Improved outcome with individualised antifibrinolytic therapy: what is the evidence?

Viscoelastic haemostatic testing (VHT) has been used to determine hyperfibrinolysis and hypofibrinolysis. When modified by addition of tissue plasminogen activator (tPA), VHT has been suggested to assess responses to antifibrinolytic therapy and to estimate the concentration of tranexamic acid in patients undergoing cardiac surgery. Despite some evidence that tPA-modified VHT might allow individualisation of antifibrinolytic therapy, further studies are warranted to prove its clinical benefit for postsurgical bleeding, transfusion of blood products, and thromboembolic events.

Predictive value of Cmmi-MHR combined with thromboelastography parameters in acute cerebral infarction.

Cerebral infarction is a common neurological disease with high rates of morbidity, mortality, and recurrence, posing a great threat to human life and health. Cerebral infarction is the second leading cause of death in the world and the leading cause of long-term disability in humans. The results of the third national retrospective sampling survey on causes of death in 2008 showed that cerebral infarction has become the leading cause of death in China and its mortality rate is 4-5 times that of European and American countries. Therefore, this article proposed a study on the predictive value of Cmmi-MHR combined with thromboelastography parameters that was performed for acute cerebral infarction. This paper mainly proposed a high frame rate imaging technology and analyzed its algorithm. In this article, in the experimental part, an in-depth analysis of the predictive value of the Monocyte-to-high-density lipoprotein cholesterol ratio (MHR) combined with thromboelastography parameters was performed for acute cerebral infarction. The final experimental results showed that HDL (OR = 1.695%, P-trend = 0.049) had a probability of death within 90 days of hospitalization (OR = 0.81, 95% CI = 1.06-3.11, P-trend = 0.523). There were no significant differences in mortality rate after 90 days. Regardless of adjusting for confounders such as age, gender, and NIHSS score, there was no significant difference in the risk of MHR or monocyte count within 90 days of hospitalization. The conclusion indicates that the combination of Cmmi-MHR and thromboelastography parameters provides a new perspective and method for the diagnosis and treatment of cerebral infarction, and provides important support for personalized treatment and management of cerebral infarction.

The value of thromboelastography in evaluating the efficacy of Xueshuantong combined with edaravone in the treatment of acute cerebral infarction.

To explore the value of thromboelastography (TEG) in evaluating the efficacy of Xueshuantong combined with edaravone for the treatment of acute cerebral infarction (ACI). We retrospectively analyzed the clinical data of 96 patients with ACI treated with Xueshuantong combined with edaravone and monitored by TEG. The correlation between the results of TEG examination and treatment outcomes in patients after treatment was analyzed. After treatment, 65 of 96 patients showed good efficacy and 31 had poor efficacy. kinetic time (KT), reaction time (RT), and the percentage of clot lysis at 30 minutes after Ma value (LY30) of patients with good therapeutic effects were significantly higher than those with poor therapeutic effects; However, maximum amplitude (MA) and coagulation index (CI) were significantly lower than those with poor efficacy (P < .05). There was a significant positive correlation between KT, RT, and LY30 and the therapeutic effect of ACI, and a significant negative correlation between the therapeutic effects of MA, CI, and ACI (P < .05). Logistic analysis confirmed that KT, RT, and LY30 were protective factors for the therapeutic effect of ACI; MA and CI were risk factors for the therapeutic effect of ACI (P < .05). TEG has a high value in evaluating the efficacy of Xueshuantong combined with edaravone in the treatment of ACI. It can clarify changes in the coagulation function of patients, thereby guiding clinical follow-up treatment.

Agreement between the thromboelastography reaction time parameter using fresh and citrated whole blood during extracorporeal membrane oxygenation with Teg®5000 and Teg®6s.

