Thromboelastography Parameters do not Discriminate for Thrombotic Events in Hospitalized Patients With COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state; leading to multiple sequelae. We sought to detect whether thromboelastography (TEG) parameters would be able to detect thromboembolic events in patients hospitalized with COVID-19. METHODS: We performed a retrospective multicenter case-control study of the Collaborative Research to Understand the Sequelae of Harm in COVID (CRUSH COVID) registry of 8 tertiary care level hospitals in the United States (US). This registry contains adult patients with COVID-19 hospitalized between March 2020 and September 2020. RESULTS: A total of 277 hospitalized COVID-19 patients were analyzed to determine whether conventional coagulation TEG parameters were associated with venous thromboembolic (VTE) and thrombotic events during hospitalization. A clotting index (CI) >3 was present in 45.8% of the population, consistent with a hypercoagulable state. Eighty-three percent of the patients had clot lysis at 30 min (LY30) = 0, consistent with fibrinolysis shutdown, with a median of 0.1%. We did not find TEG parameters (LY30 area under the receiver operating characteristic [ROC] curve [AUC] = 0.55, 95% CI: 0.44-0.65, P value = .32; alpha angle [α] AUC = 0.58, 95% CI: 0.47-0.69, P value = .17; K time AUC = 0.58, 95% CI: 0.46-0.69, P value = .67; maximum amplitude (MA) AUC = 0.54, 95% CI: 0.44-0.64, P value = .47; reaction time [R time] AUC = 0.53, 95% CI: 0.42-0.65, P value = .70) to be a good discriminator for VTE. We also did not find TEG parameters (LY30 AUC = 0.51, 95% CI: 0.42-0.60, P value = .84; R time AUC = 0.57, 95%CI: 0.48-0.67, P value .07; α AUC = 0.59, 95%CI: 0.51-0.68, P value = .02; K time AUC = 0.62, 95% CI: 0.53-0.70, P value = .07; MA AUC = 0.65, 95% CI: 0.57-0.74, P value < .01) to be a good discriminator for thrombotic events. CONCLUSIONS: In this retrospective multicenter cohort study, TEG in COVID-19 hospitalized patients may indicate a hypercoagulable state, however, its use in detecting VTE or thrombotic events is limited in this population.

Role of Thromboelastogram in monitoring the activation of the coagulation pathway and assessing the associated risk factors for hypercoagulable state in transfusion dependent thalassemia patients.

BACKGROUND: Thromboembolic events are rare but one of the fatal complications in thalassemia. Assessment of the hypercoagulable state is not done regularly, and we have assessed the utility of Thromboelastography (TEG) for monitoring the activation of the coagulation pathway in patients with thalassemia. METHODOLOGY: A prospective single-center cohort study was conducted in a tertiary care set-up. Transfusion Dependent Thalassemia patients registered with the pediatric unit were screened for hypercoagulability using TEG during six months of the study period and followed up for three years for the development of thromboembolic events. Patient demographics, history of splenectomy, Serum ferritin levels and annual red cell transfusion requirement (mL/kg/year) were assessed. TEG parameters used were R time, K time, alpha angle, Maximum amplitude, Clot index, and Lysis 30. The thrombin generation test (V Curve) obtained from the first-degree derivate of the TEG velocity curve was also used for analysis. RESULTS: A total of 34 patients were recruited during the six months study period with an average age of 10.6 years ( ± 5.47). The average pre-transfusion hemoglobin level and the volume of packed red cells received were 7.24 g/dL and 152.82 mL/kg/year respectively. The TEG tracing was suggestive of a hypercoagulable state in 58.82% of patients. The mean values of angle (70.74), MA (64.16), CI (2.65) and TG (774.43) in TDT patients compared to age matched reference range (62.81, 57.99, 0.8, 577.83 respectively) was suggestive of prothrombotic changes. Annual blood transfusion requirement was negatively correlated with hypercoagulable status (-0.344, CI= -0.68 to 0.08). One out of 34 patients developed corona radiata infarct (with annual blood requirement; 112.7 mL/kg/Year). The risk to develop a hypercoagulable state appeared to be higher when the volume of RBCs transfused was less than 154 mL/kg/Year. CONCLUSION: TDT patients are at risk of developing thromboembolism, and screening with TEG may be useful to identify those at high risk.

