A Prospective Evaluation of Acute Traumatic Coagulopathy and Effects of Damage Control Resuscitation in Military Trauma Patients in Afghanistan

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2848-2848
Author(s):  
Zachary Edward Wright ◽  
Ian Stewart ◽  
Jonathan Sosnov ◽  
Heather F Pidcoke ◽  
Fedyk Chriselda ◽  
...  

Abstract Hemorrhage remains the leading cause of preventable morality, resulting in the death of over a third of all trauma patients. Additionally, twenty-five percent of trauma patients present on admission with acute traumatic coagulopathy (ATC) which portends a mortality approaching fifty percent. ATC has been defined by multiple parameters including international normalized ratio (INR) >1.2, rotational thromboelastometry (ROTEM) clot amplitude at 5 minutes (CA5) ≤ 35 mm and lysis at 60 minutes (LI60) ≤ 85%. Damage control resuscitation (DCR), the practice of the Joint Theater Trauma System in Iraq and Afghanistan, is based on rapid hemorrhage control, permissive hypotension and transfusion of blood products in a ratio that aims to deliver the functionality of whole blood (1:1:1, red cells:plasma:platelets), in addition to limiting crystalloid resuscitation. ROTEM defined ATC has not been observed over time among DCR eligible combat casualties. The goal of this study was to identify ATC and the effects of DCR in trauma patients treated at level III trauma hospitals in Afghanistan. In this prospective observational study, 88 trauma patients were treated at Craig Air Force Theatre Hospital – Bagram, or Kandahar NATO Hospital in the Afghanistan Theatre. We included only patients from coalition forces identified as having injury that would result in the loss of life or total disability resulting in activation of DCR. Blood was obtained for analysis upon admission and at 6 and 24 hours after admission by a designated research team. Blood was analyzed by ROTEM with multiple assays (EXTEM, FIBTEM, APTEM); however, data was not available to the treatment team. Complete blood counts and INR were also obtained and Injury Severity Scores (ISS) were determined. Transfusion requirements of red blood cells (RBCs), platelets (PLT), fresh frozen plasma (FFP) and cryoprecipitate were recorded for the first 24 hours following admission. ROTEM changes over time were analyzed using Wilcoxon signed-rank test. Forty patients in the cohort had ROTEM (EXTEM) data obtained for evaluation as equipment was unavailable during a portion of the study. The median ISS was 21.5 (IQR 14-27). Four of the patients in the cohort died. The median admission hemoglobin and hematocrit were 11.1 g/dL (IQR 10.1-12) and 32.3% (IQR 29-34.5) respectively. The median INR was 1.3 (IQR 1.2-1.4). The median patient RBC to FFP to PLT ratio was 1:1:0.8. The median clot time (CT) and maximum clot firmness (MCF) were 58.5 sec (IQR 51-65.5) and 56 mm (IQR 51-60.5) respectively. Median CA5 was 37.5 mm (IQR 31-45). ATC as identified by CA5 ≤ 35 mm was present in 15 of 40 patients (38%) upon admission. The median CA5 of patients who met criteria for ATC on admission was 26 mm (IQR 15-34) which improved to 38 mm (IQR 33-44) at 24 hours (p < 0.01). Median LI45 was 98% (IQR 96-99). Hyperfibrinolysis as defined by LI45 ≤ 85% was observed in 4 of 40 patients (10%) upon admission which did not change significantly at 24 hours. The incidence of acute traumatic coagulopathy as defined by ROTEM parameters in this high risk military cohort appears to be higher compared to that reported for civilian populations. These data suggest that current DCR practices including a 1:1:1 RBC:FFP:PLT ratio appropriately target high risk trauma patients with ATC and that this strategy appears to be associated with a reduction in the burden of coagulopathy by 24 hours. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1457-1457
Author(s):  
Xiaowu Wu ◽  
Robbie Montgomery ◽  
Bin Liu ◽  
Jeffrey D Keesee ◽  
Avi Benov ◽  
...  

