Comparison of Two Viscoelastic Testing Devices in a Parturient Population.

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.

Pathophysiology of Trauma-Induced Coagulopathy.

Trauma-induced coagulopathy (TIC) is a complex hemostatic disturbance that can develop early after a major injury. There is no universally accepted definition of TIC. However, TIC primarily refers to the inability to achieve sufficient hemostasis in severely injured trauma patients, resulting in diffuse microvascular and life-threatening bleeding. Endogenous TIC is driven by the combination of hypovolemic shock and substantial tissue injury, resulting in endothelial damage, glycocalyx shedding, upregulated fibrinolysis, fibrinogen depletion, altered thrombin generation, and platelet dysfunction. Exogenous factors such as hypothermia, acidosis, hypokalemia, and dilution due to crystalloid and colloid fluid administration can further exacerbate TIC. Established TIC upon emergency room admission is a prognostic indicator and is strongly associated with poor outcomes. It has been shown that patients with TIC are prone to higher bleeding tendencies, increased requirements for allogeneic blood transfusion, higher complication rates such as multi-organ failure, and an almost fourfold increase in mortality. Thus, early recognition and individualized treatment of TIC is a cornerstone of initial trauma care. However, patients who survive the initial insult switch from hypocoagulability to hypercoagulability, also termed "late TIC," with a high risk of developing thromboembolic complications.

Antidote vs. unspecific hemostatic agents for the management of direct oral anticoagulant-related bleeding in trauma.

PURPOSE OF REVIEW: The advent of direct oral anticoagulants (DOACs) marks a significant milestone in anticoagulant treatment. However, DOACs can exacerbate bleeding, which is challenging for the treating clinician, especially when combined with traumatic injury. RECENT FINDINGS: In major bleeding associated with DOACs, rapid reversal of the anticoagulant effects is crucial. Recent observational and nonrandomized interventional trials have demonstrated the effectiveness of the specific antidotes andexanet alfa and idarucizumab as well as the unspecific prothrombin complex concentrates (PCCs) to counteract the anticoagulant effects of DOACs. The European Society of Anaesthesiology and Intensive Care guideline for severe perioperative bleeding and the European trauma guideline propose divergent recommendations for the use of andexanet alfa and PCC to obtain hemostasis in Factor Xa inhibitor-related bleeding. The conflicting recommendations are due to limited evidence from clinical studies and the potential increased risk of thromboembolic complications after the administration of andexanet. Regarding dabigatran-associated major bleeding, both guidelines recommend the specific reversal agent idarucizumab as first-line therapy. SUMMARY: Current guidelines recommend specific antidots and PCCs in DOAC-related major bleeding. Prospective randomized trials comparing specific vs. nonspecific hemostatic agents in the perioperative setting are needed to evaluate the effectiveness and safety of the hemostatic agents.

Direct oral anticoagulants in trauma patients.

PURPOSE OF REVIEW: Direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. Thus, trauma care providers are facing a steadily raising number of injured patients on DOACs. RECENT FINDINGS: Despite a predictable pharmacokinetic profile, the resulting plasma levels of trauma patients upon admission and bleeding risks remain uncertain. Therefore, recent guidelines recommend the measurement of DOAC plasma concentrations in injured patients. Alternatively, DOAC specific visco-elastic tests assays can be applied to identify DOAC patients at bleeding risk.Bleeding complications in trauma patients on DOACs are generally higher compared to nonanticoagulated subjects, but comparable to vitamin K antagonists (VKAs). In particular, a traumatic brain injury does not carry an increased risk of intracranial bleeding due to a DOAK intake compared to VKAs. Current studies demonstrated that up to 14% of patients with a hip fracture are on DOACs prior to surgery. However, the majority can be operated safely within a 24h time window without an increased bleeding rate.Specific antagonists facilitate rapid reversal of patients on DOACs. Idarucizumab for dabigatran, and andexanet alfa for apixaban and rivaroxaban have been approved for life threatening bleeding. Alternatively, prothrombin complex concentrate can be used. Dialysis is a potential treatment option for dabigatran and haemoabsorption with special filters can be applied in patients on FXa-inhibitors. SUMMARY: Current guidelines recommend the measurement of DOAC plasma levels in trauma patients. Compared to VKAs, DOACs do not carry a higher bleeding risk. DOAC specific antagonists facilitate the individual bleeding management.

