/2024] [Accepted: 07/25/2024] [Indexed: 09/01/2024] Open
Abstract
OBJECTIVE Trauma is a leading cause of death worldwide, with many incidents resulting in hemorrhage before the patient reaches the hospital. Despite advances in trauma care, the majority of deaths occur within the first three hours of hospital admission, offering a very limited window for effective intervention. Unfortunately, a significant increase in mortality from hemorrhagic trauma is primarily due to delays in hemorrhage control. Therefore, we propose a machine learning model to predict the need for urgent hemorrhage intervention. METHODS This study developed and validated an XGBoost-based machine learning model using data from the National Trauma Data Bank (NTDB) from 2017 to 2019. It focuses on demographic and clinical data from the initial hours following trauma for model training and validation, aiming to predict whether trauma patients require urgent hemorrhage intervention. RESULTS The XGBoost model demonstrated superior performance across multiple datasets, achieving an AUROC of 0.872 on the training set, 0.869 on the internal validation set, and 0.875 on the external validation set. The model also showed high sensitivity (77.8% on the external validation set) and specificity (82.1% on the external validation set), with an accuracy exceeding 81% across all datasets, highlighting its high reliability for clinical applications. CONCLUSIONS Our study shows that the XGBoost model effectively predicts urgent hemorrhage interventions using data from the National Trauma Data Bank (NTDB). It outperforms other machine learning algorithms in accuracy and robustness across various datasets. These results highlight machine learning's potential to improve emergency responses and decision-making in trauma care.
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Affiliation(s)
- Jin Zhang
- School of Health Sciences and Engineering, University of Shanghai for Science and Technology, Shanghai 200000, China; (J.Z.); (X.H.); (Z.W.)
- Department of Health Statistics, Naval Medical University, Shanghai 200433, China;
| | - Zhichao Jin
- Department of Health Statistics, Naval Medical University, Shanghai 200433, China;
| | - Bihan Tang
- Department of Health Management, Naval Medical University, Shanghai 200433, China;
| | - Xiangtong Huang
- School of Health Sciences and Engineering, University of Shanghai for Science and Technology, Shanghai 200000, China; (J.Z.); (X.H.); (Z.W.)
- Department of Health Statistics, Naval Medical University, Shanghai 200433, China;
| | - Zongyu Wang
- School of Health Sciences and Engineering, University of Shanghai for Science and Technology, Shanghai 200000, China; (J.Z.); (X.H.); (Z.W.)
- Department of Health Statistics, Naval Medical University, Shanghai 200433, China;
| | - Qi Chen
- Department of Health Statistics, Naval Medical University, Shanghai 200433, China;
| | - Jia He
- School of Health Sciences and Engineering, University of Shanghai for Science and Technology, Shanghai 200000, China; (J.Z.); (X.H.); (Z.W.)
- Department of Health Statistics, Naval Medical University, Shanghai 200433, China;
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Wang XJ, Xuan XC, Sun ZC, Shen S, Yu F, Li NN, Chu XC, Yin H, Hu YL. Risk factors associated with intraoperative persistent hypotension in pancreaticoduodenectomy. World J Gastrointest Surg 2024; 16:1582-1591. [PMID: 38983354 PMCID: PMC11230017 DOI: 10.4240/wjgs.v16.i6.1582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 04/27/2024] [Accepted: 05/16/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Intraoperative persistent hypotension (IPH) during pancreaticoduodenectomy (PD) is linked to adverse postoperative outcomes, yet its risk factors remain unclear. AIM To clarify the risk factors associated with IPH during PD, ensuring patient safety in the perioperative period. METHODS A retrospective analysis of patient records from January 2018 to December 2022 at the First Affiliated Hospital of Nanjing Medical University identified factors associated with IPH in PD. These factors included age, gender, body mass index, American Society of Anesthesiologists classification, comorbidities, medication history, operation duration, fluid balance, blood loss, urine output, and blood gas parameters. IPH was defined as sustained mean arterial pressure < 65 mmHg, requiring prolonged deoxyepinephrine infusion for > 30 min despite additional deoxyepinephrine and fluid treatments. RESULTS Among 1596 PD patients, 661 (41.42%) experienced IPH. Multivariate logistic regression identified key risk factors: increased age [odds ratio (OR): 1.20 per decade, 95% confidence interval (CI): 1.08-1.33] (P < 0.001), longer surgery duration (OR: 1.15 per additional hour, 95%CI: 1.05-1.26) (P < 0.01), and greater blood loss (OR: 1.18 per 250-mL increment, 95%CI: 1.06-1.32) (P < 0.01). A novel finding was the association of arterial blood Ca2+ < 1.05 mmol/L with IPH (OR: 2.03, 95%CI: 1.65-2.50) (P < 0.001). CONCLUSION IPH during PD is independently associated with older age, prolonged surgery, increased blood loss, and lower plasma Ca2+.
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Affiliation(s)
- Xing-Jun Wang
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Xi-Chen Xuan
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Zhao-Chu Sun
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Shi Shen
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Fan Yu
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Na-Na Li
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Xue-Chun Chu
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Hui Yin
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - You-Li Hu
- Department of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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Peng HT, Singh K, Rhind SG, da Luz L, Beckett A. Dried Plasma for Major Trauma: Past, Present, and Future. Life (Basel) 2024; 14:619. [PMID: 38792640 PMCID: PMC11122082 DOI: 10.3390/life14050619] [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: 02/29/2024] [Revised: 04/26/2024] [Accepted: 05/08/2024] [Indexed: 05/26/2024] Open
Abstract
Uncontrollable bleeding is recognized as the leading cause of preventable death among trauma patients. Early transfusion of blood products, especially plasma replacing crystalloid and colloid solutions, has been shown to increase survival of severely injured patients. However, the requirements for cold storage and thawing processes prior to transfusion present significant logistical challenges in prehospital and remote areas, resulting in a considerable delay in receiving thawed or liquid plasma, even in hospitals. In contrast, freeze- or spray-dried plasma, which can be massively produced, stockpiled, and stored at room temperature, is easily carried and can be reconstituted for transfusion in minutes, provides a promising alternative. Drawn from history, this paper provides a review of different forms of dried plasma with a focus on in vitro characterization of hemostatic properties, to assess the effects of the drying process, storage conditions in dry form and after reconstitution, their distinct safety and/or efficacy profiles currently in different phases of development, and to discuss the current expectations of these products in the context of recent preclinical and clinical trials. Future research directions are presented as well.
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Affiliation(s)
- Henry T. Peng
- Defence Research and Development Canada, Toronto Research Centre, Toronto, ON M3K 2C9, Canada; (K.S.); (S.G.R.)
| | - Kanwal Singh
- Defence Research and Development Canada, Toronto Research Centre, Toronto, ON M3K 2C9, Canada; (K.S.); (S.G.R.)
| | - Shawn G. Rhind
- Defence Research and Development Canada, Toronto Research Centre, Toronto, ON M3K 2C9, Canada; (K.S.); (S.G.R.)
| | - Luis da Luz
- Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada;
| | - Andrew Beckett
- St. Michael’s Hospital, University of Toronto, Toronto, ON M5B 1W8, Canada;
- Royal Canadian Medical Services, Ottawa, ON K1A 0K2, Canada
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Jehan F, Zangbar B, Rafieezadeh A, Shnaydman I, Klein J, Con J, Prabhakaran K. Is there a need for fresh frozen plasma and platelet transfusion in trauma patients receiving submassive transfusion? Trauma Surg Acute Care Open 2024; 9:e001310. [PMID: 38737815 PMCID: PMC11086383 DOI: 10.1136/tsaco-2023-001310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 04/09/2024] [Indexed: 05/14/2024] Open
Abstract
Background Blood transfusions have become a vital intervention in trauma care. There are limited data on the safety and effectiveness of submassive transfusion (SMT), that is defined as receiving less than 10 units packed red blood cells (PRBCs) in the first 24 hours. This study aimed to evaluate the efficacy and safety of fresh frozen plasma (FFP) and platelet transfusions in patients undergoing SMT. Methods This is a retrospective cohort, reviewing the Trauma Quality Improvement Program database spanning 3 years (2016 to 2018). Adult patients aged 18 years and older who had received at least 1 unit of PRBC within 24 hours were included in the study. We used a multivariate regression model to analyze the cut-off units of combined resuscitation (CR) (which included PRBCs along with at least one unit of FFP and/or platelets) that leads to survival improvement. Patients were then stratified into two groups: those who received PRBC alone and those who received CR. Propensity score matching was performed in a 1:1 ratio. Results The study included 85 234 patients. Based on the multivariate regression model, transfusion of more than 3 units of PRBC with at least 1 unit of FFP and/or platelets demonstrated improved mortality compared with PRBC alone. Among 66 319 patients requiring SMT and >3 units of PRBCs, 25 978 received PRBC alone, and 40 341 received CR. After propensity matching, 4215 patients were included in each group. Patients administered CR had a lower rate of complications (15% vs 26%), acute respiratory distress syndrome (3% vs 5%) and acute kidney injury (8% vs 11%). Rates of sepsis and venous thromboembolism were similar between the two groups. Multivariate regression analysis indicated that patients receiving 4 to 7 units of PRBC alone had significantly higher ORs for mortality than those receiving CR. Conclusion Trauma patients requiring more than 3 units of PRBCs who received CR with FFP and platelets experienced improved survival and reduced complications. Level of evidence Level III retrospective study.