Personality traits and preoperative lifestyle improvement are predictors of early weight loss after sleeve gastrectomy.

PURPOSE: This study investigated the associations of personality traits and preoperative lifestyle improvements with early weight loss after sleeve gastrectomy. METHODS: This was a single-center, retrospective study of 57 patients who underwent preoperative lifestyle intervention with a multidisciplinary team approach based on cognitive behavioral therapy before sleeve gastrectomy. All patients underwent preoperative psychological testing with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) and the Tokyo University Egogram New Version II (TEG II). We investigated the associations of psychological testing results and lifestyle improvements with percent total weight loss (%TWL) one year after surgery. RESULTS: The median %TWL at 1 year was 38.2% for patients with an improved lifestyle and 26.9% for those without improvement (P = 0.0008). Although TEG II factors were not associated with %TWL at 1 year, higher NEO-FFI extraversion (E) scores were significantly associated with a better %TWL at 1 year. The median %TWL at 1 year was 35.2% for patients with higher E scores and 25.4% for those with lower E scores (P = 0.0247). Lifestyle improvement and the NEO-FFI E score significantly influenced %TWL at 1 year based on a logistic regression analysis. CONCLUSION: The NEO-FFI E score and preoperative lifestyle improvement may be predictors of early weight loss after sleeve gastrectomy.

Comparison between the Rotational Thromboelastometry (ROTEM) Delta device against the Cartridge-based Thromboelastography 6s and Quantra in a healthy third trimester pregnant cohort.

Rotational Thromboelastometry (ROTEM) Delta has been described in several postpartum hemorrhage algorithms, but this device requires pipetting and careful mixing of reagents to initiate the clotting reaction. In contrast, thromboelastography (TEG 6s) and the Quantra devices operate utilizing an automated pre-mixed cartridge that only requires a blood sample to start the clot strength analysis. We compared the correlation between 3 point of care viscoelastic testing (POCVT) devices to laboratory Clauss fibrinogen and platelets, their inter-device correlation, and the total running time difference between Quantra and ROTEM. A high correlation was noted between the Clauss fibrinogen and the fibrinogen parameters from ROTEM (r = 0.76-0.84, P < 0.0001), TEG6s (r = 0.71, P < 0.0001) and Quantra (r = 0.72, P = 0.0001). A moderate correlation between laboratory platelets and the ROTEM (r = 0.54;0.45, P < 0.0001; P = 0.0013) and Quantra (r = 0.66, P = 0.0001) parameters was noted. The inter-device correlation showed to be high when comparing the fibrinogen parameters of TEG6s and Quantra to that of ROTEM (r = 0.88 and 0.74, P < 0.0001, respectively). In contrast, a moderate correlation was noted between the platelet parameters of Quantra and ROTEM (r = 0.51, p = 0.0036). The Quantra device resulted 20.9 min (95% CI -0.2 to 4.7, P = 0.07) faster than the ROTEM if the warming and pipetting of reagents of the latter were considered. All the POCVT devices demonstrated a high correlation to laboratory Clauss fibrinogen, making each beneficial for the early recognition and management of hypofibrinogenemia.

The Small RNA Teg41 Is a Pleiotropic Regulator of Virulence in Staphylococcus aureus.

Previously, our group demonstrated a role for the small RNA (sRNA) Teg41 in regulating production of the alpha phenol-soluble modulin toxins (αPSMs) in Staphylococcus aureus. Overexpressing Teg41 increased αPSM production while deleting the 3' end of Teg41 (Teg41Δ3' strain) resulted in a decrease in αPSM production, reduced hemolytic activity of S. aureus culture supernatants, and attenuated virulence in a murine abscess model of infection. In this study, we further explore the attenuation of virulence in the Teg41Δ3' strain. Using both localized and systemic models of infection, we demonstrate that the Teg41Δ3' strain is more severely attenuated than an ΔαPSM mutant, strongly suggesting that Teg41 influences more than the αPSMs. Proteomic and transcriptomic analysis of the wild-type and Teg41Δ3' strains reveals widespread alterations in transcript abundance and protein production in the absence of Teg41, confirming that Teg41 has pleiotropic effects in the cell. We go on to investigate the molecular mechanism underlying Teg41-mediated gene regulation. Surprisingly, results demonstrate that certain Teg41 target genes, including the αPSMs and ßPSMs, are transcriptionally altered in the Teg41Δ3' strain, while other targets, specifically spa (encoding surface protein A), are regulated at the level of transcript stability. Collectively, these data demonstrate that Teg41 is a pleiotropic RNA regulator in S. aureus that influences expression of a variety of genes using multiple different mechanisms.

