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Summary: In urgent clinical situations, such as trauma, urgent surgery or before thrombolysis, rapid quantification of direct oral anticoagulant plasma drug levels is warranted. Using the ClotPro® analyser, we assessed two novel viscoelastic tests for detection of clinically‐relevant plasma drug levels in trauma patients. The ecarin clotting time was used to assess the plasma concentration of dabigatran and Russell´s viper venom clotting time to determine the plasma concentration of direct factor Xa inhibitors. In parallel, plasma concentrations were analysed using plasma‐based chromogenic assays. A total of 203 simultaneous measurements were performed. Strong to very strong linear correlations were detected between ecarin clotting time and plasma concentration of dabigatran (r = 0.9693), and between Russell´s viper venom clotting time and plasma concentrations of apixaban (r = 0.7391), edoxaban (r = 0.9251) and rivaroxaban (r = 0.8792), all p < 0.001. An ecarin clotting time ≥ 189 seconds provided 100% sensitivity and 90% specificity for detecting plasma dabigatran concentrations ≥ 50 ng.ml‐1. Corresponding Russell´s viper venom clotting time cut‐off values were ≥ 136 seconds for apixaban (80% sensitivity, 88% specificity), ≥ 168 seconds for edoxaban (100% sensitivity, 100% specificity) and ≥ 177 seconds for rivaroxaban (90% sensitivity, 100% specificity). Detection of drug levels ≥ 100 ng.ml‐1 was also investigated: for dabigatran, an ecarin clotting time ≥ 315 seconds yielded 92% sensitivity and 100% specificity; while Russell´s viper venom clotting time cut‐offs of 191, 188 and 196 seconds were calculated for apixaban (67% sensitivity, 88% specificity), edoxaban (100% sensitivity, 75% specificity) and rivaroxaban (100% sensitivity, 91% specificity), respectively. We have demonstrated strong positive correlations between plasma drug levels and clotting time values in the specific ClotPro assays. Cut‐off values for detecting clinically‐relevant drug levels showed high levels of sensitivity and specificity. [ABSTRACT FROM AUTHOR]

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Background: Bleeding guidelines currently recommend use of viscoelastic testing (VET) to direct haemostatic resuscitation in severe haemorrhage. However, VET-derived parameters of clot initiation, such as clotting time (CT) and activated clotting time (ACT), might not adequately reflect a clinically relevant interaction of procoagulant and anticoagulant activity, as revealed by thrombin generation assays. The aim of this study was to evaluate the ability of CT and ACT to indicate thrombin generation activity., Methods: Citrated whole blood obtained from 13 healthy volunteers underwent a 50% crystalloid dilution (DL-50%), followed by spiking with four-factor prothrombin complex concentrate (DL-50% + 4F-PCC). Changes in thrombin generation activity were compared with the VET parameters CT and ACT derived from four commercially available viscoelastic devices (ROTEM® Delta, ClotPro®, TEG®6s, and Quantra®) and standard coagulation tests., Results: Dilution of whole blood resulted in a marked increase in velocity index, peak height, and endogenous thrombin potential (all P<0.01), with a further substantial increase after spiking with 4F-PCC (all P<0.001). In contrast, CT and ACT were significantly prolonged in response to DL-50% on all devices (all P<0.05). Subsequent spiking of diluted blood with 4F-PCC had no impact on CT and ACT derived from VET analysers, but it restored standard coagulation tests without reaching baseline values (all P<0.01)., Conclusions: Upregulated thrombin generation parameters after PCC spiking were not displayed by CT, ACT, or standard tests. Our results do not support treatment algorithms using prolonged CT or ACT as a trigger for administration of PCC to augment thrombin generation., Competing Interests: Declaration of interests HS received honoraria for participation in advisory board meetings for Bayer Healthcare, Böhringer Ingelheim, and TEM international and study grants from CSL Behring. JG has received honoraria, research funding, and travel reimbursement from Alexion, AstraZeneca, Boehringer Ingelheim, CSL Behring, Instrumentation Laboratory, Johnson & Johnson, Mitsubishi Tanabe Pharma, Octapharma, Portola, and Takeda. FS has received consulting fees from CSL Behring, Roche Diabetes and payment or honoraria for lectures, travel expenses, and scientific support from AstraZeneca, CSL Behring, enicor, and LFB. The other authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background : Viscoelastic hemostatic assays (VHAs) have become an integral diagnostic tool in guiding hemostatic therapy, offering new opportunities