[Update on point-of-care-based coagulation treatment : Systems, reagents, device-specific treatment algorithms]. / Update der Point-of-care-basierten Gerinnungstherapie : Systeme, Reagenzien, gerätespezifische Behandlungsalgorithmen.

Viscoelastic test (VET) procedures suitable for point-of-care (POC) testing are in widespread clinical use. Due to the expanded range of available devices and in particular due to the development of new test approaches and methods, the authors believe that an update of the current treatment algorithms is necessary. The aim of this article is to provide an overview of the currently available VET devices and the associated reagents. In addition, two treatment algorithms for the VET devices most commonly used in German-speaking countries are presented.

Dose-Related Effectiveness of Andexanet Alfa for Reversal of Apixaban Anticoagulation in a Porcine Polytrauma Model.

BACKGROUND: Andexanet alfa (andexanet) is a reversal agent for use in patients with life-threatening or uncontrolled bleeding treated with oral factor Xa (FXa) inhibitors. There are limited data on the dose-response relationship of andexanet and FXa inhibitor-related bleeding. OBJECTIVE: The aim of this study was to assess the dose-related effectiveness of andexanet in reducing blood loss, improving survival, and reversing apixaban anticoagulation in a porcine polytrauma model. METHODS: Apixaban was given orally to 40 male pigs for 3 days at a dose of 20 mg/d. On day 3, following bilateral femur fractures and blunt liver injury, animals (n = 8/group) received andexanet (250-mg bolus, 250-mg bolus + 300-mg 2-hour infusion, 500-mg bolus, or 500-mg bolus + 600-mg 2-hour infusion) or vehicle (control). Total blood loss was the primary endpoint. Coagulation parameters were assessed for 300 minutes or until death. Data were analyzed with a mixed-model analysis of variance. RESULTS: Administration of 250-mg bolus + 300-mg infusion, andexanet 500-mg bolus, and 500-mg bolus + 600-mg infusion significantly decreased total blood loss by 37, 58, and 61%, respectively (all p < 0.0001), with 100% survival. Andexanet 250-mg bolus was ineffective in reducing total blood loss (6%) and mortality (63% survival) versus controls. Andexanet 500-mg bolus ± infusion neutralized anti-FXa activity to less than 50 ng/mL. Andexanet neutralization of thrombin generation and thromboelastometry parameters was dose and infusion time dependent. CONCLUSION: In a porcine polytrauma model with major bleeding on apixaban, andexanet dose dependently decreased anti-FXa activity. Lower anti-FXa levels (<50 ng/mL) with andexanet 500-mg bolus ± infusion were correlated with 60% less blood loss and 100% survival versus controls.

Comparative analysis of andexanet alfa and prothrombin complex concentrate in reversing anticoagulation by rivaroxaban ex vivo.

BACKGROUND: The comparative effectiveness of the specific antidote andexanet alfa vs the nonspecific therapy four-factor prothrombin complex concentrates (4F-PCCs) as reversal agents for direct factor Xa (FXa) inhibitors in severely bleeding patients is unclear. We hypothesised that specific reversal using andexanet alfa would be more effective than a high dose of PCC (50 IU kg-1) for reversing the FXa inhibitor rivaroxaban. METHODS: The reversal potential of andexanet alfa, various 4F-PCCs, and activated PCC was investigated ex vivo in human blood anticoagulated with rivaroxaban (37.5, 75, 150, and 300 ng ml-1) using a panel of coagulation parameters, including conventional coagulation assays, thrombin generation, and a newly developed viscoelastometric device. We simulated in vivo conditions of coagulation activation and fibrin formation using flow chamber experiments of thrombogenicity potential under arterial flow conditions. RESULTS: The 4F-PCCs normalised clotting profiles only at low rivaroxaban concentrations, whereas andexanet alfa and activated PCC significantly shortened clotting time at all rivaroxaban concentrations. Only andexanet alfa restored thrombin generation to baseline. Flow chamber results showed that various 4F-PCCs concentration-dependently restored clot formation. CONCLUSIONS: In contrast to thrombin generation measurements, haemostatic reversal of rivaroxaban using high-dose 4F-PCCs exhibited similar efficacy as andexanet alfa in flow chamber experiments. The haemostatic effects of 4F-PCCs and andexanet alfa in the context of bleeding patients taking FXa inhibitors requires further study.