PURPOSE: We aimed at assessing the correlation between TEG reaction time (TEG-R) in citrated and fresh blood samples with TEG5000 and TEG 6S during heparin administration in patients with and without ECMO support. MATERIALS AND METHODS: Paired TEG5000 (fresh and citrated whole blood, kaolin and kaolin-heparinase) and TEG6S (citrated whole blood) samples were obtained, together with standard coagulation laboratory tests. Bland-Altman analysis and Lin's concordance correlation coefficient were used to assess agreement. RESULTS: Thirteen consecutive ECMO patients and eight consecutive non-ECMO patients were enrolled and TEG was performed for a total of 84 paired samples. ECMO patients received 19.2 (12.6-25.8) U/kg/h of heparin. Five of the non-ECMO patients did not receive heparin, two of them received a very low prophylactic dose (1.6 and 2.9 IU/kg/h, respectively), and one of them 13.1 U/kg/h of heparin. Using TEG®5000, TEG-R was 21.0 (-23.4; 65.5) min longer on fresh compared to citrated blood in patients receiving heparin while only 1.58 (-5.5; 8.7) min longer in patients not-receiving heparin. These differences were reverted by heparinase. CONCLUSIONS: Using citrated-recalcified blood to perform TEG might lead to underestimation of the effect of heparin.

In vitro evaluation of a new viscoelastometry-based point-of-care analyzer.

INTRODUCTION: The VCM is a point-of-care analyzer using a new viscoelastometry technique for rapid assessment of hemostasis on fresh whole blood. Its characteristics would make it suitable for use in austere environments. The purpose of this study was to evaluate the VCM in terms of repeatability, reproducibility and interanalyzer correlation, reference values in our population, correlation with standard coagulation assays and platelet count, correlation with the TEG5000 analyzer and resistance to stress conditions mimicking an austere environment. METHODS: Repeatability, reproducibility, and interanalyzer correlation were performed on quality control samples (n = 10). Reference values were determined from blood donor samples (n = 60). Correlations with standard biological assays were assessed from ICU patients (n = 30) and blood donors (n = 60) samples. Correlation with the TEG5000 was assessed from blood donor samples. Evaluation of vibration resistance was performed on blood donor (n = 5) and quality control (n = 5) samples. RESULTS: The CVs for repeatability and reproducibility ranged from 0% to 11%. Interanalyzer correlation found correlation coefficients (r2) ranging from 0.927 to 0.997. Our reference values were consistent with those provided by the manufacturer. No robust correlation was found with conventional coagulation tests. The correlation with the TEG5000 was excellent with r2 ranging from 0.75 to 0.92. Resistance to stress conditions was excellent. CONCLUSION: The VCM analyzer is a reliable, easy-to-use instrument that correlates well with the TEG5000. Despite some logistical constraints, the results suggest that it can be used in austere environments. Further studies are required before its implementation.

Impact of systematic variations in hematocrit and platelet count on thrombelastometry tissue factor activated assay parameters.

BACKGROUND: Thromboelastogram testing is increasingly being used to manage patients with massive bleeding. An earlier study found that the test results were influenced by the hematocrit (Hct) and platelet (PLT) concentrations. This study sought to determine if these factors confounded the results of a different manufacturer's thromboelastography testing. METHODS: Using freshly collected whole blood from volunteers and stored red blood cells (RBC) and plasma, the whole blood was manipulated to achieve different Hct values and PLT concentrations. Each reconstituted whole blood sample was tested in triplicate on the ROTEM Delta device and the ExTEM results were recorded. RESULTS: Many of the ExTEM results varied according to the Hct and PLT concentration. In particular, the ExTEM clot formation time (CFT) was abnormally long when the Hct was 45% and the PLT concentration was ≤75 × 109/L, normalizing only when the PLT count was ≥100 × 109/L. CFT samples with Hct 25% and 35% were also abnormal with low PLT concentrations but normalized at lower PLT concentrations compared to the Hct 45% samples. The ExTEM angle also demonstrated abnormal results when the Hct was 45% and the PLT concentration was ≤50 × 109/L. The ExTEM A10 and maximum clot firmness (MCF) tests tended to also be abnormal when the Hct was between 25% and 45% and the platelet concentrations were below 75 × 109/L. CONCLUSION: While thromboelastogram testing is gaining popularity for managing bleeding patients, clinicians should be aware of these confounding factors when making transfusion decisions based on their results.