in personalized hemostatic resuscitation. This study aims to assess the interchangeability of ClotPro® and ROTEM® delta in the unique context of parturient women. Methods : Blood samples from 217 parturient women were collected at three timepoints. A total of 631 data sets were eligible for our final analysis. The clotting times were analyzed via extrinsic and intrinsic assays, and the clot firmness parameters A5, A10, and MCF were analyzed via extrinsic, intrinsic, and fibrin polymerization assays. In parallel, the standard laboratory coagulation statuses were obtained. Device comparison was assessed using regression and Bland-Altman plots. The best cutoff calculations were used to determine the VHA values corresponding to the established standard laboratory cutoffs. Results : The clotting times in the extrinsic and intrinsic assays showed notable differences between the devices, while the extrinsic and intrinsic clot firmness results demonstrated interchangeability. The fibrinogen assays revealed higher values in ClotPro ® compared to ROTEM ® . An ROC analysis identified VHA parameters with high predictive values for coagulopathy exclusion and yet low specificity. Conclusions : In the obstetric setting, the ROTEM ® and ClotPro ® parameters demonstrate a significant variability. Device- and indication-specific transfusion algorithms are essential for the accurate interpretation of measurements and adequate hemostatic therapy.

Background: S100 B is an extensively studied neuro-trauma marker, but its specificity and subsequently interpretation in major trauma patients might be limited, since extracerebral injuries are known to increase serum levels. Thus, we evaluated the potential role of S100B in the assessment of severe traumatic brain injury (TBI) in multiple injured patients upon emergency room (ER) admission and the first days of intensive care unit (ICU) stay., Methods: Retrospective study employing trauma registry data derived from a level 1 trauma center. Four cohorts of patients were grouped: isolated TBI (iTBI), polytrauma patients with TBI (PT + TBI), polytrauma patients without TBI (PT-TBI) and patients without polytrauma or TBI (control). S100B-serum levels were assessed immediately after admission in the emergency room and during the subsequent ICU stay. Values were correlated with injury severity score (ISS), Glasgow Coma Score (GCS) and in-hospital mortality., Results: 780 predominantly male patients (76 %) with a median age of 48 (30-63) and a median ISS of 24 (17-30) were enrolled in the study. Admission S100B correlated with ISS and TBI severity defined by the GCS (both p < 0.0001) but not with head abbreviated injury score (AIS) (p = 0.38). Compared with survivors, non-survivors had significantly higher median S100B levels in the ER (6.14 μg/L vs. 2.06 μg/L; p < 0.0001) and at ICU-day 1 (0.69 μg/L vs. 0.17 μg/L; p < 0.0001). S100B in the ER predicted mortality with an area under curve (AUC) of 0.77 (95 % CI 0,70-0,83, p < 0.0001), vs. 0.86 at ICU-day 1 (95 % CI 0,80-0,91, p < 0.0001)., Conclusion: In conclusion, S100B is a valid biomarker for prediction of mortality in major trauma patients with a higher accuracy when assessed at the first day of ICU stay vs. immediately after ER admission. Since S100B did not correlate with pathologic TBI findings in multiple injured patients, it failed as predictive neuro-marker because extracerebral injuries demonstrated a higher influence on admission levels than neurotrauma. Although S100B levels are indicative for injury severity they should be interpreted with caution in polytrauma patients., Competing Interests: Declaration of Competing Interest None of the authors has a conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Due to a better safety profile, direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. However, little is known about DOAC plasma concentrations in trauma patients upon hospital admission. Thus, we investigated the frequency and extent of DOAC possible over- and underdosing in trauma patients upon hospital admission., Methods: In this single-center retrospective study, DOAC plasma concentrations of adult trauma patients were analyzed with specific calibrated anti-IIa (dabigatran) and anti-Xa (apixaban, edoxaban and rivaroxaban) tests within 4 h after hospital admission., Results: A total of 210 trauma patients, admitted between 2019 and 2022, were included in the analyses. Low DOAC levels < 30 ng/mL were detected in 13.3% of the patients. In 7.1% of the patients, DOAC plasma levels ranged between 300-399 ng/mL and further 7.1% exhibited plasma concentrations > 400 ng/mL. The highest incidence of high to very high DOAC plasma concentration was observed for patients on rivaroxaban and