Admission S100B fails as neuro-marker but is a good predictor for intrahospital mortality in major trauma patients.

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.

Circulating endothelial extracellular vesicle signatures correspond with ICU requirement: an exploratory study in COVID-19 patients.

Extracellular vesicles (EVs) represent nanometer-sized, subcellular spheres, that are released from almost any cell type and carry a wide variety of biologically relevant cargo. In severe cases of coronavirus disease 2019 (COVID-19) and other states of systemic pro-inflammatory activation, EVs, and their cargo can serve as conveyors and indicators for disease severity and progression. This information may help distinguish individuals with a less severe manifestation of the disease from patients who exhibit severe acute respiratory distress syndrome (ARDS) and require intensive care measures. Here, we investigated the potential of EVs and associated miRNAs to distinguish normal ward patients from intensive care unit (ICU) patients (N = 10/group), with 10 healthy donors serving as the control group. Blood samples from which plasma and subsequently EVs were harvested by differential ultracentrifugation (UC) were obtained at several points in time throughout treatment. EV-enriched fractions were characterized by flow cytometry (FC), nanoparticle tracking analysis (NTA), and qPCR to determine the presence of selected miRNAs. Circulating EVs showed specific protein signatures associated with endothelial and platelet origin over the course of the treatment. Additionally, significantly higher overall EV quantities corresponded with increased COVID-19 severity. MiR-223-3p, miR-191-5p, and miR-126-3p exhibited higher relative expression in the ICU group. Furthermore, EVs presenting endothelial-like protein signatures and the associated miR-126-3p showed the highest area under the curve in terms of receiver operating characteristics regarding the requirement for ICU treatment. In this exploratory investigation, we report that specific circulating EVs and miRNAs appear at higher levels in COVID-19 patients, especially when critical care measures are indicated. Our data suggest that endothelial-like EVs and associated miRNAs likely represent targets for future laboratory assays and may aid in clinical decision-making in COVID-19.

Point-of-care, goal-directed management of bleeding in trauma patients.

PURPOSE OF REVIEW: The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC). RECENT FINDINGS: Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders. Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies. Recent evidence has shown that viscoelastic tests (VETs) identify haemostatic disorders more rapidly and in more detail than SCTs. Moreover, VET results can guide coagulation therapy, allowing individualised treatment, which decreases transfusion requirements. However, the impact of VET on mortality remains uncertain. In contrast to VETs, the clinical impact of POC platelet function testing is still unproven. SUMMARY: POC SCTs are not able to characterise the complexity of trauma-associated coagulopathy. VETs provide a rapid estimation of underlying haemostatic disorders, thereby providing guidance for haemostatic therapy, which impacts allogenic blood transfusion requirements. The value of POC platelet function testing to identify platelet dysfunction and guide platelet transfusion is still uncertain.

Fibrinolytic potential as a risk factor for postpartum hemorrhage.