Abstract Background: The hemostatic and platelet functions of fresh whole blood (FWB) are well preserved when stored at 4°C for 14 days (human) or 7 days (rats). Resuscitation of either FWB or whole blood stored for 7-days at 4°C (SWB) in rats with acute traumatic coagulopathy (ATC) induced by polytrauma and hemorrhage (T/H), shows identical correction of hemodynamic and metabolic function, as well as the equivalent impact on platelet aggregation in vitro. Platelet hemostatic function is influenced by platelet number, aggregation, and platelet-leukocyte interactions. Therefore, the objective of this study is to identify the in-vivo fate and activity of platelets from FWB and SWB, and determine whether transfused platelets contribute to clot formation in tissue injury after transfusion. Method: Isoflurane anesthetized Sprague-Dawley rats underwent polytrauma, followed by 40% hemorrhage. The rats were resuscitated (20% of bled volume) 1hr after trauma using either FWB or SWB (n=5 each) collected from green fluorescence (GFP) donor rats. SWB was kept in mini-blood-bag and refrigerated at 40C for 7 days, and warmed up to 370C prior to transfusion. Sham rats had no trauma, but underwent 20% blood replacement by FWB or SWB (n=4 each). Immediately after transfusion, a liver incision was made, followed by the measurement of kidney bleeding time (both standardized incisions was made by a Surgicutt adult template device). The incisional liver sample was taken 10min after injury for immunohistochemistry stained for CD61 (platelets) and GFP. Blood samples taken from donor rats (FWB and SWB) and recipient rats at baseline, immediately before resuscitation, and 0min and 10min after transfusion were analyzed by flow cytometry using CD42d, CD45, and CD62P antibodies for defining platelets, leukocytes and activated platelets respectively. Lactadherin was used to detect phosphatidylserine (PS). Platelet-leukocyte aggregates were defined as CD42d+/CD45+. The transfused and native platelet or leukocyte was differentiated by GFP signal. Results: GFP signal intensity was equally expressed in platelets derived from either FWB or SWB. Storage at 4°C led to a significant increase in number of platelets expressing CD62P (76±2% vs. 11±4%) and PS (8.6±0.7% vs. 1.1±0.4%) as compared to FWB. SWB also showed a significant rise in intensity, but not percentage, of platelet-leukocyte aggregates (45781±6235 vs. 10978±2345 MFI). After transfusion, recipient rats showed a significant elevation in the percentage of GFP+ platelets after transfusion of FWB as compared to SWB (Sham:13.0±1.0% vs. 4.9±0.4%; T/H: 17.0±0.8% vs. 6.8±0.%). Similarly, GFP+ leukocytes aggregates from FWB were three times higher than SWB (Sham: 6.15±0.5% vs. 1.9±0.5%; T/H: 4.4±0.4% vs. 1.2±0.2%). There was greater percentage of GFP+ platelet-leukocyte aggregates in both T/H and sham rats transfused with SWB than FWB (Sham: 11.7±3.3% vs. 33.8±2.3%; T/H: 9.8±1.6% vs. 47.2±5.1%). Transfusion with SWB led to a significant increase in percentage of activated GFP+ platelets in T/H rats as compared to FWB (30.0±2.7% vs. 2.5±0.5%). However, the activity of native platelets was not significantly different between SWB and FWB in T/H rats after transfusion (3.9±1.2% vs. 3.7±0.3%). The kidney bleeding time was not significantly different in T/H rats receiving FWB and SWB (131±4 vs.127±7 seconds) under equivalent mean arterial blood pressure (82±7 vs 85±9 mmHg). The clot that formed at the site of liver incision was identified by platelet aggregates stained by the CD61 antibody. Using co-localization of CD61 and GFP, we found that the platelets from both FWB and SWB equivalently incorporated into the clot at incisional site. Conclusion: The platelets from SWB are higher in platelet activation state, clearance rate and platelet-leukocyte aggregates than FWB after transfusion in both sham rats and rats with polytrauma and hemorrhage. However, platelets from both fresh and cold-stored whole blood contribute to hemostasis of tissue injury after transfusion. This study suggests that cold-stored whole blood is an alternative resource to treat trauma patients for restoration of hemostatic function. Future study is necessary to optimize the storage of whole blood to prolong the platelet survival rate and optimize hemostatic function. This project was funded by US Army Medical Research and Material Command. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 8 (11) ◽  
pp. 3381
Author(s):  
Ruby Kataria ◽  
M. Quamar Azam ◽  
Geeta Negi ◽  
Ajay Kumar ◽  
Bhaskar Sarkar ◽  
...  

Background: Coagulopathy following major trauma is conventionally attributed to activation of coagulation factors. We hypothesized that early coagulopathy is due to tissue hypoperfusion and investigated thrombomodulin (TM) as early marker of endothelial injury in poly trauma patient.Methods: This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of TM. We assess its association with blood transfusion, length of hospital stays and mortality.Results: A total of 90 patients were enrolled. An increasing lactate was associated with high soluble TM. High TM was significantly associated with increased mortality, blood transfusion requirements, hospital stay.Conclusions: Acute traumatic coagulopathy (ATC) occurs only in the presence of tissue hypoperfusion which we have measured in form of lactate and coagulopathy measured using international normalized ratio (INR) as standard. Admission serum TM can be predictive of clinical outcomes following major trauma.


