Acute Traumatic Coagulopathy Research Articles

Self-Induced Bleeding Diathesis in Soldiers at a FOB in South Eastern Afghanistan

Modern warfare necessitates that the physician recognize risk factors and clinical scenarios that contribute to the development of acute coagulopathy of trauma and the need for massive transfusion. To date, this is the only prospective study done in an active war zone that specifically looks at a self-induced bleeding diathesis problem among soldiers. If correct, then large numbers of soldiers are exposed to bleeding abnormalities well before sustaining injury.

Reversal of acute coagulopathy during hypotensive resuscitation using small-volume 7.5% NaCl adenocaine and Mg2+ in the rat model of severe hemorrhagic shock*

Acute traumatic coagulopathy occurs early in hemorrhagic trauma and is a major contributor to mortality and morbidity. Our aim was to examine the effect of small-volume 7.5% NaCl adenocaine (adenosine and lidocaine, adenocaine) and Mg on hypotensive resuscitation and coagulopathy in the rat model of severe hemorrhagic shock. Prospective randomized laboratory investigation. A total of 68 male Sprague Dawley Rats. Post-hemorrhagic shock treatment for acute traumatic coagulopathy. Nonheparinized male Sprague-Dawley rats (300-450 g, n=68) were randomly assigned to either: 1) untreated; 2) 7.5% NaCl; 3) 7.5% NaCl adenocaine; 4) 7.5% NaCl Mg²⁺; or 5) 7.5% NaCl adenocaine/Mg²⁺. Hemorrhagic shock was induced by phlebotomy to mean arterial pressure of 35-40 mm Hg for 20 mins (~40% blood loss), and animals were left in shock for 60 mins. Bolus (0.3 mL) was injected into the femoral vein and hemodynamics monitored. Blood was collected in Na citrate (3.2%) tubes, centrifuged, and the plasma snap frozen in liquid N2 and stored at -80°C. Coagulation was assessed using activated partial thromboplastin times and prothrombin times. Small-volume 7.5% NaCl adenocaine and 7.5% NaCl adenocaine/Mg²⁺ were the only two groups that gradually increased mean arterial pressure 1.6-fold from 38-39 mm Hg to 52 and 64 mm Hg, respectively, at 60 mins (p<.05). Baseline plasma activated partial thromboplastin time was 17±0.5 secs and increased to 63±21 secs after bleeding time, and 217±32 secs after 60-min shock. At 60-min resuscitation, activated partial thromboplastin time values for untreated, 7.5% NaCl, 7.5% NaCl/Mg²⁺, and 7.5% NaCl adenocaine rats were 269±31 secs, 262±38 secs, 150±43 secs, and 244±38 secs, respectively. In contrast, activated partial thromboplastin time for 7.5% NaCl adenocaine/Mg²⁺ was 24±2 secs (p<.05). Baseline prothrombin time was 28±0.8 secs (n=8) and followed a similar pattern of correction. Plasma activated partial thromboplastin time and prothrombin time increased over 10-fold during the bleed and shock periods prior to resuscitation, and a small-volume (~1 mL/kg) IV bolus of 7.5% NaCl AL/Mg²⁺ was the only treatment group that raised mean arterial pressure into the permissive range and returned activated partial thromboplastin time and prothrombin time clotting times to baseline at 60 mins.