The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) may act as a driver or propagator of systemic inflammation. In turn, cytokine release can modify thromboelastographic (TEG) tests which are commonly used for anticoagulation monitoring. In this context, antithrombin (AT) supplementation might further modify TEG. METHODS: This is a pre-specified sub-study of the "Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation" study (investigator-initiated, randomized, single-blind, two-arm trial) conducted in two Italian ECMO referral ICUs. Adult patients requiring vv-ECMO for respiratory failure and undergoing unfractioned heparin (UFH) administration were enrolled and randomized whether to receive AT supplementation. Plasma samples for cytokine assay (IL-8, IL-10, IL-6, IL-1ß, TNF-α and Pro-ADM) and heparinase TEG were collected from every patient before ECMO start, 24 h and 72 h after ECMO start, before ECMO removal, and 7 days after ECMO removal or upon ICU discharge whichever happened first. AT concentration, coagulation and clinical data were collected before ECMO start and at pre-fixed time points. RESULTS: Thirty-nine patients were enrolled (21 treatments, 18 controls). TEG-R had a weak-to-moderate positive correlation with IL-8, IL-6, IL-10 and TNF-α and a moderate positive correlation with Pro-ADM. TEG-ANG showed a weak negative correlation with IL-8, IL-6 and TNF-α, while TEG-MA negatively correlated with IL-8, TNF-α and Pro-ADM. AT supplementation seemed to modify the association between TEG-MA and IL-8, IL-10 and Pro-ADM; conversely, AT did not affect the relationship among TEG-R or TEG-ANG and the studied cytokines. CONCLUSIONS: High concentrations of systemic cytokines correlated with longer reaction times and decreased angle and amplitude at TEG, suggesting that an increase in inflammation is related with hypocoagulability as revealed by thromboelastography.

Comparison of results obtained using clot-fibrinolysis waveform analysis and global fibrinolysis capacity assay with rotational thromboelastography.

Global fibrinolysis assays detect the fibrinolysis time of clot dissolution using tissue-type plasminogen activator (tPA). Two such assays, clot-fibrinolysis waveform analysis (CFWA) and global fibrinolysis capacity (GFC) assay, were recently developed. These were compared with rotational thromboelastography (ROTEM). Healthy donor blood samples were divided into four groups based on tPA-spiked concentrations: 0, 100, 500, and 1000 ng/mL. CFWA and GFC fibrinolysis times, including 4.1 µg/mL and 100 ng/mL tPA in the assays, were determined, denoted as CFWA-Lys and GFC-Lys, respectively. Statistical differences were recognized between tPA concentrations of 0 and 500/1000 ng/mL for CFWA-Lys, and 0 and 100/500/1000 ng/mL for GFC-Lys. The correlation coefficients with lysis onset time (LOT) of extrinsic pathway evaluation and intrinsic pathway evaluation in ROTEM were statistically significant at 0.610 and 0.590 for CFWA-Lys, and 0.939 and 0.928 for GFC-Lys, respectively (p-values < 0.0001 for all correlations). Both assays showed significant correlations with ROTEM; however, the GFC assay proved to have better agreement with ROTEM compared with the CFWA assay. These assays have the potential to reflect a hyperfibrinolysis status with high tPA concentrations.

Thromboelastographic evaluation of the effectiveness of choline or CDP-choline treatment on endotoxin-induced hemostatic alterations in dogs.

