Time Course of Coagulopathy Evaluated with Rotational Thromboelastometry in Patients with Severe Coronavirus Disease 2019.

Objectives Coronavirus disease 2019 (COVID-19) reportedly causes thromboembolic complications due to coagulopathy with hypercoagulability and a hypofibrinolytic state. We evaluated the time-course of coagulopathy in patients with severe COVID-19 from admission to discharge from our intensive-care unit (ICU). Methods We conducted a retrospective study of adults with severe COVID-19 admitted to our ICU between January 20, 2021, and March 31, 2022. We obtained clinical information, laboratory data, and rotational thromboelastometry (ROTEM) parameters at admission and discharge. Results Fifteen patients were included. Fibrinogen and D-dimer values did not change significantly but were above the normal ranges at admission and discharge. Regarding ROTEM parameters, the maximum clot firmness in fibrinogen function (FIBTEM), a marker of hypercoagulability, did not change significantly but was above the normal range at admission and discharge [median (interquartile range), admission vs. discharge: 31 (25-34) mm vs. 31 (27-32) mm, p=0.589]. The maximum lysis at 60 minutes in the extrinsic coagulation pathway (EXTEM) and intrinsic coagulation pathway (INTEM), as markers of the fibrinolytic function, were both significantly lower at discharge than at admission [median (interquartile range), admission vs. discharge: EXTEM, 3 (2-4) vs. 1 (0-2), p=0.011; INTEM, 3 (1-6) vs. 1 (0-2), p=0.008]. Conclusion This study revealed a persistent hypercoagulable state at ICU discharge and a worse hypofibrinolytic state at discharge than at admission. These results may contribute to a better understanding of coagulopathies in the acute to subacute phases of severe COVID-19.

The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition.

There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.

Green Plasma Has a Superior Hemostatic Profile Compared With Standard Color Plasma.

BACKGROUND: Limitations in available donors have dramatically reduced plasma availability over the past several decades, concurrent with increasing demand for some types of plasma. Plasma from female donors who are pregnant or taking oral contraceptives often has a green appearance, which frequently results in these units being discarded. This pilot study aimed to evaluate the hemostatic potential of green compared to standard-color plasma. MATERIALS AND METHODS: Plasma from twelve blood group-matched female and twelve male donors was obtained from the local blood center. Six of the female and all of the male units of plasma had a normal appearance (STANDARD), while six of the female units were grossly green (GREEN). The hemostatic potential was evaluated by thrombelastography (TEG), calibrated automated thrombogram (CAT), and coagulation factor level measurements. Univariate analysis was performed using Wilcoxon Rank-Sum. RESULTS: GREEN plasma was more procoagulant for all TEG values (r-value, k-time, angle, mA) when compared to STANDARD plasma. Differences were also observed in coagulation factor levels, with GREEN plasma having higher than STANDARD (factors II; VII, IX; X, XI, Protein S, and plasminogen); conversely, GREEN plasma had a longer lag time in CAT. DISCUSSION: This pilot study demonstrates that female donors with green plasma have a superior hemostatic profile than standard plasma. GREEN plasma should be further investigated for its safety profile and hemostatic potential, so if it is found to be a safe and functionally non-inferior product, it should be actively re-introduced for transfusion in bleeding patients.

"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.

Persistence of procoagulable thromboelastography results in hospitalized COVID-19 patients despite clinical improvement.

OBJECTIVE: COVID-19 patients have been shown to be hypercoagulable, increasing the risk for thromboembolic events. The kinetics of the blood coagulation process were monitored daily throughout hospitalization in COVID-19 positive patients. PATIENTS AND METHODS: Thromboelastography (TEG) was used to assess blood coagulation in 48 adult patients hospitalized for COVID-19 in this prospective cohort study. Clinical risk was assessed via National Early Warning Scores (NEWS) for each day of hospitalization. RESULTS: During hospitalization, 98% of patients had one or more procoagulable TEG result. Thromboelastography results remained prothrombotic upon discharge in 80% of patients. NEWS significantly decreased by discharge compared to the peak scores. CONCLUSIONS: Overall, patients were discharged from the hospital with significant clinical improvement, but without abnormal TEG results returning to a normal range. All patients in our study survived and few had thromboembolic events, so if and for how long these patients remain at risk for future complications warrants further investigation.

The Value of Thromboelastography (TEG) in COVID-19 Critical Illness as Illustrated by a Case Series.