Hyperfibrinolysis Elicited via Thromboelastography Predicts Mortality in Trauma

The acute coagulopathy of trauma has been identified as a critical determinant of outcomes. Antifibrinolytic agents have recently been demonstrated to improve outcomes. This prospective study was designed to assess coagulopathy in trauma patients using thromboelastography. Trauma patients meeting our institution's highest tier of trauma team activation criteria were prospectively enrolled during a 5-month period ending April 1, 2011. Thromboelastography was performed at admission, +1 hour, +2 hours, and +6 hours using citrated blood. Hyperfibrinolysis was defined as estimated percent lysis ≥15%. Patients were followed throughout their hospital course to collect clinical data and outcomes. One hundred and eighteen patients were enrolled (77.1% were male, 51.7% had penetrating trauma, 7.6% had systolic blood pressure <90 mmHg, 47.5% had Injury Severity Score >16, and 23.7% had Glasgow Coma Scale score ≤8). Hyperfibrinolysis was present in 13 patients (11.0%), with a mean time to detection of 13 minutes (range 2 to 60 minutes). By the 6-hour sampling, 8 (61.5%) of the hyperfibrinolytic patients had expired from hemorrhage. Survivors at this point demonstrated correction of coagulopathy, however, 12 patients (92.3%) ultimately expired (75% hemorrhage, 25% head injury). On stepwise logistic regression, hyperfibrinolysis was a strong predictor of early (24 hours) mortality (odds ratio = 25.0; 95% CI, 2.8-221.4; p = 0.004), predicting 53% of early deaths. Compared with patients without hyperfibrinolysis, patients with hyperfibrinolysis had a greater need for massive transfusion (76.9% vs 8.7%; adjusted odds ratio = 19.1; 95% CI, 3.6-101.3; p < 0.001) and had a greater early mortality (69.2% vs 1.9%; adjusted odds ratio = 55.8; 95% CI, 7.2-432.3; p < 0.001) and in-hospital mortality (92.3% vs 9.5%; adjusted odds ratio = 55.5; 95% CI, 4.8-649.7; p = 0.001). In this prospective analysis, hyperfibrinolysis on thromboelastography developed in approximately 10% of patients and was considerably more likely to require massive transfusion. Hyperfibrinolysis was a strong independent predictor of mortality. Additional evaluation of the role of thromboelastography-directed antifibrinolytic therapies is warranted.

Update on trauma

Background Vehicular injury causes five million deaths a year. Vehicles, interpersonal violence, falls, occupational physical injury, injuries in the home and recreational injury all contribute to make physical injury the leading cause of the loss of years of productive life worldwide. As a result, injury prevention is a societal goal in all developed, most developing, and many poor countries. Uncontrolled hemorrhage is the second leading cause of death from physical injury and its primary prevention through accident prevention, secondary prevention through trauma care systems and surgical hemorrhage control, and secondary and tertiary prevention through appropriate transfusion all contribute to saving lives and returning individuals to productive activities. These activities need to cover the almost a billion people who suffer significant physical injury each year.Aims Provide an update on blood use in trauma.Methods Literature from the last 10 years was reviewed for advances in the understanding of injury‐related bleeding, surgical hemorrhage control methods, drugs, and devices, and changing patterns of blood use. Selected examples are discussed.Results Recognition of the pH‐dependence of the plasma coagulation system activity and the temperature limits on platelet activation through von Willebrand’s factor traction on glycoprotein Ib/IX provide a clear mechanistic pathway from acidosis and hypothermia to coagulopathy and excess deaths following injury. The description of the acute coagulopathy of trauma and shock (ACoTS), an acute form of hemorrhagic DIC associated with severe injury, shock, and activation of the protein C system, has also been a major advance. The development of prehospital hemorrhage control systems such as better tourniquets, and active hemorrhage control bandages, systems for keeping patients warm, and efforts in monitoring to reduce the prehospital use of crystalloid and colloid fluids have all been noted to improve outcome. Pre‐hospital fluid restriction is now known to reduce blood loss, reduce hemodilution, and prevent platelet dysfunction. In the hospital, dedicated trauma systems, advances in imaging with ultrasound, CT, and MRI, and protocols for the rapid stabilization of physiology through surgery, interventional radiology, organ system support, and advanced nursing are improving survival and reducing complications. Hemorrhage control resuscitation, including hypotensive resuscitation to reduce blood loss during a rapid initial assessment and hemostatic resuscitation using relatively more plasma, platelets, and cryoprecipitate early appears to both save lives and reduce total blood use. Evidence supporting hemorrhage control remains Class III, but is increasingly robust. Randomized trials are in preparation. The importance of early initiation of tranexamic acid was demonstrated in the CRASH‐II. Once patients are initially stabilized, blood avoidance reduces complications. Moving beyond conventional blood components to resuscitation with coagulation factor concentrates is an area of ongoing research. Using modern prothrombin complex concentrates and fibrinogen concentrates in conjunction with early platelet transfusion allows reconstitution of the extrinsic pathway and has been demonstrated to save lives and reduce blood use.Conclusions Early and balanced use of blood products in severe trauma appears to be saving lives and reducing total blood use. Better and safer tools for hemorrhage control and resuscitation can save more lives.