dabigatran. A moderate correlation was observed between dabigatran plasma concentration and estimated glomerular filtration rate (rho = - 0.5338, p = 0.0003). For rivaroxaban no clear association between plasma concentration and liver or renal function could be detected. Patients on statins had significantly higher DOAC concentration in comparison with those not taking statins (153 (76-274) vs 108 (51-217) ng/mL, p = 0.046)., Conclusion: The current study revealed that patients on dabigatran and rivaroxaban were prone to higher DOAC plasma levels upon hospital admission in comparison with apixaban and edoxaban. DOAC plasma level measurement in trauma patients might be warranted due to unpredictively low or high plasma concentrations. However, the clinical impact of altered plasma levels on both, bleeding and thromboembolic events, remains to be determined by future studies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: There is an ever-increasing number of hip fracture (HF) patients on direct oral anticoagulants (DOAC). The impact of DOAC plasma level prior to HF surgery on perioperative blood loss and transfusion requirements has not been investigated so far., Materials and Methods: In this retrospective study of HF patients on DOACs admitted to the AUVA Trauma Center Salzburg between February 2015 and December 2021. DOAC plasma levels were analysed prior to surgery. Patients were categorized into four DOAC groups: Group A < 30 ng/mL, Group B 30-49 ng/mL, Group C 50-79 ng/mL, and Group D ≥ 80 ng/mL. Haemoglobin concentration was measured upon admission, prior to surgery, after ICU/IMC admission, and on day 1 and 2 post-surgery. Difference in the blood loss via drains, transfusion requirements and time to surgery were compared., Results: A total of 155 subjects fulfilled the predefined inclusion criteria. The median age of the predominantly female patients was 86 (80-90) years. Haemoglobin concentration in Group D was lower upon admissions but did not reach statistical significance. The decrease in haemoglobin concentration over the entire observation time was comparable between groups. Blood transfusion requirements were significantly higher in Group D compared to Group A and B (p = 0.0043). Time to surgery, intra- and postoperative blood loss via drains were not different among groups., Conclusion: No strong association between the DOAC plasma levels and perioperative blood loss was detected. Higher transfusion rates in patients with DOAC levels ≥ 80 ng/mL were primarily related to lower admission haemoglobin levels. DOAC concentration measurement is feasible and expedites time to surgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Hyperfibrinolysis (HF) frequently occurs after severe systemic hypoperfusion during major trauma and out-of-hospital cardiac arrest (OHCA). In trauma-induced HF, hypoperfusion, the activation of protein C (APC), and the release of tissue plasminogen activator (t-PA) have been identified as the driving elements of premature clot breakdown. The APC pathway also plays a role in inflammatory responses such as neutrophil extracellular trap formation (NETosis), which might contribute to lysis through cleavage of fibrin by neutrophil elastases. We investigated whether the APC and the plasminogen pathway were general drivers of HF, even in the absence of a traumatic incident. Additionally, we were interested in inflammatory activation such as the presence of NETs as potential contributing factors to HF. A total of 41 patients with OHCA were assigned to a HF and a non-HF group based on maximum lysis (ML) in thromboelastometry. Thrombin-antithrombin (TAT)-complex, soluble thrombomodulin (sTM), APC-PC inhibitor complex, t-PA, PAI-1, t-PA-PAI-1 complex, plasmin-antiplasmin (PAP), d-dimers, neutrophil elastase, histonylated DNA (hDNA) fragments, and interleukin-6 were assessed via immunoassays in the HF group vs. non-HF. APC-PC inhibitor complex is significantly higher in HF patients. Antigen levels of t-PA and PAI-1 do not differ between groups. However, t-PA activity is significantly higher and t-PA-PAI-1 complex significantly lower in the HF group. Consistent with these results, PAP and d-dimers are significantly elevated in HF. HDNA fragments and neutrophil elastase are not elevated in HF patients, but show a high level of correlation, suggesting NETosis occurs in OHCA as part of inflammatory activation and cellular decay. Just as in trauma, hypoperfusion, the activation of protein C, and the initiation of the plasminogen pathway of fibrinolysis manifest themselves in the HF of cardiac arrest. Despite features of NETosis being detectable in OHCA patients, early pro-inflammatory responses do not appear be associated with HF in cardiac arrest.

