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Management of major trauma haemorrhage: Treatment priorities and controversies
British Journal of Haematology
Abstract
The severely injured trauma patient often arrives in the emergency department bleeding, coagulopathic and in need of a blood transfusion. The diagnosis and management of these patients has vastly improved with a better understanding of acute traumatic coagulopathy (ATC). In the emergency setting, traditional laboratory coagulation screens are of limited use in the diagnosis and management of life-threatening bleeding. Whole blood assays, such as thrombelastography (TEG) and rotational thrombelastometry (ROTEM) provide a rapid evaluation of clot formation, strength and lysis. Rapid diagnosis of ATC and aggressive haemostatic transfusion strategies utilizing early high doses of plasma are associated with improved outcomes in trauma. At present there is no accurate guide for transfusion in trauma, therefore blood and clotting products are administered on an empiric basis. Targeted transfusion therapy for major trauma haemorrhage based on comprehensive and rapid measures of coagulation e.g. TEG/ROTEM may lead to improved outcomes while optimizing blood utilization. Evidence for the clinical application of TEG and ROTEM in trauma is emerging with a number of studies evaluating their ability to diagnose coagulopathy early and facilitate goal-directed transfusion. This review explores current controversies and best practice in the diagnosis and management of major haemorrhage in trauma.
... However, standard blood coagulation tests have at least 2 limitations. First, the time needed to obtain the results of these tests may lead to delayed management [7]. Second, they provide information on specific coagulation functions that could appear quantitatively preserved in early blood loss despite an inappropriate qualitative function in the case of whole blood clot formation [7][8][9]. ...
... First, the time needed to obtain the results of these tests may lead to delayed management [7]. Second, they provide information on specific coagulation functions that could appear quantitatively preserved in early blood loss despite an inappropriate qualitative function in the case of whole blood clot formation [7][8][9]. ...
... Length of stay in ICU (when alive) 8 (3-11) 11 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) Death at day 1 (%) 17 (11) 17 (20) Death at day 28 (%) 30 (19) 30 (35) Reason of death on day 28 ...
Background:
Traumatic hemorrhage guidelines include point-of-care viscoelastic tests as a standard of care. Quantra (Hemosonics) is a device based on sonic estimation of elasticity via resonance (SEER) sonorheometry to assess whole blood clot formation.
Objectives:
Our study aimed to assess the ability of an early SEER evaluation to detect blood coagulation test abnormalities in trauma patients.
Methods:
We conducted an observational retrospective cohort study with data collected at hospital admission of consecutive multiple trauma patients from September 2020 to February 2022 at a regional level 1 trauma center. We performed a receiving operator characteristic curve analysis to determine the ability of the SEER device to detect blood coagulation test abnormalities. Four values on the SEER device were analyzed: clot formation time, clot stiffness (CS), platelet contribution to CS, and fibrinogen contribution to CS.
Results:
A total of 156 trauma patients were analyzed. The clot formation time value predicted an activated partial thromboplastin time ratio of >1.5 with an area under the curve (AUC) of 0.93 (95% CI, 0.86-0.99). The AUC of the CS value in detecting an international normalized ratio of prothrombin time of >1.5 was 0.87 (95% CI, 0.79-0.95). The AUC of fibrinogen contribution to CS to detect a fibrinogen concentration of <1.5 g/L was 0.87 (95% CI, 0.80-0.94). The AUC of platelet contribution to CS to detect a platelet concentration of <50 G/L was 0.99 (95% CI, 0.99-1.00).
Conclusion:
Our results suggest that the SEER device may be useful for the detection of blood coagulation test abnormalities at trauma admission.
... However, standard blood coagulation tests have at least 2 limitations. First, the time needed to obtain the results of these tests may lead to delayed management [7]. Second, they provide information on specific coagulation functions that could appear quantitatively preserved in early blood loss despite an inappropriate qualitative function in the case of whole blood clot formation [7][8][9]. ...
... First, the time needed to obtain the results of these tests may lead to delayed management [7]. Second, they provide information on specific coagulation functions that could appear quantitatively preserved in early blood loss despite an inappropriate qualitative function in the case of whole blood clot formation [7][8][9]. ...
... Length of stay in ICU (when alive) 8 (3-11) 11 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) Death at day 1 (%) 17 (11) 17 (20) Death at day 28 (%) 30 (19) 30 (35) Reason of death on day 28 ...
... The classification process used a hierarchical system of diagnoses and procedures to create mutually exclusive groups (see Supplementary Table S1 for additional details). These underlying disorders were further classified into three clinical phenotypes of DIC on the basis of previous studies: 1) marked bleeding type (leukemia (16) , trauma (17) , obstetric diseases (18) , and aortic diseases (19) ); 2) organ failure type (sepsis (20) and pancreatitis (21) ); and 3) asymptomatic type (solid cancer (22) ). ...
... Using a national inpatient database in Japan, our study analyzed a large number of patients with DIC and revealed the associations between underlying disorders, clinical phenotypes, and actual treatment patterns. Age (years), mean (SD) 71 (17) Our results suggest that the existing clinical phenotypes of DIC are not associated with the clinical presentation of organ failure or marked bleeding in patients with various underlying disorders. Resulting in organ failure, pathophysiologically all underlying disorders of DIC share the ability to induce systemic activation of coagulation (1) . ...
Introduction:
Clinical guidelines state that disseminated intravascular coagulation (DIC) treatment should be based on three clinical phenotypes: the marked bleeding type (e.g. leukemia, trauma, obstetric diseases, or aortic diseases); organ failure type (sepsis or pancreatitis); and asymptomatic type of DIC (solid cancer). However, among the various underlying disorders of DIC, the clinical presentations of bleeding or organ failure have not to date been well documented. The present study aimed to evaluate whether underlying disorders of DIC would affect clinical outcome including death, organ failure, and bleeding.
Methods:
Using the Japanese Diagnosis Procedure Combination inpatient database, we identified all adult patients diagnosed with DIC during hospitalization from July 1, 2010, to March 31, 2018. We collected data on patient characteristics and underlying disorders of DIC including sepsis, solid cancer, leukemia, trauma, obstetric diseases, aortic diseases, pancreatitis, and miscellaneous diseases. We counted major bleeding events and calculated an organ failure score for patients during hospitalization.
Results:
We identified 337,132 patients with DIC. The major disorders underlying DIC were sepsis (42%) and solid cancer (31%). The average organ failure scores of patients with aortic diseases, sepsis, and trauma were 2.8, 2.2, and 2.2, respectively. The percentages with major bleeding events among patients with aortic diseases, trauma, obstetric diseases, and solid cancer were 24%, 15%, 10%, and 10%, respectively.
Conclusions:
This study suggests that the clinical presentations of bleeding and organ failure are not associated with the three existing clinical phenotypes of DIC or with the underlying disorders of DIC. Therefore, clinical presentation alone may not be sufficient for identifying the clinical phenotypes of DIC. Further research is necessary to develop new strategies for identifying the phenotypes of DIC and improving treatment strategies for individual patients.
... For example, even an international multi-centre retrospective analysis of over 3000 patients could not define a threshold at which massive transfusion equals poorer outcomes [5]. However, in the absence of other measures, massive and major transfusion was used here to retrospectively identify haemorrhagic patients [49]. Arguably, there is no universal approach to massive transfusion; hence, emerging evidence for the clinical application of TEG and ROTEM to detect ATC [49]. ...
... However, in the absence of other measures, massive and major transfusion was used here to retrospectively identify haemorrhagic patients [49]. Arguably, there is no universal approach to massive transfusion; hence, emerging evidence for the clinical application of TEG and ROTEM to detect ATC [49]. ...
Background:
Major haemorrhage is a leading cause of mortality following major trauma. Increasingly, Helicopter Emergency Medical Services (HEMS) in the United Kingdom provide pre-hospital transfusion with blood products, although the evidence to support this is equivocal. This study compares mortality for patients with suspected traumatic haemorrhage transfused with pre-hospital packed red blood cells (PRBC) compared to crystalloid.
Methods:
A single centre retrospective observational cohort study between 1 January 2010 and 1 February 2015. Patients triggering a pre-hospital Code Red activation were eligible. The primary outcome measure was all-cause mortality at 6 hours (h) and 28 days (d), including a sub-analysis of patients receiving a major and massive transfusion. Multivariable regression models predicted mortality. Multiple Imputation was employed, and logistic regression models were constructed for all imputed datasets.
Results:
The crystalloid (n = 103) and PRBC (n = 92) group were comparable for demographics, Injury Severity Score (p = 0.67) and mechanism of injury (p = 0.73). Observed 6 h mortality was smaller in the PRBC group (n = 10, 10%) compared to crystalloid group (n = 19, 18%). Adjusted OR was not statistically significant (OR 0.48, CI 0.19-1.19, p = 0.11). Observed mortality at 28 days was smaller in the PRBC group (n = 21, 26%) compared to crystalloid group (n = 31, 40%), p = 0.09. Adjusted OR was not statistically significant (OR 0.66, CI 0.32-1.35, p = 0.26). A statistically significant greater proportion of the crystalloid group required a major transfusion (n = 62, 60%) compared to the PRBC group (n = 41, 40%), p = 0.02. For patients requiring a massive transfusion observed mortality was smaller in the PRBC group at 28 days (p = 0.07).
Conclusion:
In a single centre UK HEMS study, in patients with suspected traumatic haemorrhage who received a PRBC transfusion there was an observed, but non-significant, reduction in mortality at 6 h and 28 days, also reflected in a massive transfusion subgroup. Patients receiving pre-hospital PRBC were significantly less likely to require an in-hospital major transfusion. Further adequately powered multi-centre prospective research is required to establish the optimum strategy for pre-hospital volume replacement in patients with traumatic haemorrhage.
... Currently, there are no accurate methods to assess acute trauma coagulopathy so the early empirical transfusion of blood and clotting factors are considered as best current treatment of coagulopathy [25]. Presumably, the extent of injury is great enough in these patients to lead to massive consumption of coagulation factors, either directly or through activation of the protein C pathway. ...
... Monitoring by Rotational elastometer (ROTEM) or Thromboelastography (TEG) can be a promising approach. In a recent Cochrane analysis, 6 studies were identified which compared clinical judgment and standard laboratory tests or both in the adult cardiac surgery and liver transplantation setting [24][25][26][27][28][29][30][31][32]. These research could not found any beneficial effect of TEG or ROTEM on patient survival but they found a positive effects in pre defined outcomes such as reduced bleeding and reduced proportion of patients requiring transfusion of platelets or plasma to save the cost. ...
... El tiempo de tromboplastina parcial activado, monitoriza la vía de contacto y la vía común (7,8). Ni el TP, ni TTPa evalúan la fibrinólisis (9,10) . ...
Introducción:
El embarazo es un estado asociado con profundos cambios en el sistema hemostático determinando un estado de hipercoagulabilidad relacionado con un aumento en generación de trombina, y como tal, un factor de riesgo bien establecido de Enfermedad Tromboembólica Venosa. El objetivo del presente trabajo es determinar y comparar la generación de trombina en los puerperios de parto con puerperios cesáreas. Evaluar el potencial de generación de trombina como un factor de riesgo adicional para decidir la indicación tromboprofilaxis.
Metodología:
Estudio analítico observacional prospectivo realizado en el Hospital Pereira Rossell, octubre de 2018 a agosto del 2019.
La medición del potencial endógeno de trombina se realizó en el analizador de coagulación BCS® XP automatizado en el Hospital de Clínicas.
Resultados:
220 embarazadas, 70 cesáreas (C) y 150 partos (P). El potencial endogeno de trombina (ETP AUC2) fue menor estadísticamente en el grupo P, valor p < 0,001.La concentración máxima de generación de trombina calculado (ETPB AUC2) fue estadísticamente menor en el grupo P valor p = 0,010.
Discusión:
Hay una diferencia estadísticamente significativa cuando comparamos los parámetros de ETP AUC2 y ETPB AUC2 de los grupos de partos vs cesárea, siendo menor para partos.
Conclusión:
Las cesáreas presentan un ETP AUC2, ETPB AUC2 mayor que los partos. Esto permitiría seleccionar pacientes con mayor riesgo de enfermedad tromboembólica venosa. La cesárea se identificó como un evento generador de trombina probablemente asociado al mayor daño endotelial que produce.