Abstract 494: Platelet Aggregation in a Model of Simulated Arterial Flow: Red Blood Cells Are Integral Players in Hemostatic Control Resuscitation

Background: Approximately one in four trauma patients exhibits an early bleeding diathesis, termed the acute coagulopathy of trauma and defined by an initial INR &gt;1.2, which is associated with a 3-fold increase in mortality. In recent years, the concept of damage control resuscitation has been developed to address this problem. This approach emphasizes hemorrhage control and early resuscitation with blood products in a 1:1:1 ratio of plasma:platelets:RBCs in an attempt to replace whole blood lost in hemorrhage. The optimal ratio of blood components has not been established and few pre-clinical studies have explored this problem under arterial shear conditions. Objective: Our objective is to establish stepped ranges of hematocrit values and platelet counts to identify the component and concentration of that component most responsible for the largest loss of platelet-collagen interaction. Methods: Donor citrated whole blood containing calcein tagged platelets was flowed at an arterial shear rate of 1000/second through a 70μm x 350μm x 5mm collagen-coated chamber at 37°C for 10 min, n=6. Images were captured every 15 seconds and analyzed for fluorescence intensity. Results: Linear regression analysis generated slopes (fluorescent intensity units/second) that were most different as hematocrit dropped below physiologic levels (HCT40control=100%, HCT25=39.5%, HCT20=21.4%, HCT18=17.4%, HCT16=11.6%). Non-linear fitting of slopes vs. HCT yielded the equation y=1.27e4 x 2 -3.51e4 x +4.43e5 describing an exponential decrease in platelet-collagen interaction with linear decreases in HCT. Conclusions: The largest drop in platelet adherence to collagen in a physiological model of arterial flow occurs as hematocrit falls from 40%. The commonly suggested 30HCT target for minimal RBC transfusion during resuscitation may not adequately support hemostasis and should be reconsidered.

Prospective comparison of point‐of‐care international normalised ratio measurement versus plasma international normalised ratio for acute traumatic coagulopathy

Early detection of acute traumatic coagulopathy (ATC) might be useful to guide trauma resuscitation. This study aimed to compare results from a point-of-care (POC) international normalised ratio (INR) measuring device with plasma INR in acute trauma patients. This was a single-centre, prospective, blinded comparative study. All trauma patients meeting trauma call-out criteria in a major trauma centre were screened. Patients predicted to have ATC were identified by the Coagulopathy of Severe Trauma score and a convenience sample of 72 patients included in this study. Whole blood was used to measure INR at the bedside, whereas blood from the same sample was sent to the hospital laboratory for plasma INR testing. Agreement between the laboratory and bedside INR was determined using a Bland-Altman plot. There were 38 (52.8%) patients with ATC by laboratory measure, defined as INR >1.5 or activated partial thrombin time >60 s, whereas the POC system identified 28 (38.9%) patients with an INR >1.5. Assuming the laboratory measure as the gold standard, the POC system had a specificity of 88.2% (95% confidence interval 71.6-96.2) and a sensitivity of 63.1% (95% confidence interval 46.0-77.7). Bland-Altman plots demonstrated inadequate agreement between the two methods of INR measurement for the major trauma patient. POC INR measurements using this method during the trauma reception and resuscitative phases cannot be used to identify or exclude patients with ATC. Further studies are required to determine if there is any role for POC INR measures during trauma resuscitation.

