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Marc Maegele - One of the best experts on this subject based on the ideXlab platform.
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An update on the Coagulopathy of trauma.
Shock (Augusta Ga.), 2020Co-Authors: Marc Maegele, Herbert Schöchl, Mitchell J CohenAbstract:Trauma remains the leading cause of death with bleeding as the primary cause of preventable mortality during the first 24 h following trauma. When death occurs, it happens quickly, typically within the first 6 h after injury. One of four patients to arrive in the emergency department after trauma is already in the state of acute traumatic Coagulopathy and shock. The principal drivers of acute traumatic Coagulopathy have been characterized by tissue hypoperfusion, inflammation, and the acute activation of the neurohumoral system. Hypoperfusion leads to an activation of protein C with cleavage of activated factors V and VIII and the inhibition of plasminogen activator inhibitor 1 with subsequent hyperfibrinolysis. Endothelial damage and activation result in Weibel-Palade body degradation and glycocalyx shedding associated with autoheparinization. In contrast, there is an iatrogenic Coagulopathy that occurs secondary to uncritical volume therapy leading to acidosis, hypothermia, and hemodilution. This Coagulopathy then may be an integral part of the "vicious cycle" when combined with acidosis and hypothermia. The present article summarizes an update on the principal mechanisms and triggers of the Coagulopathy of trauma including traumatic brain injury.
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Mechanism, frequency, transfusion and outcome of severe trauma in coagulopathic paediatric patients
European Journal of Trauma and Emergency Surgery, 2020Co-Authors: Arne Driessen, Marc Maegele, Rolf Lefering, Arasch Wafaisade, Filippo Migliorini, Matthias Fröhlich, Dariusch Arbab, Manuel MutschlerAbstract:Purpose Acute traumatic Coagulopathy can result in uncontrolled haemorrhage responsible for the majority of early deaths after adult trauma. Data on the frequency, transfusion practice and outcome of severe trauma haemorrhage in paediatric patients are inconsistent. Methods Datasets from paediatric trauma patients were retrieved from the registry of the German trauma society (TR-DGU^®) between 2009 and 2016. Coagulopathy was defined by a Quick’s value 1.4) and/or thrombocytes ≤ 100 k upon emergency room admission. Children were grouped according to age in 4 different groups (A: 1–5, B: 6–10, C: 11–15 and D: 16–17 years). Prevalence of Coagulopathy was assessed. Demographics, injury severity, haemostatic management including transfusions and mortality were described. Results 5351 primary admitted children ≤ 17 years with an abbreviated injury scale (AIS) ≥ 3 and complete datasets were included. The prevalence of Coagulopathy was 13.7% (733/5351). The majority of the children sustained blunt trauma (more than 90% independent of age group) and a combination of traumatic brain injury (TBI) and any other trauma in more than 60% (A, C, D) and in 53.8% in group B. Coagulopathy occurred the most among the youngest (A: 18.2%), followed by all other age groups with approximately 13%. Overall mortality was the highest in the youngest (A: 40.9%) and among the youngest patients with traumatic brain injury (A: 71.4% and B: 47.1%). Transfusion of packed red blood cells (pRBCs) and fresh frozen plasma (FFPs) occurred almost in a 2:1 ratio (or less) across all age subgroups. Conclusion Traumatic haemorrhage in association with Coagulopathy and severe shock is a major challenge in paediatric trauma across all age groups.