Trauma patients admitted to an intensive care unit (ICU) may potentially experience a deficiency of coagulation factor thirteen (FXIII). In this retrospective cohort study conducted at a specialized trauma center, ICU patients were studied to determine the dependency of FXIII activity levels on clinical course and substitution with blood and coagulation products. A total of 189 patients with a median injury severity score (ISS) of 25 (16−36, IQR) were included. Abbreviated injury scores for extremities (r = −0.38, p < 0.0001) but not ISS (r = −0.03, p = 0.45) showed a negative correlation with initial FXIII levels. Patients receiving FXIII concentrate presented with a median initial FXIII level of 54 (48−59)% vs. 88 (74−108)%, p < 0.0001 versus controls; they had fewer ICU-free days: 17 (0−22) vs. 22 (16−24), p = 0.0001; and received higher amounts of red blood cell units: 5 (2−9) vs. 4 (1−7), p < 0.03 before, and 4 (2−7) vs. 1 (0−2), p < 0.0001 after FXIII substitution. Matched-pair analyses based on similar initial FXIII levels did not reveal better outcome endpoints in the FXIII-substituted group. The study showed that a low initial FXIII level correlated with the clinical course in this trauma cohort, but a substitution of FXIII did not improve endpoints within the range of the studied FXIII levels. Future prospective studies should investigate the utility of FXIII measurement and lower threshold values of FXIII, which trigger substitution in trauma patients.

Trauma and bleeding are associated with a high mortality, and most of these deaths occur early after injury. Viscoelastic haemostatic tests have gained increasing importance in goal-directed transfusion and bleeding management. A new generation of small-sized and thus portable ultrasound-based viscoelastic analysers have been introduced in clinical practice. We questioned whether a promising candidate can be used in emergency helicopters, with a focus on the susceptibility to vibration stress. We investigated whether the high vibration environment of an emergency helicopter would affect the operability of an ultrasound-based viscoelastic analyser and would yield reproducible results in flight and on the ground. We drew blood from 27 healthy volunteers and performed simultaneous analyses on two TEG 6s. Each measurement was performed in-flight on board an Airbus H135 emergency helicopter and was repeated on the ground, close to the flight area. Results from both measurements were compared, and the recorded tracings and numeric results were analysed for artifacts. Vibratometric measurements were performed throughout the flight in order to quantify changes in the magnitude and character of vibrations in different phases of helicopter operation. The high vibration environment was associated with the presence of artifacts in all recorded tracings. There were significant differences in citrated Kaolin + Heparinase measurements in-flight and on the ground. All other assays increased in variability but did not show significant differences between the two time points. We observed numerous artifacts in viscoelastic measurements that were performed in flight. Some parameters that were obtained from the same sample showed significant differences between in-flight and on-ground measurements. Performing resonance-based viscoelastic tests in helicopter medical service is prone to artifacts. However, a 10 min delay between initiation of measurement and take-off might produce more reliable results.