2017 ◽  
Vol 126 (1) ◽  
pp. 115-127 ◽  
Author(s):  
Ross A. Davenport ◽  
Maria Guerreiro ◽  
Daniel Frith ◽  
Claire Rourke ◽  
Sean Platton ◽  
...  

Abstract Background Major trauma is a leading cause of morbidity and mortality worldwide with hemorrhage accounting for 40% of deaths. Acute traumatic coagulopathy exacerbates bleeding, but controversy remains over the degree to which inhibition of procoagulant pathways (anticoagulation), fibrinogen loss, and fibrinolysis drive the pathologic process. Through a combination of experimental study in a murine model of trauma hemorrhage and human observation, the authors’ objective was to determine the predominant pathophysiology of acute traumatic coagulopathy. Methods First, a prospective cohort study of 300 trauma patients admitted to a single level 1 trauma center with blood samples collected on arrival was performed. Second, a murine model of acute traumatic coagulopathy with suppressed protein C activation via genetic mutation of thrombomodulin was used. In both studies, analysis for coagulation screen, activated protein C levels, and rotational thromboelastometry (ROTEM) was performed. Results In patients with acute traumatic coagulopathy, the authors have demonstrated elevated activated protein C levels with profound fibrinolytic activity and early depletion of fibrinogen. Procoagulant pathways were only minimally inhibited with preservation of capacity to generate thrombin. Compared to factors V and VIII, proteases that do not undergo activated protein C–mediated cleavage were reduced but maintained within normal levels. In transgenic mice with reduced capacity to activate protein C, both fibrinolysis and fibrinogen depletion were significantly attenuated. Other recognized drivers of coagulopathy were associated with less significant perturbations of coagulation. Conclusions Activated protein C–associated fibrinolysis and fibrinogenolysis, rather than inhibition of procoagulant pathways, predominate in acute traumatic coagulopathy. In combination, these findings suggest a central role for the protein C pathway in acute traumatic coagulopathy and provide new translational opportunities for management of major trauma hemorrhage.


Trauma ◽  
2019 ◽  
Vol 22 (2) ◽  
pp. 112-117
Author(s):  
Sophie Thorn ◽  
Martin Tonglet ◽  
Marc Maegele ◽  
Russell Gruen ◽  
Biswadev Mitra

Purpose Early identification of trauma patients at risk of developing acute traumatic coagulopathy is important in initiating appropriate, coagulopathy-focused treatment. A clinical acute traumatic coagulopathy prediction tool is a quick, simple method to evaluate risk. The COAST score was developed in Australia and we hypothesised that it could predict coagulopathy and bleeding-related adverse outcomes in other advanced trauma systems. We validated COAST on a single-centre cohort of trauma patients from a trauma centre in Belgium. Methods The COAST score was modified to suit available data; we used entrapment, blood pressure, temperature, major chest injury and abdominal injury to calculate the score. Acute traumatic coagulopathy was defined as international normalised ratio >1.5 or activated partial thromboplastin time >60 s upon arrival of the patient to the hospital. Data were extracted from the local trauma registry on patients that presented between 1 January and 31 December 2015. Results In all, 133 patients met the inclusion criteria (>16 years old, available COAST and outcome data) for analysis. The COAST score had an area under the receiver operating characteristics curve of 0.941 (95% CI: 0.884–0.999) and at COAST ≥3, it had 80% sensitivity and 96% specificity. The score also identified patients with higher rates of mortality, blood transfusion and emergent surgery. Conclusion This retrospective cohort study demonstrated the utility of the COAST score in identifying trauma patients who are likely to have bleeding-related poor outcomes. The early identification of these patients will facilitate timely, appropriate treatment for acute traumatic coagulopathy and minimise the risk of over-treatment. It can also be used to select patients with acute traumatic coagulopathy for trials involving therapeutic agents targeted at acute traumatic coagulopathy.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3777-3777
Author(s):  
Jenny K. McDaniel ◽  
Ilan I Maizlin ◽  
Michelle C. Shroyer ◽  
Morgan E. Banks ◽  
Jean-Francois Pittet ◽  
...  