OBJECTIVE: To develop a practical thromboelastograph guided (TEG) anticoagulation protocol to guide the management of COVID-19 critically ill patients. DESIGN: An inter disciplinary team reviewed the current literature on hypercoagulability in critically ill COVID-19 patients, clinical management practices and challenges with high rates of thrombotic events despite anticoagulant therapies. SETTING: The largest tertiary care hospital within the Northwell Health System in New York. PATIENTS: COVID-19 invasively mechanically ventilated patients in Medical Intensive Care Unit Settings. METHODS: TEG was monitored in critically ill COVID-19 patients. Patterns were reviewed to guide the development of a treatment protocol leveraging TEG parameters to select anticoagulant therapy. Three patients are reported to highlight TEG profiles that led to the development of the algorithm. Clinical trajectory and treatment decisions were extracted retrospectively from the Electronic Health Record, with input from the intensivists. Anticoagulant use, laboratory and TEG values, and venous/arterial lower extremity (LE) ultrasound results were recorded. MAIN RESULTS: These patients demonstrated hypercoagulable TEG results despite prophylactic or therapeutic dosages of unfractionated heparin or low-molecular-weight heparin (LMHW). TEG surveillance identified functional fibrinogen and maximum amplitude in high-risk patients with hyper inflammatory markers. Anticoagulation assessment, TEG parameters, and LE ultrasound monitoring for venous and arterial thrombus were used to construct an algorithm to guide and escalate anticoagulant therapy. CONCLUSIONS: TEG provides patient-specific evidence for a hypercoagulable state in patients receiving all types of anticoagulant therapy. The proposed TEG algorithm guides anticoagulation management decisions to maintain or escalate anticoagulant dose and/or change choice of anticoagulant. A TEG algorithm may help negotiate the potential harm/benefit balance of full-dose anticoagulation in critically ill COVID-19 patients, by allowing for a more individualized approach that goes beyond the review of activated partial thromboplastin time (aPTT) levels.

Rotational thromboelastometry reduces blood loss and blood product usage after lung transplantation.

BACKGROUND: The shortage of blood products has become a worldwide problem, especially during the COVID-19 Pandemic. Here, we investigated whether a point of care (POC) approach to perioperative bleeding and coagulopathy based on rotational thromboelastometry (ROTEM) results could decrease perioperative blood loss and the perioperative consumption of blood products during lung transplantation. METHODS: Patients undergoing bilateral lung transplantation were randomized into two groups: In the first group, designated the "non POC" group, the management of perioperative bleeding and coagulopathy was based on the clinical experience of the anesthesiologist; in the second group, designated the "POC" group, the management of perioperative bleeding, and coagulopathy was based on the ROTEM results. RESULTS: After performing an interim statistical analysis, the project was prematurely terminated as the results were significantly in favor of the POC approach. Data were analyzed for the period January 2018 until June 2020 when 67 patients were recruited into the study. There was significantly decreased perioperative blood loss in the POC group (n = 31 patients) with p = 0.013, decreased perioperative consumption of RBC with p = 0.009, and decreased perioperative consumption of fresh frozen plasma with p < 0.0001 (practically no fresh frozen plasma was used in the POC group) without deteriorating clot formation in secondary and primary hemostasis as compared to the non POC group (n = 36). CONCLUSION: POC management of perioperative bleeding and coagulopathy based on ROTEM results is a promising strategy to decrease perioperative blood loss and the consumption of blood products in lung transplantation.

Hypercoagulable viscoelastic blood clot characteristics in critically ill coronavirus disease 2019 patients and associations with thrombotic complications.

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients have frequent thrombotic complications and laboratory evidence of hypercoagulability. The relationship of coagulation tests and thrombosis requires investigation to identify best diagnostic and treatment approaches. We assessed for hypercoagulable characteristics in critically ill COVID-19 patients using rotational thromboelastometry (ROTEM) and explored relationships of D-dimer and ROTEM measurements with thrombotic complications. METHODS: Critically ill adult COVID-19 patients receiving ROTEM testing between March and April 2020 were analyzed. Patients receiving therapeutic anticoagulation before ROTEM were excluded. Rotational thromboelastometry measurements from COVID-19 patients were compared with non-COVID-19 patients matched by age, sex, and body mass index. Intergroup differences in ROTEM measurements were assessed using t tests. Correlations of D-dimer levels to ROTEM measurements were assessed in COVID-19 patients who had available concurrent testing. Intergroup differences of D-dimer and ROTEM measurements were explored in COVID-19 patients with and without thrombosis. RESULTS: Of 30 COVID-19 patients receiving ROTEM, we identified hypercoagulability from elevated fibrinogen compared with non-COVID-19 patients (fibrinogen assay maximum clot firmness [MCF], 47 ± 13 mm vs. 20 ± 7 mm; mean intergroup difference, 27.4 mm; 95% confidence interval [CI], 22.1-32.7 mm; p < 0.0001). In our COVID-19 cohort, thrombotic complications were identified in 33%. In COVID-19 patients developing thrombotic complications, we identified higher D-dimer levels (17.5 ± 4.3 µg/mL vs. 8.0 ± 6.3 µg/mL; mean difference, 9.5 µg/mL; 95% CI, 13.9-5.1; p < 0.0001) but lower fibrinogen assay MCF (39.7 ± 10.8 mm vs. 50.1 ± 12.0 mm; mean difference, -11.2 mm; 95% CI, -2.1 to -20.2; p = 0.02) compared with patients without thrombosis. We identified negative correlations of D-dimer levels and ROTEM MCF in these patients (r = -0.61; p = 0.001). CONCLUSION: We identified elevated D-dimer levels and hypercoagulable blood clot characteristics from increased fibrinogen on ROTEM testing in critically ill COVID-19 patients. However, we identified lower, albeit still hypercoagulable, ROTEM measurements of fibrinogen in COVID-19 patients with thrombotic complications compared with those without. Further work is required to externally validate these findings and to investigate the mechanistic drivers for these relationships to identify best diagnostic and treatment approaches for these patients. LEVEL OF EVIDENCE: Epidemiologic, level IV.