Platelet dysfunction is a suggested driver of trauma-induced coagulopathy. However, there is still a paucity of data regarding the impact of injury pattern on platelet function and the association of platelet dysfunction on transfusion requirements and mortality. In this retrospective cohort study, patients were grouped into those with isolated severe traumatic brain injury (TBI group), those with major trauma without TBI (MT group), and a combination of both major trauma and traumatic brain injury (MT + TBI group). Platelet function was assessed by whole blood impedance aggregometry (Multiplate ® , MP). Three different platelet activators were used: adenosine-diphosphate (ADP test), arachidonic acid (ASPI test), and thrombin activated peptide-6 (TRAP test). Blood transfusion requirements within 6 h and 24 h and the association of platelet dysfunction on mortality was investigated. A total of 328 predominantly male patients (75.3%) with a median age of 53 (37-68) years and a median ISS of 29 (22-38) were included. No significant difference between the TBI group, the MT group, and the MT + TBI group was detected for any of the investigated platelet function tests. Unadjusted and adjusted for platelet count, the investigated MP assays revealed no significant group differences upon ER admission and were not able to sufficiently predict massive transfusion, neither within the first 6 h nor for the first 24 h after hospital admission. No association between platelet dysfunction measured by MP upon ER admission and mortality was observed. Conclusion: Injury pattern did not specifically impact platelet function measurable by MP. Platelet dysfunction upon ER admission measurable by MP was not associated with transfusion requirements and mortality. The clinical relevance of platelet function testing by MP in trauma patients not on platelet inhibitors is questionable.

Background: Heparan sulfate is an integral component of the glycocalyx that provides an anticoagulant layer close to the endothelium. Hypoperfusion, inflammation, and sympathoadrenal activation following major trauma result in glycocalyx shedding and subsequent release of heparan sulfate into the bloodstream. The possible anticoagulant effect of this "autoheparinization" has been suggested as a potential driver of trauma-induced coagulopathy. We investigated whether thromboelastometry can be used to detect trauma-induced autoheparinization., Methods: This study comprised three parts. First, in a retrospective clinical study of 264 major trauma patients, the clotting time (CT) in the intrinsic activation (INTEM) and intrinsic activation plus heparinase (HEPTEM) assays were evaluated upon emergency room admission. Second, in an in vivo experimental rat model of hemorrhagic-traumatic shock, the release of heparan sulfate was investigated with INTEM and HEPTEM analyses of whole blood. Third, in vitro spiking of whole blood from healthy volunteers was undertaken to assess the effects of clinically relevant quantities of heparan sulfate and heparin on CT in the INTEM and HEPTEM assays., Results: In the first part, severe injury and hemorrhagic shock was not associated with any increases in INTEM CT versus HEPTEM CT. Part 2 showed that an approximate threefold increase in heparan sulfate resulting from hemorrhagic traumatic shock in rats did not prolong INTEM CT, and no significant differences between INTEM CT and HEPTEM CT were observed. Third, spiking of whole blood with heparan sulfate had no impact on INTEM CT, whereas heparin elicited significant prolongation of INTEM CT., Conclusion: Despite structural similarity between heparan sulfate and heparin, the amounts of heparan sulfate shed in response to trauma did not exert an anticoagulant effect that was measurable by the intrinsically activated CT in thromboelastometry. The extent to which heparan sulfate contributes to trauma-induced coagulopathy has yet to be elucidated., Level of Evidence: Prognostic and Epidemiologic; Level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Specific antagonists have been developed for the reversal of direct oral anticoagulants (DOAC). We investigated the impact