Early Platelet Dysfunction: An Unrecognized Role in the Acute Coagulopathy of Trauma

Our aim was to determine the prevalence of platelet dysfunction using an end point of assembly into a stable thrombus after severe injury. Although the current debate on acute traumatic coagulopathy has focused on the consumption or inhibition of coagulation factors, the question of early platelet dysfunction in this setting remains unclear. Prospective platelet function in assembly and stability of the thrombus was determined within 30 minutes of injury using whole blood samples from trauma patients at the point of care using thrombelastography-based platelet functional analysis. There were 51 patients in the study. There were significant differences in the platelet response between trauma patients and healthy volunteers, such that there was impaired aggregation to these agonists. In trauma patients, the median ADP inhibition of platelet function was 86.1% (interquartile range [IQR] 38.6% to 97.7%) compared with 4.2 % (IQR 0 to 18.2%) in healthy volunteers. After trauma, the impairment of platelet function in response to arachidonic acid was 44.9% (IQR 26.6% to 59.3%) compared with 0.5% (IQR 0 to 3.02%) in volunteers (Wilcoxon nonparametric test, p < 0.0001 for both tests). In this study, we show that platelet dysfunction is manifest after major trauma and before substantial fluid or blood administration. These data suggest a potential role for early platelet transfusion in severely injured patients at risk for postinjury coagulopathy.

Acute traumatic coagulopathy

Recent therapeutic and observational studies have demonstrated improved survival with better management of haemostasis early after injury. This review delineates our current understanding of the clinical importance, aetiology and pathophysiology of acute traumatic coagulopathy (ATC). Trauma causes an acute disruption of the equilibrium between all components of haemostasis (coagulation, anticoagulation, fibrinolysis, platelets and endothelium). In patients with a combination of severe tissue damage and systemic hypoperfusion, this will progress rapidly to an endogenous coagulopathy that is independently associated with worse outcomes. New discoveries of the interactions between neurohormonal, vascular, and coagulation systems are beginning to explain how this haemostatic impairment develops and offer novel targets for therapeutic manipulation. Routine coagulation screening tests are ineffective for diagnosing ATC and guiding resuscitation in real-time. Viscoelastic coagulation tests (such as ROTEM or TEG) have emerged as practical, rapid and sensitive diagnostic modalities. Their role in therapeutic targeting requires further validation. Conventional concepts of traumatic coagulopathy as a late occurring condition in response to iatrogenic haemodilution are redundant. ATC is an endogenous impairment of haemostasis that begins at the moment of injury. Further outcome improvements are possible with better understanding of the process by which this coagulopathy develops and how it may be inhibited.

