Post-Reconstitution Hemostatic Stability Profiles of Canadian and German Freeze-Dried Plasma.

Despite the importance of the hemostatic properties of reconstituted freeze-dried plasma (FDP) for trauma resuscitation, few studies have been conducted to determine its post-reconstitution hemostatic stability. This study aimed to assess the short- (≤24 h) and long-term (≥168 h) hemostatic stabilities of Canadian and German freeze-dried plasma (CFDP and LyoPlas) after reconstitution and storage under different conditions. Post-reconstitution hemostatic profiles were determined using rotational thromboelastometry (ROTEM) and a Stago analyzer, as both are widely used as standard methods for assessing the quality of plasma. When compared to the initial reconstituted CFDP, there were no changes in ROTEM measurements for INTEM maximum clot firmness (MCF), EXTEM clotting time (CT) and MCF, and Stago measurements for prothrombin time (PT), partial thromboplastin time (PTT), D-dimer concentration, plasminogen, and protein C activities after storage at 4 °C for 24 h and room temperature (RT) (22-25 °C) for 4 h. However, an increase in INTEM CT and decreases in fibrinogen concentration, factors V and VIII, and protein S activities were observed after storage at 4 °C for 24 h, while an increase in factor V and decreases in antithrombin and protein S activities were seen after storage at RT for 4 h. Evaluation of the long-term stability of reconstituted LyoPlas showed decreased stability in both global and specific hemostatic profiles with increasing storage temperatures, particularly at 35 °C, where progressive changes in CT and MCF, PT, PTT, fibrinogen concentration, factor V, antithrombin, protein C, and protein S activities were seen even after storage for 4 h. We confirmed the short-term stability of CFDP in global hemostatic properties after reconstitution and storage at RT, consistent with the shelf life of reconstituted LyoPlas. The long-term stability analyses suggest that the post-reconstitution hemostatic stability of FDP products would decrease over time with increasing storage temperature, with a significant loss of hemostatic functions at 35 °C compared to 22 °C or below. Therefore, the shelf life of reconstituted FDP should be recommended according to the storage temperature.

Characterization of Combined Blast- and Fragment-Induced Pelvic Injuries and Hemostatic Resuscitation in Rabbits.

INTRODUCTION: To establish a blast- and fragment-induced pelvic injury animal model in rabbits, observe its injury characteristics, and explore the effects of hemostatic resuscitation combined with damage control surgery (DCS) with respect to this injury model. METHODS: Forty-eight rabbits were randomly allocated to four groups: group A rabbits were subjected to pelvic injury, group B rabbits to pelvic injury + DCS, group C rabbits to pelvic injury + DCS + resuscitation with Hextend, and group D rabbits to pelvic injury + DCS + Hextend + hemostatic resuscitation with tranexamic acid, fibrinogen concentrate, and prothrombin complex concentrate. Simulated blast and fragment-induced pelvic injury was produced by a custom-made machine. We implemented CT scanning and necropsy to assess the injury state and calculated the coefficient of variation (CV) of the cumulative abbreviated injury scale (AIS) to assess the reproducibility of the animal model. Immediately after instrumentation (0 h), and 1 h, 2 h, 4 h, and 8 h after injury, blood samples were taken for laboratory tests. RESULTS: We found that severe pelvic injury was produced with an AIS CV value of 10.32%, and the rabbits demonstrated severe physiologic impairment and coagulo-fibrinolytic derangements with high mortality. In rabbits of group D, however, physiologic and coagulo-fibrinolytic parameters were significantly enhanced with improved organ function and lowered mortality when compared with the other three groups. CONCLUSIONS: We herein established in rabbits a blast- and fragment-induced pelvic injury animal model that exhibited high reproducibility, and we demonstrated that hemostatic resuscitation plus DCS was effective in improving the outcome.