of these reversal agents on the plasma concentration and visco-elastic test results of dabigatran and factor Xa inhibitors. After baseline measurements of dabigatran, the plasma concentration, and the visco-elastic ClotPro ® ecarin clotting time (ECA-CT), we added the reversal agent Idarucizumab in vitro and these two analyses were repeated. Likewise, the baseline plasma concentration of apixaban, edoxaban, and rivaroxaban as well as ClotPro ® Russell's viper venom test clotting time (RVV-CT) were measured and reanalyzed following Andexanet alfa spiking. We analyzed fifty blood samples from 37 patients and 10 healthy volunteers. Idarucizumab decreased the measured dabigatran plasma concentration from 323.9 ± 185.4 ng/mL to 5.9 ± 2.3 ng/mL and ECA-CT from 706.2 ± 344.6 s to 70.6 ± 20.2 s, (all, p < 0.001). Andexanet alfa decreased the apixaban concentration from 165.1 ± 65.5 ng/mL to 9.8 ± 8.1 ng/mL, edoxaban from 152.4 ± 79.0 ng/mL to 36.4 ± 19.2 ng/mL, and rivaroxaban from 153.2 ± 111.8 ng/mL to 18.1 ± 9.1 ng/mL (all p < 0.001). Andexanet alfa shortened the RVV-CT of patients with apixaban from 239.2 ± 71.7 s to 151.1 ± 30.2 s, edoxaban from 288.2 ± 65.0 s to 122.7 ± 37.1 s, and rivaroxaban from 225.9 ± 49.3 s to 103.7 ± 12.1 s (all p < 0.001). In vitro spiking of dabigatran-containing blood with Idarucizumab substantially reduced the plasma concentration and ecarin-test clotting time. Andexanet alfa lowered the concentration of the investigated factor Xa-inhibitors but did not normalize the RVV-CT. In healthy volunteers' blood, Idarucizumab spiking had no impact on ECA-CT. Andexanet alfa spiking of non-anticoagulated blood prolonged RVV-CT ( p = 0.001), potentially as a consequence of a competitive antagonism with human factor Xa.

Hemorrhage after trauma remains a significant cause of preventable death. Trauma-induced coagulopathy (TIC) at the time of hospital admission is associated with an impaired outcome. Rather than a universal phenotype, TIC represents a complex hemostatic disorder, and standard coagulation tests are not designed to adequately reflect the complexity of TIC. Viscoelastic testing (VET) has gained increasing interest for the characterization of TIC because it provides a more comprehensive depiction of the coagulation process. Thus, VET has been established as a point-of-care-available hemostatic monitoring tool in many trauma centers. Damage-control resuscitation and early administration of tranexamic acid provide the basis for treating TIC. To improve survival, ratio-driven massive transfusion protocols favoring early and high-dose plasma transfusion have been implemented in many trauma centers around the world. Although plasma contains all coagulation factors and inhibitors, only high-volume plasma transfusion allows for adequate substitution of lacking coagulation proteins. However, high-volume plasma transfusion has been associated with several relevant risks. In some European trauma facilities, a more individualized hemostatic therapy concept has been implemented. The hemostatic profile of the bleeding patient is evaluated by VET. Subsequently, goal-directed hemostatic therapy is primarily based on coagulation factor concentrates such as fibrinogen concentrate or prothrombin complex concentrate. However, a clear difference in survival benefit between these two treatment strategies has not yet been shown. This concise review aims to summarize current evidence for different diagnostic and therapeutic strategies in patients with TIC., Competing Interests: Dr. Gratz reports personal fees and nonfinancial support from CSL Behring, nonfinancial support from Johnson & Johnson Medical Products, personal fees and nonfinancial support from Mitsubishi Tanabe Pharma, personal fees and nonfinancial support from Instrumentation Laboratory, and personal fees from Portola, outside the submitted work. Dr. Schöchl reports grants, personal fees, and nonfinancial support from CSL Behring, grants, personal fees, and nonfinancial support from TEM International, outside the submitted work. Dr. Oberladstätter declares that he has no potential conflicts of interest., (Thieme. All rights reserved.)

