Non-trauma uses of viscoelastic hemostatic assays in critical care: A narrative review and primer for pharmacists

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are point-of-care viscoelastic tests of whole blood that provide real-time analyses of coagulation. TEG and ROTEM are often used to guide blood product administration in the trauma and surgical settings. These tests are increasingly being explored for their use in other disease states encountered in critically ill patients and in the management of antithrombotic medications. As the medication experts, pharmacists should be familiar with how to interpret and apply viscoelastic tests to disease state and medication management. The purpose of this narrative review is to provide a primer for pharmacists on viscoelastic tests and their interpretation and to explore non-trauma indications for viscoelastic testing in critical care. Literature evaluating the use of TEG and ROTEM for patients with acute and chronic liver disease, ischemic and hemorrhagic stroke, myocardial infarction, cardiac arrest, coronavirus disease 2019, and extracorporeal membrane oxygenation are described. Current applications of viscoelastic tests by pharmacists and potential future roles of critical care pharmacists in expanding the use of viscoelastic tests are summarized.Copyright © 2023 The Authors. JACCP: Journal of the American College of Clinical Pharmacy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.

Multisystem Inflammatory Syndrome in Children Requiring ECMO: Anticoagulation strategies and Lessons Learned

Intro: Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious inflammatory response after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which can cause acute cardiac dysfunction requiring mechanical circulatory support (MCS). MCS utilization for MIS-C is complicated by a propensity for thrombosis, which threatens circuit integrity. This study describes a cohort of MIS-C patients requiring MCS, their outcomes, and the anticoagulation strategies utilized. Method(s): A retrospective case series of patients diagnosed with MIS-C needing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) at Children's Healthcare of Atlanta from March 1, 2020 to June 30, 2022. VA-ECMO variables, laboratory data, complications, and outcomes were collected. Result(s): Seven patients (all male) with severe MIS-C required VA-ECMO for acute cardiac dysfunction. Median age was 13 years (range 4-15 years). Median ICU stay was 13 days (range 6-17 days) with a median ECMO duration of 7 days (IQR 3-8 days) and median mechanical ventilation duration of 8 days (IQR 5-11 days). All seven patients survived to hospital discharge with good neurologic outcomes. Median time to qualitatively normal ventricular function by echocardiogram was 9.5 days (IQR 3-21 days). Heparin was initially used in 6 patients, bivalrudin initially used in 1 patient, and 1 patient converted from heparin to bivalirudin for refractory systemic thrombosis. Median heparin dose was 206u/kg/d (IQR 192-276u/kg/d) with median anti-Xa levels of 0.75 (IQR 0.1-1.1) and median daily PTT 102 seconds (IQR 83-107 seconds). Median daily PTT of patients receiving bivalirudin was 86 seconds (80-93 seconds). Median R-values by thromboelastography were 38 seconds (IQR 25-55 seconds). Two patients required catheter directed thrombolysis with tissue plasminogen activator (t-PA) for refractory intracardiac thrombi, both were initially started on heparin. Significant cannula thrombosis occurred in 2 patients, 1 initially started on heparin and 1 initially on bivalrudin. Bleeding resulting in compartment syndrome occurred in one patient on heparin requiring fasciotomy of the upper extremities, this patient was not receiving t-PA. Conclusion(s): Anticoagulation management for MIS-C patients requiring ECMO is fraught with challenges. A successful management strategy may necessitate higher heparin assay levels, the use of direct thrombin inhibitors for refractory thrombosis, and the deployment of catheter directed thrombolysis. In this case series, CDT was safely and successfully used in two patients. Further studies are required to understand the optimal anticoagulation strategy for these patients to minimize complications.

Correlation between heparin anti-Xa activity and thromboelastography in adult critically ill COVID-19 patients.