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Affiliation(s)
- Faisal Jehan
- Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Bardiya Zangbar
- Surgery, Westchester Medical Center, Valhalla, New York, USA
| | | | - Ilya Shnaydman
- Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Joshua Klein
- Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Jorge Con
- Surgery, Westchester Medical Center, Valhalla, New York, USA
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Saviano A, Perotti C, Zanza C, Longhitano Y, Ojetti V, Franceschi F, Bellou A, Piccioni A, Jannelli E, Ceresa IF, Savioli G. Blood Transfusion for Major Trauma in Emergency Department. Diagnostics (Basel) 2024; 14:708. [PMID: 38611621 PMCID: PMC11011783 DOI: 10.3390/diagnostics14070708] [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: 02/08/2024] [Revised: 03/23/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
Severe bleeding is the leading cause of death in patients with major trauma admitted to the emergency department. It is estimated that about 50% of deaths happen within a few minutes of the traumatic event due to massive hemorrhage; 30% of deaths are related to neurological dysfunction and typically happen within two days of trauma; and approximately 20% of patients died of multiorgan failure and sepsis within days to weeks of the traumatic event. Over the past ten years, there has been an increased understanding of the underlying mechanisms and pathophysiology associated with traumatic bleeding leading to improved management measures. Traumatic events cause significant tissue damage, with the potential for severe blood loss and the release of cytokines and hormones. They are responsible for systemic inflammation, activation of fibrinolysis pathways, and consumption of coagulation factors. As the final results of this (more complex in real life) cascade, patients can develop tissue hypoxia, acidosis, hypothermia, and severe coagulopathy, resulting in a rapid deterioration of general conditions with a high risk of mortality. Prompt and appropriate management of massive bleeding and coagulopathy in patients with trauma remains a significant challenge for emergency physicians in their daily clinical practice. Our review aims to explore literature studies providing evidence on the treatment of hemorrhage with blood support in patients with trauma admitted to the Emergency Department with a high risk of death. Advances in blood transfusion protocols, along with improvements in other resuscitation strategies, have become one of the most important issues to face and a key topic of recent clinical research in this field.
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Affiliation(s)
- Angela Saviano
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (A.S.); (F.F.)
| | - Cesare Perotti
- Division of Immunohaematology and Transfusion, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Christian Zanza
- Geriatric Medicine Residency Program, University of Rome “Tor Vergata”, 00133 Rome, Italy;
| | - Yaroslava Longhitano
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA;
- Department of Emergency Medicine-Emergency Medicine Residency Program, Humanitas University-Research Hospital, 20089 Rozzano, Italy
| | | | - Francesco Franceschi
- Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; (A.S.); (F.F.)
- Università Cattolica, 00168 Roma, Italy; (V.O.); (A.P.)
| | - Abdelouahab Bellou
- Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA;
- Institute of Sciences in Emergency Medicine, Department of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China
| | | | - Eugenio Jannelli
- Department of Orthopedics and Traumatology, Fondazione Policlinico San Matteo, 27100 Pavia, Italy;
| | | | - Gabriele Savioli
- Department of Emergency Medicine, Fondazione Policlinico San Matteo, 27100 Pavia, Italy
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Wang J, Chen J, Liu K, Zhang H, Wei Y, Suo L, Lan S, Wang Y, Luo C, Yao L. Anesthetic managements, morbidities and mortalities in retroperitoneal sarcoma patients experiencing perioperative massive blood transfusion. Front Oncol 2024; 14:1347248. [PMID: 38505594 PMCID: PMC10948446 DOI: 10.3389/fonc.2024.1347248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 02/19/2024] [Indexed: 03/21/2024] Open
Abstract
Objective Given high risks of major bleeding during retroperitoneal sarcoma(RPS) surgeries, severe complications and deaths are common to see perioperatively. Thus, effective anesthetic management is the key point to ensuring the safety of patients. This study aimed to introduce anesthesia management and mortalities in RPS patients receiving massive blood transfusions during surgeries. Methods Records of RPS surgeries under general anesthesia from January 2016 through December 2021 were retrospectively retrieved from our database. Patients who received massive blood transfusions (MBT) exceeding 20 units in 24h duration of operations were finally included in this study. Demographics, modalities of anesthesia management, blood loss, transfusion, peri-anesthesia biochemical tests as well as morbidities and mortalities were collected. Risk factors of postoperative 60d mortality were determined through logistic regression in uni-and multi-variety analysis using the statistics software STATA 17.0. Results A total of 70 patients (male 31) were included. The mean age was 50.1 ± 15.8 years. All patients received combined resections of sarcoma with involved organs under general anesthesia. Mean operation time and anesthesia time were 491.7 ± 131.1mins and 553.9 ± 132.6mins, respectively. The median intraoperative blood loss was 7000ml (IQR 5500,10000ml). Median red blood cells (RBC) and fresh frozen plasma (FFP) transfusion were 25.3u (IQR 20,28u), and 2400ml (IQR 2000,3000ml), respectively. Other blood products infusions included prothrombin complex concentrate (PCCs), fibrinogen concentrate (FC), platelet(plt) and albumin(alb) in 82.9% (58/70), 88.6% (62/70), 81.4% (57/70) and 12.9% (9/70) of patients. The postoperative severe complication rate(Clavien-Dindo grade≥3a) was 35.7%(25/70). A total of 7 patients (10%) died during the postoperative 60-day period. BMI, volumes of crystalloid infusion in anesthesia, and hemoglobin and lactate levels at the termination of operation were found significantly associated with postoperative occurrence of death in univariate analysis. In logistic multivariate analysis, extended anesthesia duration was found associated with postoperative venous thrombosis embolism (VTE) and severe complication. The lactate level at the immediate termination of the operation was the only risk factor related to perioperative death (p<0.05). Conclusion RPS patients who endure MBT in surgeries face higher risks of death postoperatively, which needs precise and effective anesthesia management in high-volume RPS centers. Increased blood lactate levels might be predictors of postoperative deaths which should be noted.