Sepsis/endotoxemia associates with coagulation abnormalities. We showed previously that exogenous choline treatment reversed the changes in platelet count and function as well as prevented disseminated intravascular coagulation (DIC) in endotoxemic dogs. The aim of this follow-up study was to evaluate the effect of treatment with choline or cytidine-5'-diphosphocholine (CDP-choline), a choline donor, on endotoxin-induced hemostatic alterations using thromboelastography (TEG). Dogs were randomized to six groups and received intravenously (iv) saline, choline (20 mg/kg) or CDP-choline (70 mg/kg) in the control groups, whereas endotoxin (0.1 mg/kg, iv) was used alone or in combination with choline or CDP-choline at the same doses in the treatment groups. TEG variables including R- and K-time (clot formation), maximum amplitude (MA) and α-angle (clot stability), G value (clot elasticity), and EPL, A, and LY30 (fibrinolysis), as well as overall assessment of coagulation (coagulation index - CI), were measured before and at 0.5-48 h after the treatments. TEG parameters did not change significantly in the control groups, except for CI parameter after choline administration. Endotoxemia resulted in increased R-time and A value (P < 0.05), decreased K-time (P < 0.05), α-angle (P < 0.001) and CI values (P < 0.01) at different time points. Treatment with either choline or CDP-choline attenuated or prevented completely the alterations in TEG parameters in endotoxemic dogs with CDP-choline being more effective. These results confirm and extend the effectiveness of choline or CDP-choline in endotoxemia by further demonstrating their efficacy in attenuating or preventing the altered viscoelastic properties of blood clot measured by TEG.

Thrombelastography and Conventional Coagulation Markers in Chronic Obstructive Pulmonary Disease: A Prospective Paired-Measurements Study Comparing Exacerbation and Stable Phases.

Chronic Obstructive Pulmonary Disease (COPD) exacerbation is known for its substantial impact on morbidity and mortality among affected patients, creating a significant healthcare burden worldwide. Coagulation abnormalities have emerged as potential contributors to exacerbation pathogenesis, raising concerns about increased thrombotic events during exacerbation. The aim of this study was to explore the differences in thrombelastography (TEG) parameters and coagulation markers in COPD patients during admission with exacerbation and at a follow-up after discharge. This was a multi-center cohort study. COPD patients were enrolled within 72 h of hospitalization. The baseline assessments were Kaolin-TEG and blood samples. Statistical analysis involved using descriptive statistics; the main analysis was a paired t-test comparing coagulation parameters between exacerbation and follow-up. One hundred patients participated, 66% of whom were female, with a median age of 78.5 years and comorbidities including atrial fibrillation (18%) and essential arterial hypertension (45%), and sixty-five individuals completed a follow-up after discharge. No significant variations were observed in Kaolin-TEG or conventional coagulation markers between exacerbation and follow-up. The Activated Partial Thromboplastin Clotting Time (APTT) results were near-significant, with p = 0.08. In conclusion, TEG parameters displayed no significant alterations between exacerbation and follow-up.

Rotational Thromboelastometry and Clot Waveform Analysis as Point-of-Care Tests for Diagnosis of Disseminated Intravascular Coagulation in Critically Ill Children in Thailand.

OBJECTIVES: This study aimed to determine the test performances of rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-based clot waveform analysis (aPTT-CWA) compared with the International Society on Thrombosis and Hemostasis disseminated intravascular coagulation (ISTH-DIC) score for diagnosis of overt disseminated intravascular coagulation (ODIC) in critically ill children. Prognostic indicators of DIC complications were also evaluated. DESIGN: A prospective cross-sectional observational study was conducted. ROTEM and aPTT-CWA were assessed alongside standard parameters based on the ISTH-DIC score and natural anticoagulants. Both conventional and global hemostatic tests were repeated on days 3-5 for nonovert DIC. SETTING: PICU of the Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. SUBJECTS: Infants and children who were admitted to PICU with underlying diseases predisposed to DIC, such as sepsis, malignancy, major surgery, trauma, or severe illness, were included in the study between July 1, 2021, and November 30, 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-four children were enrolled in this study. The prevalence of ODIC was 20.3%. Regarding ROTEM parameters, using EXTEM clot formation time (CFT) cutoff of greater than 102 seconds provided sensitivity and specificity of 90.9% and 80.9%, respectively, for diagnosing ODIC, with the area under the curve (AUC) of 0.86. In the case of aPTT-CWA performance, no biphasic waveform was observed, whereas both maximum coagulation acceleration (Min2) of less than 0.35%/s 2 and maximum coagulation deceleration of less than 0.25%/s 2 demonstrated identical sensitivities of 76.9% and specificities of 79.6%. Combining two global hemostatic tests significantly improved the diagnostic performance (INTEM CFT + EXTEM CFT + Min2 AUC 0.92 [95% CI, 0.80-1.00] vs. EXTEM CFT AUC 0.86 [95% CI, 0.75-0.96], p = 0.034). Bleeding was the most common consequence. In multivariable logistic regression analysis, Min2 of less than 0.36%/s 2 was an independent risk factor for bleeding complications, with an adjusted odds ratio of 15.08 (95% CI, 1.08-211.15, p = 0.044). CONCLUSIONS: ROTEM and aPTT-CWA were valuable diagnostic tools in critically ill children who might require point-of-care tests. Min2 showed significant clinical implications for predicting bleeding events in this population.