Puesta al día sobre transfusión masiva / Massive transfusion update / Atualização sobre transfusão maciça

La transfusión masiva plantea desafíos clínicos, organizacionales y logísticos para el personal de la salud en general y los servicios de Medicina Transfusional en particular. No existe una definición universalmente aceptada de transfusión masiva, las definiciones más comúnmente utilizadas se basan en el número de unidades de sangre administradas dentro de un cierto período de tiempo. La mayoría de los eventos de transfusión masiva ocurren en el contexto de hemorragias graves en pacientes quirúrgicos, politraumatizados, con hemorragia gastrointestinal u obstétrica. La reanimación de control de daños y los protocolos de transfusión masiva son las estrategias más utilizadas actualmente para el tratamiento inicial, seguidas de un tratamiento personalizado, dirigido por objetivos, mediante la monitorización de la coagulación en tiempo real mediante estudios viscoelásticos. Existen una serie de controversias alrededor del tratamiento óptimo, incluyendo el uso de sangre total, la relación de hemocomponentes a utilizar, el uso de concentrados de factores de la coagulación, y la indicación óptima del ácido tranexámico. El estudio de los productos ideales para el tratamiento de los pacientes con sangrado masivo se ha convertido en un área de gran interés de la investigación científica. El contexto clínico en el que ocurrió el evento hemorrágico, el número de hemocomponentes transfundidos, la edad del paciente y las comorbilidades son los predictores más importantes de la sobrevida a corto y largo plazo. Esta revisión narrativa explora el estado actual del conocimiento sobre la transfusión masiva, así como los avances que podemos esperar en el futuro cercano.

Massive transfusion poses clinical, organizational and logistic challenges for the health staff in general, and the Transfusion Medicine Services in particular. There is no universally accepted definition for massive transfusion, the most widely used being based on the number of blood units administered in a certain period of time. Most massive transfusion events occur in the context of severe hemorrhage on surgical or multiple-trauma patients or patients with gastrointestinal or obstetric bleeding. Today, damage control resuscitation and massive transfusion protocols are the most common strategies for initial treatment, followed by personalized therapy, goal-directed, my means of monitoring coagulation in real time with viscoelastic studies. There are disputes as to the best surgical treatment, including using whole blood, the relation of blood components to be used, the use of coagulation factor concentrates and the optimal indication of tranexamic acid. The study of ideal products to treat patients with massive hemorrhage has become an area of great interest for scientific research. The clinical context of the hemorrhagic event, the number of blood components transfused, patient's age and comorbilities are the most important predictors for survival in the short and long term. This narrative review explores the current state of affairs on knowledge about massive transfusion, as well as progress to be expected in the near future.

A transfusão maciça apresenta desafios clínicos, organizacionais e logísticos para o pessoal de saúde em geral e para os serviços de Medicina Transfusional em particular. Não existe uma definição universalmente aceita de transfusão maciça; as definições mais comumente usadas são baseadas no número de unidades de sangue administradas em um determinado período de tempo. A maioria dos eventos de transfusão maciça ocorre no contexto de sangramento maior em pacientes cirúrgicos, politraumatizados, com sangramento gastrointestinal ou obstétrico. Atualmente, a ressuscitação para controle de danos e os protocolos de transfusão maciça são as estratégias mais usadas para o tratamento inicial, seguidos por tratamento personalizado e orientado por objetivos usando monitoramento de coagulação em tempo real usando testes viscoelásticos. Há uma série de controvérsias em torno do tratamento ideal, incluindo o uso de sangue total, a proporção de componentes sanguíneos a serem usados, o uso de concentrados de fator de coagulação e a indicação ideal de ácido tranexâmico. O estudo dos produtos ideais para o tratamento de pacientes com sangramento maciço tornou-se uma área de grande interesse na pesquisa científica. O contexto clínico em que ocorreu o evento hemorrágico, o número de hemocomponentes transfundidos, a idade do paciente e as comorbidades são os preditores mais importantes de sobrevida a curto e longo prazo. Esta revisão narrativa explora o estado atual do conhecimento sobre transfusão maciça, bem como os avanços que podemos esperar no futuro próximo.