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Affiliation(s)
- Jun Wang
- Department of Anesthesiology, Peking University International Hospital, Beijing, China
| | - Jun Chen
- Department of Retroperitoneal Tumor Surgery, Peking University International Hospital, Beijing, China
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Kunpeng Liu
- Department of Anesthesiology, Peking University International Hospital, Beijing, China
| | - Hua Zhang
- The Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, China
| | - Yue Wei
- Department of Anesthesiology, Peking University International Hospital, Beijing, China
| | - Libin Suo
- Department of Anesthesiology, Peking University International Hospital, Beijing, China
| | - Shuang Lan
- Department of Anesthesiology, Peking University International Hospital, Beijing, China
| | - Yanzhen Wang
- Department of Anesthesiology, Peking University International Hospital, Beijing, China
| | - Chenghua Luo
- Department of Retroperitoneal Tumor Surgery, Peking University International Hospital, Beijing, China
- Department of Retroperitoneal Tumor Surgery, Peking University People’s Hospital, Beijing, China
| | - Lan Yao
- Department of Anesthesiology, Peking University International Hospital, Beijing, China
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Yu L, Yang D, Chu M, Sun Y. Advances and challenges in the purification of recombinant coagulation factors: A review. J Chromatogr A 2024; 1716:464662. [PMID: 38244305 DOI: 10.1016/j.chroma.2024.464662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 01/12/2024] [Accepted: 01/14/2024] [Indexed: 01/22/2024]
Abstract
Hemostasis is a complex process for the cessation of bleeding from an injured blood vessel, involving the interplay of 12 coagulation factors in the coagulation cascade with activated blood platelets and the vessel wall. Hence, the coagulation factors are important to control hemorrhage. However, the low abundance of many coagulation factors in human plasma proteins limited their production in therapeutic drugs and their clinical applications. With the development of modern biotechnology, commercially manufactured recombinant coagulation factors became available as hemostatic therapeutics, emerging a huge potential in pharmaceutical manufacturing market. Unlike antibodies, whose standard operation unit or platform purification processes in the industrial-scale downstream processing has been well-established, the complexity in post-translational modification and differences in structures of the coagulation factors posed specific challenges with respect to the downstream processing, which have long been limiting their industrial-scale production. This review presents a comprehensive overview of the technological development of commercially manufactured recombinant coagulation factors, with emphasis on their advances and challenges in the separation and purification processes. Firstly, the licensed products of the plasma derived and recombinant coagulation factors are summarized. Then, typical recombinant coagulation factors, i.e. factors VII, VIII and IX, are introduced with detailed discussion on their preparative separation procedures for both the licensed products of industrial-scale and the experimental cases of laboratory-scale. Finally, perspectives and challenges in the future development of the purification technology of recombinant coagulation factors are highlighted to provide new insight into the design of cost-effective purification processes of recombinant coagulation factors.
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Affiliation(s)
- Linling Yu
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Dongmei Yang
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Mengyao Chu
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Yan Sun
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.
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11
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Romanelli A, Gammaldi R, Calicchio A, Palmese S, Siglioccolo A. Relationship between sonorheometry parameters and laboratory values in a critical care setting in Italy: a retrospective cohort study. JOURNAL OF TRAUMA AND INJURY 2023; 36:210-216. [PMID: 39381701 PMCID: PMC11309283 DOI: 10.20408/jti.2023.0014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 04/21/2023] [Indexed: 10/10/2024] Open
Abstract
Purpose This preliminary retrospective cohort study analyzed the relationship between the parameters provided by sonorheometry device Quantra and the coagulation values obtained from standard venous blood samples in patients admitted in intensive care unit (ICU). Methods We reviewed medical charts of 13 ICU adult patients in whom at least one coagulation study with Quantra was performed. The relationship between Quantra and laboratory data was analyzed with the Spearman rank correlation coefficient (rho). The 95% confidence interval (CI) was computed. A P-value <0.05 was considered statistically significant. Results We collected 28 data pairs. Statistically significant moderate correlations were found for the following parameters: clot time (CT) and activated partial thromboplastin time (rho=0.516; 95% CI, 0.123-0.904; P=0.009; clot stiffness (CS) and the international normalized ratio (INR; rho=0.418; 95% CI, 0.042-0.787; P=0.039); INR and platelet contribution to CS (rho=0.459; 95% CI, 0.077-0.836; P=0.022); platelet count and platelet contribution to CS (PCS; rho=0.498; 95% CI, 0.166-0.825; P=0.008); and fibrinogen and fibrinogen contribution to CS (FCS; rho=0.620; 95% CI, 0.081-0.881; P=0.001). Conclusions Quantra can provide useful information regarding coagulation status, showing modest correlations with the parameters obtained from laboratory tests. During diffuse bleeding, CT and FCS values can guide the proper administration of clotting factors and fibrinogens. However, the correlation of INR with CS and PCS can cause misinterpretation. Further studies are needed to clarify the relationship between Quantra parameters and laboratory tests in the critical care setting and the role of sonorheometry in guiding targeted therapies and improving outcomes.
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Affiliation(s)
- Antonio Romanelli
- Department of Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria San Giovanni di Dio Ruggi d’Aragona, Salerno, Italy
| | - Renato Gammaldi
- Department of Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria San Giovanni di Dio Ruggi d’Aragona, Salerno, Italy
| | - Alessandro Calicchio
- Department of Anesthesia and Intensive Care, University of Naples Federico II, Naples, Italy
| | - Salvatore Palmese
- Department of Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria San Giovanni di Dio Ruggi d’Aragona, Salerno, Italy
| | - Antonio Siglioccolo
- Department of Anesthesia and Intensive Care Unit, Azienda Ospedaliero Universitaria San Giovanni di Dio Ruggi d’Aragona, Salerno, Italy
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12
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de Lloyd L, Jenkins PV, Bell SF, Mutch NJ, Martins Pereira JF, Badenes PM, James D, Ridgeway A, Cohen L, Roberts T, Field V, Collis RE, Collins PW. Acute obstetric coagulopathy during postpartum hemorrhage is caused by hyperfibrinolysis and dysfibrinogenemia: an observational cohort study. J Thromb Haemost 2023; 21:862-879. [PMID: 36696216 DOI: 10.1016/j.jtha.2022.11.036] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 10/21/2022] [Accepted: 11/13/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND Postpartum hemorrhage (PPH) may be exacerbated by hemostatic impairment. Information about PPH-associated coagulopathy is limited, often resulting in treatment strategies based on data derived from trauma studies. OBJECTIVES To investigate hemostatic changes associated with PPH. PATIENTS/METHODS From a population of 11 279 maternities, 518 (4.6%) women were recruited with PPH ≥ 1000 mL or placental abruption, amniotic fluid embolism, or concealed bleeding. Routine coagulation and viscoelastometric results were collated. Stored plasma samples were used to investigate women with bleeds > 2000 mL or those at increased risk of coagulopathy defined as placenta abruption, amniotic fluid embolism, or need for blood components. Procoagulant factors were assayed and global hemostasis was assessed using thrombin generation. Fibrinolysis was investigated with D-dimer and plasmin/antiplasmin complexes. Dysfibrinogenemia was assessed using the Clauss/antigen ratio. RESULTS At 1000 mL blood loss, Clauss fibrinogen was ≤2 g/L in 2.4% of women and 6/27 (22.2%) cases of abruption. Women with very large bleeds (>3000 mL) had evidence of a dilutional coagulopathy, although hemostatic impairment was uncommon. A subgroup of 12 women (1.06/1000 maternities) had a distinct coagulopathy characterized by massive fibrinolysis (plasmin/antiplasmin > 40 000 ng/mL), increased D-dimer, hypofibrinogenemia, dysfibrinogenemia, reduced factor V and factor VIII, and increased activated protein C, termed acute obstetric coagulopathy. It was associated with fetal or neonatal death in 50% of cases and increased maternal morbidity. CONCLUSIONS Clinically significant hemostatic impairment is uncommon during PPH, but a subgroup of women have a distinct and severe coagulopathy characterized by hyperfibrinolysis, low fibrinogen, and dysfibrinogenemia associated with poor fetal outcomes.
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Affiliation(s)
- Lucy de Lloyd
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Peter V Jenkins
- Department of Haematology, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK; Institute of Infection and Immunity, School of Medicine, Cardiff University, UK
| | - Sarah F Bell
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Nicola J Mutch
- Aberdeen Cardiovascular and Diabetes Centre, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, UK
| | | | | | - Donna James
- Department of Obstetrics and Gynaecology, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Anouk Ridgeway
- Department of Obstetrics and Gynaecology, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Leon Cohen
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Thomas Roberts
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Victoria Field
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Rachel E Collis
- Department of Anaesthetics and Pain Control, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK
| | - Peter W Collins
- Department of Haematology, Cardiff and Vale University Health Board, Heath Park, Cardiff, UK; Institute of Infection and Immunity, School of Medicine, Cardiff University, UK.
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13
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Volod O, Bunch CM, Miller J, Moore EE, Moore HB, Kwaan HC, Patel SS, Wiarda G, Aboukhaled M, Thomas SG, Fulkerson D, Erdman L, Tincher A, Walsh MM. Reply to Bareille et al. Are Viscoelastometric Assays of Old Generation Ready for Disposal? Comment on "Volod et al. Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices. J. Clin. Med. 2022, 11, 860". J Clin Med 2023; 12:jcm12020478. [PMID: 36675408 PMCID: PMC9862366 DOI: 10.3390/jcm12020478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 12/16/2022] [Accepted: 12/27/2022] [Indexed: 01/11/2023] Open
Abstract
We are pleased to see that Bareille et al. have written a Commentary: "Are viscoelastometric assays of old generation ready for disposal?" [...].