... Cuando se activa un protocolo de transfusión masiva, se administra una proporción determinada de componente sanguíneo que puede ser glóbulos rojos, plasma y plaquetas.8 La proporción óptima del uso de hemoderivados es incierta, pero se han adoptado algunas proporciones de glóbulos rojos y plasma fresco de 3:2 o 2:1.12,20 Respecto al antifibrinolítico, el más comúnmente prescrito es el ácido tranexámico, que ha demostrado ser benéfico al reducir el riesgo de muerte por hemorragia.8,21 ...
... Due to an ageing population, traumatic injury is also expected to become a significant cause of morbidity and mortality in older people [3,4]. Uncontrolled haemorrhage accounts for 40% of all trauma-related deaths, and, therefore, controlling haemorrhage and restoring blood volume form the core of the current therapeutic approach to trauma bleeding [5][6][7]. Injury is a global health concern, and the economic burden attributed to the management of patients with trauma haemorrhage is significant; for example, it was estimated that in England the cost of managing haemorrhage after trauma was GBP 168 million per year [8,9]. Despite extensive efforts to improve clinical management and patient outcomes, trauma remains a clinical and socioeconomic issue of major relevance for young people and is becoming a larger issue for the elderly [10]. ...
Trauma-induced coagulopathy (TIC) is a major cause of morbidity and mortality in patients with traumatic injury. It describes the spectrum of coagulation abnormalities that occur because of the trauma itself and the body’s response to the trauma. These coagulation abnormalities range from hypocoagulability and hyperfibrinolysis, resulting in potentially fatal bleeding, in the early stages of trauma to hypercoagulability, leading to widespread clot formation, in the later stages. Pathological changes in the vascular endothelium and its regulation of haemostasis, a phenomenon known as the endotheliopathy of trauma (EoT), are thought to underlie TIC. Our understanding of EoT and its contribution to TIC remains in its infancy largely due to the scarcity of experimental research. This review discusses the mechanisms employed by the vascular endothelium to regulate haemostasis and their dysregulation following traumatic injury before providing an overview of the available experimental in vitro and in vivo models of trauma and their applicability for the study of the EoT and its contribution to TIC.
... Due to an ageing population, traumatic injury is also expected to become a significant cause of morbidity and mortality in older people [3,4]. Uncontrolled haemorrhage accounts for 40% of all trauma-related deaths, and, therefore, controlling haemorrhage and restoring blood volume form the core of the current therapeutic approach to trauma bleeding [5][6][7]. Injury is a global health concern, and the economic burden attributed to the management of patients with trauma haemorrhage is significant; for example, it was estimated that in England the cost of managing haemorrhage after trauma was GBP 168 million per year [8,9]. Despite extensive efforts to improve clinical management and patient outcomes, trauma remains a clinical and socioeconomic issue of major relevance for young people and is becoming a larger issue for the elderly [10]. ...
Adipose-derived stem cells (ADSCs) as part of autologous fat grafting have anti-fibrotic and anti-inflammatory effects, but the exact mechanisms of action remain unknown. By simulating the interaction of ADSCs with fibroblasts and endothelial cells (EC) from scleroderma (SSc) skin in silico, we aim to unravel these mechanisms. Publicly available single-cell RNA sequencing data from the stromal vascular fraction of 3 lean patients and biopsies from the skin of 10 control and 12 patients with SSc were obtained from the GEO and analysed using R and Seurat. Differentially expressed genes were used to compare the fibroblast and EC transcriptome between controls and SSc. GO and KEGG functional enrichment was performed. Ligand–receptor interactions of ADSCs with fibroblasts and ECs were explored with LIANA. Pro-inflammatory and extracellular matrix (ECM) interacting fibroblasts were identified in SSc. Arterial, capillary, venous and lymphatic ECs showed a pro-fibrotic and pro-inflammatory transcriptome. Most interactions with both cell types were based on ECM proteins. Differential interactions identified included NTN1, VEGFD, MMP2, FGF2, and FNDC5. The ADSC secretome may disrupt vascular and perivascular inflammation hubs in scleroderma by promoting angiogenesis and especially lymphangiogenesis. Key phenomena observed after fat grafting remain unexplained, including modulation of fibroblast behaviour.
... Systemic anticoagulation is secondary to many biochemical processes, including the activation of proteins C and S, high levels of tissue plasminogen activator, platelet dysfunction, and consumptive coagu-lopathy manifesting as disseminated intravascular coagulation [38]. Point-of-care testing such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) allows anesthesiologists to target resuscitative therapy in the operating room to the specific etiology of any coagulopathy by examining kinetics of clot initiation, formation, strength, and breakdown (Fig. 79.3) [39,40]. ...
This chapter offers a key foundation for the anesthetic care of the trauma patient so that the surgical and anesthetic teams may coordinate care to increase the chances for a meaningful recovery for the patient. The anesthesiologist plays an integral role in the care of the patient following traumatic injury that spans multiple phases of care: arrival in the trauma bay; initial stabilization and resuscitation; management of general anesthesia; postoperative intensive care; and pain management. The physiologic derangements associated with trauma begin at the moment of injury and have often manifested by the time the patient arrives in the emergency department. Medications for airway management and the induction and maintenance of general anesthesia should be carefully selected according to the patient’s clinical status. Resuscitation of shock should be directed at identifying and correcting the underlying pathology. In the interim, treatment should be tailored based on vital signs, laboratory values, and point-of-care testing. Hemorrhagic shock is the most common etiology of shock in trauma and is best addressed with a balanced resuscitation with blood products and with constant vigilance regarding impending sequelae of vascular and organ injury that may complicate management. Special populations, such as patients with traumatic brain injury or burns, or patients who are pregnant, require particular considerations from an anesthetic standpoint.
... Studies involving viscoelastic tests are mainly based on the prediction of bleeding (hyperfibrinolysis) and the requirement for blood and blood products in the settings of trauma resuscitation and in surgery [66][67][68][69]. Apart from maximum amplitude (MA) which is a measure of hypercoagulability [70], there has not been any studies correlating fibrinolytic assessment using viscoelastic tests and adverse outcomes. ...
The occurrence of thrombotic complications, which can result in excess mortality and morbidity, represent an imbalance between the pro-thrombotic and fibrinolytic equilibrium. The mainstay treatment of these complications involves the use of antithrombotic agents but despite advances in pharmacotherapy, there remains a significant proportion of patients who continue to remain at risk. Endogenous fibrinolysis is a physiological counter-measure against lasting thrombosis and may be measured using several techniques to identify higher risk patients who may benefit from more aggressive pharmacotherapy. However, the assessment of the fibrinolytic system is not yet accepted into routine clinical practice. In this review, we will revisit the different methods of assessing endogenous fibrinolysis (factorial assays, turbidimetric lysis assays, viscoelastic and the global thrombosis tests), including the strengths, limitations, correlation to clinical outcomes of each method and how we might integrate the assessment of endogenous fibrinolysis into clinical practice in the future.
... 18 In people, abdominal haemorrhage is often associated with trauma, leading to acute traumatic coagulopathy. 9 Hypoperfusion-associated generation of thrombomodulin-thrombin formation activates protein C, which inhibits plasminogen activator inhibitor-1 and results in hyperfibrinolysis and depletion of fibrinogen. 11 Regardless whether consumption or trauma-induced coagulopathy predominates, massive bleeding leads to hypocoagulability and hyperfibrinolysis. ...
Introduction:
Rotational thromboelastometry (ROTEM) is a viscoelastic coagulation test that allows the evaluation of haemostasis from clot formation to clot dissolution. The aim of this retrospective study was to describe the changes in haemostasis using ROTEM parameters in dogs presenting with spontaneous or traumatic haemoperitoneum and to evaluate any associations between clinical and laboratory parameters at presentation with the ROTEM. We hypothesized that the dogs would show signs of hypocoagulability and hyperfibrinolysis and that these changes would correlate with the degree of hypoperfusion. Clinical records were searched for a period of 5 years for dogs presenting with a haemoperitoneum und for whom a -ROTEM analysis at presentation was carried out. Forty dogs were identified, and various clinical and laboratory parameter (heart rate, blood pressure, blood glucose, lactate, serum albumin concentration, PCV (venous and abdominal), ionized calcium, pH and base excess) were retrieved. The following ROTEM parameters were analysed: extrinsic clotting time (ExTEM CT), clot formation time (ExTEM CFT), clot firmness (ExTEM MCF) and maximum lysis (ExTEM ML), as well as fibrinogen (FibTEM) CT and MCF. Compared to institutional reference intervals, dogs with haemoabdomen showed prolongation of ExTEM and FibTEM CT, ExTEM CFT and 50% were hypocoagulable and 62% thrombocytopenic. No hyperfibrinolysis could be detected. Multiple linear regression models showed an association between decreased base excess, trauma and ROTEM signs for hypocoagulability. Furthermore, age was associated with a stronger fibrin clot. In conclusion, 50% of the dogs presented hypocoagulable and changes in ROTEM parameters are similar to those seen with consumption coagulopathy. Base excess and trauma were associated with hypocoagulability, while increasing age was associated with a stronger fibrin clot.
... Rotational thromboelastometry (ROTEM®) adopts the same principles of TEG, as a method that assess the viscoelastic property of whole blood allowing the evaluation of the initiation, formation, stability and lysis of the clot [23]. These point-of-care (POC) tests have become complementary tools to traditional static tests [25,26], and recent studies have shown that coagulation assessment and viscoelastic tests-guided therapy during high risk procedures, such as cardiovascular surgery and trauma, can have a significant impact on the reduction of transfusion of blood products and also in the morbidity and mortality of the patients [27,28]. ...
Background:
Perioperative bleeding and transfusion are important causes of morbidity and mortality in patients undergoing liver transplantation. The aim of this study is to assess whether viscoelastic tests-guided therapy with the use of synthetic factor concentrates impact transfusion rates of hemocomponents in adult patients undergoing liver transplantation.
Methods:
This is an interventional before-after comparative study. Patients undergoing liver transplantation before the implementation of a protocol using thromboelastometry and synthetic factor concentrates were compared to patients after the implementation. Primary outcome was transfusion of any hemocomponents. Secondary outcomes included: transfusion of red blood cells (RBC), fresh frozen plasma (FFP), cryoprecipitate or platelets, clinical complications, length of stay and in-hospital mortality.
Results:
A total of 183 patients were included in the control and 54 in the intervention phase. After propensity score matching, the proportion of patients receiving any transfusion of hemocomponents was lower in the intervention phase (37.0 vs 58.4%; OR, 0.42; 95% CI, 0.20-0.87; p = 0.019). Patients in the intervention phase received less RBC (30.2 vs 52.5%; OR, 0.21; 95% CI, 0.08-0.56; p = 0.002) and FFP (5.7 vs 27.3%; OR, 0.11; 95% CI, 0.03-0.43; p = 0.002). There was no difference regarding transfusion of cryoprecipitate and platelets, complications related to the procedure, hospital length of stay and mortality.
Conclusions:
Use of a viscoelastic test-guided transfusion algorithm with the use of synthetic factor concentrates reduces the transfusion rates of allogenic blood in patients submitted to liver transplantation.
Trial registration:
This trial was registered retrospectively on November 15th, 2018 - clinicaltrials.gov - Identifier: NCT03756948.
... The most important goal of first-line therapy is the prevention of further bleeding [2]. To prevent massive bleeding, hemostasis should be achieved rapidly without complications [3,4]. Patients with excessive bleeding might require a blood transfusion for the provision of various coagulation factors and to prevent shock or organ dysfunction [5]. ...
Background and objective:
Batroxobin, a snake venom thrombin-like enzyme, converts fibrinogen into fibrin by cleaving fibrinopeptide A. It is used for hemostasis; however, the supply of native batroxobin is limited. Therefore, we developed a recombinant batroxobin (r-batroxobin) from Pichia pastoris and evaluated its pharmacodynamics and safety in humans.
Methods:
A randomized, double-blind, placebo-controlled, single ascending-dose study was performed. Eight healthy subjects were enrolled in each r-batroxobin dose group (2.5, 5.0, or 10.0 BU/2.0 mL administered intravenously), and randomized to receive r-batroxobin (n = 6) or matching placebo (n = 2). Safety was evaluated during the study, and pharmacodynamics was assessed using prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen level.