Utility of viscoelastic hemostatic assay to guide hemostatic resuscitation in trauma patients: a systematic review.

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.

Balanced hemostatic resuscitation for bleeding pediatric trauma patients: A nationwide quantitative analysis of outcomes.

BACKGROUND: The administration of balanced component therapy has been associated with improvements in outcomes in adult trauma. There is little to no specific data to guide transfusion ratios in children. The aim of our study is to compare outcomes among different transfusion strategies in pediatric trauma patients. METHODS: We conducted a (2014-2016) retrospective analysis of the Trauma Quality Improvement Program. We selected all pediatric (age < 18) trauma patients who received at least one unit of packed red blood cells (PRBC) and fresh frozen plasma (FFP) within 4 h of admission. Patients were stratified based on their FFP:PRBC transfusion ratio in the first 4 h into: 1:1, 1:2, 1:3, and 1:3+. Primary outcomes were 24-mortality, in-hospital mortality. Secondary outcomes were complications and 24 h PRBC transfusion requirements. Multivariable logistic regression analysis was performed. RESULTS: A total of 1,233 patients were identified of which 637 received transfusion ratio of 1:1, 365 1:2, 116 1:3, and 115 1:3+. Mean age was 11 ± 6y, 70% were male, ISS was 27 [20-38], and 62% sustained penetrating injuries. Patients in the 1:1 group had the lowest 24 h mortality (14% vs. 18% vs. 22% vs. 24%; p = 0.01) and in-hospital mortality (32% vs. 36% vs. 40% vs. 44%; p = 0.01). No difference was found between the groups in terms of complications (22% vs. 21% vs. 23% vs. 22%; p = 0.96) such as acute respiratory distress syndrome (3.3% vs. 3.6% vs. 0.9% vs. 0%; p = 0.10), and acute kidney injury (3% vs. 2.2% vs. 0.9% vs. 0.9%; p = 0.46). Additionally the 1:1 group had the lowest PRBC transfusion requirements (3[2-7] vs. 5[2-10] vs. 6[3-8] vs. 6[4-10]; p < 0.01). On regression analysis a progressive increase in the mortality adjusted odds ratio was observed as the FFP:PRBC transfusion ratio decreased. CONCLUSION: FFP:PRBC ratios closest to 1 were associated with increased survival in children. The resuscitation of pediatric patients should target a 1:1 ratio of FFP:PRBC. Further studies are needed for the development of massive transfusion protocols for this age group. LEVEL OF EVIDENCE: Level IV STUDY TYPE: Therapeutic/Care Management.

Freeze-dried plasma: From damage control resuscitation to coronavirus disease 2019 therapy.

BACKGROUND: Freeze-dried plasma (FDP) is a promising blood component for prehospital resuscitation given its logistic advantages over fresh frozen plasma (FFP). COVID-19 convalescent (CC) plasma has been used to treat coronavirus disease 2019 (COVID-19) patients, and its corresponding FDP has potential use during future pandemics. Therefore, we conducted the study to determine if the hemostatic and immunological properties of plasma can be retained after lyophilization. STUDY DESIGN AND METHODS: Hemostatic tests were conducted with Rotational Thromboelastometry (ROTEM) and a Stago analyzer. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG (Immunoglobulin G) and neutralizing activity were analyzed using Meso Scale Diagnostics immunoassay kits. RESULTS: There were no differences in ROTEM parameters and Stago measurements for prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen and D-dimer concentrations, and antithrombin, factor V, VIII, and protein S activities between FFP and FDP for either pre-COVID-19 or CC samples. Differences were observed in INTEM clotting time and PT and PTT when comparing reconstituted FDP stored at 4°C for 24 h or room temperature for 4 h to healthy control. Both CC-FFP and CC-FDP showed two orders of magnitude higher concentrations of IgG antibodies against SARS-CoV-2 antigens than pre-COVID-19-FFP and pre-COVID-19-FDP and healthy control. Similarly, the CC samples showed approximately 4-fold higher %-inhibition of receptor binding than the pre-COVID-19 samples. There were no differences in either the antibody levels or neutralization activity between CC-FFP and CC-FDP. DISCUSSION: We demonstrated that FDP and CC-FDP retained the same hemostatic and antibody functional activities relative to their initial plasma sources, supporting clinical evaluation of their benefits in severe trauma and COVID-19 patients.