STUDY OBJECTIVE: Severe coronavirus disease 2019 (COVID-19) increases the risk of thrombotic complications with unfractionated heparin (UFH) as a commonly used agent in managing venous thromboembolism (VTE). The optimal anticoagulation intensity and monitoring parameters in intensive care unit (ICU) COVID-19 patients remains controversial. The primary study aim was to evaluate the relationship between anti-Xa and thromboelastography (TEG) reaction (R) time in patients with severe COVID-19 receiving therapeutic UFH infusions. DESIGN: Single-center, retrospective study conducted over a 15-month period (2020-2021). SETTING: Academic medical center (Banner University Medical Center Phoenix). PATIENTS: Adult patients with severe COVID-19 administered therapeutic UFH infusions with one or more corresponding TEG, and anti-Xa assessments drawn within ≤2 hours of each other were included. The primary end point was the correlation between anti-Xa and TEG R time. Secondary aims were to describe the correlation between activated partial thromboplastin time (aPTT) and TEG R time, as well as clinical outcomes. Pearson's coefficient was used to evaluate the correlation using a kappa measure of agreement.

Coagulopathies after vaccination against SARS-CoV-2: The sole solution might lead to another problem

The common reported adverse impacts of COVID-19 vaccination include the injection site's local reaction followed by various non-specific flu-like symptoms. Nevertheless, uncommon cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) following viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. This literature review was performed using PubMed and Google Scholar databases using appropriate keywords and their combinations: SARS-CoV-2, adenovirus, spike protein, thrombosis, thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia (VITT), NF-kappaB, adenoviral vector, platelet factor 4 (PF4), COVID-19 Vaccine, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, coagulopathy. The s and titles of each article were assessed by authors for screening and inclusion English reports about post-vaccine CVST and VITT in humans were also collected. Some SARS-CoV-2 vaccines based on viral vector, mRNA, or inactivated SARS-CoV-2 virus have been accepted and are being pragmatic global. Nevertheless, the recent augmented statistics of normally very infrequent types of thrombosis associated with thrombocytopenia have been stated, predominantly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The numerical prevalence of these side effects seems to associate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the meticulous molecular mechanisms are still not clear. The present review summarizes the latest data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis demonstrating that coagulopathies, including thromboses, thrombocytopenia, and other associated side effects, are correlated to an interaction of the two components in the COVID-19 vaccine.Copyright © 2022, Iranian Pediatric Hematology and Oncology Society. All rights reserved.

Utility of Thromboelastography and velocity curve derivative in diagnosing COVID-19 associated coagulopathy.

BACKGROUND: COVID-19 associated coagulopathy (CAC) can either be localized or systemic hypercoagulable state with increased risk of thromboembolism. This study looked into the usefulness of Thromboelastography (TEG) and the velocity curve (V-curve) derivative from TEG in diagnosing and differentiating different stages of CAC. MATERIALS AND METHODS: A prospective single cohort study of RT-PCR confirmed COVID-19 patients was carried out for 2 weeks. Severe COVID-19 patients in the adult critical care units with a TEG report were recruited for the study. Citrated kaolin TEG was performed on the day of admission before anticoagulation. TEG parameters included were R and K time, alpha angle, maximum amplitude, clotting index, lysis at 30 min. The first-degree velocity curve of TEG is plotted as V-curve which extrapolates thrombus generation potential. Parameters analyzed were the maximum rate of thrombus generation as well as thrombus generated (TG). RESULTS: The study included 43 patients with an average age of 58.34 (±15.35). TEG as well as V-curve of all the patients were hypercoagulable compared with age-matched reference range. We had 79.06% of patients in hypercoagulable stage. The mortality rate was 32.56% and 30.23% developed thrombotic incidents. Patients who succumbed to death had prolonged PT, aPTT, MA, Ly30, with a reduced TG (p < .05). The presence of fibrinolysis was associated with thromboembolism (OR = 6.76, CI = 1.48-25.82). Repeat TEG was done randomly in 11 patients and revealed a persistent hypercoagulable stage with increasing fibrinolysis activity. CONCLUSION: TEG is a useful tool in diagnosing and categorizing Coagulopathy associated with COVID-19.