Background: Postpartum hemorrhage (PPH) is still the leading cause of maternal morbidity and mortality worldwide. While impaired fibrin polymerization plays a crucial role in the development and progress of PPH, recent approaches using viscoelastic measurements have failed to sensitively detect early changes in fibrinolysis in PPH. This study aimed to evaluate whether women experiencing PPH show alterations in POC-VET fibrinolytic potential during childbirth and whether fibrinolytic potential offers benefits in the prediction and treatment of PPH. Methods: Blood samples were collected at three different timepoints: T0 = hospital admission (19 h ± 18 h prepartum), T1 = 30-60 min after placental separation, and T2 = first day postpartum (19 h ± 6 h postpartum). In addition to standard laboratory tests, whole-blood impedance aggregometry (Multiplate) and viscoelastic testing (VET) were performed using the ClotPro system, which included the TPA-test lysis time, to assess the POC-VET fibrinolytic potential, and selected coagulation factors were measured. The results were correlated with blood loss and clinical outcome markers. Severe PPH was defined as a hemoglobin drop > 4g/dl and/or the occurrence of shock or the need for red blood cell transfusion. Results: Blood samples of 217 parturient women were analyzed between June 2020 and December 2020 at Heidelberg University Women's Hospital, and 206 measurements were eligible for the final analysis. Women experiencing severe PPH showed increased fibrinolytic potential already at the time of hospital admission. When compared to non-PPH, the difference persisted 30-60 min after placental separation. A higher fibrinolytic potential was accompanied by a greater drop in fibrinogen and higher d-dimer values after placental separation. While 70% of women experiencing severe PPH showed fibrinolytic potential, 54% of those without PPH showed increased fibrinolytic potential as well. Conclusion: We were able to show that antepartal and peripartal fibrinolytic potential was elevated in women experiencing severe PPH. However, several women showed high fibrinolytic potential but lacked clinical signs of PPH. The findings indicate that high fibrinolytic potential is a risk factor for the development of coagulopathy, but further conditions are required to cause PPH.

DOAC plasma concentration upon hospital admission in a cohort of trauma patients. An observational real-life study.

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.

3-Factor versus 4-Factor Prothrombin Complex Concentrates for the Reversal of Vitamin K Antagonist-Associated Coagulopathy: A Systematic Review and Meta-analysis.

Long-term anticoagulation is used worldwide to prevent or treat thrombotic events. Anticoagulant therapy using vitamin K antagonists (VKAs) is well established; however, anticoagulants carry an increased risk of potentially life-threatening bleeding. In cases of bleeding or need for surgery, patients require careful management, balancing the need for rapid anticoagulant reversal with risk of thromboembolic events. Prothrombin complex concentrates (PCCs) replenish clotting factors and reverse VKA-associated coagulopathy. Two forms of PCC, 3-factor (3F-PCC) and 4-factor (4F-PCC), are available. Using PRISMA methodology, we systematically reviewed whether 4F-PCC is superior to 3F-PCC for the reversal of VKA-associated coagulopathy. Of the 392 articles identified, 48 full texts were reviewed, with 11 articles identified using criteria based on the PICOS format. Data were captured from 1,155 patients: 3F-PCC, n = 651; 4F-PCC, n = 504. ROBINS-I was used to assess bias. Nine studies showed international normalized ratio (INR) normalization to a predefined goal, ranging from ≤1.5 to ≤1.3, following PCC treatment. Meta-analysis of the data showed that 4F-PCC was favorable compared with 3F-PCC overall (odds ratio [OR]: 3.50; 95% confidence interval [CI]: 1.88-6.52, p < 0.0001) and for patients with a goal INR of ≤1.5 or ≤1.3 (OR: 3.45; 95% CI: 1.42-8.39, p = 0.006; OR: 3.25; 95% CI: 1.30-8.13, p = 0.01, respectively). However, heterogeneity was substantial (I 2 = 62%, I 2 = 70%, I 2 = 64%). Neither a significant difference in mortality (OR: 0.72; 95% CI: 0.42-1.24, p = 0.23) nor in thromboembolisms was reported. These data suggest that 4F-PCC is better suited than 3F-PCC for the treatment of patients with VKA-associated coagulopathy, but further work is required for a definitive recommendation.

Role of DOAC plasma concentration on perioperative blood loss and transfusion requirements in patients with hip fractures.

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.

Conventional and Pro-Inflammatory Pathways of Fibrinolytic Activation in Non-Traumatic Hyperfibrinolysis.

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.

Factor XIII Measurement and Substitution in Trauma Patients after Admission to an Intensive Care Unit.

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.

Operability of a Resonance-Based Viscoelastic Haemostatic Analyzer in the High-Vibration Environment of Air Medical Transport.

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.

Multiplate Platelet Function Testing upon Emergency Room Admission Fails to Provide Useful Information in Major Trauma Patients Not on Platelet Inhibitors.

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.