Targeted resuscitation improves coagulation and outcome

Acute trauma coagulopathy in seriously injured casualties may be initiated by tissue hypoperfusion. A targeted (or novel hybrid [NH]) resuscitation strategy was developed to overcome poor tissue oxygen delivery associated with prolonged hypotension. Under the Animals (Scientific Procedures) Act 1986, terminally anesthetized large white pigs were divided into four groups (n = 6). Groups 1 and 2 received blast injury and 3 and 4 no blast (sham). All were given a controlled hemorrhage (35% blood volume) and an uncompressed grade IV liver injury. Five minutes later, all were resuscitated with 0.9% saline to a systolic arterial pressure (SAP) of 80 mm Hg. After 60 minutes, the NH groups (1 and 3) were resuscitated to a SAP (110 mm Hg), whereas hypotensive groups (2 and 4) continued with SAP 80 mm Hg for up to 8 hours from onset of resuscitation. Mean survival time was shorter in group 2 (258 minutes) compared with groups 1, 3, and 4 (452 minutes, 448 minutes, and 369 minutes). By the end of the study, hypotension was associated with a significantly greater prothrombin time (1.73 ± 0.10 and 1.87 ± 0.15 times presurgery, groups 2 and 4) compared with NH (1.44 ± 0.09 and 1.36 ± 0.06, groups 1 and 3, p = 0.001). Blast versus sham had no significant effect on prothrombin time (p = 0.56). Peak levels of interleukin 6 were significantly lower in NH groups. Arterial base excess was significantly lower with hypotension (-18.4 mmol/L ± 2.7 mmol/L and -12.1 mmol/L ± 3.2 mmol/L) versus NH (-3.7 mmol/L ± 2.8 mmol/L and -1.8 mmol/L ± 1.8 mmol/L, p = 0.0001). Hematocrit was not significantly different between groups (p = 0.16). Targeted resuscitation (NH) attenuates the development of acute trauma coagulopathy and systemic inflammation with improved tissue perfusion and reduced metabolic acidosis in a model of complex injury. This emphasizes the challenge of choosing a resuscitation strategy for trauma patients where the needs of tissue perfusion must be balanced against the risk of rebleeding during resuscitation.

Plasma/platelets/red blood cell ratio in the management of the bleeding traumatized patient

The scope of this review is to describe what is known about blood product ratios and their effects on acute trauma coagulopathy. Assessing how ratios matter to trauma patients is important to improve massive transfusion strategies. A growing body of evidence supports that high ratios of fresh frozen plasma and platelets to red blood cells improve survival of the massively bleeding traumatized patient. Acting quickly is also critical. Reducing transfusion delay can be achieved through massive transfusion protocol implementations, which incorporate local agreements with blood banks and 'trauma packs' in organized trauma systems. Thawed plasma and freeze-dried plasma allow immediate delivery of plasma. Fresh frozen plasma/platelet/red blood cell ratios matter to define the content of packs immediately available within the golden hour to the right, accurately screened trauma patients. Research is needed in developing novel transfusion approaches for massively bleeding patients.

Factor IX complex for the correction of traumatic coagulopathy

Damage control resuscitation advocates correction of coagulopathy; however, options are limited and expensive. The use of prothrombin complex concentrate (PCC), also known as factor IX complex, can quickly accelerate reversal of coagulopathy at relatively low cost. The purpose of this study is to describe our experience in the use of factor IX complex in coagulopathic trauma patients. All patients receiving PCC at our Level I trauma center over a two-year period (2008-2010) were reviewed. PCC was used at the discretion of the trauma attending for treatment of coagulopathy, reversal of coumadin, and when recombinant factor VIIa was indicated. Forty-five trauma patients received 51 doses of PCC. Sixty-two per cent were male and mean Injury Severity Score was 23 (± 14.87). Standard dose was 25 units per kg and mean cost per patient was $1,022 ($504-3,484). Fifty-eight per cent of patients were on warfarin before admission. Mean international normalized ratio (INR) was decreased after PCC administration (p = 0.001). Packed red blood cell transfusion was also reduced after factor IX complex (p = 0.018). Mean INR was reduced in both the nonwarfarin (p = 0.001) and warfarin (p = 0.001) groups. Packed red blood cell transfusion was less in the nonwarfarin group (p = 0.002) however was not significant in the warfarin group. Subsequent thromboembolic events were observed in 3 of the 45 patients (7%). Mortality was 16 of 45 (36%). PCC rapidly and effectively treats coagulopathy after traumatic injury. PCC therapy leads to a significant correction in INR in all trauma patients, regardless of coumadin use, and concomitant reduction in blood product transfusion. PCC should be considered as an effective tool to treat acute coagulopathy of trauma. Further prospective studies examining the safety, efficacy, cost, and outcomes comparing PCC and recombinant factor VIIa are needed.