Results:
All subjects in each cohort completed the study. No significant changes in PT or aPTT occurred after intravenous r-batroxobin administration. Compared with the placebo group, the fibrinogen level in all r-batroxobin dose groups decreased significantly to 8.68-33.57% from the baseline within 12 h (p ≤ 0.05). The TT in the 5.0 and 10.0 BU/2.0 mL groups significantly increased to 7.53-18.48% from baseline within 12 h compared with that of the placebo group (p ≤ 0.05), whereas that of the 2.5 BU/2.0 mL group exhibited non-significant changes compared with the placebo group. No serious adverse events occurred.
Conclusions:
A single intravenous injection of r-batroxobin within a dose range of 2.5-10.0 BU/2.0 mL was well tolerated and resulted in a significant decrease in fibrinogen and prolongation of TT.
Registration:
This study is registered at the Clinical Research Information Service (CRIS, http://cris.nih.go.kr ), number KCT0002518.
... In trauma patients, the "lethal triad" should be rapidly interrupted [47][48][49][50][51][52][53]. ...
Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartmentsyndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangementsand multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinicalsituations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source ofinfection or the necessity to re-explore (as a“planned second-look”laparotomy) or complete previously initiateddamage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-traumapatients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuriesor critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consumingand represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only beconsidered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as thepatient can physiologically tolerate it. All precautions to minimize complications should be implemented.
... 62 This trauma-induced coagulopathy has been shown to be an independent predictor of multiorgan failure, septic complications, length of ICU stay, and mortality. 67 As hemorrhage continues and tissues become hypoperfused, acidosis develops. The ability to clear this acidosis, as analyzed by lactate clearance, has been correlated to survival. ...
The term “open abdomen” refers to a surgically created defect in the abdominal wall that exposes abdominal viscera. Leaving an abdominal cavity temporarily open has been well described for several indications, including damage control surgery and abdominal compartment syndrome. Although beneficial in certain patients, the act of keeping an abdominal cavity open has physiologic repercussions that must be recognized and managed during postoperative care. This review article describes these issues and provides guidelines for the critical care physician managing a patient with an open abdomen.
... There have been very limited clinical studies exploring the relationship of clot properties with clinical outcome. TEG ® and ROTEM ® have been in use for a long time in the prediction of bleeding and the requirement for blood and blood products in the settings of trauma resuscitation and in operating theatres [92][93][94][95]. Although their use in the capacity of hyperfibrinolysis is well described in the literature, with regards of hypofibrinolysis (namely thrombosis risk assessment), it has had less success [96]. ...
The processes of thrombosis and coagulation are finely regulated by endogenous fibrinolysis maintaining healthy equilibrium. When the balance is altered in favour of platelet activation and/or coagulation, or if endogenous fibrinolysis becomes less efficient, pathological thrombosis can occur. Arterial thrombosis remains a major cause of morbidity and mortality in the world despite advances in medical therapies. The role endogenous fibrinolysis in the pathogenesis of arterial thrombosis has gained increasing attention in recent years as it presents novel ways to prevent and treat existing diseases. In this review article, we discuss the role of endogenous fibrinolysis in platelet thrombus formation, methods of measurement of fibrinolytic activity, its role in predicting cardiovascular diseases and clinical outcomes and future directions.
... Of these three phases, the first phase corresponds to ATC, and the clinical features of the first phase along with the pathophysiologic factors of the second phase provide the characteristics of trauma-induced coagulopathy (Fig. 2) [22]. Recently, the clinical features and pathophysiology of trauma-induced coagulopathy have been recognized as the comprehensive condition of ATC involving resuscitationassociated coagulopathy, a systemic inflammatory response to tissue injury, and predisposing factors [23]. ...
Hemorrhage is the most important contributing factor of acute-phase mortality in trauma patients. Previously, traumatologists and investigators identified iatrogenic and resuscitation-associated causes of coagulopathic bleeding after traumatic injury, including hypothermia, metabolic acidosis, and dilutional coagulopathy that were recognized as primary drivers of bleeding after trauma. However, the last 10 years has seen a widespread paradigm shift in the resuscitation of critically injured patients, and there has been a dramatic evolution in our understanding of trauma-induced coagulopathy. Although there is no consensus regarding a definition or an approach to the classification and naming of trauma-associated coagulation impairment, trauma itself and/or traumatic shock-induced endogenous coagulopathy are both referred to as acute traumatic coagulopathy (ATC), and multifactorial trauma-associated coagulation impairment, including ATC and resuscitation-associated coagulopathy is recognized as trauma-induced coagulopathy. Understanding the pathophysiology of trauma-induced coagulopathy is vitally important, especially with respect to the critical issue of establishing therapeutic strategies for the management of patients with severe trauma.
... Uptake of fibrinogen testing following the re-audit was noted to remain poor which may reflect the need for further dissemination of information, or the requirement for a point-of-care coagulation testing system such as rotational thromboelastometry (ROTEM) [40]. The ROTEM system was utilised by the British Army in Camp Bastion, Afghanistan, as a global measure of haemostatic function, and was found to help direct use of blood products in resuscitation [40,41]. However, a recent Cochrane Review highlighted a lack of current evidence for ROTEM, and recommended interventional studies measuring the effect of the use of ROTEM on patient outcome [42]. ...
Addenbrooke’s hospital, the Major Trauma Centre for the east of England, received 1070 major trauma patients between 1st January and 31st December 2014. In order to improve care in orthopaedic trauma, an audit was performed of 59 patients meeting our own selection criteria for orthopaedic polytrauma. The Addenbrooke’s Early Appropriate Care pathway was devised through literature review, internal and external discussion. It facilitates provision of best practice care, according to NCEPOD guidelines and our own literature review, encompassing − multidisciplinary consultant decisions around the patient in our Neurological and Trauma Critical Care Unit, early full body trauma CT scans, serial measurements of lactate and fibrinogen levels, and out-of-hours orthopaedic theatre reserved for life-and-limb threatening injuries. Re-audit was conducted of 15 patients meeting selection criteria, admitted between 1st October 2014 and 31st March 2015. Significant improvements in recording of lactate and fibrinogen were demonstrated, both on admission (lactate − p < 0.000, fibrinogen − p = 0.015), and preoperatively (lactate − p = 0.003, fibrinogen − p = 0.030). Time to trauma CT was unchanged (p = 0.536) with a median time to CT of 0.53 hours at re-audit (IQR 0.48-0.75). The number of patients receiving definitive orthopaedic intervention out-of-hours reduced from 8 to zero (p = 0.195). The approach of facilitating management decisions to be made at early daytime MDT meetings has been adopted. It is anticipated that this pathway will improve outcomes in Addenbrooke’s orthopaedic polytrauma patients and it is recommended that either the GOS-E, or the EQ-5D scoring systems be introduced to assess this.
... [5][6][7][8][9][10][11][12][13] This opportunity has developed primarily through our further understanding of the role blood and, more specifically, coagulation therapy, plays in DCR. [14][15][16][17] Driving the focus on optimal transfusion support in DCR is the increasing use of major hemorrhage protocols (MHPs) to ensure early delivery of red blood cells (RBCs) and hemostatic components. 18,19 In addition, there has been a wider acceptance of the restricted use of prehospital non-blood-based fluids, in favor of waiting until MHPs can be provided within hospitals. ...
Transfusion support is a key enabler to the response to mass casualty events (MCEs). Transfusion demand and capability planning should be an integrated part of the medical planning process for emergency system preparedness. Historical reviews have recently supported demand planning for MCEs and mass gatherings; however, computer modeling offers greater insights for resource management. The challenge remains balancing demand and supply especially the demand for universal components such as group O red blood cells. The current prehospital and hospital capability has benefited from investment in the management of massive hemorrhage. The management of massive hemorrhage should address both hemorrhage control and hemostatic support. Labile blood components cannot be stockpiled and a large surge in demand is a challenge for transfusion providers. The use of blood components may need to be triaged and demand managed. Two contrasting models of transfusion planning for MCEs are described. Both illustrate an integrated approach to preparedness where blood transfusion services work closely with health care providers and the donor community. Preparedness includes appropriate stock management and resupply from other centers. However, the introduction of alternative transfusion products, transfusion triage, and the greater use of an emergency donor panel to provide whole blood may permit greater resilience.
... TEG and ROTEM measures the clot strength and clot forming time and its advantages include that they can obtain the result rapidly and reflect the whole laboratory clotting condition; they are useful in the management of trauma hemorrhage due to the quick availability of results and they can also strongly predict the need for massive transfusion [50] . More and more studies have shown that TEG and ROTEM may be better than traditional coagulation tests in diagnosing TIC because we have found that they are more sensitive than traditional coagulation tests. ...
Traumatic injury remains the leading cause of death with bleeding in the world, representing the main cause of preventable death. But if immediate management could be applied, the outcomes will be dramatically improved. Trauma-induced coagulopathy (TIC) as an early endogenous process in many traumatic patients is driven by the multi-tissue injury and shock, and is associated with increased mortality and bad outcomes in the multi-trauma patients. The understanding of the mechanisms of TIC and its effect on the outcomes of severely injured patients has been developed over the past few years. Here, we aim to review the current understanding and recent findings in the pathobiology of coagulopathy. The principal causes of TIC are hypoperfusion, inflammation response and the activation of the neurohumoral system. Hypoperfusion causes the activation of many biomarkers, like protein C, syndecan-1, plasminogen, and so on. The elevation of these markers indicates the damage of the endothelium, which will lead to autoheparinization in body. When accompanied with acidosis, hypothermia, and hemodilution, the mortality of trauma patients will rise significantly. This article aims to focus on our updated acknowledges on the principal mechanisms and causes of the TIC.
... The introduction of protocols results in a better co-ordinated response, better outcomes and a reduction in complications [3,4]. Although the optimal ratio of blood product use is uncertain there has been a move in civilian centres to adopt RCC:FFP ratios of 3:2 or 2:1 [5]. It is probable that the early use of plasma and platelets should be even higher in the severely injured. ...
... No relationship between OT and MACE was observed.TEG IN CARDIOVASCULAR DISEASE. TEG has been applied to guide the use of blood and blood products during trauma resuscitation(80) and liver and cardiac surgery(81,82), and, more recently, it has also been evaluated in obstetric patients(83). It has now been reliably demonstrated that TEG detects hyperfibrinolysis in the perioperative and trauma setting(84,85), with increasing evidence that TEG-guided algorithms can help to optimize patient management(82,86). ...
Most acute cardiovascular events are attributable to arterial thrombosis. Plaque rupture or erosion stimulates platelet activation, aggregation, and thrombosis, whilst simultaneously activating enzymatic processes that mediate endogenous fibrinolysis to physiologically maintain vessel patency. Interplay between these pathways determines clinical outcome. If proaggregatory factors predominate, the thrombus may propagate, leading to vessel occlusion. However, if balanced by a healthy fibrinolytic system, thrombosis may not occur or cause lasting occlusion. Despite abundant evidence for the fibrinolytic system regulating thrombosis, it has been overlooked compared with platelet reactivity, partly due to a lack of techniques to measure it. We evaluate evidence for endogenous fibrinolysis in arterial thrombosis and review tech- niques to assess it, including biomarkers and global assays, such as thromboelastography and the Global Thrombosis Test. Global assays, simultaneously assessing proaggregatory and fibrinolytic pathways, could play a role in risk strati- fication and in identifying impaired fibrinolysis as a potential target for pharmacological modulation. (J Am Coll Cardiol 2015;65:1683–99) © 2015 by the American College of Cardiology Foundation.
... 25,26 Viscoelastic coagulation testing by ROTEM or TEG, performed using whole blood, may provide a better reflection of the in vivo situation. [27][28][29] These methods also provide a shorter turnaround time than conventional laboratory tests. 26 Consequently, we would consider viscoelastic coagulation testing as preferable to standard laboratory tests. ...
Introduction
In a 24-hour porcine model of liver injury, we showed that fibrinogen supplementation does not downregulate endogenous fibrinogen synthesis. Here we report data from the same study showing the impact of fibrinogen on coagulation variables.
Materials and Methods
Coagulopathy was induced in 20 German land race pigs by hemodilution and blunt liver injury. Animals randomly received fibrinogen concentrate (100 mg/kg) or saline. Coagulation parameters were assessed and thromboelastometry (ROTEM) was performed.
Results
Fibrinogen concentrate significantly reduced the prolongations of EXTEM clotting time, EXTEM clot formation time, and prothrombin time induced by hemodilution and liver injury. A decrease in clot strength was also ameliorated. Endogenous thrombin potential was significantly higher in the fibrinogen group than in the control group, 20 minutes (353 ± 24 vs 289 ± 22 nmol/L·min; P < .05) and 100 minutes (315 ± 40 vs 263 ± 38 nmol/L·min; P < .05) after the start of infusion. However, no significant between-group differences were seen in other thrombin generation parameters or in d-dimer or thrombin–antithrombin levels. Fibrinogen–platelet binding was reduced following liver injury, with no significant differences between groups. No significant between-group differences were observed in any parameter at ∼12 and ∼24 hours.
Conclusion
This study suggests that, in trauma, fibrinogen supplementation may shorten some measurements of the speed of coagulation initiation and produce a short-lived increase in endogenous thrombin potential, potentially through increased clotting substrate availability. Approximately 12 and 24 hours after starting fibrinogen concentrate/saline infusion, all parameters measured in this study were comparable in the 2 study groups.
... Massive hemorrhage is a major cause of early trauma death [1][2][3]. In severely injured trauma patients, trauma-induced coagulopathy commonly occurs [4], and resuscitation with only large volumes of crystalloid or red blood cells causes dilution coagulopathy [5]. Trauma resuscitation with red blood cells, fresh frozen plasma, platelet concentrates, and clotting factors is recommended [3,6]. ...
Background. Damage control surgery (DCS) is a surgical strategy consisting of abbreviated laparotomy and open abdomen (OA) in patients presenting with a deranged physiology in trauma and nontrauma contexts.Method. A literature search was performed and surgical guidelines were accurately reviewed.Diagnosis. DCS is indicated in trauma patients presenting with a deranged physiology, hypotension, acidosis, hypothermia, and coagulopathy. Moreover, OA is indicated in patients with peritonitis and a severe physiological derangement, a need for a deferred anastomosis or a planned second-look for bowel ischemia, a persistent source of peritonitis with the failure of source control, or an extensive visceral edema with the concern for development of abdominal compartment syndrome.Treatment. OA management consists in intentionally leaving the fascial edges of the paired rectus abdominus muscles unapproximated. The abdomen should be reexplored within 24–48 h and closed as soon as possible. Several techniques have been described, with negative pressure wound therapy with continuous fascial traction resulting as the most effective in obtaining delayed fascial closure and reducing complications. The beneficial effect of DCS and OA must be accurately weighted together with its possible complications. Further evidence is required and additional studies are strongly encouraged.KeywordsDamage control surgeryOpen abdomenDamage control resuscitationTraumaPeritonitisGuidelines
Background and Objective: Abdominal trauma is one of the most common causes of death in trauma patients, occurring in 20% of cases. Kidney damage is the most common complication of non-penetrating abdominal trauma. In patients with abdominal trauma, it is important to diagnose and treat possible abdominal injuries. The presence of hematuria and clinical examinations often have little sensitivity and specificity to diagnose intra-abdominal injury. Although Computed Tomography (CT) scan is the standard diagnostic method for abdominal trauma, it has its drawbacks, including radiation. On the contrary, ultrasound is a cheaper, more repetitive, and non-invasive procedure. The present study aimed to determine the diagnostic value of Focused Assessment with Sonography for Trauma (FAST) scan and ultrasound by a radiologist in comparison with abdomen and pelvis CT scan with intravenous (IV) contrast in determining the severity of kidney damage in patients with microscopic hematuria due to non-penetrating abdominal and pelvic trauma. Materials and Methods: This forward-looking study was conducted on patients with blunt abdominal trauma with hematuria in Hamadan Besat Educational and Medical Center in 2018 and 2019. The sampling was performed by census method based on inclusion and exclusion criteria. Patient demographic information, as well as accident information that led to abdominal trauma, were recorded in a checklist. All participants were trained by a third-year emergency medicine assistant and then by a third-or fourth-year radiology assistant via FAST ultrasound to diagnose free abdominal fluid. In the next step, all participants were examined after IV contrast injection using a CT scan device. Finally, the data were analyzed in SPSS software (version 22) using appropriate statistical methods. Results: In this study, 60 eligible patients, including 47 males (78.4%) and 13 females (21.6%) with a mean age of 37.16±37.75 years, were examined. The percentage of agreement between the FAST ultrasound findings performed in the emergency and radiology departments was 93.3%. The agreement between the two methods was significant, with a coefficient of 0.837 (P>0.001). Sensitivity (75 and 80), specificity (100 and 5.92), positive (100 and 2.84), and negative (8.8 and 2.90) predictive values, as well as the Accuracy (91.6 and 3.88) of FAST ultrasound, in both emergency and radiology groups, were acceptable in comparison with CT scan. Conclusion: As evidenced by the obtained results, it can be concluded that ultrasound is a reliable tool for examining patients with abdominal trauma with suspected kidney damage.
Background and importance
Appropriate decision-making is critical for transfusions to prevent unnecessary adverse outcomes; however, transfusion in the emergency department (ED) can only be decided based on sparse evidence in a limited time window.
Objectives
This study aimed to identify factors associated with appropriate red blood cell (RBC) transfusion in the ED by analyzing retrospective data of patients who received transfusions at a single center.
Outcome measures and analysis
This study analyzed associations between transfusion appropriateness and sex, age, initial vital signs, an ED triage score [the Korean Triage and Acuity Scale (KTAS)], the length of stay, and the hemoglobin (Hb) concentration.
Main results
Of 10 490 transfusions, 10 109 were deemed appropriate, and 381 were considered inappropriate. A younger age ( P < 0.001) and a KTAS level of 3–5 ( P = 0.028) were associated with inappropriate transfusions, after adjusting for O 2 saturation and the Hb level.
Conclusions
In this single-center retrospective study, younger age and higher ED triage scores were associated with the appropriateness of RBC transfusions.
Purpose:
We investigated factors contributing to coagulopathy in patients with acute type A aortic dissection (ATAAD) and coagulopathy's influence on patient outcomes.
Methods:
We grouped 420 patients who underwent ATAAD repair-none under anticoagulation therapy or with liver disease-by the prothrombin time-international normalized ratio (PT-INR) at admission: < 1.2 (no coagulopathy, n = 371), 1.2-1.49 (mild coagulopathy, n = 33), or ≥ 1.5 (severe coagulopathy, n = 16). We then compared the clinical presentation, dissection morphology, and outcomes among the groups. We assessed the PT-INR in relation to the preoperative hemodynamics and searched for factors predictive of a PT-INR ≥ 1.2.
Results:
The transfusion volume and operation time were increased among patients with coagulopathy (P < 0.05). The in-hospital mortality (15.2-37.5% vs. 5.1%, P < 0.001) and 5-year survival (61.1-74.4% vs. 87.6%) were relatively poor for these patients. The median PT-INR was 1.03 (0.97-1.1) for patients with stable hemodynamics (n = 318), 1.11 (1.02-1.21) for those in shock (blood pressure < 80 mmHg) not given cardiopulmonary resuscitation (CPR) (n = 81), and 1.1 (1.0-1.54) for those in shock given CPR (n = 21) (P < 0.001). A multivariable analysis identified shock (P < 0.001), a partially thrombosed false lumen (P = 0.006), and mesenteric malperfusion (P = 0.016) as predictive variables.
Conclusions:
Shock, a partially thrombosed false lumen, and mesenteric malperfusion appear to be predictive of dissection-related coagulopathy, which influences outcomes negatively.
Background
The reliability of the electrocardiogram (ECG) after return of spontaneous circulation (ROSC) is unclear. While its predictive value has previously been described, no studies have looked at the influence of time on the post-ROSC ECG.
Aim
This study aimed to evaluate the predictive value of the ECG immediately after ROSC and between 1 and 5 hours later to assess whether time influences its ability to accurately predict the need for percutaneous coronary intervention.
Methods
A single-centre, retrospective, observational 1-year analysis examined the records of post-ROSC patients who underwent coronary angiography and for whom prehospital and delayed post-ROSC ECGs were available for analysis.
Findings
Forty-two post-ROSC ECGs were reviewed alongside angiographic findings. Sensitivities of 25% and 69%, specificities of 60% and 100% and an accuracies of 33% and 76% were calculated for the prehospital and delayed hospital ECGs respectively. A chi-squared value of 7.78 (P=0.0053) suggests there is statistical significance between the two.
Conclusions
The delayed post-ROSC ECG is statistically significantly more accurate, suggesting that time influences the reliability of the post-ROSC ECG.
Systemic inflammation is complex and likely drives clinical outcomes in critical illness such as that which ensues following severe injury. We obtained time course data on multiple inflammatory mediators in the blood of blunt trauma patients. Using dynamic network analyses, we inferred a novel control architecture for systemic inflammation: a three-way switch comprising the chemokines MCP-1/CCL2, MIG/CXCL9, and IP-10/CXCL10. To test this hypothesis, we created a logical model comprising this putative architecture. This model predicted key qualitative features of systemic inflammation in patient sub-groups, as well as the different patterns of hospital discharge of moderately vs. severely injured patients. Thus, a rational transition from data to data-driven models to mechanistic models suggests a novel, chemokine-based mechanism for control of acute inflammation in humans and points to the potential utility of this workflow in defining novel features in other complex diseases.
Objective
To assess whether the introduction of point‐of‐care rotational thromboelastometry (ROTEM) analysis influences blood product transfusion and coagulation management in a modern Australian level 1 trauma centre.
Methods
Retrospective blood transfusion data collection from all level 1 trauma patients with an Injury Severity Score (ISS) >12 presenting to the Royal Adelaide Hospital in 2016 and 2018. Evaluation of changes in blood product administration with the addition of point‐of‐care viscoelastic testing in the ED in 2018.
Results
A total of 774 patients were analysed with 380 in 2016 and 394 in 2018. Almost a quarter of all 2018 trauma patients (93/394) had ROTEM performed within 24 h of ED arrival, 42% of these having an ISS >25. There was a significant increase in the number of patients receiving cryoprecipitate following the introduction of ROTEM (P = 0.01). In those receiving cryoprecipitate, there was a significant reduction in subsequent platelet and fresh frozen plasma use (P < 0.001). Overall, there was a reduction in expenditure on red cells, platelets and fresh frozen plasma from 2016 to 2018.
Conclusion
Point‐of‐care ROTEM was performed in a small proportion of patients, mainly those with a higher ISS. ROTEM introduction in the ED altered blood product transfusion practices for major trauma patients with an ISS >12, leading to a potentially safer transfusion strategy and cost savings for key blood products.
Objective The aim of this study was to describe the coagulation status of traumatized dogs over the first 24 hours after admission.
Study Design In 33 dogs presenting within 6 hours after trauma blood was sampled for rotational thromboelastometry (ROTEM), thrombocyte number and venous blood gas analysis at presentation and 6 and 24 hours thereafter. At each time point, dogs were defined as hypo-, normo- or hypercoagulable based on extrinsic, intrinsic and fibrinogen ROTEM profiles.
Results Significantly more dogs (11/33) presented hypocoagulable compared with 6 hours (p = 0.046) and 24 hours (p = 0.008) thereafter and none presented hypercoagulable. Significantly more dogs were hypercoagulable (6/23, p = 0.014) and no dog was hypocoagulable at 24 hours compared with presentation. All evaluated ROTEM parameters except maximum lysis were significantly more hypocoagulable at presentation compared with 24 hours thereafter.
Conclusion Hypocoagulability is more common in acutely traumatized dogs than previously described. Dogs were hypo- or normocoagulable at presentation and the coagulation status changed to normo- or hypercoagulability over the first 24 hours. Clotting times, clot formation and clot firmness but not clot lysis were significantly altered at presentation compared with 24 hours and fibrinogen concentration or function may play an important role in the dynamic change of coagulation state over time.
Unpredictability, breadth of content and the frequent need for speed are the challenges, which characterize emergency medicine. Emergency medicine has, therefore, always found itself in something of an interdisciplinary void; an area in which a broad basis of medical knowledge, complementary structures of traumatology and methods of anesthesiology and intensive medicine are required to act in symphony. Declared a special science at the “International Congress for
Rescue Services” in 1908 [1], emergency medicine requires the composition of internal, traumasurgical, neurological, psychiatric and intensive care expertise. The combination of broad expertise and specific skills is the only way in which the entire rescue-chain, from the site of the event to the final stabilization of acutely ill patients, can be completed. A quick and accurate diagnosis is essential before any acute treatment. The broad canon of diagnostic measures has evolved from general “basics” to rapidly emerging “high-end” diagnostics.
A complete discussion of diagnostics in emergency medicine is clearly not feasible within the scope of this essay. However, this article intends to provide an overview of emergency diagnostics. The diagnostic methods addressed herein should be part of the basic diagnostic armamentarium of all clinicians and can be largely applied not only to patients at an emergency department but likewise to patients at a general ward.
Objective:
Haemorrhage in paediatric trauma remains a significant cause of morbidity and mortality. Over recent years there has been increasing attention to the role of fibrinogen in traumatic haemorrhage and the association of low fibrinogen levels with poor patient outcomes. In addition, there has been a move towards using viscoelastic haemostatic assays (VHAs) to rapidly assess coagulation status and guide clinicians in the replacement of coagulation factors, including fibrinogen. In the paediatric population, there has been limited uptake of these principles and a paucity of data to support a change in practice. This paper summarises the available evidence in the published literature through a systematic review, presented in narrative format.
Results:
There is limited high-quality prospective data on the use of VHA in the management of acute traumatic coagulopathy in the paediatric population. While the use of fibrinogen early in major haemorrhage is becoming standard practice, there are currently no randomised prospective studies comparing fibrinogen concentrate to cryoprecipitate.
Conclusions:
The early identification of hypo-fibrinogenemia and acute traumatic coagulopathy in paediatric trauma using VHA testing and subsequent early fibrinogen replacement with a concentrated off the shelf product is an attractive treatment option. However, there is currently insufficient high-level evidence to support the use of fibrinogen concentrate over cryoprecipitate in the paediatric trauma population. Pilot studies currently under way will go some way to addressing this important knowledge gap, and facilitate the design of larger definitive multi-centre randomised trials.
It is important to manage multiple injury patients so as not to experience the lethal triad of hypothermia, metabolic acidosis, and coagulopathy. The treatment method in patients with massive exsanguination is greatly different from that of elective surgery patients, and it is necessary to implement damage control surgery (DCS), based on the patient’s general condition. The strategy is divided into DCS for controlling surgical bleeding and damage control resuscitation (DCR) for nonsurgical bleeding. Damage control surgery consists primarily of abbreviated lifesaving surgery, and DCR consists of maneuvers to avoid the lethal triad and administer critical care such as permissive hypotension, resuscitative fluid administration, and hemostatic resuscitation. Managing multiple trauma with traumatic brain injury (TBI) is different from managing single torso injury and takes into account factors such as avoiding hypotension and abdominal compartment syndrome, the effect of resuscitative endovascular balloon occlusion of the aorta on intracranial pressure, adverse effects of colloids on hemostasis, and indications for higher platelet administration, which are introduced in this chapter, respectively. The management of patients with multiple trauma and TBI remains mostly unknown, although evidence has been steadily accumulated.
Objective:
For patients with end-stage renal disease on hemodialysis, the durability of vascular access (VA) is still far from optimal, and access survival after intervention for access failure is an important aspect. Procoagulant status is a leading cause of access failure. Coagulation-fibrinolysis imbalance can occur in hemodialyzed patients, but the influence of the imbalance has not been fully elucidated.
Methods:
We prospectively examined coagulation-fibrinolysis balance to assess the risk of access failure after the intervention of revascularization in a cohort of 462 hemodialysis patients. Thrombin-antithrombin complex (TAT) and plasmin-α2-plasmin inhibitor complex (PIC) are markers for coagulation and fibrinolysis. Median follow-up was 243 days. The end point was clinical access failure: revascularization or access revision. The survival curve for VA patency was assessed using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression models that allowed adjustment for baseline differences in age, sex, dialysis vintage, diabetes mellitus, and various factors (quantity of blood flow, prothrombin time-international normalized ratio, fibrin degradation products, C-reactive protein, interleukin-6, tumor necrosis factor-α, and pentraxin-3) were used.
Results:
The 162 patients who reached an end point had smaller access flow volume and smaller percentage of arteriovenous fistula and higher TAT/PIC ratio. Kaplan-Meier analysis indicated that the patients with elevated TAT/PIC ratio showed poorer outcome (P < .001). On Cox regression modeling, elevated TAT/PIC was an independent risk factor for access failure (hazard ratio, 1.58; P = .03).
Conclusions:
Our results suggest that coagulation-fibrinolysis imbalance is a significant risk factor for access failure and may predict VA failure in hemodialyzed patients after access intervention.
Background : The Committee for Future Planning of the Japanese Association for the Surgery of Trauma conducted the Japanese Observational Study for Coagulation and Thrombolysis in Early Trauma, a multicenter, retrospective observational study. The purpose of this study were to clarify the pathophysiology of trauma-associated coagulopathy, and to establish the novel hemostatic resuscitation strategy. Methods : Data were collected from trauma patients, age≥18 years and with ISS≥16, admitted between January and December 2012. Results : Fifteen institutions participated, and 796 patients were registered. A median age was 59 (38-72), male 589, and 790 were injured from blunt mechanism. A median ISS was 24 (17-27), probability of survival 0.918 (0.767-0.967). Hemostatic surgery and interventional radiology were required in 93 (11.7%), 110 (13.8%), respectively, and tranexamic acid was administered in 281 (35.3%) within 3 hr. Blood transfusion within 6 hr were required in 207 (26.0%), and 58.5% of 207 were transfused≧10units within 24 hr. 28-day mortality was 14.7%. Conclusions : This multicenter study will contribute to clarify the pathophysiology of trauma-associated coagulopathy and to establish the novel hemostatic strategy.
要旨
重症頭部外傷では頭蓋内圧制御は生命・機能予後に強い影響を与える。標準治療に反応のない難治性の頭蓋内圧上昇は予後不良の徴候であり，さらなる治療介入として内減圧術が選択されることがある。今回2度の開頭血腫除去＋減圧開頭術と内科治療に反応しなかった症例に対して，優位半球の頭頂葉・側頭葉の内減圧術を行い良好な転帰を得た。9歳の男児，乗用車に接触し受傷した。病院到着時瞳孔散大，対光反射は両側消失し，CTでは肺挫傷，血気胸，肝，右腎，右副腎損傷に加え，左急性硬膜下血腫，脳ヘルニア徴候を認めた。緊急開頭血腫除去術と減圧開頭術を施行し瞳孔所見は改善した。ICUに入室し頭蓋内圧センサー挿入，バルビツレート昏睡療法，浸透圧療法，平温療法を開始した。入室後，肝，右腎，右副腎からの出血が増悪し，動脈塞栓術を施行した。その後左急性硬膜下血腫が増大し，再度開頭血腫除去と減圧開頭を施行した。術後も瞳孔不同，頭蓋内圧亢進が持続したため，頭頂葉・左側頭葉の内減圧術を施行した。術後は頭蓋内圧20mmHg以下となり，意識は徐々に改善した。第15病日にICUを退室した。右上肢麻痺は残るが独歩可能，日常会話も可能となったため，第155病日に退院し，復学した。局所性脳損傷で内科的治療や減圧開頭で制御できない脳圧亢進が持続する場合は内減圧術を検討すべきである。
Injury is a major public health problem: it is the leading cause of death in the first four decades of life (Krug et al. 2000; Eastridge et al. 2006). Exsanguination accounts for up to 50 % of trauma deaths in the first 24 h and for up to 80 % in the operating theater (Association of Anaesthetists of Great et al. 2010). Despite significant advances in trauma care, exsanguination remains the leading cause of preventable death (Sauaia et al. 1995; Demetriades et al. 2004; Kauvar and Wade 2005; Gruen et al. 2006; Kauvar et al. 2006; Cothren et al. 2007). Caring for a severely injured and bleeding patient is to face a challenge of timely and effective hemorrhage control and rapid restoration of physiology.
Background
Despite the early uses of tourniquets and haemostatic dressings, blood loss still accounts for the vast majority of preventable deaths on the battlefield. Over the last few years, progress has been made in the management of such injuries, especially with the use of damage control resuscitation concepts. The early application of these procedures, on the field, may constitute the best opportunity to improve survival from combat injury during remote operations.
Data sources
Currently available literature relating to trauma-induced coagulopathy treatment and far-forward transfusion was identified by searches of electronic databases. The level of evidence and methodology of the research were reviewed for each article. The appropriateness for field utilisation of each medication was then discussed to take into account the characteristics of remote military operations.
Conclusions
In tactical situations, in association with haemostatic procedures (tourniquet, suture, etc), tranexamic acid should be the first medication used according to the current guidelines. The use of fibrinogen concentrate should also be considered for patients in haemorrhagic shock, especially if point-of-care (POC) testing of haemostasis or shock severity is available. If POC evaluation is not available, it seems reasonable to still administer this treatment after clinical assessment, particularly if the evacuation is delayed. In this situation, lyophilised plasma may also be given as a resuscitation fluid while respecting permissive hypotension. Whole blood transfusion in the field deserves special attention. In addition to the aforementioned treatments, if the field care is prolonged, whole blood transfusion must be considered if it does not delay the evacuation.
In acute gastrointestinal bleeding, hypovolemic shock results from the loss of plasma volume and red blood cell (RBC) mass, and can induce an inadequate tissue perfusion of oxygen and substrates. Hypovolemia is managed initially by restoring volume, commonly with infusion of crystalloids through a large-bore intravenous line. Such volume restitution is critical to restore tissue perfusion and optimize oxygen delivery, hemodynamics, and cardiac function rapidly. RBCs are used to improve oxygen delivery to tissues in case of severe anemia and only rarely as part of fluid resuscitation in an actively bleeding patient. RBC transfusion may be lifesaving in patients with massive exsanguinating bleeding. However, in most cases hemorrhage is not so severe and transfusion is aimed to address anemia rather than to fluid resuscitation. Available evidence favors initiating RBC when hemoglobin levels decrease to less than 7 g/dL, with a target level of 7–9 g/dL, in the absence of symptomatic cardiovascular diseases. In a recent RCT such a restrictive transfusion strategy significantly improved survival at 6 weeks and further bleeding as compared with a liberal transfusion strategy in patients with acute upper gastrointestinal bleeding. This is the currently recommended threshold for transfusion in international guidelines. However, the threshold for transfusion may be higher in patients with massive hemorrhage or in those with underlying conditions that preclude an adequate physiological response to acute anemia such as the existence of cardiac disease. A single hemoglobin “trigger” may help to decide transfusion. However, the final decisions regarding RBC transfusion should be made on the basis of the individual patient, and other factors should be considered in addition to hemoglobin level.
Abstract
- Ein Großschadensereignis ist für ein Krankenhaus eine Herausforderung, auf die es vorbereitet sein muss.
- Die Vorgaben für Krankenhäuser sind aufgrund der föderalen Struktur der Bundesrepublik unterschiedlich. Weitgehend festgelegt ist die Notwendigkeit eines Katastrophenplans.
- Eine Krankenhauseinsatzleitung ist zur erfolgreichen Bewältigung einer Katastrophenlage unabdingbar. Daneben ist die Kommunikation im Krisenfall eine übergeordnete Herausforderung.
- Grundprinzip der medizinischen Schadensbewältigung ist die Sichtung der betroffenen Patienten und die Etablierung von Behandlungsbereichen mit festen Behandlungsteams.
- Eine Schulung der Mitarbeiter und regelmäßige Übungen sind zwingend erforderlich.
A common national MTP was jointly implemented in 2011 by the national blood service (Blood Services Group) and seven participating acute hospitals to provide rapid access to transfusion support for massively haemorrhaging patients treated in all acute care hospitals.
Through a systematic clinical workflow, blood components are transfused in a ratio of 1:1:1 (pRBC: whole blood-derived platelets: FFP), together with cryoprecipitate for fibrinogen replacement. The composition of components for the MTP is fixed, although operational aspects of the MTP can be adapted by individual hospitals to suit local hospital workflow. The MTP could be activated in support of any patient with critical bleeding and at risk of massive transfusion, including trauma and non-trauma general medical, surgical and obstetric patients.
There were 434 activations of the MTP from October 2011 to October 2013. Thirty-nine per cent were for trauma patients, and 30% were for surgical patients with heavy intra-operative bleeding, with 25% and 6% for patients with gastrointestinal bleeding and peri-partum haemorrhage, respectively. Several hospitals reported reduction in mean time between request and arrival of blood. Mean transfusion ratio achieved was one red cell unit: 0·8 FFP units: 0·8 whole blood-derived platelet units: 0·4 units of cryoprecipitate. Although cryoprecipitate usage more than doubled after introduction of MTP, there was no significant rise in overall red cells, platelet and FFP usage following implementation.
This successful collaboration shows that shared transfusion protocols are feasible and potentially advantageous for hospitals sharing a central blood provider.
© 2015 International Society of Blood Transfusion.
Background:
Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients.
Methods:
This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919.
Findings:
10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077).
Interpretation:
Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.
Funding:
UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.
BACKGROUND: Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. METHODS: This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. FINDINGS: 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077). INTERPRETATION: Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. FUNDING: UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.
Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients.
This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919.
10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077).
Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.
UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.
The aim of the CRASH-2 trial was to assess the effects of early administration of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage. Tranexamic acid significantly reduced all-cause mortality. Because tranexamic acid is thought to exert its effect through inhibition of fibrinolysis, we undertook exploratory analyses of its effect on death due to bleeding.
The CRASH-2 trial was undertaken in 274 hospitals in 40 countries. 20,211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min followed by infusion of 1 g over 8 h) or placebo. Patients were randomly assigned by selection of the lowest numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation. We examined the effect of tranexamic acid on death due to bleeding according to time to treatment, severity of haemorrhage as assessed by systolic blood pressure, Glasgow coma score (GCS), and type of injury. All analyses were by intention to treat. The trial is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258, and South African Clinical Trial Register/Department of Health DOH-27-0607-1919.
10,096 patients were allocated to tranexamic acid and 10,115 to placebo, of whom 10,060 and 10,067, respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0.0001). Early treatment (≤1 h from injury) significantly reduced the risk of death due to bleeding (198/3747 [5.3%] events in tranexamic acid group vs 286/3704 [7.7%] in placebo group; relative risk [RR] 0.68, 95% CI 0.57-0.82; p<0.0001). Treatment given between 1 and 3 h also reduced the risk of death due to bleeding (147/3037 [4.8%] vs 184/2996 [6.1%]; RR 0.79, 0.64-0.97; p=0.03). Treatment given after 3 h seemed to increase the risk of death due to bleeding (144/3272 [4.4%] vs 103/3362 [3.1%]; RR 1.44, 1.12-1.84; p=0.004). We recorded no evidence that the effect of tranexamic acid on death due to bleeding varied by systolic blood pressure, Glasgow coma score, or type of injury.
Tranexamic acid should be given as early as possible to bleeding trauma patients. For trauma patients admitted late after injury, tranexamic acid is less effective and could be harmful.
UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.
Prothrombin complex concentrates (PCCs) are used mainly for emergency reversal of vitamin K antagonist therapy. Historically, the major drawback with PCCs has been the risk of thrombotic complications. The aims of the present review are to examine thrombotic complications reported with PCCs, and to compare the safety of PCCs with human fresh frozen plasma. The risk of thrombotic complications may be increased by underlying disease, high or frequent PCC dosing, and poorly balanced PCC constituents. The causes of PCC thrombogenicity remain uncertain but accumulating evidence indicates the importance of factor II (prothrombin). With the inclusion of coagulation inhibitors and other manufacturing improvements, today's PCCs may be considered safer than earlier products. PCCs may be considered preferable to fresh frozen plasma for emergency anticoagulant reversal, and this is reflected in the latest British and American guidelines. Care should be taken to avoid excessive substitution with prothrombin, however, and accurate monitoring of patients' coagulation status may allow thrombotic risk to be reduced. The risk of a thrombotic complication due to treatment with PCCs should be weighed against the need for rapid and effective correction of coagulopathy.
The massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and lack supporting clinical evidence. Damage-control resuscitation regimens of modern trauma care are targeted to the early correction of acute traumatic coagulopathy. The aim of this study was to identify a clinically relevant definition of trauma massive transfusion based on clinical outcomes. We also examined whether the concept was useful in that early prediction of massive transfusion requirements could allow early activation of blood bank protocols.
Datasets on trauma admissions over a 1 or 2-year period were obtained from the trauma registries of five large trauma research networks. A fractional polynomial was used to model the transfusion-associated probability of death. A logistic regression model for the prediction of massive transfusion, defined as 10 or more units of red cell transfusions, was developed.
In total, 5,693 patient records were available for analysis. Mortality increased as transfusion requirements increased, but the model indicated no threshold effect. Mortality was 9% in patients who received none to five PRBC units, 22% in patients receiving six to nine PRBC units, and 42% in patients receiving 10 or more units. A logistic model for prediction of massive transfusion was developed and validated at multiple sites but achieved only moderate performance. The area under the receiver operating characteristic curve was 0.81, with specificity of only 50% at a sensitivity of 90% for the prediction of 10 or more PRBC units. Performance varied widely at different trauma centers, with specificity varying from 48% to 91%.
No threshold for definition exists at which a massive transfusion specifically results in worse outcomes. Even with a large sample size across multiple trauma datasets, it was not possible to develop a transportable and clinically useful prediction model based on available admission parameters. Massive transfusion as a concept in trauma has limited utility, and emphasis should be placed on identifying patients with massive hemorrhage and acute traumatic coagulopathy.
Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4-fold higher mortality, increased transfusion requirements and organ failure.
The purpose of the present study was to develop a clinically relevant definition of ATC and understand the etiology of this endogenous coagulopathy.
We conducted a retrospective cohort study of trauma patients admitted to five international trauma centers and corroborated our findings in a novel rat model of ATC. Coagulation status on emergency department arrival was correlated with trauma and shock severity, mortality and transfusion requirements. 3646 complete records were available for analysis.
Patients arriving with a prothrombin time ratio (PTr) > 1.2 had significantly higher mortality and transfusion requirements than patients with a normal PTr (mortality: 22.7% vs. 7.0%; P < 0.001. Packed red blood cells: 3.5 vs. 1.2 units; P < 0.001. Fresh frozen plasma: 2.1 vs. 0.8 units; P < 0.001). The severity of ATC correlated strongly with the combined degree of injury and shock. The rat model controlled for exogenously induced coagulopathy and mirrored the clinical findings. Significant coagulopathy developed only in animals subjected to both trauma and hemorrhagic shock (PTr: 1.30. APTTr: 1.36; both P < 0.001 compared with sham controls).
ATC develops endogenously in response to a combination of tissue damage and shock. It is associated with increased mortality and transfusion requirements in a dose-dependent manner. When defined by standard clotting times, a PTr > 1.2 should be adopted as a clinically relevant definition of ATC.
The appropriate strategy for trauma-induced coagulopathy management is under debate. We report the treatment of major trauma using mainly coagulation factor concentrates.
This retrospective analysis included trauma patients who received >or= 5 units of red blood cell concentrate within 24 hours. Coagulation management was guided by thromboelastometry (ROTEM). Fibrinogen concentrate was given as first-line haemostatic therapy when maximum clot firmness (MCF) measured by FibTEM (fibrin-based test) was <10 mm. Prothrombin complex concentrate (PCC) was given in case of recent coumarin intake or clotting time measured by extrinsic activation test (EXTEM) >1.5 times normal. Lack of improvement in EXTEM MCF after fibrinogen concentrate administration was an indication for platelet concentrate. The observed mortality was compared with the mortality predicted by the trauma injury severity score (TRISS) and by the revised injury severity classification (RISC) score.
Of 131 patients included, 128 received fibrinogen concentrate as first-line therapy, 98 additionally received PCC, while 3 patients with recent coumarin intake received only PCC. Twelve patients received FFP and 29 received platelet concentrate. The observed mortality was 24.4%, lower than the TRISS mortality of 33.7% (P = 0.032) and the RISC mortality of 28.7% (P > 0.05). After excluding 17 patients with traumatic brain injury, the difference in mortality was 14% observed versus 27.8% predicted by TRISS (P = 0.0018) and 24.3% predicted by RISC (P = 0.014).
ROTEM-guided haemostatic therapy, with fibrinogen concentrate as first-line haemostatic therapy and additional PCC, was goal-directed and fast. A favourable survival rate was observed. Prospective, randomized trials to investigate this therapeutic alternative further appear warranted.
Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes.
The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.
Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.
This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.
Death due to trauma is the leading cause of lost life years worldwide, with haemorrhage being responsible for 30-40% of trauma mortality and accounting for almost 50% of the deaths the initial 24 h. On admission, 25-35% of trauma patients present with coagulopathy, which is associated with a several-fold increase in morbidity and mortality. The recent introduction of haemostatic control resuscitation along with emerging understanding of acute post-traumatic coagulability, are important means to improve therapy and outcome in exsanguinating trauma patients. This change in therapy has emphasized the urgent need for adequate haemostatic assays to monitor traumatic coagulopathy and guide therapy. Based on the cell-based model of haemostasis, there is emerging consensus that plasma-based routine coagulation tests (RCoT), like prothrombin time (PT) and activated partial thromboplastin time (APTT), are inappropriate for monitoring coagulopathy and guide therapy in trauma. The necessity to analyze whole blood to accurately identify relevant coagulopathies, has led to a revival of the interest in viscoelastic haemostatic assays (VHA) such as Thromboelastography (TEG®) and Rotation Thromboelastometry (ROTEM®). Clinical studies including about 5000 surgical and/or trauma patients have reported on the benefit of using the VHA as compared to plasma-based assays, to identify coagulopathy and guide therapy.
This article reviews the basic principles of VHA, the correlation between the VHA whole blood clot formation in accordance with the cell-based model of haemostasis, the current use of VHA-guided therapy in trauma and massive transfusion (haemostatic control resuscitation), limitations of VHA and future perspectives of this assay in trauma.
Thromboelastometry is a whole blood assay performed to evaluate the viscoelastic properties during blood clot formation and lysis. Rotation thromboelastography (ROTEM), Pentapharm GmbH, Munich, Germany) has overcome some of the limitations of classic thromboelastography. So far, no clinical validation on reproducibility (inter- and intra-assay variability) and sample stability over time has been published.
To evaluate the pre-analytic aspects, sample stability over time was assessed in 48 patients in eight age groups. Citrated blood was stored at room temperature. Tests measured every 30 min from T 0 min up to T 120 min on two ROTEM devices were INTEM (ellagic acid activated intrinsic pathway), EXTEM (tissue factor-triggered extrinsic pathway) and FIBTEM (with platelet inhibitor (cytochalasin D) evaluating the contribution of fibrinogen to clot formation). Precision by intra- and inter-assay variability was evaluated at two points of time in 10 volunteers. Finally, reference intervals and effect of age and sex were evaluated.
Blood was stable over 120 min and no significant differences in ROTEM results were found. Maximum clot firmness measurements had a coefficient of variation of <3% for EXTEM, <5% for INTEM and <6% for FIBTEM. For clot formation time, the coefficient of variation was <4% for EXTEM and <3% for INTEM. Coefficient of variation for angle alpha was <3% for EXTEM and <6% for INTEM. The coefficient of variation for clotting time was <15% for both EXTEM and INTEM. Small but significant differences between ROTEM devices were found for maximum clot firmness in FIBTEM and INTEM as well as clot formation time and alpha angle in INTEM.
ROTEM yields stable results over 120 min with a minimal variability on the same ROTEM device. However, small but significant differences between ROTEM devices were observed. Analysis should be performed on the same ROTEM device if small differences are of importance for treatment.
Objective:
To determine if blood transfusion is a consistent risk factor for postinjury multiple organ failure (MOF), independent of other shock indexes.Design:
A 55-month inception cohort study ending on August 30, 1995. Data characterizing postinjury MOF were prospectively collected. Multiple logistic regression analysis was performed on 5 sets of data. Set 1 included admission data (age, sex, comorbidity, injury mechanism, Glasgow Coma Scale, Injury Severity Score, and systolic blood pressure determined in the emergency department) plus the amount of blood transfused within the first 12 hours. In the subsequent 4 data sets, other indexes of shock (early base deficit, early lactate level, late base deficit, and late lactate level) were sequentially added. Additionally, the same multiple logistic regression analyses were performed with early MOF and late MOF as the outcome variables.Setting:
Denver General Hospital, Denver, Colo, is a regional level I trauma center.Patients:
Five hundred thirteen consecutive trauma patients admitted to the trauma intensive care unit with an Injury Severity Score greater than 15 who were older than 16 years and who survived longer than 48 hours.Interventions:
None.Main Outcome Measures:
The relationship of blood transfusions and other shock indexes with the outcome variable, MOF.Results:
A dose-response relationship between early blood transfusion and the later development of MOF was identified. Despite the inclusion of other indexes of shock, blood transfusion was identified as an independent risk factor in 13 of the 15 multiple logistic regression models tested; the odds ratios were high, especially in the early MOF models.Conclusion:
Blood transfusion is an early consistent risk factor for postinjury MOF, independent of other indexes of shock.Arch Surg. 1997;132:620-625
Objective:
Recognizing the impact of the 1977 San Francisco study of trauma deaths in trauma care, our purpose was to reassess those findings in a contemporary trauma system.
Design:
Cross-sectional.
Material and methods:
All trauma deaths occurring in Denver City and County during 1992 were reviewed; data were obtained by cross-referencing four databases: paramedic trip reports, trauma registries, coroner autopsy reports and police reports.
Measurements and main results:
There were 289 postinjury fatalities; mean age was 36.8 +/- 1.2 years and mean Injury Severity Score (ISS) was 35.7 +/- 1.2. Predominant injury mechanisms were gunshot wounds in 121 (42%), motorvehicle accidents in 75 (38%) and falls in 23 (8%) cases. Seven (2%) individuals sustained lethal burns. Ninety eight (34%) deaths occurred in the pre-hospital setting. The remaining 191 (66%) patients were transported to the hospital. Of these, 154 (81%) died in the first 48 hours (acute), 11 (6%) within three to seven days (early) and 26 (14%) after seven days (late). Central nervous system injuries were the most frequent cause of death (42%), followed by exsanguination (39%) and organ failure (7%). While acute and early deaths were mostly due to the first two causes, organ failure was the most common cause of late death (61%).
Conclusions:
In comparison with the previous report, we observed similar injury mechanisms, demographics and causes of death. However, in our experience, there was an improved access to the medical system, greater proportion of late deaths due to brain injury and lack of the classic trimodal distribution.
The central event of the hemostatic process is the generation of thrombin through the tissue factor pathway. This is a highly regulated, dynamic process in which thrombin itself plays many roles, positively and negatively its production and destruction. The hemostatic process is essential to normal physiology and is also the Achilles heel of our aging population. The inappropriate generation of thrombin may lead to vascular occlusion with the consequence of myocardial infarction, stroke, pulmonary embolism, or venous thrombosis. In this review, we summarize our present views regarding the tissue factor pathway by which thrombin is generated and the roles played by extrinsic and intrinsic factor Xa generating complexes in hemostasis and the roles of the stoichiometric and dynamic inhibitors that regulate thrombin generation.
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The indications for transfusing fresh-frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of transmitting infection are similar to those of other blood components unless a pathogen-reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion-related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near-patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non-UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.
Background:
To test whether an acute transfusion practice of packed red blood cells (pRBC) : fresh-frozen plasma (FFP) 1 : 1 would be associated with reduced mortality in acute bleeding multiply injury.
Methods:
Retrospective analysis using the TR-DGU database (Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie 2002-2006) on primary admissions with substantial injury (Injury Severity Score > 16) and massive transfusion (> 10 pRBCs). Seven hundred thirteen patients were divided into three groups according to the pRBC : FFP ratio transfused, that is, (i) pRBC : FFP > 1.1; (ii) pRBC : FFP 0.9-1.1 (1 : 1); and (iii) pRBC : FFP < 0.9, and mortality rates were compared.
Results:
Four hundred ninety-seven (69.7%) of patients were male, the mean age was 40.1 (+/- 18.3) years. Injury characteristics and pathophysiological state upon emergency room arrival were comparable between groups. Out of 713, 484 patients had undergone massive transfusion with pRBC : FFP > 1.1, 114 with pRBC : FFP 0.9-1.1 (1 : 1), and 115 with pRBC : FFP < 0.9 ratios. Acute mortality (< 6 h) rates for pRBC : FFP > 1.1, pRBC : FFP 0.9-1.1 (1 : 1), and pRBC : FFP < 0.9 ratios were 24.6, 9.6 and 3.5% (P < 0.0001), 24-h mortality rates were 32.6, 16.7 and 11.3% (P < 0.0001), and 30-day mortality rates were 45.5, 35.1 and 24.3% (P < 0.001). The frequency for septic complications and organ failure was higher in the pRBC : FFP 0.9-1.1 (1 : 1) group, ventilator days and length of stays for intensive care unit and overall in-hospital were highest in the pRBC : FFP < 0.9 ratio group (P < 0.0005).
Conclusions:
An association between pRBC : FFP transfusion ratios and mortality to favour early aggressive FFP administration was observed. Further investigation is necessary prior to recommending routine 1 : 1 or more aggressive FFP use in exsanguinating patients.
To identify an appropriate diagnostic tool for the early diagnosis of acute traumatic coagulopathy and validate this modality through prediction of transfusion requirements in trauma hemorrhage.
Prospective observational cohort study.
Level 1 trauma center.
Adult trauma patients who met the local criteria for full trauma team activation. Exclusion criteria included emergency department arrival >2 hrs after injury, >2000 mL of intravenous fluid before emergency department arrival, or transfer from another hospital.
None.
Blood was collected on arrival in the emergency department and analyzed with laboratory prothrombin time, point-of-care prothrombin time, and rotational thromboelastometry. Prothrombin time ratio was calculated and acute traumatic coagulopathy defined as laboratory prothrombin time ratio >1.2. Transfusion requirements were recorded for the first 12 hrs following admission.
Three hundred patients were included in the study. Laboratory prothrombin time results were available at a median of 78 (62-103) mins. Point-of-care prothrombin time ratio had reduced agreement with laboratory prothrombin time ratio in patients with acute traumatic coagulopathy, with 29% false-negative results. In acute traumatic coagulopathy, the rotational thromboelastometry clot amplitude at 5 mins was diminished by 42%, and this persisted throughout clot maturation. Rotational thromboelastometry clotting time was not significantly prolonged. Clot amplitude at a 5-min threshold of ≤35 mm had a detection rate of 77% for acute traumatic coagulopathy with a false-positive rate of 13%. Patients with clot amplitude at 5 mins ≤35 mm were more likely to receive red cell (46% vs. 17%, p < .001) and plasma (37% vs. 11%, p < .001) transfusions. The clot amplitude at 5 mins could identify patients who would require massive transfusion (detection rate of 71%, vs. 43% for prothrombin time ratio >1.2, p < .001).
In trauma hemorrhage, prothrombin time ratio is not rapidly available from the laboratory and point-of-care devices can be inaccurate. Acute traumatic coagulopathy is functionally characterized by a reduction in clot strength. With a threshold of clot amplitude at 5 mins of ≤35 mm, rotational thromboelastometry can identify acute traumatic coagulopathy at 5 mins and predict the need for massive transfusion.
Coagulopathy in trauma patients is currently defined by the results of standard laboratory tests (prothrombin time and activated partial thromboplastin time). These results offer little in the hemostatic resuscitation that occurs in the treatment of battlefield patients who receive massive transfusions. Thromboelastometry (TEM) is a technique that can offer rapid, near-patient testing of coagulation status.
A prospective observational field study was performed in a deployed military setting to determine the feasibility of using TEM to assess the coagulation status of patients admitted to the emergency department and who subsequently received a massive transfusion.
TEM was performed on 31 patients, 25 were direct admissions to the emergency department, 19 of whom were enrolled into the massive transfusion protocol, and 60% were involved in a blast incident. Standard laboratory testing showed that 10% of all patients were coagulopathic on admission compared with 64% with an abnormal TEM trace (p = 0.0005). All patients had abnormal maximum clot firmness. The TEM amplitude at 10 minutes is associated with the subsequent development of abnormal maximum clot firmness. Two exemplar cases are discussed, which illustrate the potential benefit of using TEM to monitor and guide and individualize therapy during a massive transfusion.
It is feasible to use TEM in a deployed military setting. We have shown that rotational thromboelastometry significantly detects more abnormalities in the coagulation status than the standard laboratory tests (prothrombin time, and activated partial thromboplastin time).
The pattern of tests employed and technologies developed within hemostasis laboratories has changed considerably within the last 10 years. These changes have presented challenges to external quality assessment (EQA) providers, including the United Kingdom National External Quality Assessment Scheme (NEQAS). EQA for point-of-care devices used for monitoring oral anticoagulant therapy has focused on provision of suitable material to assess performance of devices designed for capillary blood testing, and on education of a user group not usually trained in laboratory quality control procedures. Development of novel therapeutic agents for hemophilia has presented challenges regarding standardization of assays for monitoring treatment, whereas advances related to laboratory testing and automation have not always been accompanied by improved accuracy and precision. EQA provision has also been shown to be of value in molecular genetic screening tests for thrombophilia, and in highlighting standardization issues related to D-dimer measurement in the exclusion of deep vein thrombosis. The increasing prevalence of screening tests of global hemostasis, such as thrombin generation tests and thromboelastography, presents additional challenges to EQA providers in the attempt to standardize these new and potentially beneficial technologies.
A balanced transfusion of red blood cells, fresh frozen plasma and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for fresh frozen plasma and/or platelet transfusions.
To provide a review of the literature covering the application of fibrinogen concentrates in trauma care.
PubMed and Cochrane database search, 'fibrinogen' and ('concentrate' or 'trauma'), not 'congenital', 10 years.
Only four papers were identified. None were randomized controlled trials. The main conclusion of these papers was that administration of fibrinogen sometimes together with prothrombin complex concentrate might improve haemostasis in trauma patients resuscitated with synthetic colloids.
Evidence for the use of fibrinogen concentrate to trauma patients with massive bleeding is lacking. Well-designed prospective, randomized, double-blinded studies evaluating the effect of fibrinogen concentrate, as the only intervention, are urgently needed.
The empiric use of a high plasma to packed red-blood-cell [fresh frozen plasma:red-blood-cells (FFP:RBC)] ratio in trauma resuscitation for patients with massive bleeding has become well accepted without clear or objective indications. Increased plasma transfusion is associated with worse outcome in some patient populations. While previous studies analyse only patients who received a massive transfusion, this study analyses those that are at risk to receive a massive transfusion, based on the trauma-associated severe haemorrhage (TASH) score, to objectively determine which patients after severe trauma would benefit or have increased complications by the use of a high FFP:RBC ratio.
Multicentre retrospective study from the Trauma Registry of the German Trauma Society. Multivariate logistic regression and statistical risk adjustments utilized in analyses.
A high ratio of FFP:RBC in the ≥15 TASH group was independently associated with survival, with an odds ratio of 2·5 (1·6-4·0), while the <15 TASH group was associated with increased multi-organ failure, 47% vs. 38%, (P<0·005).
A predictive model of massive transfusion upon admission might be able to rapidly identify which severe trauma patients would benefit or have increased complications from the immediate application of a high ratio of FFP:RBCs. This study helps to identify the appropriate population for a prospective, interventional trial.