A systematic review of thromboelastography utilization in vascular and endovascular surgery.

OBJECTIVE: Thromboelastography (TEG) is diagnostic modality that analyzes real-time blood coagulation parameters. Clinically, TEG primarily allows for directed blood component resuscitation among patients with acute blood loss and coagulopathy. The utilization of TEG has been widely adopted in among other surgical specialties; however, its use in vascular surgery is less prominent. We aimed to provide an up-to-date review of TEG utilization in vascular and endovascular surgery. METHODS: Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a literature review with the Medical Subject Headings (MeSH) terms "TEG and arterial events", "TEG and vascular surgery", "TEG and vascular", "TEG and endovascular surgery", "TEG and endovascular", "TEG and peripheral artery disease", "TEG and prediction of arterial events", "TEG and prediction of complications ", "TEG and prediction of thrombosis", "TEG and prediction of amputation", and "TEG and amputation" was performed in Cochrane and PubMed databases to identify all peer-reviewed studies of TEG utilization in vascular surgery, written between 2000 and 2021 in the English language. The free-text and MeSH subheadings search terms included diagnosis, complications, physiopathology, surgery, mortality, and therapy to further restrict the articles. Studies were excluded if they were not in humans or pertaining to vascular or endovascular surgery. Additionally, case reports and studies with limited information regarding TEG utilization were excluded. Each study was independently reviewed by two researchers to assess for eligibility. RESULTS: Of the 262 studies identified through the MeSH strategy, 15 studies met inclusion criteria and were reviewed and summarized. Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n = 3), peripheral arterial disease (n = 3), arteriovenous malformations (n = 1), venous thromboembolic events (n = 7), and perioperative bleeding and transfusion (n = 1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyze platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyze the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations. Finally, TEG can be utilized in the postoperative setting to predict hemorrhage and transfusion requirements. CONCLUSIONS: This systematic review provides an up-to-date summarization of TEG utilization in multiple facets of vascular and endovascular surgery.

Thromboelastography profiles in critically ill children with multisystem inflammatory syndrome.

OBJECTIVES: To describe critically ill children's coagulation profile with the multisystem inflammatory syndrome (MIS-C) related to coronavirus. STUDY DESIGN: Single-center, observational study at a tertiary, pediatric intensive care unit (PICU) in children aged 1 month to 18 years. MEASUREMENTS AND MAIN RESULTS: Sixteen children, with a median age of 5.4 years (interquartile range [IQR] 2.1, 11.75), 56% female, admission Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score of 3.5 (IQR 2, 5), and median PICU length of stay 3 days (IQR 1.5, 4), met criteria of MIS-C. All patients received acetylsalicylic acid (80-100 mg/kg) and none received anticoagulation. Sixty-three percent (10/16) of children had out-of-normal range values on thromboelastography (TEG) (44% [7/16] with hypercoagulability and 19% [3/16] with hypocoagulability). Of those with hypercoagulability, 19% (3/16) had rapid clot formation, and 25% (4/16) had increased clot strength. In 69% (11/16) of children, there was impaired fibrinolysis (0% lysis at 30 minutes) on TEG. Seventy-five percent (12/16) of children had out-of-normal range value on standard coagulation assays (37.5% [6/16] with hypocoagulability and 37.5% [6/16] with hypercoagulability). TEG-G (clot strength as measured by TEG) value (ρ -.553, p = .033) and platelet count (ρ -.840, p < .0001) were correlated with admission PELOD-2 score. TEG-G value (ρ -.506, p = .04) and platelet count (ρ -.539, p = .03) were correlated with the duration of intensive care unit stay. CONCLUSIONS: Coagulation abnormalities are frequent in children with MIS-C. TEG parameter and platelet count are correlated with the severity of multiorgan dysfunction and the duration of intensive care stay. Multicenter studies are needed to confirm the clinical implications of these coagulation abnormalities.