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Early prediction of acute traumatic Coagulopathy: a validation of the COAST score using the German Trauma Registry
European Journal of Trauma and Emergency Surgery, 2019Co-Authors: Sophie Thorn, Rolf Lefering, Marc Maegele, Russell L. Gruen, Biswadev MitraAbstract:Background Early identification of trauma patients at risk of developing acute traumatic Coagulopathy (ATC) is important for initiating appropriate, Coagulopathy-focused treatment. A clinical ATC prediction tool is a quick, simple method to evaluate risk. The COAST score was developed and validated in Australia but is yet to be validated on a European population. We validated the ability of the COAST score to predict Coagulopathy and adverse bleeding-related outcomes on a large European trauma population. Methods The COAST score was modified and applied to a retrospective cohort of trauma patients from the German Trauma Registry (TR-DGU). The primary outcome was Coagulopathy defined as INR > 1.5 or aPTT > 60 s. Secondary outcomes were massive transfusion, blood product requirements, urgent surgery and mortality. The cohort included adult trauma patients with Injury Severity Score > 15 treated in Germany/Austria in 2012–2016. Results 15,370 cases were included, of which 10.9% were coagulopathic. The COAST score performed with sensitivity 21.6% and specificity 94.2% at a threshold of COAST ≥ 3. The AUROC was 0.625 (95% CI 0.61–0.64). The COAST score also identified patients who had more massive transfusions (15.3% v 1.6%), more emergency surgery (49.6% v 28.2%), and higher early (21.7% v 5.4%) and total in-hospital mortality (38.1% v 14.5%). Conclusion This large retrospective study demonstrated that the modified COAST score predicts Coagulopathy with low sensitivity but high specificity. A positive COAST score identified a group of patients with bleeding-related adverse outcomes. This score appears adequate to act as an inclusion criterion for clinical trials targeting ATC.
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Coagulopathy after traumatic brain injury incidence pathogenesis and treatment options
Transfusion, 2013Co-Authors: Marc MaegeleAbstract:Coagulopathy after traumatic brain injury (TBI) is frequent and represents a powerful predictor related to outcome and prognosis. The complex pathophysiological mechanisms of the Coagulopathy of TBI are multifactorial and remain still undefined. The nature of the coagulation abnormalities differs between severe TBI and non-TBI with somatic injuries. The current hypothesis for the development of Coagulopathy after TBI includes combinations of both hypo- and hypercoagulable states promoted by the magnitude and the extent of the injury resulting in a variable degree of secondary injury via subsequent ischemic and hemorrhagic lesioning. The proposed underlying mechanisms may comprise the release of tissue factor (TF), hyperfibrinolysis, shock, and hypoperfusion thus triggering the protein C pathway, disseminated intravascular coagulation, and platelet dysfunction. Hemocoagulative disorders after TBI may be amenable to treatment, and adequate and timely management may protect from secondary injury and poor outcomes. Functional assays such as viscoelastic tests may be supportive in early detection, diagnosis, and guidance of treatment. This review summarizes the current understanding with regard to frequency, pathogenesis, diagnosis, and treatment of the Coagulopathy after TBI.
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Coagulopathy and shock on admission is associated with mortality for children with traumatic injuries at combat support hospitals
Pediatric Critical Care Medicine, 2012Co-Authors: Jason T Patregnani, Marc Maegele, Charles E Wade, Philip C Spinella, Matthew A Borgman, Lorne H BlackbourneAbstract:OBJECTIVE:: In adults, early traumatic Coagulopathy and shock are both common and independently associated with mortality. There are little data regarding both the incidence and association of early Coagulopathy and shock on outcomes in pediatric patients with traumatic injuries. Our objective was to determine whether Coagulopathy and shock on admission are independently associated with mortality in children with traumatic injuries. METHODS:: A retrospective review of the Joint Theater Trauma Registry from U.S. combat support hospitals in Iraq and Afghanistan from 2002 to 2009 was performed. Coagulopathy was defined as an international normalized ratio of ≥1.5 and shock as a base deficit of ≥6. Laboratory values were measured on admission. Primary outcome was inhospital mortality. Univariate analyses were performed on all admission variables followed by reverse stepwise multivariate logistic regression to determine independent associations. SETTING:: Combat support hospitals in Iraq and Afghanistan. PATIENTS:: Patients Language: en
Jeanfrancois Pittet - One of the best experts on this subject based on the ideXlab platform.