Severe bleeding remains a prominent cause of early in-hospital mortality in major trauma patients. Thus, prompt prediction of patients at risk of massive transfusion (MT) is crucial. We investigated the ability of the inflammatory marker interleukin (IL)-6 to forecast MT in severely injured trauma patients. IL-6 plasma levels were measured upon admission. Receiver operating characteristic curves (ROCs) were calculated, and sensitivity and specificity were determined. In this retrospective study, a total of 468 predominantly male (77.8%) patients, with a median injury severity score (ISS) of 25 (17-34), were included. The Youden index for the prediction of MT within 6 and 24 h was 351 pg/mL. Patients were dichotomized into two groups: (i) low-IL-6 < 350 pg/mL and (ii) high-IL-6 ≥ 350 pg/mL. IL-6 ≥ 350 pg/mL was associated with a lower prothrombin time index, a higher activated partial thromboplastin time, and a lower fibrinogen concentration compared with IL-6 < 350 pg/mL ( p <0.0001 for all). Thromboelastometric parameters were significantly different between groups ( p <0.03 in all). More patients in the high-IL-6 group received MT ( p <0.0001). The ROCs revealed an area under the curve of 0.76 vs. 0.82 for the high-IL-6 group for receiving MT in the first 6 and 24 h. IL-6 ≥ 350 pg/mL predicted MT within 6 and 24 h with a sensitivity of 45% and 58%, respectively, and a specificity of 89%. IL-6 ≥ 350 pg/mL appears to be a reasonable early predictor for coagulopathy and MT within the first 6 and 24 h intervals. Large-scale prospective studies are warranted to confirm these findings.

Introduction: Trauma care providers are facing an increasing number of elderly patients on direct oral anticoagulants prior to injury. For dabigatran etexilate (DAB), the specific antagonist idarucizumab (IDA) has been approved since 2015 as a reversal agent. However, only limited data regarding the use of IDA in trauma patients are available., Methods: We performed a retrospective analysis of trauma patients under DAB for whom IDA administration was deemed necessary to reverse DAB's antithrombotic effect., Results: A total of 15 (9 male) patients were treated with IDA during the study period. The mean age was 81 ± 10 years. Intracranial haemorrhage (n = 7) and long bone fractures (n = 5) were the most common types of injury. Three patients were diagnosed as polytrauma. In all but one patient, atrial fibrillation was the indication for DAB intake. The median dose of IDA was 2.5 g (IQR 2.5-5). IDA administration decreased DAB plasma levels from 112.4 (IQR 73.4-123.4) to 5 (IQR 4-12) ng/mL (p = 0.031), thrombin time from 114.8 ± 48.3 to 16.2 ± 0.5 s (p < 0.0001) and activated partial thromboplastin time form 45.4 ± 11.3 to 34.2 ± 7.0 s (p = 0.0025). No thromboembolic events or side effects attributed to IDA were observed. All patients survived until hospital discharge., Conclusions: In trauma patients under DAB prior to injury, IDA decreased DAB plasma levels and normalized coagulation parameters. IDA appears to be safe, and no serious side effects were observed in this small cohort of patients.

Background: Many trauma centres have adopted the administration of fixed ratios of packed red blood cells (PRBCs), platelet concentrates and fresh frozen plasma (FFP) for bleeding patients. However, the haemostatic efficacy of this concept is not well proven., Objective: Our objective was to characterise the haemostatic profile of different ratios (2 : 1 : 1, 1 : 1 : 1 and 1 : 1 : 2) of PRBCs, platelet concentrates and FFP in comparison with coagulation factor concentrates (fibrinogen and/or prothrombin complex concentrate)., Design: An in vitro study., Setting: Research laboratories of the department of transfusion medicine, Linz, Austria., Materials: Whole blood donations from a total of 20 male volunteers., Intervention: Reconstitution of blood at different ratios of PRBCs, platelet concentrates and FFP or coagulation factor concentrates., Main Outcome Measures: Cell count, conventional and thromboelastometric coagulation parameters, single coagulation factor activities as well as endogenous thrombin potential., Results: Fibrinogen levels and haematocrit were lower in the FFP group at any ratio compared with the concentrate-based groups (P < 0.0001). Reconstitution of blood with FFP at different ratios resulted in haematocrit or fibrinogen levels that were borderline with regard to recommended substitution triggers (haematocrit 41 ± 2% and fibrinogen 1.5 ± 0.3 g l at the 2 : 1 : 1 ratio vs. 21 ± 1% and 2.1 ± 0.4 g l respectively at the 1 : 1 : 2 ratio). Compared with FFP at any ratio, maximum clot firmness showed higher values in the groups using fibrinogen concentrate (P < 0.0001), whereas endogenous thrombin potential revealed higher values in the groups using prothrombin complex concentrate (P < 0.0001)., Conclusion: Use of coagulation factor concentrates for the reconstitution of blood allows for delivery of a higher haematocrit and a higher fibrinogen content compared with FFP. However, prothrombin complex concentrate might result in an unnecessary excess of thrombin generation. Clinical studies are warranted to further investigate these in vitro findings.