Viscoelastic testing: an illustrated review of technology and clinical applications.

Viscoelastic testing (VET), including thromboelastography and thromboelastometry, provides a rapid and comprehensive picture of whole blood coagulation dynamics and hemostasis that can be reviewed and evaluated at the point-of-care. This technology is over 50 years old; however, over the past few years, there has been a significant increase in research examining the use of VET. Best practice guidelines for the use of VET exist in both the United States and Europe, particularly for elective cardiac surgery, although recommendations for implementation are somewhat limited in some clinical areas by the lack of studies constituting high-grade evidence. Other challenges to implementation surround validation of the technology in some care settings as well as lack of training. Nevertheless, there is a wide range of potential clinical applications, such as treating coagulopathies in liver disease and transplant surgery, critical care, as well as within obstetrical hemorrhage. In this illustrated review, we provide an overview of viscoelastic testing technology (also called viscoelastic hemostatic assays) and describe how the assays can be used to provide a broad overview of hemostasis from clot formation to clot lysis, while highlighting the contribution of coagulation factors and platelets. We then summarize the major clinical applications for viscoelastic testing, including more recent applications, such as in COVID-19. Each section describes the clinical context, and key publications, followed by a representative algorithm and key guidelines.

Correlation between partial thromboplastin time and thromboelastography in adult critically ill patients requiring bivalirudin for extracorporeal membrane oxygenation.

STUDY OBJECTIVE: Thromboelastography (TEG) offers a more dynamic assessment of hemostasis over activated partial thromboplastin time (aPTT). However, the clinical utility of TEG in monitoring bivalirudin during extracorporeal membrane oxygenation (ECMO) remains unknown. The purpose of this study was to evaluate the correlation between aPTT and TEG in adult ECMO patients anticoagulated with bivalirudin. DESIGN: Multicenter, retrospective, cohort study conducted over a 2-year period. SETTING: Two academic university medical centers (Banner University Medical Center) in Phoenix and Tucson, AZ. PATIENTS: Adult patients requiring ECMO and bivalirudin therapy with ≥1 corresponding standard TEG and aPTT plasma samples drawn ≤4 h of each other were included. The primary endpoint was to determine the correlation coefficient between the standard TEG reaction (R) time and bivalirudin aPTT serum concentrations. MEASUREMENTS AND MAIN RESULTS: A total of 104 patients consisting of 848 concurrent laboratory assessments of R time and aPTT were included. A moderate correlation between TEG R time and aPTT was demonstrated in the study population (r = 0.41; p < 0.001). Overall, 502 (59.2%) concurrent assessments of TEG R time and aPTT values showed agreement on whether they were sub-, supra-, or therapeutic according to the institution's classification for bivalirudin. The 42.2% (n = 271/642) discordant TEG R times among "therapeutic" aPTT were almost equally distributed between subtherapeutic and supratherapeutic categories. CONCLUSIONS: Moderate correlation was found between TEG R time and aPTT associated with bivalirudin during ECMO in critically ill adults. Further research is warranted to address the optimal test to guide clinical decision-making for anticoagulation dosing in ECMO patients.

Milrinone-induced platelet inhibition in patients supported on veno-aterial extracorporal membrane oxygenation: a case series