Amplitude at 10 min in thromboelastography predicts maximum amplitude: a single-center observational study.

Thromboelastography is a quantitative test widely used to measure the efficiency of blood clotting. However, awaiting the results of maximum amplitude (MA) is necessary for determining the need for platelet- and fibrinogen-containing products. A more rapid prediction of MA could facilitate faster preparation and administration of blood transfusion products, thereby resulting in coagulation improvement. In this retrospective study, we hypothesized that early amplitude at 10 min (A10) could be a predictor of MA. Therefore, we investigated whether MA can be rapidly inferred from thromboelastographic 6 s (TEG6s) measurements and evaluated its correlation with A10. We extracted TEG6s measurements obtained in operating rooms and intensive care units of our hospital between January 2018 and December 2022. The correlation of MA with display items of TEG6s results, including reaction time, kinetics, α angle, activated clotting time, and A10, was evaluated. The relationship between citrated rapid TEG (CRT)-A10 and CRT-MA, as well as between citrated functional fibrinogen (CFF)-A10 and CFF-MA, were evaluated if A10 and MA showed a good correlation. The results showed good correlations between CRT-A10 and CRT-MA, as well as between CFF-A10 and CFF-MA. Therefore, evaluating A10 using TEG6s could predict MA.

Fibrinogen levels in severe trauma: A preliminary comparison of Clauss Fibrinogen, ROTEM Sigma, ROTEM Delta and TEG 6s assays from the FEISTY pilot randomised clinical trial.

OBJECTIVE: To describe the relationships between different methods of measuring functional fibrinogen levels in severely injured, bleeding trauma patients across multiple timepoints during hospitalisation. METHODS: In 100 adult trauma patients enrolled in the FEISTY pilot randomised clinical trial at four tertiary trauma centres in Australia, blood samples were collected prospectively. Consistency of agreement was calculated, comparing functional fibrinogen levels measured by four methods - ROTEM® Delta and Sigma FIBTEM A5, TEG® 6s CFF MA, and gold-standard Clauss Fibrinogen. RESULTS: Comparing the ROTEM® Delta and new-generation ROTEM® Sigma machine, consistency of agreement for FIBTEM A5, measured by calculating intraclass correlation coefficients (ICCs), was ≥0.73 across all analysed timepoints, with mean differences (Sigma minus Delta) of 0.10-3.57 mm. Corresponding values comparing the ROTEM® Sigma FIBTEM A5 and TEG® 6s CFF MA were ICC = 0.55-0.82 and ICC = 4.69-7.97 (CFF MA minus A5). Comparing ROTEM® Sigma FIBTEM A5 and Clauss Fibrinogen Analysis (CFA), among statistically significant simple linear regression models, R2 was 0.25-0.67, and comparing TEG® 6s CFF MA and CFA (CFA) 0.65-0.82, although not all differences were significant with the latter comparison. Relationships across all timepoints combined were Clauss Fibrinogen (CF) (g/L) = 0.21𝑥 + 0.004 (where 𝑥 = ROTEM® Sigma FIBTEM A5 in mm) and (g/L) = 0.16𝑥 - 0.06 (where 𝑥 = TEG® 6s CFF MA in mm). CONCLUSIONS: The present study revealed acceptable agreement between four different assays measuring functional fibrinogen, with current- and previous-generation ROTEM® machines (Sigma, Delta) performing similarly measuring functional fibrinogen via FIBTEM assay. This suggests that haemostatic resuscitation algorithms designed for the ROTEM® Delta can be applied to the ROTEM® Sigma to guide fibrinogen replacement.