Providing whole blood for an urban paramedical ambulance system.

INTRODUCTION: Hemorrhage is the second leading cause of death among urban trauma patients, and the provision of prehospital blood-based resuscitation can be lifesaving. We developed an efficient system to support blood-based resuscitation by an urban advanced life support ambulance system. METHODS: We worked with our state health department for permission for fire department paramedics to initiate blood transfusion and built protocols for field whole blood resuscitation. Our regional trauma center transfusion service provided 2 units of O positive, low-titer, leukoreduced whole blood in an internally monitored and sealed ice box weighing 10 pounds to the fire department paramedic supervisor. When notified, the supervisor transported the blood to the sites of anticipated need. Total blood use and wastage were recorded. RESULTS: Following two public hearings, we obtained state-wide approval for the initiation of emergency uncrossmatched blood transfusion by paramedics. Over a 1-year period beginning August 27, 2019, 160 units of whole blood were made available for use, and 51 units were transfused to 39 patients, 30 of whom were trauma patients. Other recipients include patients in shock from massive gastrointestinal, peripartum, or other suspected bleeding. Unused units were returned to the providing transfusion service after 1 week and used for hospital patient care without loss. The estimated cost of providing blood per mission was $0.28 and per patient transfused was $1138. CONCLUSIONS: With appropriate attention to detail, it is possible to provide whole blood to an urban paramedical ambulance system with efficient blood component usage, minimal blood wastage, and low cost.

Hemostatic Resuscitation in Children.

Trauma is a major source of morbidity and mortality for children worldwide; life-threatening hemorrhage is a primary cause of preventable death. Essential interventions in children with life-threatening hemorrhage include hemostatic resuscitation and mechanical control of bleeding. Herein we review pediatric hemostatic resuscitation, a strategy that addresses both hemorrhagic shock and the coagulopathic complications described in patients with major hemorrhage. Some components of hemostatic resuscitation may include: early and aggressive resuscitation with blood products, minimizing crystalloid and hemodilution, antifibrinolytic adjuncts such as tranexamic acid, and the novel use of low-titer group O whole-blood (LTOWB) transfusion in injured children. The following selection of important publications address the current state of hemostatic resuscitation strategies in pediatric trauma patients as well as the remaining knowledge gaps and areas for further research.

It is time for TEG in pediatric trauma: unveiling meaningful alterations in children who undergo massive transfusion.

BACKGROUND: Hemorrhage is the leading cause of preventable death in pediatric trauma patients. In adults, goal-directed thrombelastography (TEG) has been shown to reduce mortality when used to guide massive transfusion (MT) resuscitation. There remains a paucity of data on the utility of TEG in directing resuscitation of pediatric trauma patients. We hypothesize that abnormalities on admission TEG will differ in pediatric trauma patients who undergo MT, compared to those who do not. METHODS: Pediatric patients (≤ 18 years) who were highest level trauma activations at two trauma centers from 2015 to 2018 were analyzed. We included patients who had admission TEGs and excluded those who did not. Patients were stratified into two groups: those who received MT (> 40 cc/kg total blood product within 6 h of admission) and those who did not. We defined TEG abnormalities based on each institution's normative values and compared TEG abnormalities between the groups. RESULTS: Of 117 children included, 39 had MT. MT patients had higher injury severity scores (30 vs. 23, p = 0.0004), lactates levels (7.0 vs. 3.5, p < 0.001), base deficit levels ( - 12.2 vs. - 5.8, p < 0.001), and INR values (1.8 vs. 1.3, p < 0.001). MT patients had significantly shortened alpha-angles (35.9% vs. 15.4%, p = 0.023), maximum amplitude (MA) values (43.6% vs. 10.3%, p < 0.001), and significantly lower platelet counts (165 vs. 281, p < 0.001) compared to those who did not receive MT. There was no difference in the trends in R-time, LY30 (lysis or shutdown), or fibrinogen concentration between the groups. Logistic regression identified a decreased MA as a significant predictor for MT [OR 3.68 (CI 1.29-10.52)] CONCLUSIONS: Pediatric trauma patients who undergo MT are more likely to have lower alpha-angles and MA values, as well as lower platelet counts. These findings support the use of TEG to identify hemorrhaging pediatric trauma patients, who may benefit from cryoprecipitate and/or platelet transfusions. TEG provides real-time information on coagulation status, which may expedite the delivery of specific blood products during trauma resuscitation. LEVEL OF EVIDENCE: LEVEL III: Type of study: Retrospective comparative study.