Case Report: Purpose: Milrinone is an inodilator that is used in the treatment of cardiogenic dysfunction and shock. It causes increased cardiac output by stimulating myocardial contractility, enhancing cardiac relaxation, and reducing afterload via phosphodiesterase III inhibition, preventing cyclic adenosine monophosphate (cAMP) degradation. Increased cAMP concentrations are known to inhibit platelet aggregation. Veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal treatment option for inotrope-refractory cardiogenic shock and is often used in conjunction with inodilators. Often, patients supported on ECMO require systemic anticoagulation to prevent clotting complications. Therefore, thromboelastography (TEG) with platelet mapping is used to help gauge a patient's clotting status and gives clinicians information about the degree of platelet inhibition present. We present the case of two patients, both supported on VA-ECMO, who developed platelet inhibition with clinically significant bleeding while on milrinone, requiring the cessation of the milrinone infusion. Cases: First, we present an adult female in her fourth decade of life who required VA-ECMO for Covid-19 ARDS and cardiogenic shock. TEG platelet mapping was obtained for clinically significant bleeding from her trachea and gastrointestinal tract. Ten days after starting milrinone, adenosine-5'-diphosphate (ADP) inhibition was elevated at 67.4% and arachidonic acid (AA) inhibition normal at 1.8%. Twenty days after starting milrinone, ADP inhibition was 93.3% and AA inhibition was 76.4%. Milrinone discontinued and repeat TEG platelet mapping (10 days after discontinuation) showed ADP inhibition of 76.8% and AA inhibition of 0%. Her lowest ADP inhibition was 41.9%, approximately 1 month after milrinone discontinuation. Milrinone again attempted and ADP inhibition was 87.9% and AA inhibition 89.2% within 24 hours of initiation. No data available for platelet inhibition prior to starting milrinone. Next, we present a 9 year old female with acute myeloid leukemia who required VA-ECMO for septic shock. Initial TEG platelet mapping, obtained 2 days after milrinone initiation, showed ADP inhibition of 43.6% and AA inhibition of 98.7%. Two days after discontinuation of milrinone, her ADP inhibition was 19.6% but AA inhibition remained elevated at 91.9%. However, after 4 days off milrinone, her ADP inhibition was normal at 15.5% and AA inhibition mildly elevated at 33.6%. No data available for platelet inhibition prior to starting milrinone. Conclusion(s): Milrinone is a known platelet inhibitor due to increased intracellular cAMP concentrations. For patients on ECMO and milrinone, care should be given to the degree of platelet inhibition and potential risk of clinically significant bleeding. Further studies are needed to further investigate the correlation between milrinone, platelet inhibition, and clinically significant bleeding in ECMO patients. Copyright © 2023 Southern Society for Clinical Investigation.

Are Viscoelastometric Assays of Old Generation Ready for Disposal? Comment on Volod et al. Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices. J. Clin. Med. 2022, 11, 860.

With the advent of new viscoelastometric hemostatic assay (VHA) devices, with ready-to-use cartridge reagents allowing for their use by people without special laboratory skills, the appreciation of the actual clinical value of VHAs in settings such as severe trauma, post-partum hemorrhage, cardiac surgery and liver transplantation still needs to be fully validated. While two of the newest versions remain based on a 'cup and pin' system (ROTEM® sigma, ClotPro®), two other new devices (TEG® 6s, Quantra®) rely on very different technologies: clotting blood is no longer in contact with the probe and challenged by oscillation of one of the components but explored with ultrasound exposure. A systematic literature search (including Sonoclot®) retrieved 20 observational studies (19 prospective). Most studies pointed to imperfect agreements, highlighting the non-interchangeability of devices. Only a few studies, often with a limited number of patients enrolled, used a clinical outcome. No study compared VHA results with conventional laboratory assays obtained through a rapid tests panel. Clinical evidence of the utility of the new VHAs largely remains to be proven through randomized clinical trials, with clinically relevant outcomes, and compared to rapid panel hemostasis testing. The availability of new, improved VHA devices provides an impetus and an opportunity to do so.

Clinical Application of Thromboelastography in Acute Ischemic Stroke.

Acute ischemic stroke (AIS), characterized by high morbidity and mortality, has imposed a considerable burden on society. Despite rapid development in the treatment of AIS, there is still a high risk of recurrence. Furthermore, there is a time delay in waiting for the results of conventional coagulation tests in candidate patients for intravenous thrombolysis therapy. Heterogeneous responses to antiplatelet, intravascular thrombolysis, and endovascular therapies also worsen the situation. Thromboelastography (TEG), as a global and portable detection method for hemostasis, facilitates clinicians in disease monitoring, treatment evaluation, and prognosis prediction in AIS. In this narrative review, we provided a comprehensive summary of the clinical application of TEG in ischemic stroke and gave insights to further studies.