Early Goal-Directed Hemostatic Therapy for Severe Acute Bleeding Management in the Intensive Care Unit: A Narrative Review.

This is a narrative review of the published evidence for bleeding management in critically ill patients in different clinical settings in the intensive care unit (ICU). We aimed to describe "The Ten Steps" approach to early goal-directed hemostatic therapy (EGDHT) using point-of-care testing (POCT), coagulation factor concentrates, and hemostatic drugs, according to the individual needs of each patient. We searched National Library of Medicine, MEDLINE for publications relevant to management of critical ill bleeding patients in different settings in the ICU. Bibliographies of included articles were also searched to identify additional relevant studies. English-language systematic reviews, meta-analyses, randomized trials, observational studies, and case reports were reviewed. Data related to study methodology, patient population, bleeding management strategy, and clinical outcomes were qualitatively evaluated. According to systematic reviews and meta-analyses, EGDHT guided by viscoelastic testing (VET) has been associated with a reduction in transfusion utilization, improved morbidity and outcome in patients with active bleeding. Furthermore, literature data showed an increased risk of severe adverse events and poor clinical outcomes with inappropriate prophylactic uses of blood components to correct altered conventional coagulation tests (CCTs). Finally, prospective, randomized, controlled trials point to the role of goal-directed fibrinogen substitution to reduce bleeding and the amount of red blood cell (RBC) transfusion with the potential to decrease mortality. In conclusion, severe acute bleeding management in the ICU is still a major challenge for intensive care physicians. The organized and sequential approach to the bleeding patient, guided by POCT allows for rapid and effective bleeding control, through the rational use of blood components and hemostatic drugs, since VET can identify specific coagulation disorders in real time, guiding hemostatic therapy with coagulation factor concentrates and hemostatic drugs with individual goals.

Thromboelastographic evaluation after cardiac surgery optimizes transfusion requirements in the intensive care unit: a single-center retrospective cohort study using an inverse probability weighting method.

OBJECTIVE: There are no reports from Japan showing the effects of using the thromboelastography algorithm on transfusion requirements after Intensive Care Unit (ICU) admission, and post-implementation knowledge regarding the thromboelastography algorithm under the Japanese healthcare system is insufficient. Therefore, this study aimed to clarify the effect of the TEG6s thromboelastography algorithm on transfusion requirements for patients in the ICU after cardiac surgery. METHODS: We retrospectively compared the requirements for blood transfusion up to 24 h after ICU admission using the thromboelastography algorithm (January 2021 to April 2022) (thromboelastography group; n = 201) and specialist consultation with surgeons and anesthesiologists (January 2018 to December 2020) (non-thromboelastography group; n = 494). RESULTS: There were no significant between-group differences in terms of age, height, weight, body mass index, operative procedure, duration of surgery or cardiopulmonary bypass, body temperature, or urine volume during surgical intervention. Moreover, there was no significant between-group difference in the amount of drainage at 24 h after ICU admission. However, crystalloid and urine volumes were significantly higher in the thromboelastography group than in the non-thromboelastography group. Additionally, fresh-frozen plasma (FFP) transfusion volumes were significantly lower in the thromboelastography group. However, there were no significant between-group differences in red blood cell count or platelet transfusion volume. After variable adjustment, the amount of FFP used from the operating room to 24 h after ICU admission was significantly reduced in the thromboelastography group. CONCLUSIONS: The thromboelastography algorithm optimized transfusion requirements at 24 h after admission to the ICU following cardiac surgery.