Experimental characterization of a commercial TEG device under mimicked operating conditions.

A long-standingzT= 1 barrier is still present in commercial thermoelectric generator devices (TEG) and is typically not overcome. Although it is possible to accept the current limits of such devices, the performances reported on the datasheets are frequently not obtainable when these thermoelectric devices are arranged for use in the actual operating conditions. Despite this, the current primary energy prices and ongoing climate change make their use attractive for many industrial sectors. An experimental investigation is here proposed on a single type of TEG available on the market; the temperature relationships of the electrical resistivity, Seebeck coefficient, and thermal conductivity in a thermostatic chamber were first determined. A piece of apparatus was assembled to mimic the operating conditions of the TEG device and verify its performance, but some critical issues were highlighted regarding the heat transfer and its ability to maintain an adequate contact pressure on the hot and cold sides of the module. In order to extend the recovery of waste heat to a non-excessively high temperature in the hot forging process, the maximum temperature attained on the hot side of the TEG in the performed experiments was not allowed to exceed 180 °C. With temperatures of around 160 °C on the hot side and just over 40 °C on the cold side, the conversion efficiency was close to 3%. Considering this conversion efficiency and the operating conditions, the estimated order of magnitude of the electricity that could be produced by recovering heat waste in the Italian hot forging sector could be in the region of some hundreds of MWh per year.

The evolution of clot strength in critically ill COVID-19 patients: a prospective observational thromboelastography study.

The authors have done commendable work in exploring the utility of a comprehensive viscoelastic test for assessment of the coagulation cascade in Coronavirus disease 2019 (COVID-19) patients. This article published in your esteemed journal in November 2021 "The evolution of clot strength in critically-ill COVID-19 patients: a prospective observational thromboelastography study" found hypercoagulability in most of the patients at Intensive Care Unit (ICU) admission and also noted a persistently increased fibrin contribution to clot strength. However, we would like to comment upon a few points which may be of importance to the readers.

Evaluation of direct oral anticoagulant use on thromboelastography in an emergency department population.

BACKGROUND: Direct oral anticoagulant (DOAC) use presents a challenge to all providers involved in emergency care of patients since widely accepted laboratory tests to assess the level of anticoagulation for such medications are lacking. Viscoelastic tests such as thromboelastography (TEG) tests are increasingly used throughout major trauma centers to help guide resuscitation efforts in patients presenting with trauma and/or hemorrhagic shock. OBJECTIVE: The primary outcome compared TEG parameters between emergency department trauma patients reporting DOAC therapy and known normal TEG parameter values. The secondary outcome evaluated patients who reported time of last known DOAC dose within a preferred time frame of <12 h for once daily dosing DOAC therapy or < 6 h for twice daily dosing DOAC therapy. METHODS: This single-center, retrospective cohort study assessed TEG values in patients receiving DOAC therapy and compared these to institution TEG ranges considered normal. TEG values of reaction time (R time), kinetics (K), alpha angle (AA), maximum amplitude (MA), and percent lysis in 30 min (LY30) were collected for patients reporting DOAC therapy. RESULTS: 40 patients were included in this study. 19 patients reported apixaban therapy and 21 reported rivaroxaban therapy. 5 (12.5%) patients had an elevated R time and 1 (2.5%) patient had a reduced MA. All other TEG values did not suggest hypocoagulability. For the secondary outcome assessing patients reporting last known dose within the preferred time frame, only the R time was elevated in 2 (14.3%) patients. Lastly, in a subgroup analysis of patients with elevated low-molecular-weight heparin (LMWH) orAnti- Xa levels, the R time was the only parameter affected in 25% of patients. CONCLUSION: TEG values were typically not affected by rivaroxaban or apixaban use in an emergency department trauma population suggesting that TEG is not sensitive for Xa inhibitor detection and should not be relied upon for assessing anticoagulation in such settings.

Application of a TEG-Platelet Mapping Algorithm to Guide Reversal of Antiplatelet Agents in Adults with Mild-to-Moderate Traumatic Brain Injury: An Observational Pilot Study.