Fibrinolysis Shutdown Subtype of Early Allograft Dysfunction Represents the Predominant Cohort of Patients with Graft Failure Following Liver Transplantation

Purpose: Early allograft dysfunction (EAD) is associated with an increased rate of graft failure in liver transplantation (LT), but a mechanism remains unclear. Recent experience with COVID-19 has identified that microvascular clots related to fibrinolysis shutdown [ SD (lack of ability to break down clot)] drives organ failure, which can be treated with tissue plasminogen activator (tPA). It remains unclear how SD interacts with EAD, and if it may be associated with a worse outcome in LT. We hypothesize that fibrinolysis shutdown with EAD would be an unfavorable combination with an increased risk of graft failure compared to patients with EAD without SD. Method(s): Adult liver transplant recipients underwent thrombelastography (TEG) on post-operative day-1 to assess for fibrinolysis shutdown. Fibrinolysis activity was quantified by the amount of clot strength lost from peak clot strength in 30-minutes (LY30) in the presence of tPA (75ng/ml). SD was defined as an LY30 of 0%, indicative or no fibrinolytic activity in the presence of a fibrinolytic activator (median LY30 = 8% in healthy volunteers). EAD was defined on laboratory measurements defined and validated by Olthoff et al. Graft survival analysis was conducted with logistic regression analysis when controlling for recipient severity of liver disease (MELD) and graft quality (donor risk index). Survival time was assessed with Kaplan Meier curve. Result(s): 230 liver transplant patient recipients with a median laboratory MELD of 23 were included in the analysis. Graft failure rate was 13% with a median follow up time of 345 days. EAD occurred in 31%, and SD was present in 45%. The combination of EAD and SD was associated with a 46% graft loss rate which was significantly higher than EAD without SD (8% p<0.001). When controlling for MELD, and donor risk index, EAD (OR 3.3 95%CI 1.3-8.4 p=0.014) and fibrinolysis shutdown (OR 2.9 95%CI 1.1-7.9 p=0.034) were independent predictors of graft failure. Graft survival times were significantly different when patients were stratified by EAD and SD (figure p<0.001). Conclusion(s): The combination of EAD and SD bodes poor prognosis following liver transplantation. The stark difference in survival warrants further investigation if activation of the fibrinolytic system can safely improve graft survival time in LT recipients with EAD without the risk of excessive bleeding. (Figure Presented).

Thromboelastographic method for early decision on anticoagulant therapy in moderate to severe COVID-19 patients

BACKGROUND Coagulopathy is a serious COVID-19 complication that requires rapid diagnosis and anticoagulation. This study aimed to determine the role of coagulation examination using thromboelastography (TEG) on the decision-making time of anticoagulant therapy in COVID-19 patients and its clinical outcomes. METHODS A prospective observational study was conducted in Cipto Mangunkusumo Hospital, Indonesia, from October 2020 to March 2021. We consecutively recruited moderate and severe COVID-19 patients in the high and intensive care units. Turnaround time, time to anticoagulant therapy decision, and clinical outcomes (length of stay and 30-day mortality) were compared between those who had a TEG examination in addition to the standard coagulation profile examination (thrombocyte count, PT, APTT, D-dimer, and fibrinogen) and those who had only a standard coagulation profile laboratory examination. RESULTS Among 100 moderate to severe COVID-19 patients recruited, 50 patients had a TEG examination. The turnaround time of TEG was 45 (15–102) min versus 82 (19– 164) min in the standard examination (p<0.001). The time to decision was significantly faster in the TEG group than the standard group (75 [42–133] min versus 184 [92–353] min, p<0.001). The turnaround time was positively correlated with time to decision (r = 0.760, p<0.001). However, TEG did not improve clinical outcomes such as length of stay (10.5 [3–20] versus 9 [2–39] days) and 30-day mortality (66% versus 64%). CONCLUSIONS The TEG method significantly enables quicker decision-making time for moderate to severe coagulation disorder in COVID-19 patients.