Abstract Background: Acute traumatic coagulopathy occurs in both pediatric and adult trauma patients and is associated with an increased risk of mortality. Trauma patients not only have increased risk for hemorrhagic complications, but also are at increased risk for thrombosis due to multiple factors including local tissue injury, inflammation, and immobility. The complex underlying pathophysiology of coagulation abnormalities associated with traumatic injury have yet to be fully elucidated. Additionally, there are significant differences in the hemostatic system of pediatric patients compared to adults. Objectives: The purpose of this study was to determine the levels of coagulation parameters including von Willebrand factor (VWF) antigen and ADAMTS13 activity in pediatric trauma patients and evaluate for possible association with injury severity and/or mortality. Methods: This study utilized plasma specimens collected from pediatric trauma patients that presented to our institution over a 2-year time period. The specimens were collected at initial presentation and 24 hours later. The injury severity was estimated using both the Glasgow Coma Scale (GCS) and Injury Severity Score (ISS). A cohort of control samples was obtained from pediatric patients for elective surgical procedures over the same time period. Plasma VWF antigen was determined by a sandwich ELISA; plasma ADAMTS13 activity was determined by FRETS-VWF73. The results were determined by nonparametric tests for the differences in median values. Results: A total of 106 trauma patient samples at initial time point, 78 trauma samples at 24 hour time point, and 54 control samples were obtained and utilized for study. There were statistically significant differences (p<0.05) in the plasma levels of VWF antigen, ADAMTS13 activity, and the ratio of ADAMTS13 activity to VWF antigen for the trauma patient samples at initial presentation when compared to controls (Table 1). At 24 hours, there were still statistically significant differences between ADAMTS13 activity and the ratio of ADAMTS13 activity to VWF antigen in trauma patients compared to controls, but there was no significant difference in VWF antigen between the two cohorts (Table 2). There was a significant difference between the decrease in ADAMTS13 activity and injury severity as estimated by ISS ³ 15 or GCS < 8 at both time points; however, ADAMTS13 activity was not statistically different in survivors vs. non-survivors. A higher VWF antigen level at initial presentation was the only factor found to be significantly different in non-survivors. Conclusions: This study demonstrates significant differences in plasma ADAMTS13 activity and VWF antigen in pediatric trauma patients compared to controls. In patients with more severe injuries as estimated by GCS and ISS, there was also a significant association with decreased levels of ADAMTS13 activity. These finding may underlie part of the prothrombotic propensity in microcirculation that occurs in patients post-trauma. Further investigation is warranted to better understand the mechanisms of acute traumatic coagulopathy and potential prognostic factors, and to determine the most effective interventions for acute traumatic coagulopathy in the pediatric population. Disclosures Zheng: Ablynx: Consultancy; Alexion: Research Funding.


2020 ◽  
Vol 5 (3) ◽  
pp. 23-30
Author(s):  
Simon Robinson ◽  
Jordan Kirton

<sec id="s1">Introduction: Recognising acute traumatic coagulopathy (ATC) poses a significant challenge to improving survival in emergency care. Paramedics are in a prime position to identify ATC in pre-hospital major trauma and initiate appropriate coagulopathy management. </sec> <sec id="s2">Method: A database literature review was conducted using Scopus, CINAHL and MEDLINE. </sec> <sec id="s3">Results: Two themes were identified from four studies: prediction tools, and point-of-care testing. Prediction tools identified key common ATC markers in the pre-hospital setting, including: systolic blood pressure, reduced Glasgow Coma Score and trauma to the chest, abdomen and pelvis. Point-of-care testing was found to have limited value. </sec> <sec id="s4">Conclusion: Future research needs to explore paramedics using prediction tools in identifying ATC, which could alert hospitals to prepare for blood products for damage control resuscitation. </sec>


2021 ◽  
Author(s):  
JiaQing Gong ◽  
MingHui Pang ◽  
Wei Li ◽  
GuoDe Luo ◽  
ZhiBing Yuan ◽  
...  

Abstract BackgroundPatients with extremely high-risk abdominal trauma and full-thickness necrosis and defects of the partial abdominal wall are clinically rare, and the treatments for these patients are very difficult and complex . In this study, we will explore the key factors for successful treatment of these patients . MethodsThree patients with extremely high-risk abdominal trauma and partial full-thickness abdominal wall defects were involved in this retrospective study, and one representative case was emphatically reviewed. According to the theory of damage control surgery,the consultation and coordinated treatment of multidisciplinary team(MDT) were involved firstly, then, stepped multiple operations,such as partial perforated small bowel resection, full-thickness abdominal wall defects repair, vacuum sealing drainage (VSD), and wounds skin grafts, were performed, meanwhile, systemic life resuscitation was strengthened. ResultsTwo patients were cured and discharged after 3 and 9 operations respectively. One patient suffered 2 operations and eventually died of lung infection and respiratory failure. ConclusionThe determination and responsibility of surgeons, rational use of damage control theory and multidisciplinary cooperation should be the keys for successful treatment.


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