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Affiliation(s)
- Oksana Volod
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Correspondence:
| | - Connor M. Bunch
- Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48402, USA
- Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Joseph Miller
- Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48402, USA
| | - Ernest E. Moore
- Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health, University of Colorado Health Sciences Center, Denver, CO 80204, USA
| | - Hunter B. Moore
- Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health, University of Colorado Health Sciences Center, Denver, CO 80204, USA
| | - Hau C. Kwaan
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Shivani S. Patel
- Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Grant Wiarda
- Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Michael Aboukhaled
- Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Scott G. Thomas
- Department of Trauma Surgery, Memorial Leighton Trauma Center, Beacon Health System, South Bend, IN 46601, USA
| | - Daniel Fulkerson
- Department of Trauma Surgery, Memorial Leighton Trauma Center, Beacon Health System, South Bend, IN 46601, USA
| | - Lee Erdman
- Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Anna Tincher
- Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Mark M. Walsh
- Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
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14
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Shah A, Kerner V, Stanworth SJ, Agarwal S. Major haemorrhage: past, present and future. Anaesthesia 2023; 78:93-104. [PMID: 36089857 PMCID: PMC10087440 DOI: 10.1111/anae.15866] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/29/2022] [Indexed: 12/15/2022]
Abstract
Major haemorrhage is a leading cause of morbidity and mortality worldwide. Successful treatment requires early recognition, planned responses, readily available resources (such as blood products) and rapid access to surgery or interventional radiology. Major haemorrhage is often accompanied by volume loss, haemodilution, acidaemia, hypothermia and coagulopathy (factor consumption and fibrinolysis). Management of major haemorrhage over the past decade has evolved to now deliver a 'package' of haemostatic resuscitation including: surgical or radiological control of bleeding; regular monitoring of haemostasis; advanced critical care support; and avoidance of the lethal triad of hypothermia, acidaemia and coagulopathy. Recent trial data advocate for a more personalised approach depending on the clinical scenario. Fresh frozen plasma should be given as early as possible in major trauma in a 1:1 ratio with red blood cells until the results of coagulation tests are available. Tranexamic acid is a cheap, life-saving drug and is advocated in major trauma, postpartum haemorrhage and surgery, but not in patients with gastrointestinal bleeding. Fibrinogen levels should be maintained > 2 g.l-1 in postpartum haemorrhage and > 1.5 g.l-1 in other haemorrhage. Improving outcomes after major traumatic haemorrhage is now driving research to include extending blood-product resuscitation into prehospital care.
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Affiliation(s)
- A. Shah
- Nuffield Department of Clinical NeurosciencesUniversity of OxfordUK
| | - V. Kerner
- Nuffield Department of AnaesthesiaOxford University Hospitals NHS Foundation TrustOxfordUK
| | | | - S. Agarwal
- Department of AnaesthesiaManchester University NHS Foundation TrustManchesterUK
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15
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Abstract
Platelet transfusions are commonly administered for the prevention or treatment of bleeding in patients with acquired thrombocytopenia across a range of clinical contexts. Recent data, including randomized trials, have highlighted uncertainties in the risk-benefit balance of this therapy, which is the subject of this review. Hemovigilance systems report that platelets are the most frequently implicated component in transfusion reactions. There is considerable variation in platelet count increment after platelet transfusion, and limited evidence of efficacy for clinical outcomes, including prevention of bleeding. Bleeding events commonly occur despite the different policies for platelet transfusion prophylaxis. The underlying mechanisms of harm reported in randomized trials may be related to the role of platelets beyond hemostasis, including mediating inflammation. Research supports the implementation of a restrictive platelet transfusion policy. Research is needed to better understand the impact of platelet donation characteristics on outcomes, and to determine the optimal thresholds for platelet transfusion before invasive procedures or major surgery (eg, laparotomy). Platelet transfusion policies should move toward a risk-adapted approach that does not focus solely on platelet count.
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16
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Bunch CM, Berquist M, Ansari A, McCoy ML, Langford JH, Brenner TJ, Aboukhaled M, Thomas SJ, Peck E, Patel S, Cancel E, Al-Fadhl MD, Zackariya N, Thomas AV, Aversa JG, Greene RB, Seder CW, Speybroeck J, Miller JB, Kwaan HC, Walsh MM. The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition. Semin Thromb Hemost 2022; 48:769-784. [PMID: 36174601 DOI: 10.1055/s-0042-1756302] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.
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Affiliation(s)
- Connor M Bunch
- Department of Emergency Medicine, Henry Ford Hospital, Detroit, Michigan
| | - Margaret Berquist
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Aida Ansari
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Max L McCoy
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Jack H Langford
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Toby J Brenner
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Michael Aboukhaled
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Samuel J Thomas
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Ethan Peck
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Shivani Patel
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Emily Cancel
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
| | - Mahmoud D Al-Fadhl
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Nuha Zackariya
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - Anthony V Thomas
- Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
| | - John G Aversa
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | - Ryan B Greene
- Department of Interventional Radiology, St. Joseph Regional Medical Center, Mishawaka, Indiana
| | - Christopher W Seder
- Department of Cardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, Illinois
| | - Jacob Speybroeck
- Department of Orthopedic Surgery, Case Western Medical Center, Cleveland, Ohio
| | - Joseph B Miller
- Department of Emergency Medicine, Henry Ford Hospital, Detroit, Michigan
| | - Hau C Kwaan
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Mark M Walsh
- Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana.,Indiana University School of Medicine, Notre Dame Campus, South Bend, Indiana
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17
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Utility of viscoelastic hemostatic assay to guide hemostatic resuscitation in trauma patients: a systematic review. World J Emerg Surg 2022; 17:48. [PMID: 36100918 PMCID: PMC9472418 DOI: 10.1186/s13017-022-00454-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 09/05/2022] [Indexed: 11/15/2022] Open
Abstract
Objective Viscoelastic hemostatic assay (VHA) provides a graphical representation of a clot’s lifespan and reflects the real time of coagulation. It has been used to guide trauma resuscitation; however, evidence of the effectiveness of VHAs is still limited. This systematic review aims to summarize the published evidence to evaluate the VHA-guided strategy in resuscitating trauma patients. Methods The PubMed, Embase, and Web of Science databases were searched from their inception to December 13, 2021. Randomized controlled trials (RCTs) or observational studies comparing VHA-guided transfusion to controls in resuscitating trauma patients were included in this systematic review. Results Of the 7743 records screened, ten studies, including two RCTs and eight observational studies, met the inclusion criteria. There was great heterogeneity concerning study design, enrollment criterion, VHA device, VHA-guided strategy, and control strategy. Thrombelastography (TEG) was used as a guiding tool for transfusion in eight studies, and rotational thromboelastometry (ROTEM), and TEG or ROTEM were used in the other two studies. The overall risk of bias assessment was severe or mild in RCTs and was severe or moderate in observational studies. The main outcomes reported from the included studies were blood transfusion (n = 10), mortality (n = 10), hospital length of stay (LOS) (n = 7), intensive care unit LOS (n = 7), and cost (n = 4). The effect of the VHA-guided strategy was not always superior to the control. Most of the studies did not find significant differences in the transfusion amount of red blood cells (n = 7), plasma (n = 5), platelet (n = 7), cryoprecipitate/fibrinogen (n = 7), and mortality (n = 8) between the VHA-guided group and control group. Notable, two RCTs showed that the VHA-guided strategy was superior or equal to the conventional coagulation test-guided strategy in reducing mortality, respectively. Conclusion Although some studies demonstrated VHA-guided strategy probable benefit in reducing the need for blood transfusion and mortality when resuscitating trauma patients, the evidence is still not robust. The quality of evidence was primarily downgraded by the limited number of included studies and great heterogeneity and severe risk of bias in these. Further studies are strongly recommended. Supplementary Information The online version contains supplementary material available at 10.1186/s13017-022-00454-8.