Viscoelastic Testing in Pediatric Mechanical Circulatory Support.

Pediatric mechanical circulatory support can be lifesaving. However, managing anticoagulation is one of the most challenging aspects of care in patients requiring mechanical circulatory support. Effective anticoagulation is even more difficult in pediatric patients due to the smaller size of their blood vessels, increased turbulent flow, and developmental hemostasis. Recently, viscoelastic testing (VET) has been used as a qualitative measure of anticoagulation efficacy in patients receiving extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD). Thromboelastography (TEG®) and thromboelastometry (ROTEM®) provide a global qualitative assessment of hemostatic function from initiation of clot formation with the platelet-fibrin interaction, platelet aggregation, clot strength, and clot lysis. This review focuses on the TEG®/ROTEM® and important laboratory and patient considerations for interpretation in the ECMO and VAD population. We summarize the adult and pediatric ECMO/VAD literature regarding VET values, VET-platelet mapping, utility over standard laboratory monitoring, and association with outcome measures such as blood product utilization, bleeding, and thrombosis.

Wound complications in patients with acute lower limb venous thrombosis associated with COVID-19

The course of the reparative process in surgical pathology directly depends on hemomicrocirculation, nutrition and oxygen supply in tissues, as well as the activity of lipid peroxidation processes. A novel coronavirus infection can slow down the reparative process and potentiate the development of wound complications. Aim - to study the features of the tissue healing process in patients with deep vein thrombosis of the lower extremities against the background of a new coronavirus infection. Material and methods. 130 patients were monitored: group 1 - 48 patients with acute thrombosis of the veins of the lower extremities, group 2 - 82 patients with acute deep vein thrombosis of the lower extremities, combined with coronavirus infection. Patients underwent thrombectomy followed by plication. On the 2nd, 4th and 7th days, a comprehensive study of the state of the tissues of the area of surgical intervention was carried out to determine the nature and rate of healing, the development of wound complications. Results. In a quantitative analysis of the developed complications on the side of the wound after surgery, it turned out that their number in patients with coronavirus infection was more than 7 times higher (p<0.001). A feature of the wound process as a whole was prolonged lymphorrhea. Cytological signs of impaired tissue healing in the wound area were established. So, in group 2 two days after the operation the number of neutrophilic leukocytes in the wound exudate was 48.2% more than in the group 1, by day 7th - 69.5% more. Weak dynamics of the regenerative-degenerative index was noted. The number of tissue polyblasts in patients of group 2, was 4.2-100.2% lower than those of group 1 at all stages of observation, and lymphoid polyblasts - 47.0-159.1% higher. Patients with coronavirus infection have more significant microcirculatory disorders. According to thromboelastography data, in patients of group 2, an imbalance in the blood coagulation system was registered with a predominance of thrombosis. Conclusion. In patients with acute deep vein thrombosis of the lower limb against the background of coronavirus infection, the wound healing process, which underlies the development of wound complications, slows down. One of the factors that reduce the rate of tissue healing are microcirculation disorders against the background of pronounced disorders in the hemostasis system. The most significant changes in the microenvironment of regenerating structures occur in the first 2-4 days after surgery.