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Coagulopathy After Severe Pediatric Trauma
Shock, 2020Co-Authors: Sarah C Christiaans, Jeffrey D Kerby, Amy L Duhachek-stapelman, Robert T. Russell, Steven J. Lisco, Jeanfrancois PittetAbstract:Trauma remains the leading cause of morbidity and mortality in the United States among children from the age 1 year to 21 years old. The most common cause of lethality in pediatric trauma is traumatic brain injury (TBI). Early Coagulopathy has been commonly observed after severe trauma and is usually associated with severe hemorrhage and/or traumatic brain injury. In contrast to adult patients, massive bleeding is less common after pediatric trauma. The classical drivers of trauma-induced Coagulopathy (TIC) include hypothermia, acidosis, hemodilution and consumption of coagulation factors secondary to local activation of the coagulation system following severe traumatic injury. Furthermore, there is also recent evidence for a distinct mechanism of TIC that involves the activation of the anticoagulant protein C pathway. Whether this new mechanism of posttraumatic Coagulopathy plays a role in children is still unknown. The goal of this review is to summarize the current knowledge on the incidence and potential mechanisms of Coagulopathy after pediatric trauma and the role of rapid diagnostic tests for early identification of Coagulopathy. Finally, we discuss different options for treating Coagulopathy after severe pediatric trauma. Language: en
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early Coagulopathy is an independent predictor of mortality in children after severe trauma
Shock, 2013Co-Authors: Brent Whittaker, Sarah C Christiaans, Jessica L Altice, Mike K Chen, Alfred A Bartolucci, Charity J Morgan, Jeffrey D Kerby, Jeanfrancois PittetAbstract:To determine whether early Coagulopathy affects the mortality associated with severe civilian pediatric trauma, trauma patients 24 hours after injury were excluded. Age, gender, race, mechanism of injury, initial systolic blood pressure (SBP), Glasgow Coma Scale (GCS) score, Injury Severity Score (ISS), prothrombin time (PT), partial thromboplastin time (PTT), platelet count and International Normalized Ratio (INR) were recorded. An arterial or venous blood gas was performed, if clinically indicated. Coagulopathy was defined as an INR > 1.2. The primary outcome was in-hospital mortality. Secondary outcomes were lengths of ICU and hospital stay. Eight hundred three patients were included in the study. Overall mortality was 13.4%. The incidence of age-adjusted hypotension was 5.4%. Early Coagulopathy was observed in 37.9% of patients. High ISS and/or hypotension were associated with early Coagulopathy and higher mortality. Early Coagulopathy was associated with a modest increase in mortality in pediatric trauma patients without traumatic brain injury (TBI). In contrast, the combination of TBI and early Coagulopathy was associated with a four-fold increase in mortality in this patient population. Early Coagulopathy is an independent predictor of mortality in civilian pediatric patients with severe trauma. The increase in mortality was particularly significant in patients with TBI either isolated or combined with other injuries, suggesting that a rapid correction of this Coagulopathy could substantially decrease the mortality after TBI in pediatric trauma patients.
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critical role of activated protein c in early Coagulopathy and later organ failure infection and death in trauma patients
Annals of Surgery, 2012Co-Authors: Mitchell J Cohen, Karim Brohi, Mariah Call, Mary F Nelson, Carolyn S Calfee, Charles T Esmon, Jeanfrancois PittetAbstract:Background:Recent studies have identified an acute traumatic Coagulopathy that is present on admission to the hospital and is independent of iatrogenic causes. We have previously reported that this Coagulopathy is due to the association of severe injury and shock and is characterized by a decrease i
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early Coagulopathy after traumatic brain injury the role of hypoperfusion and the protein c pathway