Prohemostatic Interventions in Trauma: Resuscitation-Associated Coagulopathy, Acute Traumatic Coagulopathy, Hemostatic Resuscitation, and Other Hemostatic Interventions

Trauma is the most common cause of death in the young and hemorrhage is the most important cause of death in patients with trauma. Recently redefined pathways of inflammation and coagulation, together with hypothermia and acidosis contribute to trauma-associated coagulopathy and aggravation of bleeding. Pharmacological prohemostatic agents may be useful to (partly) correct the coagulopathy in trauma patients and may serve as useful adjunctive treatment options in patients with severe blood loss after trauma. Recombinant factor VIIa, fibrinogen and prothrombin complex concentrates, and antifibrinolytic agents have been evaluated in clinical trials. These interventions show promising effects but their efficacy in reducing clinically important outcome parameters need to be confirmed in clinical studies.

Critical Role of Activated Protein C in Early Coagulopathy and Later Organ Failure, Infection and Death in Trauma Patients

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 in plasma protein C (PC) levels. Whether this early coagulopathy and later propensity to infection, multiple organ failure and mortality are associated with the activation of PC pathway has not been demonstrated and constitutes the aim of this study. This was a prospective cohort study of 203 major trauma patients. Serial blood samples were drawn on arrival in the emergency department, and at 6, 12, and 24 hours after admission to the hospital. PT, PTT, Va, VIIIa, PC aPC t-PA, and D-dimer levels were assayed. Comprehensive injury, resuscitation, and outcome data were prospectively collected. A total of 203 patients were enrolled. Patients with tissue hypoperfusion and severe traumatic injury showed a strong activation of the PC which was associated with a coagulopathy characterized by inactivation of the coagulation factors V and VIII and a derepression of the fibrinolysis with high plasma levels of plasminogen activator and high D-dimers. Elevated plasma levels of activated PC were significantly associated with increased mortality, organ injury, increased blood transfusion requirements, and reduced ICU ventilator-free days. Finally early depletion of PC after trauma is associated with a propensity to posttraumatic ventilator-associated pneumonia. Acute traumatic coagulopathy occurs in the presence of tissue hypoperfusion and severe traumatic injury and is mediated by activation of the PC pathway. Higher plasma levels of aPC upon admission are predictive of poor clinical outcomes after major trauma. After activation, patients who fail to recover physiologic plasma values of PC have an increased propensity to later nosocomial lung infection.

Predicting on-going hemorrhage and transfusion requirement after severe trauma: a validation of six scoring systems and algorithms on the TraumaRegister DGU®

IntroductionThe early aggressive management of the acute coagulopathy of trauma may improve survival in the trauma population. However, the timely identification of lethal exsanguination remains challenging. This study validated six scoring systems and algorithms to stratify patients for the risk of massive transfusion (MT) at a very early stage after trauma on one single dataset of severely injured patients derived from the TR-DGU (TraumaRegister DGU® of the German Trauma Society (DGU)) database.MethodsRetrospective internal and external validation of six scoring systems and algorithms (four civilian and two military systems) to predict the risk of massive transfusion at a very early stage after trauma on one single dataset of severely injured patients derived from the TraumaRegister DGU® database (2002-2010). Scoring systems and algorithms assessed were: TASH (Trauma-Associated Severe Hemorrhage) score, PWH (Prince of Wales Hospital/Rainer) score, Vandromme score, ABC (Assessment of Blood Consumption/Nunez) score, Schreiber score and Larsen score. Data from 56,573 patients were screened to extract one complete dataset matching all variables needed to calculate all systems assessed in this study. Scores were applied and area-under-the-receiver-operating-characteristic curves (AUCs) were calculated. From the AUC curves the cut-off with the best relation of sensitivity-to-specificity was used to recalculate sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV).ResultsA total of 5,147 patients with blunt trauma (95%) was extracted from the TR-DGU. The mean age of patients was 45.7 ± 19.3 years with a mean ISS of 24.3 ± 13.2. The overall MT rate was 5.6% (n = 289). 95% (n = 4,889) patients had sustained a blunt trauma. The TASH score had the highest overall accuracy as reflected by an AUC of 0.889 followed by the PWH-Score (0.860). At the defined cut-off values for each score the highest sensitivity was observed for the Schreiber score (85.8%) but also the lowest specificity (61.7%). The TASH score at a cut-off ≥ 8.5 showed a sensitivity of 84.4% and also a high specificity (78.4%). The PWH score had a lower sensitivity (80.6%) with comparable specificity. The Larson score showed the lowest sensitivity (70.9%) at a specificity of 80.4%.ConclusionsWeighted and more sophisticated systems such as TASH and PWH scores including higher numbers of variables perform superior over simple non-weighted models. Prospective validations are needed to improve the development process and use of scoring systems in the future.