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18
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Stanworth SJ, Dowling K, Curry N, Doughty H, Hunt BJ, Fraser L, Narayan S, Smith J, Sullivan I, Green L. A guideline for the haematological management of major haemorrhage: a British Society for Haematology Guideline. Br J Haematol 2022; 198:654-667. [PMID: 35687716 DOI: 10.1111/bjh.18275] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/07/2022] [Accepted: 05/09/2022] [Indexed: 12/17/2022]
Affiliation(s)
- Simon J Stanworth
- Transfusion Medicine, NHS Blood and Transplant, Oxford, UK.,Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.,Radcliffe Department of Medicine, University of Oxford, and NIHR Oxford Biomedical Research Centre, Oxford, UK
| | - Kerry Dowling
- Transfusion Laboratory Manager, Southampton University Hospitals NHS Foundation Trust, Southampton, UK
| | - Nikki Curry
- Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.,Radcliffe Department of Medicine, University of Oxford, and NIHR Oxford Biomedical Research Centre, Oxford, UK
| | - Heidi Doughty
- Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.,NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham, UK
| | - Beverley J Hunt
- Department of Haematology, Guy's and St Thomas's Hospital, London, UK
| | - Laura Fraser
- Transfusion Practitioner, NHS Lanarkshire, University Hospital Wishaw, Wishaw, UK.,National Services Scotland/Scottish National Blood Transfusion, Edinburgh, UK
| | - Shruthi Narayan
- Medical director, Serious Hazards of Transfusion, Manchester, UK
| | - Juliet Smith
- Lead Transfusion Practitioner, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Ian Sullivan
- Transfusion Laboratory Manager, Royal Cornwall Hospitals NHS Trust, Truro, UK
| | - Laura Green
- Transfusion Medicine, NHS Blood and Transplant, London, UK.,Barts Health NHS Trust, London, UK.,Blizzard Institute, Queen Mary University of London, London, UK
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19
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Lier H, Fries D. Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care. Transfus Med Hemother 2022; 48:366-376. [PMID: 35082568 DOI: 10.1159/000519696] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 09/08/2021] [Indexed: 11/19/2022] Open
Abstract
Uncontrolled and massive bleeding with derangement of coagulation is a major challenge in the management of both surgical and seriously injured patients. The underlying mechanism of trauma-induced or -associated coagulopathy is tissue injury in the presence of shock and acidosis provoking endothelial damage, activation of inflammation, and coagulation disbalancing. Furthermore, the combination of ongoing blood loss and consumption of blood components that are essential for effective coagulation worsens uncontrolled hemorrhage. Additionally, therapeutic actions, such as resuscitation with replacement fluids or allogeneic blood products, can further aggravate coagulopathy. Of the coagulation factors essential to the clotting process, fibrinogen is the first to be consumed to critical levels during acute bleeding and current evidence suggests that normalizing fibrinogen levels in bleeding patients improves clot formation and clot strength, thereby controlling hemorrhage. Three different therapeutic approaches are discussed controversially. Whole blood transfusion is used especially in the military scenario and is also becoming more and more popular in the civilian world, although it is accompanied by a strong lack of evidence and severe safety issues. Transfusion of allogeneic blood concentrates in fixed ratios without any targets has been investigated extensively with disappointing results. Individualized and target-controlled coagulation management based on point-of-care diagnostics with respect to the huge heterogeneity of massive bleeding situations is an alternative and advanced approach to managing coagulopathy associated with massive bleeding in the trauma as well as the perioperative setting.
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Affiliation(s)
- Heiko Lier
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinic for Anesthesiology and Intensive Care Medicine, Cologne, Germany
| | - Dietmar Fries
- Department of Anesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
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20
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Lantry JH, Mason P, Logsdon MG, Bunch CM, Peck EE, Moore EE, Moore HB, Neal MD, Thomas SG, Khan RZ, Gillespie L, Florance C, Korzan J, Preuss FR, Mason D, Saleh T, Marsee MK, Vande Lune S, Ayoub Q, Fries D, Walsh MM. Hemorrhagic Resuscitation Guided by Viscoelastography in Far-Forward Combat and Austere Civilian Environments: Goal-Directed Whole-Blood and Blood-Component Therapy Far from the Trauma Center. J Clin Med 2022; 11:356. [PMID: 35054050 PMCID: PMC8778082 DOI: 10.3390/jcm11020356] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 12/31/2021] [Accepted: 01/10/2022] [Indexed: 12/18/2022] Open
Abstract
Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy-especially in austere or challenging environments-is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.
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Affiliation(s)
- James H. Lantry
- Department of Medicine Critical Care Services, Inova Fairfax Medical Campus, Falls Church, VA 22042, USA;
| | - Phillip Mason
- Department of Critical Care Medicine, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA;
| | - Matthew G. Logsdon
- Department of Emergency Medicine, Indiana University School of Medicine—South Bend, Notre Dame, IN 46617, USA; (M.G.L.); (C.M.B.)
- Department of Emergency Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (E.E.P.); (C.F.); (J.K.)
| | - Connor M. Bunch
- Department of Emergency Medicine, Indiana University School of Medicine—South Bend, Notre Dame, IN 46617, USA; (M.G.L.); (C.M.B.)
- Department of Emergency Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (E.E.P.); (C.F.); (J.K.)
| | - Ethan E. Peck
- Department of Emergency Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (E.E.P.); (C.F.); (J.K.)
| | - Ernest E. Moore
- Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health and University of Colorado Health Sciences Center, Denver, CO 80204, USA; (E.E.M.); (H.B.M.)
| | - Hunter B. Moore
- Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health and University of Colorado Health Sciences Center, Denver, CO 80204, USA; (E.E.M.); (H.B.M.)
| | - Matthew D. Neal
- Pittsburgh Trauma Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA;
| | - Scott G. Thomas
- Department of Trauma Surgery, Memorial Leighton Trauma Center, Beacon Health System, South Bend, IN 46601, USA;
| | - Rashid Z. Khan
- Department of Hematology, Michiana Hematology Oncology, Mishawaka, IN 46545, USA;
| | - Laura Gillespie
- Department of Quality Assurance and Performance Improvement, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA;
| | - Charles Florance
- Department of Emergency Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (E.E.P.); (C.F.); (J.K.)
| | - Josh Korzan
- Department of Emergency Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (E.E.P.); (C.F.); (J.K.)
| | - Fletcher R. Preuss
- Department of Orthopaedic Surgery, UCLA Santa Monica Medical Center and Orthopaedic Institute, Santa Monica, CA 90404, USA;
| | - Dan Mason
- Department of Medical Science and Devices, Haemonetics Corporation, Braintree, MA 02184, USA;
| | - Tarek Saleh
- Department of Critical Care Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA;
| | - Mathew K. Marsee
- Department of Graduate Medical Education, Naval Medical Center Portsmouth, Portsmouth, VA 23708, USA;
| | - Stefani Vande Lune
- Department of Emergency Medicine, Naval Medical Center Portsmouth, Portsmouth, VA 23708, USA;
| | | | - Dietmar Fries
- Department of Surgical and General Care Medicine, Medical University of Innsbruck, 6020 Innsbruck, Austria;
| | - Mark M. Walsh
- Department of Emergency Medicine, Indiana University School of Medicine—South Bend, Notre Dame, IN 46617, USA; (M.G.L.); (C.M.B.)
- Department of Emergency Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (E.E.P.); (C.F.); (J.K.)
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21
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Bradbury JL, Thomas SG, Sorg NR, Mjaess N, Berquist MR, Brenner TJ, Langford JH, Marsee MK, Moody AN, Bunch CM, Sing SR, Al-Fadhl MD, Salamah Q, Saleh T, Patel NB, Shaikh KA, Smith SM, Langheinrich WS, Fulkerson DH, Sixta S. Viscoelastic Testing and Coagulopathy of Traumatic Brain Injury. J Clin Med 2021; 10:jcm10215039. [PMID: 34768556 PMCID: PMC8584585 DOI: 10.3390/jcm10215039] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/24/2021] [Accepted: 10/27/2021] [Indexed: 12/14/2022] Open
Abstract
A unique coagulopathy often manifests following traumatic brain injury, leading the clinician down a difficult decision path on appropriate prophylaxis and therapy. Conventional coagulation assays—such as prothrombin time, partial thromboplastin time, and international normalized ratio—have historically been utilized to assess hemostasis and guide treatment following traumatic brain injury. However, these plasma-based assays alone often lack the sensitivity to diagnose and adequately treat coagulopathy associated with traumatic brain injury. Here, we review the whole blood coagulation assays termed viscoelastic tests and their use in traumatic brain injury. Modified viscoelastic tests with platelet function assays have helped elucidate the underlying pathophysiology and guide clinical decisions in a goal-directed fashion. Platelet dysfunction appears to underlie most coagulopathies in this patient population, particularly at the adenosine diphosphate and/or arachidonic acid receptors. Future research will focus not only on the utility of viscoelastic tests in diagnosing coagulopathy in traumatic brain injury, but also on better defining the use of these tests as evidence-based and/or precision-based tools to improve patient outcomes.