BACKGROUND: Traumatic intracranial hemorrhages expand in one third of cases, and antiplatelet medications may exacerbate hematoma expansion. However, the reversal of an antiplatelet effect with platelet transfusion has been associated with harm. We sought to determine whether a thromboelastography platelet mapping (TEG-PM)-guided algorithm could limit platelet transfusion in patients with hemorrhagic traumatic brain injury (TBI) prescribed antiplatelet medications without a resultant clinically significant increase in hemorrhage volume, late hemostatic treatments, or delayed operative intervention. METHODS: A total of 175 consecutive patients with TBI were admitted to our university-affiliated, level I trauma center between March 2016 and December 2019: 54 preintervention patients (control) and 121 patients with TEG-PM (study). After exclusion for anticoagulant administration, availability of neuroimaging and emergent neurosurgery, 62 study patients and 37 control patients remained. Intervention consisted of administration of desmopressin (DDAVP) for nonsurgical patients with significant inhibition at the arachidonic acid or adenosine diphosphate receptor sites. For surgical patients with significant inhibition, dual therapy with DDAVP and platelet transfusion was employed. Study patients were compared with a group of historical controls, which were identified from a prospectively maintained registry and typically treated with empiric platelet transfusion. RESULTS: Median age was 75 years (interquartile range 85-67) and 77 years (interquartile range 81-65) in the TEG-PM and control patient groups, respectively. Admission hemorrhage volumes were similar (10.7 cm3 [20.1] in patients with TEG-PM vs. 14.1 cm3 [19.7] in controls; p = 0.41). There were no significant differences in admission Glasgow Coma Scale, mechanism of trauma, or baseline comorbidities. A total of 57% of controls versus 10% of patients with TEG-PM (p < 0.001) were transfused platelets; 52% of intervention patients and 0% controls were treated with DDAVP. Expansion hemorrhage volumes were not significantly different (14.0 cm3 [20.2] patients with TEG-PM versus 13.6 cm3 [23.7] controls; p = 0.93). There was no significant difference in rates of clinical deterioration, delayed neurosurgical intervention, or late platelet transfusion between groups. CONCLUSIONS: Among patients with hemorrhagic TBI prescribed preinjury antiplatelet therapy, our study suggests that the use of a TEG-PM algorithm may reduce platelet transfusions without a concurrent increase in clinically significant hematoma expansion. Further study is required to prove a causative relationship.

Comparison of Thromboelastography Devices TEG®6S Point of Care Device vs. TEG®5000 in Pediatric Patients Undergoing Cardiac Surgery.

Thromboelastography (TEG) can predict bleeding in pediatric patients undergoing cardiac surgery. We hypothesized that results obtained from TEG®5000 correlate with the new point-of-care TEG®6S system and that TEG®6S rewarming maximum amplitude (MA) is associated with surrogate endpoints for perioperative bleeding in pediatric patients who underwent complex cardiac surgery. We describe a retrospective study of pediatric (≤18 years) patients who underwent complex cardiac surgery on cardiopulmonary bypass. Citrate whole-blood samples were used to compared TEG®5000 vs.TEG®6S and TEG®6S-FLEV (with fibrinogen measurement) vs. Clauss-fibrinogen methods. TEG®6S parameters obtained during rewarming were compared to the surrogate endpoints for perioperative bleeding using linear regression analysis. Among 100 patients, 225 TEG®5000 vs.TEG®6S comparisons and 54 TEG®6S-FLEV were analyzed. Good correlation was observed for all parameters comparing TEG®5000 to TEG®6S and TEG®6S-FLEV to the Clauss-fibrinogen method (Pearson r ≥ .7). Similar to rewarming TEG®5000 MA, rewarming TEG®6S MA was the only parameter independently associated with risk for perioperative bleeding (median [interquartile range {IQR}] in bleeding vs. nonbleeding patients: 35 [29, 48] vs. 37 [32, 55]; p = .02). A platelet transfusion calculator was developed based on TEG®6S results by determining the relationship between platelet transfusion volume (mL/kg) and percent change in MA using linear regression analysis. TEG®6S is a good alternative point-of-care method to analyze a patient's coagulation profile and it is comparable to TEG®5000 in pediatric patients undergoing cardiac surgery on cardiopulmonary bypass. Lower TEG®6S MA during rewarming is associated with increased risk for perioperative bleeding. TEG analysis during rewarming may be useful in customizing platelet transfusion therapy by reducing the risk of bleeding while minimizing excessive blood product transfusions.

An overview of solutions for airborne viral transmission reduction related to HVAC systems including liquid desiccant air-scrubbing.

The spread of the coronavirus SARS-CoV-2 affects the health of people and the economy worldwide. As air transmits the virus, heating, ventilation and air-conditioning (HVAC) systems in buildings, enclosed spaces and public transport play a significant role in limiting the transmission of airborne pathogens at the expenses of increased energy consumption and possibly reduced thermal comfort. On the other hand, liquid desiccant technology could be adopted as an air scrubber to increase indoor air quality and inactivate pathogens through temperature and humidity control, making them less favourable to the growth, proliferation and infectivity of microorganisms. The objectives of this study are to review the role of HVAC in airborne viral transmission, estimate its energy penalty associated with the adoption of HVAC for transmission reduction and understand the potential of liquid desiccant technology. Factors affecting the inactivation of pathogens by liquid desiccant solutions and possible modifications to increase their heat and mass transfer and sanitising characteristics are also described, followed by an economic evaluation. It is concluded that the liquid desiccant technology could be beneficial in buildings (requiring humidity control or moisture removal in particular when viruses are likely to present) or in high-footfall enclosed spaces (during virus outbreaks).

Probing thermostability of detergent-solubilized CB2 receptor by parallel G protein-activation and ligand-binding assays.

G protein-coupled receptors (GPCRs) comprise a large class of integral membrane proteins involved in the regulation of a broad spectrum of physiological processes and are a major target for pharmaceutical drug development. Structural studies can help advance the rational design of novel specific pharmaceuticals that target GPCRs, but such studies require expression of significant quantities of these proteins in pure, homogenous, and sufficiently stable form. An essential precursor for these structural studies is an assessment of protein stability under experimental conditions. Here we report that solubilization of a GPCR, type II cannabinoid receptor CB2, in a Façade detergent enables radioligand thermostability assessments of this receptor with low background from nonspecific interactions with lipophilic cannabinoid ligand. Furthermore, this detergent is compatible with a [35S]GTPγS radionucleotide exchange assay measuring guanine exchange factor activity that can be applied after heat treatment to further assess receptor thermostability. We demonstrate that both assays can be utilized to determine differences in CB2 thermostability caused by mutations, detergent composition, and the presence of stabilizing ligands. We report that a constitutively active CB2 variant has higher thermostability than the WT receptor, a result that differs from a previous thermostability assessment of the analogous CB1 mutation. We conclude that both ligand-binding and activity-based assays under optimized detergent conditions can support selection of thermostable variants of experimentally demanding GPCRs.

The evolution of clot strength in critically-ill COVID-19 patients: a prospective observational thromboelastography study.

BACKGROUND: Few studies detail the evolution of COVID-19 associated coagulopathy. We performed serial thromboelastography (TEG) and laboratory coagulation studies in 40 critically-ill, mechanically ventilated COVID-19 patients over a 14-day period and analysed differences between 30-day survivors and non-survivors. METHODS: Single-center prospective, observational study including 40 patients with severe COVID-19 pneumonia admitted to the intensive care unit (ICU) for mechanical ventilation. TEG analysis was performed on days 1, 7 and 14 of ICU admission and laboratory coagulation studies were performed on days 1 and 14. Coagulation variables were evaluated for change over the 14-day observation period. Differences between survivors and non-survivors at 30-days were analysed and compared. RESULTS: On admission, TEG maximum amplitude (MA) with heparinase correction was above the upper limit of the reference range in 32 (80%) patients while 33 (82.5%) presented with absent clot lysis at 30 min. The functional fibrinogen MA was also elevated above the upper limit of the reference range in 37 (92.5%) patients. All patients had elevated D-dimer and fibrinogen levels, mildly prolonged prothrombin times (PT), normal platelet counts and normal activated partial thromboplastin times (aPTT). The heparinase MA decreased significantly with time and normalised after 14 days (p = < 0.001) while the increased fibrin contribution to clot strength persisted with time (p = 0.113). No significant differences in TEG analysis were noted between 30-day survivors and non-survivors at all time points. No patients developed disseminated intravascular coagulopathy (DIC) after 14-days, however thrombosis and bleeding were each reported in 3 (7.5%) patients. CONCLUSION: Critically-ill patients with COVID-19 present in a hypercoagulable state characterised by an increased clot strength. This state normalises after 14 days despite a persistently increased fibrin contribution to clot strength. We were unable to demonstrate any significant differences in TEG parameters between 30-day survivors and non-survivors at all time points.

TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product.

Despite extensive usage of gene therapy medicinal products (GTMPs) in clinical studies and recent approval of chimeric antigen receptor (CAR) T cell therapy, little information has been made available on the precise molecular characterization and possible variations in terms of insert integrity and vector copy numbers of different GTMPs during the complete production chain. Within this context, we characterize αßT cells engineered to express a defined γδT cell engineered to express a defined γδT receptor (TEG) currently used in a first-in-human clinical study (NTR6541). Utilizing targeted locus amplification in combination with next generation sequencing for the vector producer clone and TEG001 products, we report on five single-nucleotide variants and nine intact vector copies integrated in the producer clone. The vector copy number in TEG001 cells was on average a factor 0.72 (SD 0.11) below that of the producer cell clone. All nucleotide variants were transferred to TEG001 without having an effect on cellular proliferation during extensive in vitro culture. Based on an environmental risk assessment of the five nucleotide variants present in the non-coding viral region of the TEG001 insert, there was no altered environmental impact of TEG001 cells. We conclude that TEG001 cells do not have an increased risk for malignant transformation in vivo.

Thromboelastography findings in critically ill COVID-19 patients.

The rate of venous and arterial thrombotic events among patients infected with severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) is high. This may be due to a hypercoagulable state induced by the severe inflammation that results from the SAR-CoV-2 infection. We aimed to determine hypercoagulable states' incidence based on thromboelastography study and its association with thrombotic events in critically ill patients with coronavirus disease 2019 (COVID-19). Fifty-two COVID-19 patients who had thromboelastography study were retrospectively included. All patients received pharmacologic thromboprophylaxis. The hypercoagulable state was observed in 16 patients (30.8%). Among them, maximum amplitude and a-angle were elevated in 75% and 25%, respectively. Reaction time and K were low in only 12.5% for both of them. Inflammatory and coagulation markers, as well as thromboprophylaxis regimens, were not associated with a hypercoagulable state. Fourteen patients (27%) experienced a total of 16 thrombotic events, including 8 (57%) deep venous thrombosis, 6 (43%) pulmonary embolism, and 2 (14.3%) arterial thrombosis. The hypercoagulable state was not significantly associated with thrombotic events. In summary, we observed a lower rate of hypercoagulable state on thromboelastography study in critically ill COVID-19 patients. Also, the hypercoagulable state was not associated with the occurrence of thrombotic events.

It is time for TEG in pediatric trauma: unveiling meaningful alterations in children who undergo massive transfusion.

BACKGROUND: Hemorrhage is the leading cause of preventable death in pediatric trauma patients. In adults, goal-directed thrombelastography (TEG) has been shown to reduce mortality when used to guide massive transfusion (MT) resuscitation. There remains a paucity of data on the utility of TEG in directing resuscitation of pediatric trauma patients. We hypothesize that abnormalities on admission TEG will differ in pediatric trauma patients who undergo MT, compared to those who do not. METHODS: Pediatric patients (≤ 18 years) who were highest level trauma activations at two trauma centers from 2015 to 2018 were analyzed. We included patients who had admission TEGs and excluded those who did not. Patients were stratified into two groups: those who received MT (> 40 cc/kg total blood product within 6 h of admission) and those who did not. We defined TEG abnormalities based on each institution's normative values and compared TEG abnormalities between the groups. RESULTS: Of 117 children included, 39 had MT. MT patients had higher injury severity scores (30 vs. 23, p = 0.0004), lactates levels (7.0 vs. 3.5, p < 0.001), base deficit levels ( - 12.2 vs. - 5.8, p < 0.001), and INR values (1.8 vs. 1.3, p < 0.001). MT patients had significantly shortened alpha-angles (35.9% vs. 15.4%, p = 0.023), maximum amplitude (MA) values (43.6% vs. 10.3%, p < 0.001), and significantly lower platelet counts (165 vs. 281, p < 0.001) compared to those who did not receive MT. There was no difference in the trends in R-time, LY30 (lysis or shutdown), or fibrinogen concentration between the groups. Logistic regression identified a decreased MA as a significant predictor for MT [OR 3.68 (CI 1.29-10.52)] CONCLUSIONS: Pediatric trauma patients who undergo MT are more likely to have lower alpha-angles and MA values, as well as lower platelet counts. These findings support the use of TEG to identify hemorrhaging pediatric trauma patients, who may benefit from cryoprecipitate and/or platelet transfusions. TEG provides real-time information on coagulation status, which may expedite the delivery of specific blood products during trauma resuscitation. LEVEL OF EVIDENCE: LEVEL III: Type of study: Retrospective comparative study.