Mechanism of Injury Affects Acute Coagulopathy of Trauma in Combat Casualties

Mechanism of Injury Affects Acute Coagulopathy of Trauma in Combat Casualties

Acute traumatic coagulopathy decreased actual survival rate when compared with predicted survival rate in severe trauma

ObjectiveTo determine whether acute traumatic coagulopathy (ATC) should be combined with the trauma and injury severity score (TRISS) to predict outcome in severe trauma patients and investigate effects of the...

Acute Traumatic Coagulopathy in Severe Injury

Clinical observation and research findings show that acute traumatic coagulopathy (ATC) is a major factor that must be addressed in the care of severely injured patients. In this review article, we discuss the incidence and causes of ATC, the potential means of early risk stratification for it, and recommendations for its treatment. We selectively reviewed the pertinent literature and retrospectively analyzed data from the Trauma Registry of the German Trauma Society (Traumaregister der Deutschen Gesellschaft für Unfallchirurgie, TR-DGU) relating to the incidence, causes, and outcome of ATC. We provide an overview of current treatment recommendations, supplemented by our own findings regarding the ratio of packed red blood cell concentrate (pRBC) to fresh-frozen plasma (FFP) transfusion and regarding coagulation-factor-based treatments for coagulopathy in the acute phase after trauma. ATC, a condition associated with increased morbidity and mortality, is seen on admission in one out of four patients with major trauma. The main causes of ATC are tissue damage, hypoperfusion, hemodilution, hypothermia, acidosis, and inflammation. It may be possible to identify patients at risk for ATC early on through the use of rapidly calculable, predictive numerical scales (McLaughlinScore, TASH, and ABC), laboratory tests, and imaging studies (FAST and CT). Acute treatment is focused on the control of bleeding and support of the coagulation system according to the current guidelines. Patients at high risk may benefit from a balanced transfusion strategy. Innovative strategies currently under study include point-of-care-guided treatment and coagulation-factor-concentrate-based treatment.

Functional definition and characterization of acute traumatic coagulopathy

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.

Abstract 280: Reversal of Acute Coagulopathy Using Small-Volume 7.5% NaCl with Adenocaine and Mg 2+ Resuscitation in a Rat Model of Severe Hemorrhagic Shock