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Affiliation(s)
- Jamie L. Bradbury
- Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - Scott G. Thomas
- Department of Trauma Surgery, Memorial Hospital, South Bend, IN 46601, USA;
| | - Nikki R. Sorg
- Department of Emergency Medicine, Indiana University School of Medicine—South Bend, South Bend, IN 46617, USA; (N.R.S.); (A.N.M.); (S.R.S.)
| | - Nicolas Mjaess
- Department of Intensive Care Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (N.M.); (M.R.B.); (T.J.B.); (J.H.L.); (M.D.A.-F.); (Q.S.); (T.S.)
| | - Margaret R. Berquist
- Department of Intensive Care Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (N.M.); (M.R.B.); (T.J.B.); (J.H.L.); (M.D.A.-F.); (Q.S.); (T.S.)
| | - Toby J. Brenner
- Department of Intensive Care Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (N.M.); (M.R.B.); (T.J.B.); (J.H.L.); (M.D.A.-F.); (Q.S.); (T.S.)
| | - Jack H. Langford
- Department of Intensive Care Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (N.M.); (M.R.B.); (T.J.B.); (J.H.L.); (M.D.A.-F.); (Q.S.); (T.S.)
| | - Mathew K. Marsee
- Department of Otolaryngology, Portsmouth Naval Medical Center, Portsmouth, VA 23708, USA;
| | - Ashton N. Moody
- Department of Emergency Medicine, Indiana University School of Medicine—South Bend, South Bend, IN 46617, USA; (N.R.S.); (A.N.M.); (S.R.S.)
| | - Connor M. Bunch
- Department of Emergency Medicine, Indiana University School of Medicine—South Bend, South Bend, IN 46617, USA; (N.R.S.); (A.N.M.); (S.R.S.)
- Correspondence:
| | - Sandeep R. Sing
- Department of Emergency Medicine, Indiana University School of Medicine—South Bend, South Bend, IN 46617, USA; (N.R.S.); (A.N.M.); (S.R.S.)
| | - Mahmoud D. Al-Fadhl
- Department of Intensive Care Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (N.M.); (M.R.B.); (T.J.B.); (J.H.L.); (M.D.A.-F.); (Q.S.); (T.S.)
| | - Qussai Salamah
- Department of Intensive Care Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (N.M.); (M.R.B.); (T.J.B.); (J.H.L.); (M.D.A.-F.); (Q.S.); (T.S.)
| | - Tarek Saleh
- Department of Intensive Care Medicine, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA; (N.M.); (M.R.B.); (T.J.B.); (J.H.L.); (M.D.A.-F.); (Q.S.); (T.S.)
| | - Neal B. Patel
- Department of Neurosurgery, Memorial Hospital, South Bend, IN 46601, USA; (N.B.P.); (K.A.S.); (S.M.S.); (W.S.L.); (D.H.F.)
- Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Kashif A. Shaikh
- Department of Neurosurgery, Memorial Hospital, South Bend, IN 46601, USA; (N.B.P.); (K.A.S.); (S.M.S.); (W.S.L.); (D.H.F.)
- Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Stephen M. Smith
- Department of Neurosurgery, Memorial Hospital, South Bend, IN 46601, USA; (N.B.P.); (K.A.S.); (S.M.S.); (W.S.L.); (D.H.F.)
- Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Walter S. Langheinrich
- Department of Neurosurgery, Memorial Hospital, South Bend, IN 46601, USA; (N.B.P.); (K.A.S.); (S.M.S.); (W.S.L.); (D.H.F.)
- Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Daniel H. Fulkerson
- Department of Neurosurgery, Memorial Hospital, South Bend, IN 46601, USA; (N.B.P.); (K.A.S.); (S.M.S.); (W.S.L.); (D.H.F.)
- Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Sherry Sixta
- Department of Trauma Surgery, Envision Physician Services, Plano, TX 75093, USA;
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22
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Liu W, Yang X, Li P, Sang F, Cao L, Zhang B, Meng Z, Ma Z, Shi C. Thrombin Embedded in eMPs@Thr/Sponge with Enhanced Procoagulant Ability for Uncompressible and Massive Hemorrhage Control. ACS APPLIED BIO MATERIALS 2021; 4:7643-7652. [DOI: 10.1021/acsabm.1c00882] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Wen Liu
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325011, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China
| | - Xiao Yang
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325011, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China
| | - Pengpeng Li
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Feng Sang
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Lina Cao
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Bingxu Zhang
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
| | - Zhizhen Meng
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Zhaipu Ma
- School of Life Sciences, Hebei University, Baoding, Hebei 071000, China
| | - Changcan Shi
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325011, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325001, China
- School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
- The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
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23
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Walsh M, Grisoli A, Zackariya N, Thomas AV, Sualeh A. Randomized controlled trials and Cochrane analyses versus precision-based medicine for tranexamic acid and viscoelastic testing in trauma. ANZ J Surg 2021; 90:415-416. [PMID: 32339433 DOI: 10.1111/ans.15557] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 10/07/2019] [Accepted: 10/10/2019] [Indexed: 11/29/2022]
Affiliation(s)
- Mark Walsh
- Department of Emergency Medicine and Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Department of Trauma, Memorial Hospital, South Bend, Indiana, USA.,Indiana University School of Medicine South Bend Campus, Notre Dame, Indiana, USA.,W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA
| | - Annie Grisoli
- Indiana University School of Medicine South Bend Campus, Notre Dame, Indiana, USA
| | - Nuha Zackariya
- Department of Emergency Medicine and Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Department of Trauma, Memorial Hospital, South Bend, Indiana, USA
| | - Anthony V Thomas
- Department of Emergency Medicine and Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Department of Trauma, Memorial Hospital, South Bend, Indiana, USA
| | - Ali Sualeh
- Department of Emergency Medicine and Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Department of Trauma, Memorial Hospital, South Bend, Indiana, USA
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24
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Walsh M, Moore EE, Moore HB, Thomas S, Kwaan HC, Speybroeck J, Marsee M, Bunch CM, Stillson J, Thomas AV, Grisoli A, Aversa J, Fulkerson D, Vande Lune S, Sjeklocha L, Tran QK. Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review. J Clin Med 2021; 10:320. [PMID: 33477257 PMCID: PMC7830337 DOI: 10.3390/jcm10020320] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/15/2021] [Accepted: 01/15/2021] [Indexed: 12/21/2022] Open
Abstract
This narrative review explores the pathophysiology, geographic variation, and historical developments underlying the selection of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. We also detail a physiologically driven and goal-directed alternative to fixed ratio and whole blood, whereby viscoelastic testing guides the administration of blood components and factor concentrates to the severely bleeding trauma patient. The major studies of each resuscitation method are highlighted, and upcoming comparative trials are detailed.
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Affiliation(s)
- Mark Walsh
- Notre Dame Campus, Indiana University School of Medicine, South Bend, IN 46617, USA; (M.W.); (J.S.); (M.M.); (C.M.B.); (J.S.); (A.V.T.); (A.G.)