Comparison of New Viscoelastic Coagulation Monitor with Standard of Care Thromboelastography for Anticoagulation Monitoring during 72-Hour Extracorporeal Life Support

Introduction: Management of coagulation remains the foremost challenge during extracorporeal life support (ECLS). Thromboelastography (TEG) and other viscoelastic clotting tests have shown utility for assessing coagulation status in trauma and ECLS patients and have also been utilized in COVID 19 patients. However, with few exceptions, these methods are performed in a laboratory setting, not at the bedside, and rely on cumbersome, non-portable equipment. The Viscoelastic Coagulation Monitor (VCM;Entegrion;Durham, NC) is a portable device/test developed for use at the bedside and outside hospitals to assess clot formation and lysis using a small sample of whole blood. Blood coagulation is activated by contact with the glass surface on the cartridge, and measurements are derived pertaining to clot formation, stability, and lysis - similar to metrics obtained by the TEG 5000 (Haemonetics;Boston, MA). In a recent study, the relationship of VCM results and heparin dose administered in 36 COVID-19 patients was investigated;however, use of VCM for ECLS with application of heparinase has not been reported. We investigated efficacy of the VCM for coagulation monitoring during 72 hours of continuous ECLS in swine and hypothesized that the VCM with heparinase correlates with TEG heparinase. Methods: Female Yorkshire swine (n=3, 53.4±1.6kg) were anesthetized, mechanically ventilated, and systemically heparinized. Blood samples were collected at baseline, post ECLS, 6, 24, 48, and 72-hours post ECLS initiation. For the VCM, 350μL of whole blood was added to a 0.05 IU heparinase vial, mixed, and then added to a VCM cartridge. For TEG, 340μL of citrated whole blood was added to 20μL 0.2 M CaCl2, and samples were activated with a kaolin reagent. Heparinase cups (Haemonetics;Boston, MA) were used for testing. Spearman correlation was performed to compare standard VCM metrics (clotting time [CT], clot formation time [CFT], alpha, maximum clot firmness [MCF], clot retraction/fibrinolysis [LI30]) to the respective TEG metrics (reaction time [R], clot formation time [K], alpha, maximum amplitude [MA], clot retraction/fibrinolysis [LY30]), and also to other conventional coagulation measurements such as prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FIB), and platelet count (PLT) for each timepoint. A p-value of 0.05 was used for significance. Results: All VCM metrics significantly correlated with the respective TEG measurements (see Table 1). Both VCM and TEG show the same positive and negative correlation relationships for clot formation time, clot kinetics, and clot retraction with conventional coagulation tests (see Table 2). Additionally, clotting time and maximum clot firmness did not show moderate or significant correlation with conventional tests. Prothrombin time did not correlate with any values. Conclusion: The VCM is comparable to TEG in assessing coagulation status in heparinized swine and can be used during austere care with ECLS application. In the next round of experiments, we will validate the VCM in clinically-relevant trauma with and without ECLS.

ECMO 2022 Annual Meeting Abstracts

The proceedings contain 59 papers. The topics discussed include: transapical cannulation with a dual lumen cannula for mechanical circulatory support in cardiogenic shock;prolonged ECMO support of an adult with SARS-CoV-2 ARDS and right heart failure in a children's hospital;pushing geographical boundaries: interfacility transport and remote ECMO cannulation of patients during COVID pandemic;comparison of new viscoelastic coagulation monitor with standard of care thromboelastography for anticoagulation monitoring during 72-hour extracorporeal life support;comparison of NO metabolite levels during ex vivo extracorporeal circulation of blood using NO-eluting and NO-generating surface coatings;ex vivo evaluation of a nitric oxide catalyst surface coating for extracorporeal life support application;and practice variation in perceived optimal genetic testing across CHNC ECMO centers.

Thromboelastography Profile Is Associated with Lung Aeration Assessed by Point-of-Care Ultrasound in COVID-19 Critically Ill Patients: An Observational Retrospective Study.

Background. To evaluate relationships between lung aeration assessed by lung ultrasound (LUS) with viscoelastic profiles obtained by thromboelastography (TEG) in COVID-19 respiratory failure. Methods. Retrospective analysis in a tertiary ICU in Rome, Italy. Forty invasively ventilated adults with COVID-19 underwent LUS and TEG assessment. A simplified LUS protocol consisting in scanning six areas, three per side, was adopted. A score from 0 to 3 was assigned to each area. TEG®6s was used to obtain viscoelastic hemostatic assay parameters which were compared to LUS score. Results. There was a significant inverse correlation between LUS score and static compliance of the respiratory system (Crs, rs -0.75; p < 0.001). We found a significant association between LUS and functional fibrinogen maximum amplitude (FF-MA): among 18 patients with LUS score ≤ 12, median FF-MA was 31 mm [IQR 28-39] whilst, among 22 patients with LUS score > 12, it was 46.3 mm [IQR 40-53], p = 0.0004. Median of the citrated recalcified kaolin-activated maximum amplitude (CK-MA) was 66.1 mm [64.4-68] in the LUS score ≤ 12 group, and 69.6 [68.5-70.7] when LUS score > 12, p < 0.002. Conclusions. The hypercoagulable profile as defined by elevated FF-MA and CK-MA may be associated with a low degree of lung aeration as assessed by LUS.

"Death Diamond" Tracing on Thromboelastography as a Marker of Poor Survival After Trauma.

BACKGROUND: Improvements in health care innovations have resulted in an enhanced ability to extend patient viability. As a consequence, resources are being increasingly utilized at an unsustainable level. As we implement novel treatments, identifying futility should be a focus. The "death diamond" (DD) is a unique thrombelastography (TEG) tracing that is indicative of failure of the coagulation system, with a mortality rate exceeding 90%. The purpose of this study was to determine if the DD was a consistent marker of poor survival in a multicenter study population. We hypothesize that the DD, while an infrequent occurrence, predicts poor survival and can be used to stratify patients in whom resuscitation efforts are futile. METHODS: A retrospective multi-institutional study of trauma patients presenting with TEG DDs between 8/2008 and 12/2018 at four American College of Surgeons trauma centers was completed. Demographics, injury mechanisms, TEG results, management, and survival were examined. RESULTS: A total of 50 trauma patients presented with DD tracings, with a 94% (n = 47) mortality rate. Twenty-six (52%) patients received a repeat TEG with 10 patients re-demonstrating the DD tracing. There was 100% mortality in patients with serial DD tracings. The median use of total blood products was 18 units (interquartile range 6, 34.25) per patient. DISCUSSION: The DD is highly predictive of trauma-associated mortality. This multicenter study highlights that serial DDs may represent a possible biomarker of futility.

Clinical Characteristics and Laboratory Testing of Patients With COVID-19: A Retrospective Analysis

Objective: To explore the early warning signs of deterioration of patients with COVID-19. Methods: The data of thirty-six patients who were admitted to Handan Infectious Disease Hospital was collected. The clinical features and laboratory testing were analyzed retrospectively. The initial laboratory testing included blood chemistries, blood routine, D-dimer, coagulation function, etc. The patients were divided into mild/common group and severe/critical group. Results: The lymphocyte count, monocyte count, hemoglobin, and albumin levels in severe/critical group were lower compared with those in mild/common group, while the fibrinogen was higher. The lymphocyte count and monocyte count were positively correlated with hemoglobin, pre-albumin respectively. Conclusion: In conclusion, patients with lower initial prealbumin and hemoglobin level were more likely to progress into severe conditions. Decreased prealbumin and hemoglobin, combined with lymphocyte count and monocyte count, could be the early warning signs of deterioration of patients with COVID-19.

Fibrin Strands Will Grow from Soluble Fibrin and Hang Up in an In Vitro Microcirculatory Viscoelastic Model: Is This a Major Cause of COVID-19 Associated Coagulopathy?

Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in corona virus disease 2019 (COVID-19) associated coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill COVID-19 patients with an associated elevation of d-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes-thrombin, Factor XIIIa and plasmin-must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein, we describe a novel method illuminating aspects of this unexplored area. In addition, we created an in vitro blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing the determination of soluble fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows the determination of the SF level at which fibrin microclots begin to form.