Journal of Trauma-injury Infection and Critical Care, 2007Co-Authors: Mitchell J Cohen, Karim Brohi, Michael T Ganter, Geoffrey T Manley, Robert C Mackersie, Jeanfrancois PittetAbstract:Introduction: Early Coagulopathy after traumatic brain injury (TBI) is thought to be the result of injury-mediated local release of tissue factor, although the precise mechanisms that cause hypoperfusion and early systemic Coagulopathy in TBI patients are unknown. We have previously reported that early systemic Coagulopathy after trauma is present only when tissue injury is associated with severe hypoperfusion leading to the activation of the protein C pathway. However, the role of hypoperfusion as an important mechanism for the development of Coagulopathy early after TBI is unclear. The objective of the present study was to determine the importance of hypoperfusion and protein C activation in causing early Coagulopathy in TBI patients. Materials: We performed a prospective cohort study including patients with isolated brain injury admitted to a single trauma center. Blood was drawn on average 32 minutes after injury. Plasma samples were assayed for protein C and thrombomodulin by standard laboratory techniques. Routine coagulation measures (prothrombin time, partial thromboplastin time) and arterial blood gas analysis were performed concurrently. Severe hypoperfusion was evidenced by the presence of an arterial base deficit greater than 6. ReSUltS: Thirty-nine TBI patients were included in the study during a 15-month period. TBI patients without concurrent hypoperfusion (n = 28) did not develop an early Coagulopathy after trauma, no matter the severity of injury. In contrast, patients with TBI who also had severe hypoperfusion (BD >6) (n = 11) were coagulopathic early after injury. Indeed, these patients had higher prothrombin time and partial thromboplastin time, compared with those with TBI and a BD 6 (56 ± 32 vs. 85 ± 35, p = 0.03) and thrombomodulin levels were significantly higher (48 ± 26 vs. 35 ± 10, p = 0.04). Without hypoperfusion, there was no effect of increasing brain injury on protein C pathway or fibrinolysis pathway mediators. Conclusions: TBI alone does not cause early Coagulopathy, but must be coupled with hypoperfusion to lead to coagulation derangements, associated with the activation of the protein C pathway. This novel finding has significant implications for the treatment of Coagulopathy after severe brain injury.
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acute traumatic Coagulopathy initiated by hypoperfusion modulated through the protein c pathway
Annals of Surgery, 2007Co-Authors: Karim Brohi, Mitchell J Cohen, Michael T Ganter, Robert C Mackersie, Michael A Matthay, Jeanfrancois PittetAbstract:Trauma remains the leading cause of death and disability in adults, eclipsing ischemic heart disease, cerebrovascular disease, and HIV/AIDS.1 Worldwide, 1 in 7 deaths is due to injury, and this is expected to rise to 1 in 5 in the next 15 years, despite advances in resuscitation, trauma surgery, and critical care.2 Coagulation abnormalities are common following major trauma, and are associated with poor outcomes.3 Classically, traumatic Coagulopathy is thought to be due to the consumption of coagulation factors and dilution from intravenous blood and fluid therapy.4 Coagulopathy is therefore currently managed by coagulation factor replacement such as with fresh frozen plasma and cryoprecipitate.5 Consistent with this concept, recombinant factor VIIa has recently been investigated as another therapy for traumatic Coagulopathy.6 Two recent studies have identified an acute Coagulopathy that is present on arrival in the emergency department in approximately one quarter of major trauma patients.7,8 Patients arriving with a Coagulopathy were 4 times more likely to die than those with normal coagulation. This effect was independent of injury severity and hence unlikely to be exclusively due to tissue injury and coagulation factor consumption. Apart from the severity of injury, shock with tissue hypoperfusion is also known to be an independent predictor of mortality and morbidity in severe trauma. Elevated admission base deficit (BD) levels are associated with an increase in transfusion requirements, acute lung injury, multiple organ failure, and mortality.9–13 We hypothesized that acute traumatic Coagulopathy is primarily caused by tissue hypoperfusion resulting in activation of the anticoagulant protein C pathway, not the consumption of coagulation factors. An increase in thrombomodulin induced by hypoperfusion would divert thrombin from fibrin generation to the activation of protein C, leading to anticoagulation and inhibition of further thrombin generation.14 The first aim of this study was therefore to identify the mechanisms responsible for the acute Coagulopathy that is evident early in the clinical course of victims of major trauma. Since Coagulopathy is an independent predictor of mortality after trauma,7,8 the second aim was to identify the prognostic significance of early alterations in the thrombomodulin-protein C pathway.
Philip C Spinella - One of the best experts on this subject based on the ideXlab platform.