- Departments of Emergency & Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
| | - Ernest E. Moore
- Ernest E. Moore Shock Trauma Center, Denver Health, Denver, CO 80204, USA;
- Department of Surgery, University of Colorado Health Science Center, Denver, CO 80204, USA;
| | - Hunter B. Moore
- Department of Surgery, University of Colorado Health Science Center, Denver, CO 80204, USA;
| | - Scott Thomas
- Department of Trauma Surgery, Memorial Leighton Trauma Center, Beacon Health System, South Bend, IN 46601, USA;
| | - Hau C. Kwaan
- Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA;
| | - Jacob Speybroeck
- Notre Dame Campus, Indiana University School of Medicine, South Bend, IN 46617, USA; (M.W.); (J.S.); (M.M.); (C.M.B.); (J.S.); (A.V.T.); (A.G.)
| | - Mathew Marsee
- Notre Dame Campus, Indiana University School of Medicine, South Bend, IN 46617, USA; (M.W.); (J.S.); (M.M.); (C.M.B.); (J.S.); (A.V.T.); (A.G.)
| | - Connor M. Bunch
- Notre Dame Campus, Indiana University School of Medicine, South Bend, IN 46617, USA; (M.W.); (J.S.); (M.M.); (C.M.B.); (J.S.); (A.V.T.); (A.G.)
| | - John Stillson
- Notre Dame Campus, Indiana University School of Medicine, South Bend, IN 46617, USA; (M.W.); (J.S.); (M.M.); (C.M.B.); (J.S.); (A.V.T.); (A.G.)
| | - Anthony V. Thomas
- Notre Dame Campus, Indiana University School of Medicine, South Bend, IN 46617, USA; (M.W.); (J.S.); (M.M.); (C.M.B.); (J.S.); (A.V.T.); (A.G.)
| | - Annie Grisoli
- Notre Dame Campus, Indiana University School of Medicine, South Bend, IN 46617, USA; (M.W.); (J.S.); (M.M.); (C.M.B.); (J.S.); (A.V.T.); (A.G.)
| | - John Aversa
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - Daniel Fulkerson
- Department of Neurosurgery, Beacon Medical Group, South Bend, IN 46601, USA;
| | - Stefani Vande Lune
- Emergency Medicine Department, Navy Medicine Readiness and Training Command, Portsmouth, VA 23708, USA;
| | - Lucas Sjeklocha
- The R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Quincy K. Tran
- The R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
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25
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Individualised Risk Assessments for Recurrent Venous Thromboembolism: New Frontiers in the Era of Direct Oral Anticoagulants. HEMATO 2021. [DOI: 10.3390/hemato2010003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality and is associated with high recurrence rates. The introduction of direct oral anticoagulants (DOACs) in the 2010s has changed the landscape of VTE management. DOACs have become the preferred anticoagulant therapy for their ease of use, predictable pharmacokinetics, and improved safety profile. Increasingly, guidelines have recommended long term anticoagulation for some indications such as following first unprovoked major VTE, although an objective individualised risk assessment for VTE recurrence remains elusive. The balance of preventing VTE recurrence needs to be weighed against the not insignificant bleeding risk, which is cumulative with prolonged use. Hence, there is a need for an individualised, targeted approach for assessing the risk of VTE recurrence, especially in those patients in whom the balance between benefit and risk of long-term anticoagulation is not clear. Clinical factors alone do not provide the level of discrimination required on an individual level. Laboratory data from global coagulation assays and biomarkers may provide enhanced risk assessment ability and are an active area of research. A review of the prediction models and biomarkers for assessing VTE recurrence risk is provided, with an emphasis on contemporary developments in the era of DOACs and global coagulation assays.
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26
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The Calcilytic Drug Calhex-231 Ameliorates Vascular Hyporesponsiveness in Traumatic Hemorrhagic Shock by Inhibiting Oxidative Stress and miR-208a-Mediated Mitochondrial Fission. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:4132785. [PMID: 33343806 PMCID: PMC7732383 DOI: 10.1155/2020/4132785] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/27/2020] [Accepted: 11/26/2020] [Indexed: 12/29/2022]
Abstract
Background The calcium-sensing receptor (CaSR) plays a fundamental role in extracellular calcium homeostasis in humans. Surprisingly, CaSR is also expressed in nonhomeostatic tissues and is involved in regulating diverse cellular functions. The objective of this study was to determine if Calhex-231 (Cal), a negative modulator of CaSR, may be beneficial in the treatment of traumatic hemorrhagic shock (THS) by improving cardiovascular function and investigated the mechanisms. Methods Rats that had been subjected to THS and hypoxia-treated vascular smooth muscle cells (VSMCs) were used in this study. The effects of Cal on cardiovascular function, animal survival, hemodynamics, and vital organ function in THS rats and the relationship to oxidative stress, mitochondrial fusion-fission, and microRNA (miR-208a) were investigated. Results Cal significantly improved hemodynamics, elevated blood pressure, increased vital organ blood perfusion and local oxygen supply, and markedly improved the survival outcomes of THS rats. Furthermore, Cal significantly improved vascular reactivity after THS in vivo and in vitro. Cal also restored the THS-induced decrease in myosin light chain (MLC) phosphorylation (the key element for VSMC contraction). Inhibition of MLC phosphorylation antagonized the Cal-induced restoration of vascular reactivity following THS. Cal suppressed oxidative stress in THS rats and hypoxic-VSMCs. Meanwhile, THS induced expression of mitochondrial fission proteins Drp1 and Fis1 and decreased expression of mitochondrial fusion protein Mfn1 in vascular tissues. Cal reduced expression of Drp1 and Fis1. In hypoxic-VSMCs, Cal inhibited mitochondrial fragmentation and preserved mitochondrial morphology. In addition, miR-208a mimic decreased Fis1 expression, and miR-208a inhibitor prevented Cal-induced Fis1 downregulation in hypoxic-VSMCs. Conclusion Calhex-231 exhibits outstanding potential for effective therapy of traumatic hemorrhagic shock, and the beneficial effects result from its protection of vascular function via inhibition of oxidative stress and miR-208a-mediated mitochondrial fission.
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27
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Walsh M, Patel S, Zackariya S, Al-Fadhl M, Marsee M. Value of viscoelastic testing in detecting fibrinolysis and coagulopathy in malignancy-associated coagulopathy and orthopaedic trauma. ANZ J Surg 2020; 90:422-423. [PMID: 32339427 DOI: 10.1111/ans.15675] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 11/27/2019] [Accepted: 12/08/2019] [Indexed: 11/28/2022]
Affiliation(s)
- Mark Walsh
- Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Memorial Hospital Trauma Center, South Bend, Indiana, USA.,Indiana University School of Medicine, Notre Dame, Indiana, USA.,W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA
| | - Shivani Patel
- Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Memorial Hospital Trauma Center, South Bend, Indiana, USA
| | - Sufyan Zackariya
- Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Memorial Hospital Trauma Center, South Bend, Indiana, USA
| | - Mahmoud Al-Fadhl
- Saint Joseph Regional Medical Center, Mishawaka, Indiana, USA.,Memorial Hospital Trauma Center, South Bend, Indiana, USA
| | - Mathew Marsee
- Indiana University School of Medicine, Notre Dame, Indiana, USA
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28
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Bjerkvig C, Sivertsen J, Braathen H, Lunde THF, Strandenes G, Assmus J, Hervig T, Cap A, Kristoffersen EK, Fosse T, Apelseth TO. Cold-stored whole blood in a Norwegian emergency helicopter service: an observational study on storage conditions and product quality. Transfusion 2020; 60:1544-1551. [PMID: 32319702 DOI: 10.1111/trf.15802] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 02/16/2020] [Accepted: 02/26/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Increasing numbers of emergency medical service agencies and hospitals are developing the capability to administer blood products to patients with hemorrhagic shock. Cold-stored whole blood (WB) is the only single product available to prehospital providers who aim to deliver a balanced resuscitation strategy. However, there are no data on the safety and in vitro characteristics of prehospital stored WB. This study aimed to describe the effects on in vitro quality of storing WB at remote helicopter bases in thermal insulating containers. STUDY DESIGN AND METHODS We conducted a two-armed single-center study. Twenty units (test) were stored in airtight thermal insulating containers, and 20 units (controls) were stored according to routine procedures in the Haukeland University Hospital Blood Bank. Storage conditions were continuously monitored during emergency medical services missions and throughout remote and blood bank storage. Hematologic and metabolic variables, viscoelastic properties, and platelet (PLT) aggregation were measured on Days 1, 8, 14, and 21. RESULTS Storage conditions complied with the EU guidelines throughout remote and in-hospital storage for 21 days. There were no significant differences in PLT aggregation, viscoelastic properties, and hematology variables between the two groups. Minor significantly lower pH, glucose, and base excess and higher lactate were observed after storage in airtight containers. CONCLUSION Forward cold storage of WB is safe and complies with EU standards. No difference is observed in hemostatic properties. Minor differences in metabolic variables may be related to the anaerobic conditions within the thermal box.