Damage control in the emergency department, a bridge to life.

Patients with hemodynamic instability have a sustained systolic blood pressure less or equal to 90 mmHg, a heart rate greater or equal to 120 beats per minute and an acute compromise of the ventilation/oxygenation ratio and/or an altered state of consciousness upon admission. These patients have higher mortality rates due to massive hemorrhage, airway injury and/or impaired ventilation. Damage control resuscitation is a systematic approach that aims to limit physiologic deterioration through strategies that address the physiologic debt of trauma. This article aims to describe the experience earned by the Trauma and Emergency Surgery Group (CTE) of Cali, Colombia in the management of the severely injured trauma patient in the emergency department following the basic principles of damage control surgery. Since bleeding is the main cause of death, the management of the severely injured trauma patient in the emergency department requires a multidisciplinary team that performs damage control maneuvers aimed at rapidly controlling bleeding, hemostatic resuscitation, and/or prompt transfer to the operating room, if required.

Un paciente politraumatizado hemodinámicamente inestable es aquel que ingresa al servicio de urgencias con una presión arterial sistólica menor o igual de 90 mmHg, una frecuencia cardiaca mayor o igual a 120 latidos por minuto y un compromiso agudo de la relación ventilación/oxigenación y/o del estado de conciencia. Por esta razón, existe una alta mortalidad dentro de las primeras horas de un trauma severo ya sea por una hemorragia masiva, una lesión de la vía aérea y/o una alteración de la ventilación. Siendo el objetivo de este artículo describir el manejo en urgencias del paciente politraumatizado hemodinámicamente inestable de acuerdo con los principios de control de daños. El manejo del paciente politraumatizado es una estrategia dinámica de alto impacto que requiere de un equipo multidisciplinario de experiencia. El cual debe de evolucionar conjunto a las nuevas herramientas de diagnóstico y tratamiento endovascular que buscan ser un puente para lograr una menor repercusión hemodinámica en el paciente y una más rápida y efectiva estabilización con mayores tasas de sobrevida.

Damage control in the emergency department, a bridge to life / Control de daños en la sala de emergencias: un puente hacia la vida

Abstract Patients with hemodynamic instability have a sustained systolic blood pressure less or equal to 90 mmHg, a heart rate greater or equal to 120 beats per minute and an acute compromise of the ventilation/oxygenation ratio and/or an altered state of consciousness upon admission. These patients have higher mortality rates due to massive hemorrhage, airway injury and/or impaired ventilation. Damage control resuscitation is a systematic approach that aims to limit physiologic deterioration through strategies that address the physiologic debt of trauma. This article aims to describe the experience earned by the Trauma and Emergency Surgery Group (CTE) of Cali, Colombia in the management of the severely injured trauma patient in the emergency department following the basic principles of damage control surgery. Since bleeding is the main cause of death, the management of the severely injured trauma patient in the emergency department requires a multidisciplinary team that performs damage control maneuvers aimed at rapidly controlling bleeding, hemostatic resuscitation, and/or prompt transfer to the operating room, if required.