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Coagulopathy and shock on admission is associated with mortality for children with traumatic injuries at combat support hospitals
Pediatric Critical Care Medicine, 2012Co-Authors: Jason T Patregnani, Marc Maegele, Charles E Wade, Philip C Spinella, Matthew A Borgman, Lorne H BlackbourneAbstract:OBJECTIVE:: In adults, early traumatic Coagulopathy and shock are both common and independently associated with mortality. There are little data regarding both the incidence and association of early Coagulopathy and shock on outcomes in pediatric patients with traumatic injuries. Our objective was to determine whether Coagulopathy and shock on admission are independently associated with mortality in children with traumatic injuries. METHODS:: A retrospective review of the Joint Theater Trauma Registry from U.S. combat support hospitals in Iraq and Afghanistan from 2002 to 2009 was performed. Coagulopathy was defined as an international normalized ratio of ≥1.5 and shock as a base deficit of ≥6. Laboratory values were measured on admission. Primary outcome was inhospital mortality. Univariate analyses were performed on all admission variables followed by reverse stepwise multivariate logistic regression to determine independent associations. SETTING:: Combat support hospitals in Iraq and Afghanistan. PATIENTS:: Patients Language: en
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increased mortality associated with the early Coagulopathy of trauma in combat casualties
Journal of Trauma-injury Infection and Critical Care, 2008Co-Authors: Sarah E Niles, Daniel F Mclaughlin, Jeremy G Perkins, Charles E Wade, Yuanzhang Li, Philip C Spinella, John B HolcombAbstract:Background: Recent civilian studies have documented a relationship between increased mortality and the presence of an early Coagulopathy of trauma diagnosed in the emergency department (ED). We hypothesized that acute Coagulopathy (international normalized ratio ≥1.5) in combat casualties was associated with increased injury severity and mortality as is seen in civilian trauma patients. Methods: A retrospective study of combat casualties who received a blood transfusion at a single combat support hospital between September 2003 and December 2004 was performed. Coagulation status, pH, base deficit, and temperature were recorded at arrival to the ED. These were analyzed by Injury Severity Score (ISS), associated injury patterns, and mortality. Results: A total of 3,287 patients were treated at the combat support hospital during the study period. Of these, 391 patients were transfused and primarily admitted, thus meeting the study criteria, 347 had coagulation data, and 92% had a penetrating mechanism. The prevalence of acute Coagulopathy in transfused casualties measured with point-of-care devices at arrival in the ED was 38%. Mortality in those who were coagulopathic at arrival to the ED was 24% (32/133) versus 4% (8/214) in those not presenting with Coagulopathy (p < 0.001). The prevalence of mortality by Coagulopathy increased as ISS increased. Coagulopathy and acidosis were associated with mortality, odds ratio (OR), 5.38 [95% confidence interval (CI), 1.55-11.37] and 6.9 (95% CI, 2.1-19.5), respectively. Temperature did not affect outcomes (OR, 1.1; 95% CI, 0.4-2.6). Conclusions: The early Coagulopathy of trauma was rapidly diagnosed in the ED and present in more than one-third of combat casualties who received a transfusion, similar to the incidence found in civilian trauma patients. Coagulopathy, independent of hypothermia but strongly correlated with acidosis and ISS, was associated with mortality in combat casualties, similar to that found in civilian trauma patients. Early diagnosis and treatment of acute traumatic Coagulopathy with new resuscitation paradigms may improve outcomes.
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the ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital
Journal of Trauma-injury Infection and Critical Care, 2007Co-Authors: Matthew A Borgman, Jeremy G Perkins, Charles E Wade, Philip C Spinella, Kurt W Grathwohl, Thomas Repine, Alec C Beekley, James A Sebesta, Donald H Jenkins, John B HolcombAbstract:Background:Patients with severe traumatic injuries often present with Coagulopathy and require massive transfusion. The risk of death from hemorrhagic shock increases in this population. To treat the Coagulopathy of trauma, some have suggested early, aggressive correction using a 1:1 ratio of plasma
Karim Brohi - One of the best experts on this subject based on the ideXlab platform.
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critical role of activated protein c in early Coagulopathy and later organ failure infection and death in trauma patients
Annals of Surgery, 2012Co-Authors: Mitchell J Cohen, Karim Brohi, Mariah Call, Mary F Nelson, Carolyn S Calfee, Charles T Esmon, Jeanfrancois PittetAbstract:Background:Recent studies have identified an acute traumatic Coagulopathy that is present on admission to the hospital and is independent of iatrogenic causes. We have previously reported that this Coagulopathy is due to the association of severe injury and shock and is characterized by a decrease i
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the acute Coagulopathy of trauma shock clinical relevance
Surgeon-journal of The Royal Colleges of Surgeons of Edinburgh and Ireland, 2010Co-Authors: Daniel Frith, Karim BrohiAbstract:Abstract Recent observational studies have identified an acute Coagulopathy in trauma victims that is present on arrival in the emergency room. It has been associated with a four-fold increase in mortality and increased incidence of organ failure. Conventional trauma resuscitation and transfusion protocols are designed for dilutional Coagulopathy and appear inadequate in the management of acute traumatic Coagulopathy and massive transfusion. Acute Coagulopathy of Trauma Shock (ACoTS) is caused by a combination of tissue injury and shock, and may occur without significant fluid administration, clotting factor depletion or hypothermia. The mechanism through which acute Coagulopathy develops is unclear but activation of the protein C pathway has been implicated. Standard coagulation tests do not identify cases in a timely fashion and ACoTS should be suspected in any trauma patient with a significant magnitude of injury and shock, as evidenced by an abnormal admission base deficit on blood gas. Development of point of care coagulometers and whole blood coagulation analysers, such as rotational thromboelastometry, may enable earlier laboratory identification of this group. Retrospective studies performed by the American military indicate that resuscitation of severely injured patients with higher ratios of plasma given early may improve outcome and reduce overall blood product use. The place of adjunctive pharmaceutical agents within this strategy remains unclear. There is an acute Coagulopathy associated with trauma and shock that is an independent predictor of outcomes. Delineation of this entity, with directed management protocols should lead to a reduction in avoidable deaths from haemorrhage after trauma.
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the Coagulopathy of trauma a review of mechanisms
Journal of Trauma-injury Infection and Critical Care, 2008Co-Authors: John B Holcomb, John R Hess, Karim Brohi, Richard P Dutton, Carl J Hauser, Yoram Kluger, Kevin Mackwayjones, Michael Parr, Sandro RizoliAbstract:Background: Bleeding is the most frequent cause of preventable death after severe injury. Coagulopathy associated with severe injury complicates the control of bleeding and is associated with increased morbidity and mortality in trauma patients. The causes and mechanisms are multiple and yet to be clearly defined. Methods: Articles addressing the causes and consequences of trauma-associated Coagulopathy were identified and reviewed. Clinical situations in which the various mechanistic causes are important were sought along with quantitative estimates of their importance. Results: Coagulopathy associated with traumatic injury is the result of multiple independent but interacting mechanisms. Early Coagulopathy is driven by shock and requires thrombin generation from tissue injury as an initiator. Initiation of coagulation occurs with activation of anticoagulant and fibrinolytic pathways. This Acute Coagulopathy of Trauma-Shock is altered by subsequent events and medical therapies, in particular acidemia, hypothermia, and dilution. There is significant interplay between all mechanisms. Conclusions: There is limited understanding of the mechanisms by which tissue trauma, shock, and inflammation initiate trauma Coagulopathy. Acute Coagulopathy of Trauma-Shock should be considered distinct from disseminated intravascular coagulation as described in other conditions. Rapid diagnosis and directed interventions are important areas for future research.
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early Coagulopathy after traumatic brain injury the role of hypoperfusion and the protein c pathway
Journal of Trauma-injury Infection and Critical Care, 2007Co-Authors: Mitchell J Cohen, Karim Brohi, Michael T Ganter, Geoffrey T Manley, Robert C Mackersie, Jeanfrancois PittetAbstract:Introduction: Early Coagulopathy after traumatic brain injury (TBI) is thought to be the result of injury-mediated local release of tissue factor, although the precise mechanisms that cause hypoperfusion and early systemic Coagulopathy in TBI patients are unknown. We have previously reported that early systemic Coagulopathy after trauma is present only when tissue injury is associated with severe hypoperfusion leading to the activation of the protein C pathway. However, the role of hypoperfusion as an important mechanism for the development of Coagulopathy early after TBI is unclear. The objective of the present study was to determine the importance of hypoperfusion and protein C activation in causing early Coagulopathy in TBI patients. Materials: We performed a prospective cohort study including patients with isolated brain injury admitted to a single trauma center. Blood was drawn on average 32 minutes after injury. Plasma samples were assayed for protein C and thrombomodulin by standard laboratory techniques. Routine coagulation measures (prothrombin time, partial thromboplastin time) and arterial blood gas analysis were performed concurrently. Severe hypoperfusion was evidenced by the presence of an arterial base deficit greater than 6. ReSUltS: Thirty-nine TBI patients were included in the study during a 15-month period. TBI patients without concurrent hypoperfusion (n = 28) did not develop an early Coagulopathy after trauma, no matter the severity of injury. In contrast, patients with TBI who also had severe hypoperfusion (BD >6) (n = 11) were coagulopathic early after injury. Indeed, these patients had higher prothrombin time and partial thromboplastin time, compared with those with TBI and a BD 6 (56 ± 32 vs. 85 ± 35, p = 0.03) and thrombomodulin levels were significantly higher (48 ± 26 vs. 35 ± 10, p = 0.04). Without hypoperfusion, there was no effect of increasing brain injury on protein C pathway or fibrinolysis pathway mediators. Conclusions: TBI alone does not cause early Coagulopathy, but must be coupled with hypoperfusion to lead to coagulation derangements, associated with the activation of the protein C pathway. This novel finding has significant implications for the treatment of Coagulopathy after severe brain injury.
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acute traumatic Coagulopathy initiated by hypoperfusion modulated through the protein c pathway
Annals of Surgery, 2007Co-Authors: Karim Brohi, Mitchell J Cohen, Michael T Ganter, Robert C Mackersie, Michael A Matthay, Jeanfrancois PittetAbstract:Trauma remains the leading cause of death and disability in adults, eclipsing ischemic heart disease, cerebrovascular disease, and HIV/AIDS.1 Worldwide, 1 in 7 deaths is due to injury, and this is expected to rise to 1 in 5 in the next 15 years, despite advances in resuscitation, trauma surgery, and critical care.2 Coagulation abnormalities are common following major trauma, and are associated with poor outcomes.3 Classically, traumatic Coagulopathy is thought to be due to the consumption of coagulation factors and dilution from intravenous blood and fluid therapy.4 Coagulopathy is therefore currently managed by coagulation factor replacement such as with fresh frozen plasma and cryoprecipitate.5 Consistent with this concept, recombinant factor VIIa has recently been investigated as another therapy for traumatic Coagulopathy.6 Two recent studies have identified an acute Coagulopathy that is present on arrival in the emergency department in approximately one quarter of major trauma patients.7,8 Patients arriving with a Coagulopathy were 4 times more likely to die than those with normal coagulation. This effect was independent of injury severity and hence unlikely to be exclusively due to tissue injury and coagulation factor consumption. Apart from the severity of injury, shock with tissue hypoperfusion is also known to be an independent predictor of mortality and morbidity in severe trauma. Elevated admission base deficit (BD) levels are associated with an increase in transfusion requirements, acute lung injury, multiple organ failure, and mortality.9–13 We hypothesized that acute traumatic Coagulopathy is primarily caused by tissue hypoperfusion resulting in activation of the anticoagulant protein C pathway, not the consumption of coagulation factors. An increase in thrombomodulin induced by hypoperfusion would divert thrombin from fibrin generation to the activation of protein C, leading to anticoagulation and inhibition of further thrombin generation.14 The first aim of this study was therefore to identify the mechanisms responsible for the acute Coagulopathy that is evident early in the clinical course of victims of major trauma. Since Coagulopathy is an independent predictor of mortality after trauma,7,8 the second aim was to identify the prognostic significance of early alterations in the thrombomodulin-protein C pathway.
Beverley J Hunt - One of the best experts on this subject based on the ideXlab platform.