Systematic reviews are accepted as a robust and less biased means of appraising and synthesizing results from high-quality studies. This report collated and summarized all the systematic review evidence relating to the diagnosis and management of trauma-related coagulopathy and transfusion, thereby covering the widest possible body of literature. We defined 4 key clinical questions: (1) What are the best methods of predicting and diagnosing trauma-related coagulopathy? (2) Which methods of clinical management correct coagulopathy? (3) Which methods of clinical management correct bleeding? and (4) What are the outcomes of transfusion in trauma? Thirty-seven systematic reviews were identified through searches of MEDLINE (1950-July 2010), EMBASE (1980-July 2010), The Cochrane Library (Issue 7, 2010), National Guidelines Clearing House, National Library for Health Guidelines Finder, and UKBTS SRI Transfusion Evidence Library (www.transfusionevidencelibrary.com). The evidence from the systematic review literature was scanty with many gaps, and we were not able to conclusively answer any of our 4 questions. Much more needs to be understood about how coagulopathy and bleeding in trauma are altered by transfusion practices and, most importantly, whether this translates into improved survival. There is a need for randomized controlled trials to answer these questions. The approach described in this report provides a framework for incorporating new evidence.
Prothrombin complex concentrates (PCCs) are used mainly for emergency reversal of vitamin K antagonist therapy. Historically, the major drawback with PCCs has been the risk of thrombotic complications. The aims of the present review are to examine thrombotic complications reported with PCCs, and to compare the safety of PCCs with human fresh frozen plasma. The risk of thrombotic complications may be increased by underlying disease, high or frequent PCC dosing, and poorly balanced PCC constituents. The causes of PCC thrombogenicity remain uncertain but accumulating evidence indicates the importance of factor II (prothrombin). With the inclusion of coagulation inhibitors and other manufacturing improvements, today's PCCs may be considered safer than earlier products. PCCs may be considered preferable to fresh frozen plasma for emergency anticoagulant reversal, and this is reflected in the latest British and American guidelines. Care should be taken to avoid excessive substitution with prothrombin, however, and accurate monitoring of patients' coagulation status may allow thrombotic risk to be reduced. The risk of a thrombotic complication due to treatment with PCCs should be weighed against the need for rapid and effective correction of coagulopathy.
Damage control resuscitation targets acute traumatic coagulopathy with the early administration of high-dose fresh frozen plasma (FFP). FFP is administered empirically and as a ratio with the number of packed red blood cells (PRBC). There is controversy over the optimal FFP:PRBC ratio with respect to outcomes, and their hemostatic effects have not been studied. We report preliminary findings on the effects of different FFP:PRBC ratios on coagulation.
This is a prospective observational cohort study of trauma patients requiring >4 U of PRBCs. Blood was drawn before and after each 4-U PRBC interval for prothrombin time and analysis by rotational thromboelastometry. Interval change in coagulation parameters were compared with the FFP:PRBC ratio received during each interval.
Sixty 4-U PRBC intervals from 50 patients were available for analysis. All measures of coagulation deteriorated with low FFP:PRBC ratios (<1:2). Maximal hemostatic effect was observed in the 1:2 to 3:4 group: 12% decrease in prothrombin time (p=0.006), 56% decrease in clotting time (p=0.047), and 38% increase in maximum clot firmness (p=0.024). Transfusion with ≥1:1 ratio did not confer any additional improvement. There was a marked variability in response to FFP, and hemostatic function deteriorated in some patients exposed to 1:1 ratios. The beneficial effects of plasma were confined to patients with coagulopathy.
Interim results from this prospective study suggest that FFP:PRBC ratios of ≥1:1 do not confer any additional advantage over ratios of 1:2 to 3:4. Hemostatic benefits of plasma therapy are limited to patients with coagulopathy.
Early prediction of massive transfusion (MT) is critical in the management of severely injured trauma patients. Variables available early after injury including physiologic, laboratory, and rotation thromboelastometric (ROTEM) parameters were evaluated as predictors for the need of MT.
After Institutional Review Board approval, we retrospectively reviewed a cohort of severely injured trauma patients (Injury Severity Score ≥ 16) admitted to a Level I trauma center with available ROTEM measurements on hospital admission during a 1-year study period. Patients with isolated head injury (Abbreviated Injury Scale head ≥ 3 and Abbreviated Injury Scale chest, abdomen, and extremity < 3) and patients with a penetrating mechanism of injury were excluded. Patients who received a MT (≥ 10 units packed red blood cell within 24 hours of admission) were compared with patients who did not. Variables independently associated with MT were identified using stepwise logistic regression.
A total of 53 patients met inclusion criteria. Of these, 18 patients (34.0%) received a MT and 35 patients (66.0%) did not. Massively transfused patients had significantly lower baseline hemoglobin values (7.9 g/dL ± 0.4 g/dL vs. 11.4 g/dL ± 0.4 g/dL; p < 0.001) and a trend toward higher lactate (4.8 mmol/L ± 0.8 mmol/L vs. 3.0 mmol/L ± 0.3 mmol/L; p = 0.056) and base deficit values (5.9 mmol/L ± 1.1 mmol/L vs. 3.6 mmol/L ± 0.6 mmol/L; p = 0.052). Mean international normalized ratio (1.46 ± 0.07 vs. 1.22 ± 0.05; p = 0.001) and partial thromboplastin times (42.4 seconds ± 5.0 seconds vs. 29.7 seconds ± 1.8 seconds; p < 0.001) were significantly higher in MT patients. Patients receiving a MT had significantly altered ROTEM values on admission compared with non-MT patients. An increase in the clot formation time (471.3 seconds ± 169.9 seconds vs. 178.1 seconds ± 19.9 seconds; p = 0.001), a shortening of the maximum clot firmness (37.5 mm ± 2.9 mm vs. 50.7 mm ± 1.4 mm; p < 0.001), and a shortening of the clot amplitude at all time points (10/20/30 minutes) were observed in massively transfused trauma patients. Variables independently associated with MT included a hemoglobin level ≤ 10 g/dL and an abnormal maximum clot firmness value (area under the receiver operator characteristic curve: 0.831 [95% confidence interval: 0.719-0.942; p < 0.001]).
Hemoglobin ≤ 10 g/dL and an abnormal maximum cloth firmness measured by rotation thromboelastometry on admission reliably predict the need for MT. Prospective validation of the effectiveness of thromboelastometry to guide the transfusion practice after trauma is warranted.
Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes.
We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases.
Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts.
rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.
Coagulation defects related to severe trauma, trauma-induced coagulopathy (TIC), have a number of causal factors including:
major blood loss with consumption of clotting factors and platelets, and dilutional coagulopathy after administration of crystalloids
and colloids to maintain blood pressure. In addition, activation of the fibrinolytic system or hyperfibrinolysis, hypothermia,
acidosis, and metabolic changes can also affect the coagulation system. All of these directly affect fibrinogen polymerization
and metabolism. Other bleeding-related deficiencies usually develop later in massive bleeding related to severe multiple trauma.
In major blood loss, fibrinogen reaches a critical value earlier than other procoagulatory factors, or platelets. The question
of the critical threshold value is presently the subject of heated debate. A threshold of 100 mg dl−1 has been recommended, but recent clinical data have shown that at a fibrinogen level of <150–200 mg dl−1, there is already an increased tendency to peri- and postoperative bleeding. A high fibrinogen count exerts a protective
effect with regard to the amount of blood loss. In multiple trauma patients, priority must be given to early and effective
correction of impaired fibrin polymerization by administering fibrinogen concentrate.
Damage control laparotomy (DCL) improves outcomes when used in patients with severe hemorrhage. Correction of coagulopathy with close ratio resuscitation while limiting crystalloid forms a new methodology known as damage control resuscitation (DCR). We hypothesize a survival advantage in DCL patients managed with DCR when compared with DCL patients managed with conventional resuscitation efforts (CRE).
This study is a 4-year retrospective study of all DCL patients who required >or=10 units of packed red blood cells (PRBC) during surgery. A 2-year period after institution of DCR (DCL and DCR) was compared with the preceding 2 years (DCL and CRE). Univariate analysis of continuous data was done with Student's t test followed by multiple logistic regression.
One Hundred twenty-four and 72 patients were managed during the DCL and CRE and DCL and DCR time periods, respectively. Baseline patient characteristics of age, Injury Severity Score, % penetrating, blood pressure, hemoglobin, base deficit, and INR were similar between groups. There was no difference in quantity of intraoperative PRBC utilization between DCL and CRE and DCL and DCR study periods: 21.7 units versus 25.5 units (p = 0.53); however, when compared with DCL and CRE group, patients in the DCL and DCR group received less intraoperative crystalloids, 4.7 L versus 14.2 L (p = 0.009); more fresh frozen plasma (FFP), 18.2 versus 6.4 (p = 0.002); a closer FFP to PRBC ratio, 1 to 1.2 versus 1 to 4.2 (p = 0.002); platelets to PRBC ratio, 1:2.3 versus 1:5.9 (0.002); shorter mean trauma intensive care unit length of stay, 11 days versus 20 days (p = 0.01); and greater 30-day survival, 73.6% versus 54.8% (p < 0.009). The addition of DCR to DCL conveyed a survival benefit (odds ratio; 95% confidence interval: 0.19 (0.05-0.33), p = 0.005).
This is the first civilian study that analyses the impact of DCR in patients managed with DCL. During the DCL and DCR study period more PRBC, FFP, and platelets with less crystalloid solution was used intraoperatively. DCL and DCR were associated with a survival advantage and shorter trauma intensive care unit length of stay in patients with severe hemorrhage when compared with DCL and CRE.
For trauma patients requiring massive blood transfusion, aggressive plasma usage has been demonstrated to confer a survival advantage. The aim of this study was to evaluate the impact of plasma administration in nonmassively transfused patients.
Trauma patients admitted to a Level I trauma center (2000-2005) requiring a nonmassive transfusion (<10 U packed RBC [PRBC] within 12 hours of admission) were identified retrospectively. Propensity scores were calculated to match and compare patients receiving plasma in the first 12 hours with those who did not.
The 1,716 patients (86.1% of 1,933 who received PRBC transfusion) received a nonmassive transfusion. After exclusion of 31 (1.8%) early deaths, 284 patients receiving plasma were matched to patients who did not. There was no improvement in survival with plasma transfusion (17.3% versus 14.1%; p = 0.30) irrespective of the plasma-to-PRBC ratio achieved. However, the overall complication rate was significantly higher for patients receiving plasma (26.8% versus 18.3%, odds ratio [OR] = 1.7; 95% CI, 1.1-2.4; p = 0.016). As the volume of plasma increased, an increase in complications was seen, reaching 37.5% for patients receiving >6 U. The ARDS rate specifically was also significantly higher in patients receiving plasma (9.9% versus 3.5%, OR = 3.0; 95% CI, 1.4-6.2; p = 0.004]. Patients receiving >6 U plasma had a 12-fold increase in ARDS, a 6-fold increase in multiple organ dysfunction syndrome, and a 4-fold increase in pneumonia and sepsis.
For nonmassively transfused trauma patients, plasma administration was associated with a substantial increase in complications, in particular ARDS, with no improvement in survival. An increase in multiple organ dysfunction, pneumonia, and sepsis was likewise seen as increasing volumes of plasma were transfused. The optimal trigger for initiation of a protocol for aggressive plasma infusion warrants prospective evaluation.
Plasma transfusion is increasingly performed without clear consensus on indications. We systematically reviewed the literature to summarize the available evidence regarding the benefits and harms of plasma transfusion in common clinical settings.
We searched electronic databases from inception through August 2009. Eligible studies enrolled adult patients transfused with plasma and compared to a control group. Paired reviewers independently assessed studies for eligibility and extracted quality and outcome data.
Thirty-seven studies met eligibility criteria, most of which were observational. In patients undergoing massive transfusion, plasma infusion at high plasma : red blood cell ratios was associated with a significant reduction in the risk of death (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.24-0.60) and multiorgan failure (OR, 0.40; 95% CI, 0.26-0.60). However, the quality of this evidence was very low due to significant unexplained heterogeneity and several other biases. In a single retrospective study, plasma transfusion was associated with reduced mortality in anticoagulated patients with intracranial hemorrhage (OR, 0.29; 95% CI, 0.09-0.98). In patients undergoing surgery without massive transfusion, plasma infusion was associated with a trend toward increased mortality (OR, 1.22; 95% CI, 0.73-2.03). Plasma transfusion was associated with increased risk of developing acute lung injury (OR, 2.92; 95% CI, 1.99-4.29).
Very-low-quality evidence suggests that plasma infusion in the setting of massive transfusion for trauma patients may be associated with a reduction in the risk of death and multiorgan failure. A survival benefit was not demonstrated in most other transfusion populations.