Resumen Un paciente politraumatizado hemodinámicamente inestable es aquel que ingresa al servicio de urgencias con una presión arterial sistólica menor o igual de 90 mmHg, una frecuencia cardiaca mayor o igual a 120 latidos por minuto y un compromiso agudo de la relación ventilación/oxigenación y/o del estado de conciencia. Por esta razón, existe una alta mortalidad dentro de las primeras horas de un trauma severo ya sea por una hemorragia masiva, una lesión de la vía aérea y/o una alteración de la ventilación. Siendo el objetivo de este artículo describir el manejo en urgencias del paciente politraumatizado hemodinámicamente inestable de acuerdo con los principios de control de daños. El manejo del paciente politraumatizado es una estrategia dinámica de alto impacto que requiere de un equipo multidisciplinario de experiencia. El cual debe de evolucionar conjunto a las nuevas herramientas de diagnóstico y tratamiento endovascular que buscan ser un puente para lograr una menor repercusión hemodinámica en el paciente y una más rápida y efectiva estabilización con mayores tasas de sobrevida.

Lessons Learned From the Battlefield and Applicability to Veterinary Medicine - Part 2: Transfusion Advances.

Since the inception of recent conflicts in Afghanistan and Iraq, transfusion practices in human military medicine have advanced considerably. Today, US military physicians recognize the need to replace the functionality of lost blood in traumatic hemorrhagic shock and whole blood is now the trauma resuscitation product of choice on the battlefield. Building on wartime experiences, military medicine is now one of the country's strongest advocates for the principle of hemostatic resuscitation using whole blood or balanced blood components as the primary means of resuscitation as early as possibly following severe trauma. Based on strong evidence to support this practice in human combat casualties and in civilian trauma care, military veterinarians strive to practice similar hemostatic resuscitation for injured Military Working Dogs. To this end, canine whole blood has become increasingly available in forward environments, and non-traditional storage options for canine blood and blood components are being explored for use in canine trauma. Blood products with improved shelf-life and ease of use are not only useful for military applications, but may also enable civilian general and specialty practices to more easily incorporate hemostatic resuscitation approaches to canine trauma care.

Normalization of blood clotting characteristics using prothrombin complex concentrate, fibrinogen and FXIII in an albumin based fluid: experimental studies in thromboelastometry.

BACKGROUND: Colloid fluids supplemented with adequate combinations of coagulation factor concentrates with the capability to restore coagulation could be a desirable future treatment component in massive transfusion. METHODS: Starting from a coagulation factor and blood cell-free albumin solution we added Prothrombin Complex Concentrate, Fibrinogen Concentrate and Factor XIII in different combinations and concentrations to analyze their properties to restore thromboelastometry parameters without the use of plasma. Further analysis under the presence of platelets was performed for comparability to whole blood conditions. RESULTS: Albumin solutions enriched with Fibrinogen Concentrate, Factor XIII and Prothrombin Complex Concentrate at optimized concentrations show restoring coagulation potential. Prothrombin Complex Concentrate showed sufficient thrombin formation for inducing fibrinogen polymerization. The combination of Prothrombin Complex Concentrate and Fibrinogen Concentrate led to the formation of a stable in vitro fibrin clot. Fibrinogen and Factor XIII showed excellent capacity to improve fibrin clot firmness expressed as Amplitude at 10 min and Maximal Clot Firmness. Fibrinogen alone, or in combination with Factor XIII, was able to restore normal Amplitude at 10 min and Maximal Clot Firmness values. In the presence of platelets, the thromboelastometry surrogate parameter for thrombin generation (Clotting Time) improves and normalizes when compared to whole blood. CONCLUSIONS: Combinations of coagulation factor concentrates suspended in albumin solutions can restore thromboelastometry parameters in the absence of plasma. This kind of artificial colloid fluids with coagulation-restoring characteristics might offer new treatment alternatives for massive transfusion. TRIAL REGISTRATION: Study registered at the institutional ethic committee "Institut de Recerca, Hospital Santa Creu i Sant Pau, with protocol number IIBSP-CFC-2013-165.