Viscoelastic Coagulation Monitor as a Novel Device to Assess Coagulation at the Bedside. A Single-Center Experience During the COVID-19 Pandemic.

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.

The role of rotational thromboelastometry during the COVID-19 pandemic: a narrative review.

The coronavirus disease 2019 (COVID-19) pandemic is currently recognized as a global health crisis. This viral infection is frequently associated with hypercoagulability, with a high incidence of thromboembolic complications that can be fatal. In many situations, the standard coagulation tests (SCT) fail to detect this state of hypercoagulability in patients with COVID-19 since clotting times are either not or only mildly affected. The role of viscoelastic tests such as rotational thromboelastometry (ROTEM®) during this pandemic is explored in this review. COVID-19-associated coagulopathy, as measured using the rotational thromboelastometry parameters, can vary from hypercoagulability due to increased fibrin polymerization and decreased fibrinolysis to bleeding from hypocoagulability. The use of a multimodal diagnostic and monitoring approach, including both rotational thromboelastometry and SCT, such as plasma fibrinogen and D-dimer concentrations, is recommended. Rotational thromboelastometry provides comprehensive information about the full coagulation status of each patient and detects individual variations. Since COVID-19-associated coagulopathy is a very dynamic process, the phenotype can change during the course of infection and in response to anticoagulation therapy. Data from published literature provide evidence that the combination of rotational thromboelastometry and SCT analysis is helpful in detecting hemostasis issues, guiding anticoagulant therapy, and improving outcomes in COVID-19 patients. However, more research is needed to develop evidence-based guidelines and protocols.

Coagulation profile of COVID-19 patients admitted to the ICU: An exploratory study.

BACKGROUND: Coagulation abnormalities in COVID-19 patients have not been addressed in depth. OBJECTIVE: To perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19. METHODS: Conventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10. RESULTS: Thirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM-FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ​​than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability. CONCLUSION: COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system.

Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis.

BACKGROUND: There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required. METHODS: We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients. RESULTS: Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction. CONCLUSIONS: The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.

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.

Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients.

PURPOSE: The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients. MATERIAL AND METHODS: We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75-100 IU/kg subcutaneously). RESULTS: Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity. CONCLUSIONS: Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.

Evaluation of coagulation status using viscoelastic testing in intensive care patients with coronavirus disease 2019 (COVID-19): An observational point prevalence cohort study.

BACKGROUND: Coronavirus Disease-19 (COVID-19) is associated with a high rate of thrombosis, the pathophysiology of which is not well defined. Viscoelastic testing may identify and characterise hypercoagulable states which are not apparent using conventional coagulation assays. OBJECTIVES: The objective of this study was to undertake viscoelastic evaluation of the coagulation state in critically ill adults with COVID-19-associated respiratory failure METHODS: This was a single-centre observational point prevalence cohort study of adults with COVID-19-associated respiratory failure requiring respiratory support in the intensive care unit. Coagulation status was evaluated using rotational thromboelastometry (ROTEM®) in conjunction with laboratory markers of coagulation. RESULTS: Six patients fulfilled inclusion criteria. Each patient had one ROTEM® performed. All patients had supranormal clot amplitude at 10 min (A10) and supranormal clot firmness (maximal clot firmness) measured in at least one ROTEM® pathway, and five were supranormal on all pathways. Minimal clot lysis was present on all analyses. Fibrinogen and D-dimer were elevated and routine markers of coagulation within normal ranges in all patients. CONCLUSION: Patients with COVID-19-associated respiratory failure admitted to the intensive care unit exhibit a hypercoagulable state which is not appreciable on conventional tests of coagulation. Supranormal clot firmness, minimal fibrinolysis, and hyperfibrinogenaemia are key findings. Further research is required into the pathophysiology of this hypercoagulable state, as well as the harms and benefits of different anticoagulation strategies.

Hyper- and hypocoagulability in COVID-19 as assessed by thromboelastometry -two case reports.

BACKGROUND: Coronavirus disease (COVID-19)-associated coagulopathy is most often characterized by elevated D-dimer, interleukin-6, and plasma fibrinogen concentrations as well as hypercoagulability in thromboelastometry with increased clot firmness in the EXTEM, INTEM, and FIBTEM assays. Clinically, it manifests with a very high incidence of thrombosis, particularly in the pulmonary system, whereas bleeding complications are infrequent. CASE: Here, we describe two critically ill patients with COVID-19 admitted to our intensive care unit demonstrating different thromboelastometry and biomarker patterns. One patient presented with hypercoagulability and the other patient with hypocoagulability and fibrinolysis shutdown in thromboelastometry. The pathophysiology and the potential impact on treatment options are discussed. CONCLUSIONS: A combination of biomarkers and thromboelastometry results can be helpful in the future to decide which therapeutic strategy might be most appropriate for critically ill patients with COVID-19. This would be an important step to establish precision medicine in this high-risk patient population.