Background: Gastric dilation is frequently observed in trauma patients. However, little is known about average gastric volumes comprising food, fluids and air. Although literature suggests a relevant risk of gastric insufflation when endotracheal intubation (ETI) is required in the pre-hospital setting, this assumption is still unproven., Methods: Primary whole body computed tomographic (CT) studies of 315 major trauma patients admitted to our Level 1 Trauma Centre Salzburg during a 7-year period were retrospectively assessed. Gastric volumes were calculated employing a CT volume rendering software. Patients intubated in the pre-hospital setting by emergency physicians (PHI, N = 245) were compared with spontaneously breathing patients requiring ETI immediately after arrival in the emergency room (ERI, N = 70)., Results: The median (range) total gastric content and air volume was 402 (26-2401) and 94 (0-1902) mL in PHI vs. 466 (59-1915) and 120 (1-997) mL in ERI patients (p = .59 and p = .35). PHI patients were more severely injured when compared with the ERI group (injury severity score (ISS) 33 (9-75) vs. 25 (9-75); p = .004). Mortality was higher in the PHI vs. ERI group (26.8% vs. 8.6%, p = .001). When PHI and ERI patients were matched for sex, age, body mass index and ISS (N = 50 per group), total gastric content and air volume was 496 (59-1915) and 119 (0-997) mL in the PHI vs. 429 (36-1726) and 121 (4-1191) mL in the ERI group (p = .85 and p = .98). Radiologic findings indicative for aspiration were observed in 8.1% of PHI vs. 4.3% of ERI patients (p = .31). Gastric air volume in patients who showed signs of aspiration was 194 (0-1355) mL vs. 98 (1-1902) mL in those without pulmonary CT findings (p = .08)., Conclusion: In major trauma patients, overall stomach volume deriving from food, fluids and air must be expected to be around 400-500 mL. Gastric dilation caused by air is common but not typically associated with pre-hospital airway management. The amount of air in the stomach seems to be associated with the risk of aspiration. Further studies, specifically addressing patients after difficult airway management situations are warranted.

Background: Pre-hospital emergency anaesthesia and tracheal intubation are life-saving interventions in trauma patients. However, there is evidence suggesting that the risks associated with both procedures outweigh the benefits. Thus, we assessed whether induction of anaesthesia and tracheal intubation of trauma patients can be postponed in spontaneously breathing patients until emergency room (ER) admission without increasing mortality., Methods: Retrospective analysis of major trauma patients either intubated on-scene by an emergency medical service (EMS) physician (pre-hospital intubation, PHI) or within the first 10 min after admission at a level 1 trauma centre (emergency room intubation, ERI). Data was extracted from the German Trauma Registry, hospital patient data management and electronic clinical information system., Results: From a total of 946 major trauma cases documented between 2010 and 2017, 294 patients matched the study inclusion criteria. Mortality rate of PHI (N = 258) vs. ERI (N = 36) patients was 26.4% vs. 16.7% (p = 0.3). After exclusion of patients with severe traumatic brain injury and/or pre-hospital cardiac arrest, mortality rate of PHI (N = 100) vs. ERI patients (N = 29) was 6% vs. 17.2%, (p = 0.07). Median on-scene time was significantly (p < 0.01) longer in PHI (30 min; IQR: 21-40) vs. ERI patients (20 min; IQR: 15-28)., Conclusions: There was no statistical difference in mortality rates of spontaneously breathing trauma patients intubated on-scene when compared with patients intubated immediately after hospital admission. Due to the retrospective study design and small case number, further studies evaluating the impact of airway management timing in sufficiently breathing trauma patients are warranted.