Hemostatic defects in massive transfusion: an update and treatment recommendations.

INTRODUCTION: Acute hemorrhage is a global healthcare issue, and remains the leading preventable cause of death in trauma. Acute severe hemorrhage can be related to traumatic, peripartum, gastrointestinal, and procedural causes. Hemostatic defects occur early in patients requiring massive transfusion. Early recognition and treatment of hemorrhage and hemostatic defects are required to save lives and to achieve optimal patient outcomes. AREAS COVERED: This review discusses current evidence and trials aimed at identifying the optimal treatment for hemostatic defects in hemorrhage and massive transfusion. Literature search included PubMed and Embase. EXPERT OPINION: Patients with acute hemorrhage requiring massive transfusion commonly develop coagulopathy due to specific hemostatic defects, and accurate diagnosis and prompt correction are required for definitive hemorrhage control. Damage control resuscitation and massive transfusion protocols are optimal initial treatment strategies, followed by goal-directed individualized resuscitation using real-time coagulation monitoring. Distinct phenotypes exist in trauma-induced coagulopathy, including 'Bleeding' or 'Thrombotic' phenotypes, and hyperfibrinolysis vs. fibrinolysis shutdown. The trauma 'lethal triad' (hypothermia, coagulopathy, acidosis) has been updated to the 'lethal diamond' (including hypocalcemia). A number of controversies in optimal management exist, including whole blood vs. component therapy, use of factor concentrates vs. blood products, optimal use of tranexamic acid, and prehospital plasma and tranexamic acid administration.

A clinical coagulopathy score concurrent with viscoelastic testing defines opportunities to improve hemostatic resuscitation and enhance blood product utilization during liver transplantation.

BACKGROUND: An NIH clinical coagulopathy score has been devised for trauma patients, but no such clinical score exists in transplantation surgery. We hypothesize that that this coagulopathy score can effectively identify laboratory defined coagulopathy during liver transplantation and correlates to blood product utilization. METHODS: TEGs were performed and coagulopathy scores (1, normal bleeding - 5, diffuse coagulopathic bleeding) were assigned by the surgeons at 5 intra-operative time points. Blood products used during the case were recorded between time points. Statistical analyses were performed to identify correlations between coagulopathy scores, TEG-detected abnormalities, and blood product utilization. RESULT: Transfusions rarely correlated with the appropriate TEG measurements of coagulation dysfunction. Coagulopathy score had significant correlation to various transfusions and TEG-detected coagulopathies at multiple points during the case. High aggregate coagulopathy scores identified patients receiving more transfusions, re-operations, and longer hospital stays CONCLUSION: The combination of viscoelastic testing and a standardized clinical coagulopathy score has the potential to optimize transfusions if used in tandem as well as standardize communication between surgery and anesthesia teams about clinically evident coagulopathy.

Viscoelastic Monitoring to Guide the Correction of Perioperative Coagulopathy and Massive Transfusion in Patients with Life-Threatening Hemorrhage.

The resuscitation of patients with traumatic hemorrhage remains a challenging clinical scenario. The appropriate and aggressive support of the patient's coagulation is of critical importance. Conventional coagulation assays present several shortcomings in this setting. The integration of viscoelastic monitoring in clinical practice has the potential to result in significant improvements. In order to be successful, the provider must understand basics of the methodology, read outs, and the limitations of the technique.

A Pilot Study of Viscoelastic Monitoring in Pediatric Trauma: Outcomes and Lessons Learned.