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Affiliation(s)
- Christopher Bjerkvig
- Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.,Norwegian Naval Special Operations Commando, Norwegian Armed Forces, Bergen, Norway.,Institute of Clinical Sciences, University of Bergen, Bergen, Norway
| | - Joar Sivertsen
- Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
| | - Hanne Braathen
- Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
| | - Turid Helen Felli Lunde
- Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
| | - Geir Strandenes
- Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway.,Department of War Surgery and Emergency Medicine, Norwegian Armed Forces Medical Services, Oslo, Norway
| | - Jörg Assmus
- Department of Research and Development, Haukeland University Hospital, Bergen, Norway
| | - Tor Hervig
- Institute of Clinical Sciences, University of Bergen, Bergen, Norway.,Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
| | - Andrew Cap
- U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas, USA
| | - Einar K Kristoffersen
- Institute of Clinical Sciences, University of Bergen, Bergen, Norway.,Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway
| | - Theodor Fosse
- Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.,Norwegian Naval Special Operations Commando, Norwegian Armed Forces, Bergen, Norway.,Institute of Clinical Sciences, University of Bergen, Bergen, Norway
| | - Torunn Oveland Apelseth
- Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
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29
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Abstract
Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma. A significant number of deaths due to hemorrhage occur before and in the first hour after hospital arrival. A literature search was performed through PubMed, Scopus, and Institute of Scientific Information databases for English language articles using terms relating to hemostatic agents, prehospital, battlefield or combat dressings, and prehospital hemostatic resuscitation, followed by cross-reference searching. Abstracts were screened to determine relevance and whether appropriate further review of the original articles was warranted. Based on these findings, this paper provides a review of a variety of hemostatic agents ranging from clinically approved products for human use to newly developed concepts with great potential for use in prehospital settings. These hemostatic agents can be administered either systemically or locally to stop bleeding through different mechanisms of action. Comparisons of current hemostatic products and further directions for prehospital hemorrhage control are also discussed.
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Affiliation(s)
- Henry T Peng
- Defence Research and Development Canada, Toronto Research Centre, 1133 Sheppard Avenue West, Toronto, ON, M3K 2C9, Canada.
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30
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Shah A, Palmer AJR, Klein AA. Strategies to minimize intraoperative blood loss during major surgery. Br J Surg 2020; 107:e26-e38. [DOI: 10.1002/bjs.11393] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 09/12/2019] [Indexed: 12/19/2022]
Abstract
Abstract
Background
Reducing operative blood loss improves patient outcomes and reduces healthcare costs. The aim of this article was to review current surgical, anaesthetic and haemostatic intraoperative blood conservation strategies.
Methods
This narrative review was based on a literature search of relevant databases up to 31 July 2019 for publications relevant to reducing blood loss in the surgical patient.
Results
Interventions can begin early in the preoperative phase through identification of patients at high risk of bleeding. Directly acting anticoagulants can be stopped 48 h before most surgery in the presence of normal renal function. Aspirin can be continued for most procedures. Intraoperative cell salvage is recommended when anticipated blood loss is greater than 500 ml and this can be continued after surgery in certain situations. Tranexamic acid is safe, cheap and effective, and routine administration is recommended when anticipated blood loss is high. However, the optimal dose, timing and route of administration remain unclear. The use of topical agents, tourniquet and drains remains at the discretion of the surgeon. Anaesthetic techniques include correct patient positioning, avoidance of hypothermia and regional anaesthesia. Permissive hypotension may be beneficial in selected patients. Promising haemostatic strategies include use of pharmacological agents such as desmopressin, prothrombin complex concentrate and fibrinogen concentrate, and use of viscoelastic haemostatic assays.
Conclusion
Reducing perioperative blood loss requires a multimodal and multidisciplinary approach. Although high-quality evidence exists in certain areas, the overall evidence base for reducing intraoperative blood loss remains limited.
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Affiliation(s)
- A Shah
- Radcliffe Department of Medicine, University of Oxford, Oxford, UK
- Nuffield Department of Anaesthetics, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - A J R Palmer
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - A A Klein
- Department of Anaesthesia and Intensive Care, Royal Papworth Hospital, Cambridge, UK
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31
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Jehan F, Con J, McIntyre M, Khan M, Azim A, Prabhakaran K, Latifi R. Pre-hospital shock index correlates with transfusion, resource utilization and mortality; The role of patient first vitals. Am J Surg 2019; 218:1169-1174. [DOI: 10.1016/j.amjsurg.2019.08.028] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 08/26/2019] [Accepted: 08/30/2019] [Indexed: 12/21/2022]
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Walsh M, Moore EE, Moore H, Thomas S, Lune SV, Zimmer D, Dynako J, Hake D, Crowell Z, McCauley R, Larson EE, Miller M, Pohlman T, Achneck HE, Martin P, Nielsen N, Shariff F, Ploplis VA, Castellino FJ. Use of Viscoelastography in Malignancy-Associated Coagulopathy and Thrombosis: A Review. Semin Thromb Hemost 2019; 45:354-372. [PMID: 31108555 PMCID: PMC7707018 DOI: 10.1055/s-0039-1688497] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The relationship between malignancy and coagulopathy is one that is well documented yet incompletely understood. Clinicians have attempted to quantify the hypercoagulable state produced in various malignancies using common coagulation tests such as prothrombin time, activated partial thromboplastin time, and platelet count; however, due to these tests' focus on individual aspects of coagulation during one specific time point, they have failed to provide clinicians the complete picture of malignancy-associated coagulopathy (MAC). Viscoelastic tests (VETs), such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are whole blood analyses that have the advantage of providing information related to the cumulative effects of plasma clotting factors, platelets, leukocytes, and red cells during all stages of the coagulation and fibrinolytic processes. VETs have gained popularity in the care of trauma patients to objectively measure trauma-induced coagulopathy (TIC), but the utility of VETs remains yet unrealized in many other medical specialties. The authors discuss the similarities and differences between TIC and MAC, and propose a mechanism for the hypercoagulable state of MAC that revolves around the thrombomodulin-thrombin complex as it switches between activating the protein C anticoagulation pathway or the thrombin activatable fibrinolysis inhibitor coagulation pathway. Additionally, they review the current literature on the use of TEG and ROTEM in patients with various malignancies. Although limited research is currently available, early results demonstrate the utility of both TEG and ROTEM in the prediction of hypercoagulable states and thromboembolic complications in oncologic patients.
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Affiliation(s)
- Mark Walsh
- Saint Joseph Regional Medical Center, Mishawaka, Indiana
- Beacon Medical Group Trauma & Surgical Research Services, South Bend, Indiana
- Indiana University School of Medicine, South Bend Campus, South Bend, Indiana
| | - Ernest E. Moore
- Ernest E. Moore Trauma Center Denver General Hospital, University of Colorado School of Medicine, Denver, Colorado
| | - Hunter Moore
- Ernest E. Moore Trauma Center Denver General Hospital, University of Colorado School of Medicine, Denver, Colorado
| | - Scott Thomas
- Beacon Medical Group Trauma & Surgical Research Services, South Bend, Indiana
| | - Stefani Vande Lune
- Indiana University School of Medicine, South Bend Campus, South Bend, Indiana
| | - David Zimmer
- Indiana University School of Medicine, South Bend Campus, South Bend, Indiana
| | - Joseph Dynako
- Indiana University School of Medicine, South Bend Campus, South Bend, Indiana
| | - Daniel Hake
- Chicago College of Osteopathic Medicine at Midwestern University, Downers Grove, Illinois
| | - Zachary Crowell
- Chicago College of Osteopathic Medicine at Midwestern University, Downers Grove, Illinois
| | - Ross McCauley
- Indiana University School of Medicine, South Bend Campus, South Bend, Indiana
| | - Emilee E. Larson
- Indiana University School of Medicine, South Bend Campus, South Bend, Indiana
| | - Michael Miller
- Beacon Medical Group Trauma & Surgical Research Services, South Bend, Indiana
| | - Tim Pohlman
- Beacon Medical Group Trauma & Surgical Research Services, South Bend, Indiana
| | | | - Peter Martin
- Department of Emergency Medicine, Tulane School of Medicine, New Orleans, Louisiana
| | - Nathan Nielsen
- Division of Pulmonary Diseases, Critical Care and Environmental Medicine, Tulane School of Medicine, New Orleans, Louisiana
| | - Faisal Shariff
- Indiana University School of Medicine, South Bend Campus, South Bend, Indiana
| | - Victoria A. Ploplis
- W.M. Keck Center for Transgene Research, The University of Notre Dame, Notre Dame, Indiana
- Department of Chemistry and Biochemistry, The University of Notre Dame, Notre Dame, Indiana
| | - Francis J. Castellino
- W.M. Keck Center for Transgene Research, The University of Notre Dame, Notre Dame, Indiana
- Department of Chemistry and Biochemistry, The University of Notre Dame, Notre Dame, Indiana
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