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the pathogenesis of traumatic Coagulopathy
Anaesthesia, 2015Co-Authors: Beverley J HuntAbstract:Abstract : Over the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are bleeding when they come in to the emergency department have an established Coagulopathy before the haemodilution effects of fluid resuscitation. This has led to the use of new terminology: acute traumatic Coagulopathy, acute Coagulopathy of trauma shock or trauma-induced Coagulopathy. The recognition of acute traumatic Coagulopathy is important, because we now understand that its presence is a prognostic indicator, as it is associated with poor clinical outcome. This has driven a change in clinical management, so that the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with Coagulopathy, has changed to haemostatic resuscitation as early as possible. While there is as yet no universally accepted assay or definition, many experts use prolongation of the prothrombin time to indicate that there is, indeed, a Coagulopathy. Hypoxia, acidosis and hypothermia and hormonal, immunological and cytokine production, alongside consumption and blood loss, and the dilutional effects of resuscitation may occur to varying extents depending on the type of tissue damaged, the type and extent of injury, predisposing to, or amplifying, activation of coagulation, platelets, fibrinolysis. These are discussed in detail within the article.
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Bleeding and Coagulopathies in Critical Care
The New England Journal of Medicine, 2014Co-Authors: Beverley J HuntAbstract:The definition of Coagulopathy is “a condition in which the blood’s ability to clot is impaired.” However, for some clinicians, the term also covers thrombotic states, and because of the complexity of the hemostatic pathways, the two conditions can exist simultaneously. Some practitioners would consider that mildly abnormal results on coagulation screening without bleeding can also indicate a Coagulopathy. This review is confined to the original definition of Coagulopathy as given above. Such states are common in patients in the intensive care unit (ICU) and require a clinicopathological approach to ensure that the correct diagnosis is made and the appropriate treatment administered. The lack of evidence for managing coagulopathies in critical care is striking. This review will highlight selected areas in which there is high-quality evidence and at the same time point out areas for which there is poor evidence. In the latter case, there is little consensus on management.
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Transfusion strategies for traumatic Coagulopathy
Blood Reviews, 2012Co-Authors: Nicola Curry, Beverley J Hunt, Ross Davenport, Simon J. StanworthAbstract:Abstract Uncontrolled bleeding is the most common preventable cause of death for patients with severe injury. Coagulopathy inevitably accompanies severe bleeding, exacerbated by the ongoing blood loss and the treatments administered. There is debate about the underlying pathophysiological mechanisms of early traumatic Coagulopathy and uncertainty about whether injury induces a unique Coagulopathy when compared to other forms of major haemorrhage. This review describes current understanding of the Coagulopathy of major blood loss and focuses on the early coagulation changes that occur following severe injury. It then reports on the contemporary management of coagulopathic bleeding using new transfusion strategies. Finally this review presents some practical points to the delivery of transfusion for major blood loss in the modern hospital setting.
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the pathogenesis and management of the Coagulopathy of acute promyelocytic leukaemia
British Journal of Haematology, 2012Co-Authors: Karen Breen, David Grimwade, Beverley J HuntAbstract:Summary Coagulopathy occurs in most patients with (APML) and is life-threatening; therefore prompt diagnosis and recognition of any coagulation defect is imperative. Unfortunately haemorrhage remains a major cause of early death, preventing some from reaching treatment. The Coagulopathy is caused directly or indirectly by the leukaemic cells through expression of activators of coagulation and fibrinolysis, proteases and cytokine generation, compounded by failure of platelet production due to marrow invasion. At presentation the predominant feature is usually hyperfibrinolysis. Since the introduction of all-trans retinoic acid (ATRA), patient outcome has dramatically improved; yet, haemorrhagic complications remain the most frequent cause of mortality. Thrombotic complications occur but are less well recognized and potentially underreported. Supportive measures and prompt initiation of ATRA currently represent the mainstay of treatment of the Coagulopathy in patients with suspected APML, but unanswered questions remain as to the optimal approach to further decrease the associated haemorrhagic and thrombotic risks. In particular, it is unclear how to best predict and monitor the Coagulopathy; whether there is a role for the early use of antifibrinolytics; the most appropriate trigger for giving fibrinogen replacement and the value of low-dose anticoagulation to suppress coagulation activation once fibrinolysis has been suppressed.