BACKGROUND: Examine the characteristics and outcomes of pediatric trauma patients at risk for coagulopathy following implementation of viscoelastic monitoring. MATERIALS AND METHODS: Injured children, aged <18 years, from September 7, 2014, to December 21, 2015, at risk for trauma-induced coagulopathy were identified from a single, level-1 American College of Surgeons verified pediatric trauma center. Patients were grouped by coagulation assessment: no assessment (NA), conventional coagulation testing alone (CCT), and conventional coagulation testing with rapid thromboelastography (rTEG). Coagulation assessment was provider preference with all monitoring options continuously available. Groups were compared and outcomes were evaluated including blood product utilization, Intensive Care Unit (ICU) utilization, duration of mechanical ventilation, and mortality. RESULTS: A total of 155 patients were identified (NA = 78, CCT = 54, and rTEG = 23). There was no difference in age, gender, race, or mechanism. In practice, rTEG patients were more severely injured, more anemic, and received more blood products and crystalloid (P < 0.001). rTEG patients also had increased mortality with fewer ventilator and ICU-free days. Multivariate logistic regression and covariance analysis indicated that while rTEG use was not associated with mortality, it was associated with increased use of blood products, duration of mechanical ventilation, and ICU length of stay. CONCLUSIONS: Viscoelastic monitoring was infrequently performed, but utilized in more severely injured patients. Well-designed prospective studies in patients at high risk of coagulopathy are needed to evaluate goal-directed hemostatic resuscitation strategies in children.

Thromboelastometry in trauma care: a place in the 2018 Belgian health care system?

Introduction Evidence supporting the use of Thromboelastography (TEG®) and rotational thromboelastometric (ROTEM®) in the trauma setting remains limited. We present the results of a practical evaluation of the potential interest of ROTEM® in the diagnosis of acute coagulopathy and the need for emergent blood product transfusion in the general trauma population of a non-trauma Belgian emergency department. Methods Extracting a convenience cohort from the initial prospective TICCS study, we performed a retrospective analysis to test the following hypothesis: ROTEM® might be helpful to discriminate trauma patients with or without acute coagulopathy. Fifty patients were included and ROTEM® results were compared to conventional coagulation tests results, blood transfusion need and outcome. Results With a negative predictive value of 97.6% and a positive predictive value of 42.9%, a strictly normal ROTEM® profile at the time of admission seems to be able to exclude the presence of acute coagulopathy. ROTEM® also seems to be accurate in identifying patients without the need for emergent blood product transfusions. Conclusion In a population of trauma patients of a Belgian general emergency department, a strictly normal coagulation profile evaluated by ROTEM® at hospital entry is associated with a normal coagulation profile evaluated by INR and fibrinogen levels and the absence of any indication of blood product transfusion. ROTEM® may be useful for preselection of trauma patients at risk for coagulopathy within the global trauma population. This, however, would need confirmation in further investigations. TRIAL REGISTRATION: clinicaltrials.gov NCT02132208 Registered 6 May 2014.

Fluid Management in Patients with Trauma: Restrictive Versus Liberal Approach.

Massive hemorrhage remains a major cause of traumatic deaths. The ideal fluid resuscitative strategy is much debated. Research has provided inconsistent results regarding which fluid strategy is ideal; the optimum fluid type, timing, and volume remains elusive. Aggressive large-volume resuscitation has been the mainstay based on controlled hemorrhage animal models. For uncontrolled hemorrhagic shock, liberal fluid resuscitative strategies exacerbate the lethal triad, invoke resuscitative injury, and increase mortality while more restrictive fluid strategies tend to ameliorate trauma-induced coagulopathy and favor a greater chance of survival. This article discusses the current evidence regarding liberal and restrictive fluid strategies for trauma.

Blood Transfusion Strategies for Hemostatic Resuscitation in Massive Trauma.

Massive transfusion practices were transformed during the 1970s without solid evidence supporting the use of component therapy. A manual literature search was performed for all references to the lethal triad, acute or early coagulopathy of trauma, fresh whole blood, and component transfusion therapy in massive trauma, and damage control resuscitation. Data from recent wars suggest traditional component therapy causes a nonhemostatic resuscitation worsening the propagation of the lethal triad hastening death. These same studies also indicate the advantage of fresh whole blood over component therapy even when administered in a 1:1:1 replacement ratio.