The effect of hyperoxia on the hemostasiological status of severely burned patients.

The state of the hemostasis system was studied in 9 patients of the middle age group (44 ± 9.94 years) who received thermal trauma on an area of more than 32% (49.4 ± 18.3) of the body surface, accompanied by the development of burn shock. The standard therapy for burn injury was supplemented with HBO sessions. Treatment with hyperbaric oxygen was carried out in pressure chambers BLKS-307, BLKS-307/1. The state of the coagulation, anticoagulant and fibrinolytic links of the hemostasis system, as well as the viscoelastic properties of the blood, were assessed immediately before the HBO session and immediately after it. The total number of comparison pairs was 45. Under the influence of HBO therapy, there was an increase in the activity of antithrombin III (ATIII), protein C (PrS) and a decrease in the viscoelastic properties of blood (p <0.05). Positive deviations in the values of ATIII, Pr C, von Willebrand factor, APTT, prothrombin and thrombin time, fibrinogen, factor XIII, XIIa-dependent fibrinolysis, D-dimers and thromboelastography parameters were revealed. The maximum frequency of their occurrence was recorded for ATIII (95%), the minimum - for the D-dimer (62%). After HBO procedures, undesirable deviations of the hemostatic system parameters were also noted. They were chaotic, were compensated by an increase in the activity of physiological anticoagulants and were not accompanied by complications of a thrombogenic nature. Thus, conducting HBO therapy sessions in the acute period of burn disease increases the activity of physiological anticoagulants and stabilizes the viscoelastic properties of blood. There is a high frequency of occurrence of positive effects of hyperoxia on the components of the hemostasis system. The identification of its undesirable effects indicates the need to monitor the state of the hemostasis system during HBO procedures.

Viscoelastic testing in oncology patients (including for the diagnosis of fibrinolysis): Review of existing evidence, technology comparison, and clinical utility.

The quantification of the coagulopathic state associated with oncologic and hematologic diseases is imperfectly assessed by common coagulation tests such as prothrombin time, activated partial thromboplastin time, fibrinogen levels, and platelet count. These tests provide a static representation of a component of hemostatic integrity, presenting an incomplete picture of coagulation in these patients. Viscoelastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), as whole blood analyses, provide data related to the cumulative effects of blood components and all stages of the coagulation and fibrinolytic processes. The utility of VETs has been demonstrated since the late 1960s in guiding blood component therapy for patients undergoing liver transplantation. Since then, the scope of viscoelastic testing has expanded to become routinely used for cardiac surgery, obstetrics, and trauma. In the past decade, VETs' expanded usage has been most significant in trauma resuscitation. However, use of VETs for patients with malignancy-associated coagulopathy (MAC) and hematologic malignancies is increasing. For the purposes of this narrative review, we discuss the similarities between trauma-induced coagulopathy (TIC) and MAC. These similarities center on the thrombomodulin-thrombin complex as it switches between the thrombin-activatable fibrinolysis inhibitor coagulation pathway and activating the protein C anticoagulation pathway. This produces a spectrum of coagulopathy and fibrinolytic alterations ranging from shutdown to hyperfibrinolysis that are common to TIC, MAC, and hematologic malignancies. There is expanding literature regarding the utility of TEG and ROTEM to describe the hemostatic integrity of patients with oncologic and hematologic conditions, which we review here.