Principal component analysis of a swine injury model identifies multiple phenotypes in trauma.

BACKGROUND: Trauma is the third leading cause of death in the United States and the primary cause of death for people between the ages of 1 year and 44 years. In addition to tissue damage, trauma may also activate an inflammatory state known as trauma-induced coagulopathy (TIC) that is associated with clotting malfunctions, acidemia, and end-organ dysfunction. Prior work has also demonstrated benefit to acknowledging the type and severity of endothelial injury, coagulation derangements, and systemic inflammation in the management of trauma patients. This study builds upon prior work by combining laboratory, metabolic, and clinical metrics into an analysis of trauma phenotypes, evolution of phenotypes over time after trauma, and significance of trauma phenotype on mortality. METHODS: Seventy 3-month-old female Yorkshire crossbred swine were randomized to injury and resuscitation groups. Principal component analysis (PCA) of longitudinal swine TEG data (Reaction time, Alpha-Angle, Maximum Amplitude, and Clot Lysis at 30 minutes), pH, lactate, and MAP was completed in R at baseline, 1 hour postinjury, 3 hours postinjury, 6 hours postinjury, and 12 hours postinjury. Subjects were compared by principal component factor scores to assess differences in survival, injury severity, and treatment group. RESULTS: Among injured animals, three phenotypes were observed at each time point. Five phenotypes were associated with differences in survival, and of these, four were associated with differences in injury severity. Phenotype alignment was not significantly different by treatment group. CONCLUSION: This application of PCA to a set of coagulation, hemodynamic, and organ perfusion variables has identified multiple evolving phenotypes after trauma. Some of these phenotypes may correlate with injury severity and may have implications for survival. Next steps include validating these findings over greater numbers of subjects and exploring other machine-learning techniques for phenotype identification. LEVEL OF EVIDENCE: Level IV, Therapeutic/Care Management.

Global hemostasis assays in acute myeloid leukemia: results of an observational prospective study.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by a complex spectrum of coagulopathy ranging from hemorrhagic to thrombotic symptoms. To date, platelet count (PLT) and conventional coagulation tests (CCTs) cannot predict hemorrhagic events and thrombotic risk. Thromboelastography (TEG) measures the viscoelastic properties of the clot, thus providing information on the entire process of blood coagulation. The primary aim of the study was to assess the hemostatic balance from AML diagnosis to the end of chemotherapy (CHT) by TEG. MATERIAL AND METHODS: Here we present the results of a prospective study enrolling newly diagnosed AML patients treated with chemotherapy. Patients had complete blood counts (CBCs), TEG and CCTs performed at three time points: 1) diagnosis (T0); 2) during the first cycle of CHT (T1); and 3) at the end of CHT (T2). An algorithm of TEG indirectly calculated thrombin generation (TG). Patients underwent daily follow-up for bleeding and thrombotic episodes up to the time of hospital discharge or death. RESULTS: Eighty consecutive patients were evaluated; forty were eligible for the study, and 21 completed the entire study. At T1, maximum amplitude (MA), TG and K-time were significantly shifted toward a hypocoagulability state compared to T0 (p<0.05), while a hypercoagulable state at T2 was shown by changes in α-angle, MA and TG values. Otherwise, there were no statistically significant differences in CCTs between the evaluated time points. DISCUSSION: Overall, TEG revealed complex and dynamic coagulation abnormalities in patients with AML according to both the course of disease and therapy. Further studies are needed to investigate more fully the role of TEG in defining the hemostatic profile in patients with AML.

Thromboelastometry and prediction of in-hospital mortality in neonates with sepsis.

INTRODUCTION: This study aimed at evaluating the role of rotational thromboelastometry (ROTEM) assays in the prediction of in-hospital mortality of neonates with sepsis. METHODS: Over a 6-year period, 129 neonates with confirmed sepsis, hospitalized in our neonatal intensive care unit (NICU) were included in the study. Demographics, clinical, and laboratory data were recorded at the sepsis onset and ROTEM assays were performed. Modified neonatal multiple organ dysfunction (NEOMOD) and neonatal sequential organ failure assessment (nSOFA) were calculated simultaneously. Mortality during in-hospital stay was the main outcome measure. RESULTS: In-hospital mortality was associated with patient intense hypocoagulability expressed by lower ROTEM MCF in the INTEM assay. The INTEM MCF demonstrated the best prognostic performance for NICU mortality in septic neonates among the other ROTEM parameters but without statistical significance (area under the curve [AUC] = 0.731; 95% confidence interval [CI]: 0.593-0.869). CONCLUSION: Our results indicate that ROTEM INTEM MCF parameter has good predictive capacity for in-hospital mortality of septic neonates, similar to that of modified NEOMOD score, nSOFA score, and platelet count, highlighting the integral role of coagulation in sepsis pathophysiology. Hence, ROTEM could serve as a valuable monitoring tool to identify neonates at risk.

Comparison of Rapid-, Kaolin-, and Native-TEG Parameters in Burn Patient Cohorts With Acute Burn-induced Coagulopathy and Abnormal Fibrinolytic Function.

Although use of thromboelastography (TEG) to diagnose coagulopathy and guide clinical decision-making is increasing, relative performance of different TEG methods has not been well-defined. Rapid-TEG (rTEG), kaolin-TEG (kTEG), and native-TEG (nTEG) were performed on blood samples from burn patients presenting to a regional center from admission to 21 days. Patients were categorized by burn severity, mortality, and fibrinolytic phenotypes (Shutdown [SD], Physiologic [PHYS], and Hyperfibrinolytic [HF]). Manufacturer ranges and published TEG cutoffs were examined. Concordance correlations (Rc) of TEG parameters (R, α-angle, maximum amplitude [MA], LY30) measured agreement and Cohen's Kappa (κ) determined interclass reliability. Patients (n = 121) were mostly male (n = 84; 69.4%), with median age 40 years, median TBSA burn 13%, and mortality 17% (n = 21). Severe burns (≥40% TBSA) were associated with lower admission α-angle for rTEG (P = .03) and lower MA for rTEG (P = .02) and kTEG (P = .01). MA was lower in patients who died (nTEG, P = .04; kTEG, P = .02; rTEG, P = .003). Admission HF was associated with increased mortality (OR, 10.45; 95% CI, 2.54-43.31, P = .001) on rTEG only. Delayed SD was associated with mortality using rTEG and nTEG (OR 9.46; 95% CI, 1.96-45.73; P = .005 and OR, 6.91; 95% CI, 1.35-35.48; P = .02). Admission TEGs showed poor agreement on R-time (Rc, 0.00-0.56) and α-angle (0.40 to 0.55), and moderate agreement on MA (0.67-0.81) and LY30 (0.72-0.93). Interclass reliability was lowest for R-time (κ, -0.07 to 0.01) and α-angle (-0.06 to 0.17) and highest for MA (0.22-0.51) and LY30 (0.29-0.49). Choice of TEG method may impact clinical decision-making. rTEG appeared most sensitive in parameter-specific associations with injury severity, abnormal fibrinolysis, and mortality.

Increased platelet mitochondrial function correlates with clot strength in a rodent fracture model.

BACKGROUND: Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging because of a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function but has not yet been correlated with functional coagulation studies. METHODS: Wistar rats underwent anesthesia and either immediate sacrifice for baseline values (n = 6) or (1) bilateral hindlimb orthopedic injury (n = 12), versus (2) sham anesthesia (n = 12) with terminal phlebotomy/hepatectomy after 24 hours. High-resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex I- and Complex II-driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate. RESULTS: Citrated native TEG maximal amplitude was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared with sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol O 2 /[s × 10 8 cells], p = 0.045), with similar trends in mitochondrial leak rate ( p = 0.19) when compared with sham animals. Overall, platelet basal respiration significantly correlated with TEG maximal amplitude ( r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex I-driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e - /min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen. CONCLUSION: Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.