Acute traumatic coagulopathy occurs early in hemorrhagic trauma and is a major contributor to further bleeding, inflammation and mortality. Previously we showed that a small intravenous (IV) bolus of 7.5% NaCl with Adenocaine (adenosine and lidocaine) and Mg2+ could resuscitate mean arterial blood pressure (MAP) to within a permissive hypotensive range. Our aim was to examine the effect of the same fluid on activated partial thromboplastin times (aPTT) and prothrombin times (PT) following 60 min of resuscitation. Methods: Male fed Sprague-Dawley rats (444 ± 10g, n=64) were anesthetized, non-heparinized and randomly assigned to one of eight groups: 1) Baseline blood, 2) 20 min bleed, 3) 60 min shock, 4) Untreated resuscitation, 5) 7.5% NaCl, 6) 7.5% NaCl Adenocaine, 7) 7.5% NaCl Mg2+ and 8) 7.5% NaCl, Adenocaine Mg2+. Hemorrhagic shock was induced by phlebotomy until MAP was 35-40 mmHg and continued for 20 min (~40% blood loss). Animals were left in shock for 60 min at 34°C. 0.3 ml IV bolus was injected over 2 sec. Arterial blood pressures, MAP, heart rate and rectal temperature were monitored. Arterial blood was collected in 3.2% Na-citrate tubes, centrifuged and the plasma was snap-frozen (-196°C) and stored at -80°C. aPTT and PT were measured on an Amelung KC4A microcoagulometer. Results: Baseline aPTT and PT values were 17 ± 0.5 sec and 28 ± 0.8 sec, and increased significantly to 63 ± 21 and 107 ± 33 sec after blood withdrawal (20 min), and over 10 times baseline after 60 min shock. The large increases during shock were not due to hypothermia. Sixty minutes after 0.3 ml bolus resuscitation, the hypocoagulopathy worsened in all groups with the exception of 7.5% NaCl Adenocaine and Mg2+ with aPTT of 24 ± 1.7 sec and PT of 33 ± 1 sec. A partial restoration occurred with 7.5% NaCl Mg2+ (aPTT of 150 ± 43 and PT of 182 ± 47 sec) but was not significantly different from 7.5% NaCl alone. Conclusion: aPTT and PT clotting times significantly increased during bleeding and shock prior to resuscitation. The hypocoagulopathy increased with 7.5% NaCl and was nearly completely reversed with 7.5% NaCl Adenocaine and Mg2+. We speculate that the mechanism(s) of reversal may shed light on understanding acute traumatic coagulopathy in out-of-hospital and far forward military settings.

Mechanistic Determinants of the Acute Coagulopathy of Trauma (ACoT) in Patients Undergoing Emergency Surgery,

Abstract 3319 Introduction:Acute coagulopathy of trauma (ACoT) is a highly lethal phenomenon whose mechanisms have yet to be clearly defined. While likely multi-factorial, it has been reported to only occur in the presence of blunt injury. The purpose of this study was to identify variables that might influence or contribute to the early development of ACoT. Methods:Retrospective review of all patients admitted to a Level 1 trauma center 01/2004–12/2009 who underwent emergent laparotomy. Emergent laparotomy was defined as laparotomy performed within two hours of admission. ACoT(+) was defined as arrival INR >= 1.5, while ACoT(−) was defined as arrival INR<1.5. Univariate and multivariate analyses performed. Primary outcome was the identification of those factors predicting the presence of ACoT on admission. Results:1218 patients were included, 337 (27%) presented with ACoT(+), 881 (73%) did not. The groups had similar demographics and pre-hospital and ED fluids. Arrival base deficit (median 8.5 vs. 4.0) and ISS (25 vs. 16) were higher in ACoT(+) as were intra-operative RBC (median 4 vs. 0 U) and plasma (3 vs. 0 U); all p<0.05. 40% of ACoT(+) patients sustained penetrating injury. Six-hour (12% vs. 1%), 24-hour (15% vs. 1%), and 30-day (23% vs. 4%) mortality were significantly greater in ACoT(+); all p<0.001. Linear regression found INR values independently associated with arrival base deficit (p<0.001) but not ISS. Controlling for age, gender, mechanism of injury, and pre-hospital resuscitation, multiple logistic regression demonstrated that arrival base deficit was an independent predictor of developing ACoT.Odds ratio95% C.I.p-valueArrival base value0.9220.870, 0.9780.007Injury severity score1.051.025, 1.083<0.001Pre-hospital SBP, mmHg0.980.968, 0.9910.001 Conclusion:The current study found ACoT independently associated with metabolic (base deficit), physiologic (blood pressure) and anatomic insults (ISS). Attempts to address ACoT should focus on correcting each of these components. Moreover, contrary to prior data, 40% of ACoT(+) patients sustained penetrating mechanism. Disclosures:No relevant conflicts of interest to declare.