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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-1β, 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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Viscoelastic coagulation monitor (VCM) is a portable device developed to evaluate the viscoelastic properties of whole blood activated by contact with glass. In this study, VCM was employed to analyze the viscoelastic profiles of 36 COVID-19 intensive care patients. Full anticoagulant dose heparin (unfractionated [UFH]; low molecular weight [LMWH]) was administrated to all patients. The association between VCM and laboratory parameters was retrospectively analyzed. The administration of UFH-influenced VCM parameters prolonging clotting time (CT) and clot formation time (CFT) and reducing angle (alpha) and amplitudes of the VCM tracings (A10, A20, and maximum clot firmness [MCF]) compared with LMWH therapy. A tendency toward hypercoagulation was observed by short CT and CFT in patients receiving LMWH. Clotting time was correlated with UFH dose (Spearman's rho = 0.48, p ≤ 0.001), and no correlation was found between CT and LMWH. All VCM tracings failed to show lysis at 30 and 45 minutes, indicating the absence of fibrinolysis. A10, A20, and MCF exhibited very-good to good diagnostic accuracy for detecting platelet count and fibrinogen above the upper reference limit of the laboratory. In conclusion, VCM provided reliable results in COVID-19 patients and was easy to perform with minimal training at the bedside., Competing Interests: Disclosure: Dr. Dalton is a consultant for Innovative ECMO Concepts. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Background: The severe inflammatory state secondary to COVID-19 leads to a severe derangement of hemostasis that has been recently described as a state of disseminated intravascular coagulation (DIC) and consumption coagulopathy, defined as decreased platelet count, increased fibrin(ogen) degradation products such as D-dimer, as well as low fibrinogen., Aims: Whole blood from 24 patients admitted at the intensive care unit because of COVID-19 was collected and evaluated with thromboelastography by the TEG point-of-care device on a single occasion and six underwent repeated measurements on two consecutive days for a total of 30 observations. Plasma was evaluated for the other parameters of hemostasis., Results: TEG parameters are consistent with a state of hypercoagulability as shown by decreased values, and increased values of K angle and MA. Platelet count was normal or increased, prothrombin time and activated partial thromboplastin time were near(normal). Fibrinogen was increased and D-dimer was dramatically increased. C-reactive protein was increased. Factor VIII and von Willebrand factor (n = 11) were increased. Antithrombin (n = 11) was marginally decreased and protein C (n = 11) was increased., Conclusion: The results of this cohort of patients with COVID-19 are not consistent with acute DIC, rather they support hypercoagulability together with a severe inflammatory state. These findings may explain the events of venous thromboembolism observed in some of these patients and support antithrombotic prophylaxis/treatment. Clinical trials are urgently needed to establish the type of drug, dosage, and optimal duration of prophylaxis., (© 2020 International Society on Thrombosis and Haemostasis.)

We evaluated the prevalence of a thromboelastography reaction time (R time) >90 min ("flat-line") reversible with heparinase during extracorporeal membrane oxygenation (ECMO). We evaluated the association between "flat-line" thromboelastography, other coagulation tests, and risk of bleeding during ECMO. Thirty-two consecutive patients on ECMO were included. Anticoagulation was provided by continuous infusion of unfractionated heparin to maintain an activated partial thromboplastin time (aPTT) ratio between 1.5 and 2.0. Activated clotting times (ACTs) thromboelastography without and with heparinase were measured. Occurrence of bleeding was recorded. Median heparin infusion rate was 16 (12-20) IU/kg/h, aPTT ratio was 1.67 (1.48-1.96), and ACT was 173 (161-184) sec. One hundred forty-five (46%) of 316 paired thromboelastography samples were "flat lines" all reversed with heparinase. Patients with "flat-line" thromboelastography received more heparin (p = 0.001) but had similar platelet count (p = 0.164) and fibrinogen level (p = 0.952) than those without. Activated partial thromboplastin time, ACT, and R time without heparinase weakly correlated between each other (Spearman correlation ≤0.36) with poor agreement (Cohen's κ ≤0.10). Major bleeding occurred in seven (22%) patients. Bleeding during ECMO was not predicted by any of the used test. In conclusion, adjusting heparin infusion to maintain aPTT ratio between 1.5 and 2.0 frequently resulted in "flat-line" thromboelastography.

Introduction: Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality., Methods: This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge., Results: UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6-13) vs 5 (4-7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93-0.98, p = 0.003)., Conclusions: Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality.