Rotational Thromboelastometry Tests Research Articles

A multi-center, double-blind, placebo-controlled, randomized, parallel-group, non-inferiority study to compare the efficacy of goal-directed tranexamic acid administration based on viscoelastic test versus preemptive tranexamic acid administration on postoperative bleeding in cardiovascular surgery (GDT trial)

BackgroundTranexamic acid (TXA) effectively attenuates hyperfibrinolysis and preemptive administration has been employed to reduce bleeding and blood transfusions in various surgical settings. However, TXA administration could be associated with adverse effects, such as seizures and thromboembolic risks. While patients with fibrinolysis shutdown showed greater thromboembolic complications and mortality, TXA administration may aggravate the degree of shutdown in these patients.Selective TXA administration based on the results of rotational thromboelastometry (ROTEM) would be non-inferior to preemptive TXA administration in reducing postoperative bleeding and beneficial in reducing its risks in patients undergoing cardiovascular surgery.MethodsThis non-inferiority, randomized, double-blind, placebo-controlled, multicenter trial will be performed in 3 tertiary university hospitals from August 2023 to March 2025. Seven hundred sixty-four patients undergoing cardiovascular surgery will be randomly allocated to get TXA as a preemptive (Group-P) or goal-directed strategy (Group-GDT) in each institution (with a 1:1 allocation ratio). After anesthesia induction, TXA (10 mg/kg and 2 mg/kg/h) and a placebo are administered after anesthesia induction in Group-P and Group-GDT, respectively. ROTEM tests are performed immediately before weaning from CPB and at the considerable bleeding post-CPB period. After getting the test results, a placebo is administered in Group-P (regardless of the test results). In Group-GDT, placebo or TXA is administered according to the results: placebo is administered if the amplitude at 10 min (A10-EXTEM) is ≥ 40 mm and lysis within 60 min (LI60-EXTEM) of EXTEM assay is ≥ 85%, or TXA (20 mg/kg) is administered if A10-EXTEM is < 40 mm or LI60-EXTEM is < 85%. The primary outcome is inter-group comparisons of postoperative bleeding (for 24 h). The secondary measures include comparisons of perioperative blood transfusion, coagulation profiles, reoperation, thromboembolic complications, seizures, in-hospital mortality, fibrinolysis phenotypes, and hospital costs.DiscussionThe absence of inter-group differences in postoperative bleeding would support the selective strategy’s non-inferiority in reducing postoperative bleeding in these patients. The possible reduction in thromboembolic risks, seizures, and fibrinolysis shutdown in Group-GDT would support its superiority in reducing TXA-induced adverse events and the cost of their management.Trial registrationThis trial was registered at ClinicalTrials.gov with the registration number NCT05806346 on March 28, 2023.Trial status: recruiting.Issue date: 2023 March 28 (by Tae-Yop Kim, MD, PhD).The trial was registered in the clinical registration on March 28, 2023 (ClinicalTrials.gov, NCT05806346) and revised to the latest version of its protocol (version no. 8, August 26, 2024) approved by the institutional review boards (IRBs) of all 3 university hospitals (Konkuk University Medical Center, 2023–07-005–001, Asan Medical Center, 2023–0248, and Samsung Medical Center, SMC 2023–06-048–002). Its recruitment was started on August 1, 2023, and will be completed on December 31, 2024.Protocol amendment number: 08 (protocol version 08, August 26, 2024).Revision chronology:2023 March 28:Original.2023 April 10:Amendment No 01. The primary reason for the amendment is the modification of Arms (adding one arm for sub-group analyses) and Interventions, Outcome Measures, Study Design, Study Description, Study Status, Eligibility, and Study Identification.2023 May 03:Amendment No 02. The primary reason for the amendment is to modify the Outcome Measures and update the study status.2023 July 06:Amendment No 03. The primary reason for amendment is to update the chronological study status.2023 July 07:Amendment No 04. The primary reason for the amendment is the modification of study information (the treatment category was changed to diagnostic, and Phase 4 was changed to not applicable) and a chronological update on the study status.2023 September 12:Amendment No 06. The primary reason for the amendment is a chronological update in the study status and the inclusion of additional information regarding contacts/locations and oversight.2023 December 29:Amendment No 07. The primary reason for the amendment is to modify the outcome measures (including detailed information on outcome measures, addition of extra secondary measures, and chronological updates in study status).2024 August 26:Amendment No 08. The primary reason for the amendment is to add detailed descriptions regarding data handling and the names and roles of the participating institutions and to update the chronological process of the trial.

Comparison of the Quantra QPlus and ROTEM Goal-Directed Transfusion Protocols in Cardiothoracic Surgery Patients: A Prospective Observational Study

To compare the designed treatment protocols for the Quantra QPlus and rotational thromboelastometry (ROTEM) with regard to transfusion advice. Prospective observational study. Maastricht University Medical Center, The Netherlands. Adults with elective cardiopulmonary bypass surgery with a ROTEM test. ROTEM tests were performed postoperatively for standard monitoring of coagulation status and clinical decision making. Simultaneously, a concurrent sample was analyzed for the Quantra QPlus. A total of 100 samples were analyzed using both the ROTEM and Quantra QPlus. Agreement between the transfusion advice for the ROTEM and Quantra QPlus protocols were compared using Cohen κ values for i.a. fibrinogen, platelet concentrates, and fresh frozen plasma (FFP). The agreement between ROTEM and Quantra QPlus was poor for overall transfusion (0.174) and fibrinogen transfusion (0.300). The agreement of cutoff values for fibrinogen clot stiffness for the Quantra QPlus and EXTEM A10 for the ROTEM was poor (0.160). The fibrinogen clot stiffness and FIBTEM A10 had a moderate agreement (0.731). A Cohen κ could not be calculated for the agreement of protamine, thrombocytes, FFP or cutoff values for these transfusions since frequencies included zero in these cases. The Quantra QPlus transfusion protocol advises transfusion in many non-bleeders, adjustments appear to be necessary. In a small group of cases in which clinically relevant blood loss was observed, the Quantra QPlus advised administration of transfusion products, whereas the ROTEM tests did not. ROTEM-guided and Quantra-guided transfusion did not correspond in this patient group, and agreement was moderate at best. Specificity and sensitivity for transfusion within protocols were heterogeneous between the methods. More clinical research in high-bleeding risk populations is needed to determine the clinical impact of the different protocols.

Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.

Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Of 44 patients analyzed, the mean age was 64years, 57% were female, and the median ICH volume was 23mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.

Prevalence and predictors of hypercoagulability detected by rotational thromboelastometry in peritoneal malignancy patients undergoing cytoreductive surgery

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment for peritoneal malignancy. A hypercoagulable state in these patients and the associated risk of venous thromboembolism (VTE), remains the most common cause of 30-day mortality. This study aimed to evaluate the prevalence and perioperative factors associated with baseline hypercoagulability detected by rotational thromboelastometry (ROTEM), a point-of-care haemostatic assay, in peritoneal malignancy patients. Methods: A retrospective cohort study was performed in a peritoneal malignancy unit on patients undergoing CRS between 2019 and 2023, who underwent preoperative ROTEM testing. Patients were divided into group A (hypercoagulable) and Group B (normal coagulation). Baseline characteristics, pathology results, operative details and post operative outcomes were reviewed. Univariate and multivariate analysis were used to identify factors associated with baseline hypercoagulability. Results: The 70 patients were included, 23 patients in group A (32.9%) and 47 patients in group B (67.1%). Group A had a lower preoperative haemoglobin (p&lt;0.001), higher platelet count (p&lt;0.001) and median peritoneal carcinomatosis index (33 vs 10, p=0.003). Appendiceal primary was associated with hypercoagulability (47.8% vs 23.4%, p=0.039). Group A required more intraoperative transfusion with red blood cells (p=0.014) but not platelets (p=0.6) or cryoprecipitate (p=0.8). Although group A had a higher incidence of VTE events (30.4% vs 23.4%) this was not statistically significant. Conclusions: Baseline hypercoagulability exists in one-third of patients with peritoneal malignancy and was associated with increased tumour burden and appendiceal primary. The increasing use of ROTEM is a valuable tool for perioperative management of complex peritoneal malignancy patients.

Abstract TP158: Baseline Viscoelastic Hemostatic Assays and Associations With Poor Long-Term Intracerebral Hemorrhage Outcomes

Introduction: Viscoelastic hemostatic assays can detect coagulopathy relevant for intracerebral hemorrhage (ICH) patients at risk for hematoma expansion. However, it is unclear whether these assays associate with long term ICH outcomes. We sought to assess whether baseline coagulopathy detectable via viscoelastic hemostatic assay associates with poor 6-month neurological outcomes after ICH. Methods: Spontaneous ICH patients enrolled in a single-center prospective observational study from 2013 to 2020 who received baseline viscoelastic hemostatic assay testing via Rotational Thromboelastometry (ROTEM) were included. Patients with prior anticoagulant use were excluded. ROTEM assessments of coagulation kinetics and clot strength were the primary exposure variables. Poor 6-month neurological outcome was defined as modified Rankin Scale (mRS) 4-6. Multivariable logistic regression analyses assessed the relationships of ROTEM parameters with 6-month outcomes after adjusting for ICH score, hemoglobin, and sex. Results: Of 44 patients included for analysis, the mean age was 64, 57% were female, 52% had deep ICH, and the median ICH volume was 23.3 mL. Poor 6-month outcome was seen in 61%. We identified that slower coagulation kinetics was associated with poor 6-month outcome as assessed in both extrinsic and intrinsic pathways (EXTEM CFT: adjusted OR 1.06, 95% CI: 1.02-1.12, p=0.02; INTEM CFT: adjusted OR 1.05, 95% CI: 1.01-1.10, p=0.05, respectively). Weaker clot strength was also associated with poor 6-month outcome (EXTEM MCF: adjusted OR 0.78, 95% CI: 0.59-0.93, p=0.03; INTEM MCF: adjusted OR 0.83, 95% CI: 0.68-0.97). We did not identify similar relationships using conventional coagulation assays (ie., PT/PTT/INR, platelet count). Conclusions: We identified that baseline impaired coagulation kinetics and weaker clot strength seen using ROTEM testing associate with poor 6-month ICH outcomes. Further work is needed to clarify the generalizability of these findings and the mechanisms driving these relationships to assess whether viscoelastic guided therapies can potentially be used to improve long-term ICH outcomes.

Precision medicine in hemostasis: a review of prothrombin complex concentrates and the role of viscoelastic tests in tailoring therapy

This review explores the role of precision medicine in the management of bleeding disorders and anticoagulation therapy, with a focus on the use of visco-elastic tests such as Thromboelastography (TEG) and Rotational Thromboelastometry (ROTEM). These tests provide real-time, dynamic insight into a patient's coagulation status, guiding the choice between three-factor prothrombin complex concentrate (PCC3) and four-factor PCC (PCC4), as well as the use of activated four-factor PCC (FEIBA). The specific ROTEM tests, INTEM and EXTEM, further enhance our understanding of the intrinsic and extrinsic coagulation pathways. Moreover, the use of tranexamic acid (TXA) and fibrinogen, guided by these visco-elastic tests, has shown promise in trauma patients. TXA has been associated with survival benefit when administered immediately or within 3 hours of injury. Fibrinogen, a key factor in clot formation, can be monitored and supplemented as needed to optimize hemostasis. In conclusion, the practice of precision medicine, with the aid of TEG and ROTEM, offers the potential to enhance the safety and efficacy of PCC therapy, TXA administration, and fibrinogen supplementation. These tools are invaluable in tailoring therapy to the specific needs of each patient, potentially optimizing patient outcomes and minimizing the risk of adverse events.

Pilot study to evaluate hypercoagulation and inflammation using rotational thromboelastometry and calprotectin in COVID-19 patients.

Abnormal coagulation and inflammation are hallmarks of SARs-COV-19. Stratifying affected patients on admission to hospital may help identify those who at are risk of developing severe disease early on. Rotational Thromboelastometry (ROTEM) is a point of care test that can be used to measure abnormal coagulation and calprotectin is a measure of inflammation. Assess if ROTEM can measure hypercoagulability on admission and identify those who will develop severe disease early on. Assess if calprotectin can measure inflammation and if there is a correlation with ROTEM and calprotectin. COVID-19 patients were recruited on admission and ROTEM testing was undertaken daily for a period of 7 days. Additionally inflammatory marker calprotectin was also tested for the same period. 33 patients were recruited to the study out of which 13 were admitted to ITU and 20 were treated on the ward. ROTEM detected a hypercoagulable state on admission but did not stratify between those admitted to a ward or escalated to ITU. Calprotectin levels were raised but there was no statistical difference (p = 0.73) between patients admitted to a ward or escalated to ITU. Significant correlations were observed between FIBA5 (r = 0.62; p<0.00), FIBCFT (r = -0.57; p<0.00), FIBMCF (r = 0.64; p<0.00) and INMCF (r = 0.57; p<0.00) and calprotectin. COVID-19 patients were hypercoagulable on admission. The correlations between ROTEM and calprotectin underline the interactions between inflammation and coagulation.

In seeking diagnostic tool for laboratory monitoring of FXII-targeting agents, could assessment of rotational thromboelastometry (ROTEM) in patients with factor XII deficiency be useful?

Introduction: Targeting factor XII (FXII) is a new concept for safe thrombosis prophylaxis. Global hemostasis tests offer promise in terms of the laboratory monitoring of FXII inhibition. The present study examines selected parameters of rotational thromboelastometry (ROTEM) in patients with FXII deficiency. The objective of this study was to assess the impact of FXII deficiency on selected parameters of ROTEM, which can be significant in the laboratory monitoring of FXII inhibition. Material and methods : The study included 20 patients with FXII deficiency ≤40% and 21 volunteers free of it. Clotting time (CT), clot formation time (CFT), alpha angle (α), maximum clot firmness (MCF), and maximum lysis (ML) were recorded in ROTEM. Results: For the INTEM test, CT and CFT readings were markedly higher in FXII deficient patients than in controls. No marked differences in relation to MCF and ML were found. Conclusion: The results of ROTEM show that FXII deficiency has a great impact on the initiation and amplification of coagulation. This was confirmed by a number of marked correlations between FXII activity and certain ROTEM parameters. ROTEM tests merit further investigation as treatment control strategies in the context of FXII inhibition.

Comparison of Jugular vs. Saphenous Blood Samples, Intrarater and In-Between Device Reliability of Clinically Used ROTEM S Parameters in Dogs.

Simple SummaryViscoelastic coagulation tests such as rotational Thromboelastometry (ROTEM) have many theoretical advantages compared to traditional coagulation testing. As a point-of-care diagnostic device, ROTEM results are directly part of treatment decisions. Therefore, it is crucial to know its reliability and precision. Most recommendations for ROTEM S analyses originate from Thromboelastography (TEG), another viscoelastic coagulation assay. However, evidence about how preanalytical and analytical factors, such as sample collection technique, sample handling and the analysis itself, influence ROTEM results is scarce. Due to the absence of a gold standard method, we assessed accuracy with the coefficient of variation and intraclass correlation coefficient and examined the influence of blood collection site, as well as intrarater and in-between device variability, on ROTEM S results of clinically healthy dogs. We found significant changes between ROTEM S parameters from different blood collection sites and significant intrarater and in-between device variability. These findings were most prominent in tissue-factor-activated tests. To ensure patient safety, we therefore suggest running duplicate measurements and to interpret results obtained from tissue-factor-activated tests with caution, since some of their coefficients of variation were moderate to high.Rotational Thromboelastometry (ROTEM) allows for the global assessment of hemostasis in whole blood samples. Preanalytical and analytical factors may influence test results, and data about the reliability and reproducibility of lyophilized ROTEM tests are scarce. Therefore, the objective of this study was to evaluate the influence of blood collection site on ROTEM S parameters and to assess intrarater and in-between device variability. A total of thirty, healthy, staff-owned dogs were included. Blood collection and ROTEM analysis were performed by trained staff according to a standardized protocol. Extrinsically activated (tissue factor; Ex-TEM S), with the addition of cytochalasin for platelet inhibition (Fib-TEM S), and intrinsically activated (In-TEM) analyses were performed. Analysis of our data showed significant variability for various Ex-TEM S and Fib-TEM S parameters from different collection sites and intrarater and in-between device measurements. We conclude that serial monitoring with ROTEM should be performed on the same device, with blood always taken from the same collection site using a standardized blood sampling technique. While In-TEM S, apart from maximum lysis, showed very stable and reliable results, we suggest interpreting especially clotting and clot formation parameters from Ex-TEM S and Fib-TEM S tests with caution and using duplicate measurements to detect outliers and to prevent initiation of incorrect therapies.

Investigation of Blood Coagulation Using Impedance Spectroscopy: Toward Innovative Biomarkers to Assess Fibrinogenesis and Clot Retraction.

This study focused on a coagulation assessment based on the novel technique of blood-impedance-magnitude measurement. With the impedance characterization of recalcified human blood, it was possible to identify two significative biomarkers (i.e., measurable indicators) related to fibrin formation (1st marker) and clot retraction (2nd marker). The confocal microscopy of clotting blood provided a complete visual analysis of all the events occurring during coagulation, validating the significance of the impedance biomarkers. By analyzing the impedance phase angle (Φ) of blood during coagulation, as well as those of the clot and serum expelled after retraction, it was possible to further clarify the origin of the 2nd marker. Finally, an impedance-magnitude analysis and a rotational thromboelastometry test (ROTEM®) were simultaneously performed on blood sampled from the same donor; the results pointed out that the 1st marker was related to clotting time. The developed technique gives rise to a comprehensive and evolutive insight into coagulation, making it possible to progressively follow the whole process in real time. Moreover, this approach allows coagulation to be tested on any materials’ surface, laying the ground for new studies related to contact coagulation, meaning, thrombosis occurring on artificial implants. In a near future, impedance spectroscopy could be employed in the material characterization of cardiovascular prostheses whose properties could be monitored in situ and/or online using effective biomarkers.

Implementation of Viscoelastic Hemostatic Assay-guided Therapy to Evaluate and Manage Trauma-related Bleeding: A Pilot Study from a Level 1 Trauma Center in Bangkok, Thailand

Objective: To evaluate the effectiveness of viscoelastic hemostatic assay (VHA)-guided therapy for assessing and managing trauma-related bleeding using a multidisciplinary team approach at a level 1 trauma center.Materials and Methods: This retrospective pilot study included trauma-related hemorrhagic patients who underwent rotational thromboelastometry (ROTEM) during September 2019-May 2020. ROTEM trace results were compared with those of conventional coagulation tests (CCT).Results: Thirteen patients (median age: 29.1 years; male: 76.92%) were included. The median (range) days of ventilator support, ICU length of stay, and hospital length of stay was 4 [0-65], 5 [1-65], and 6 [1-83], respectively. ROTEM-guided therapy was applied 26 times, and was repeated in 7 cases. Of those, four cases were repeated to correct coagulopathy. The median time-to-confirmed hemostasis for ROTEM was substantially shorter than for CCT (92 minutes [70-110] vs. 287 minutes [204-354], respectively). The coagulation results from 26 ROTEM tests were also compared between those requiring and not requiring a massive transfusion protocol (MTP). MTP with ROTEM-guided therapy was activated in 6/13 cases. Following the resuscitation endpoints in traumatic shock, four of those had their median serum lactate levels decreased from 10.9 d/L (2.1-16.8) to 3.9 d/L (1.7-17.7). ROTEM traces detected cases with low fibrinogen that only required cryoprecipitate transfusion, and red blood cell and fresh frozen plasma use was less in ROTEM than in conventional MTP.Conclusion: VHA-guided therapy was shown to effectively facilitate goal-directed hemostatic resuscitation and efficient blood product use during resuscitation, definitive treatment, and postoperative intensive care.

Evaluation of novel coagulation and platelet function assays in patients with chronic kidney disease

BackgroundHemostasis evaluation in chronic kidney disease (CKD) is critical for optimal management of thrombotic and bleeding events. Standard coagulation screens are inadequate for predicting coagulopathy in CKD. ObjectiveTo evaluate hemostasis parameters in patients with different stages of CKD using novel coagulation assays. Patients/MethodsCross‐sectional study of 30 healthy controls (HC) and 120 CKD patients (10 Stage 2, 20 Stage 3, 20 Stage 4, 20 Stage 5 not requiring renal replacement therapy, 20 transplant, 10 newly started on hemodialysis [HD], 20 established on HD). Standard laboratory tests were performed in addition to rotational thromboelastometry (ROTEM), multiple electrode aggregometry (MEA), thrombin generation assays, D‐dimer, and markers of thrombogenesis (thrombin‐antithrombin [TAT]), fibrinolysis, and endothelial activation (intercellular adhesion molecule‐1 [ICAM‐1]). ResultsD‐dimer, TAT, and ICAM‐1 concentrations were significantly higher in patients with CKD than HC (P < .01). ROTEM maximum clot firmness was significantly higher in patients than in HC (P < .01). In CKD Stage 5 patients (pre‐HD and started HD) adenosine diphosphate and thrombin receptor activating peptide MEA tests were significantly lower than HC indicating platelet aggregation defect (P < .05). Multivariate analysis confirmed the direct effect of estimated glomerular filtration rate (eGFR) in the variance of ROTEM and MEA tests. Endogenous thrombin potential and peak thrombin were not statistically different between groups, but Stage 5 CKD patients had prolonged lag time (7.91 vs. 6.33, P < .001) and time to thrombin peak (10.8 vs. 9.5, P < .05) compared to HC. ConclusionsPatients with CKD exhibit features of concomitant hypercoagulability measured by ROTEM and platelet dysfunction measured with MEA. eGFR was an independent determinant of platelet dysfunction and hypercoagulability.

Abstract WP117: Post-procedural Screening With ROTEM For Risk Of Hemorrhage Following Revascularization Therapy For Acute Ischemic Stroke

Introduction: Hyperfibrinolysis is associated with intracerebral hemorrhage (ICH) after the use of tPA for acute ischemic stroke (AIS). Point-of-care Rotational ThromboElastoMetry (ROTEM) testing may rapidly detect hyperfibrinolysis and identify AIS patients at high risk for hemorrhage. Hypothesis: Evidence of fibrinogen depletion on ROTEM will accurately predict bleeding following revascularization therapy for AIS. Methods: We reviewed medical records of AIS patients who underwent revascularization therapy between 2019-2020. All patients underwent ROTEM testing post-procedure to facilitate targeted blood product transfusion should hemorrhage occur. However, transfusion was not performed prophylactically. Repeat imaging with dual-energy CT was performed within 24 hours. A quality control registry of all AIS patients who undergo revascularization is maintained for purposes of Joint Commission certification. All variables, including ROTEM values and occurrence of intra- and extracranial hemorrhage, were entered prospectively. We examined the predictive value of a FIBTEM-A10 &lt;10mm for post-procedural hemorrhage. Results: A total of 52 patients were included. Median age was 68 years (Interquartile Range, IQR 60-83), and median admission NIHSS was 16 (IQR 10-20). Thirty-four patients (65%) received tPA, 46 (88%) received mechanical thrombectomy, and 28 (54%) received both. Median post-procedure FIBTEM-A10 was 16mm (IQR 14-22); 5 patients had values &lt;10mm. Overall, 19 (37%) suffered radiographic ICH, 5 (10%) symptomatic ICH, and 3 (6%) extracranial hemorrhage. FIBTEM-A10 &lt;10mm had sensitivity 17% and specificity 97% for any post-procedural hemorrhage. For symptomatic ICH, sensitivity was 0% and specificity 89%. Conclusions: The use of ROTEM to identify hyperfibrinolysis following AIS revascularization therapy achieved poor sensitivity and high specificity for prediction of any post-procedural hemorrhage, but was inaccurate for the prediction of symptomatic ICH.

Laboratory Approaches to Test the Function of Antiphospholipid Antibodies

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder caused by the presence of aPLs (antiphospholipid antibodies, i.e., anti-β2-glycoprotein I and anti-cardiolipin). Everyday practice in terms of laboratory diagnostics of APS includes determination of aPLs and well-known functional assays assessing for lupus anticoagulant (LA), in turn using various tests. According to recent guidelines, the recommended method for LA identification or exclusion is based on the Russell Viper Venom test and a sensitive activated partial thromboplastin time assay. Despite the fact that LA can be quantified in laboratory practice in this way, LA is still used as a binary parameter that is just one of the risk factors of thrombosis in APS. As of today, there are no other functional assays to routinely assess the risk of thrombosis in APS. It is well-known that APS patients display a wide range of clinical outcomes although they may express very similar laboratory findings. One way to solve this dilemma, could be if antibodies could be further delineated using more advanced functional tests. Therefore, we review the diagnostic approaches to test the function of aPLs. We further discuss how thrombin generation assays, and rotational thromboelastometry tests can be influenced by LA, and how experimental methods, such as flow cytometric platelet activation, surface plasmon resonance, or nano differential scanning fluorimetry can bring us closer to the puzzling interaction of aPLs with platelets as well as with their soluble protein ligand. These novel approaches may eventually enable better characterization of aPL, and also provide a better linkage to APS pathophysiology.

Rotational thromboelastometry and conventional coagulation tests in patients undergoing major cardiac or aortic surgery: a retrospective single-center cohort study

Algorithms for treatment of diffuse bleeding in cardiac surgery are based on intervention thresholds of coagulation tests, such as rotational thromboelastometry (ROTEM) or conventional laboratory tests. The relationship between these two approaches is unclear in patients with increased risk of coagulation abnormalities. We retrospectively analyzed the data of 248 patients undergoing major cardiac and/or aortic surgery. ROTEM and conventional laboratory tests were performed simultaneously after termination of cardiopulmonary bypass and protamine administration to investigate the extrinsic and intrinsic system, and to determine deficiencies in platelets and fibrinogen. We evaluated the association between ROTEM and conventional tests by linear regression analysis and compared the frequency of exceeding established thresholds for clinical intervention. Significant linear associations between ROTEM 10 min after the start of coagulation, and plasma fibrinogen concentration or platelet count (FIBTEM A10, R2 = 0.67, p < 0.001; EXTEM A10, R2 = 0.47, p < 0.001) were obtained. However, the 95% prediction intervals exceeded clinically useful ranges (92–233 mg/dL fibrinogen at the intervention threshold of FIBTEM A10 = 10 mm; 14 × 103–122 × 103/µL platelets at the intervention threshold of EXTEM A10 = 40 mm). The association between EXTEM and INR (R2 = 0.23), and INTEM and aPTT (R2 = 0.095) was poor. The frequency of exceeding intervention thresholds and, consequently, of triggering treatment, varied markedly between ROTEM and conventional tests (p < 0.001 for all comparisons). The predictability of conventional coagulation test results by ROTEM is limited, thus hampering the interchangeability of methods in clinical practice.

Determining the optimal storage time and temperature for performing platelet function assays and global hemostasis assays

Platelet function assays and global haemostasis assays are essential in diagnosing bleeding tendencies, with light transmission aggregometry (LTA) as golden standard. The Multiple Electrode Aggregation (Multiplate), platelet function assay (PFA) and rotational thromboelastometry (ROTEM) are mostly used as whole-blood screening tests. Currently, patients have to travel to specialized laboratories to undergo these tests, since specific expertise is required. Pre-analytical variables, like storage time and temperature during transport, are still considered to be the most vulnerable part of the process and may lead to discrepancies in the test results. We aim to give a first impression on the stability of blood samples from healthy volunteers during storage and investigate the effect of storage time (1, 3, 6 and 24 hours) and temperature (4°C, room temperature and 37°C) on the Multiplate, PFA, ROTEM and LTA test results. Our data indicated that, for the PFA, whole blood can be stored for 3 hours at room temperature. Whole blood used for the Multiplate and ROTEM can be stored for 6 hours of storage. For LTA, PRP and whole blood were stable up to 3 hours at 4°C or room temperature and 6 hours at room temperature, respectively.

Serial EXTEM, FIBTEM, and tPA Rotational Thromboelastometry Observations in the Maastricht Intensive Care COVID Cohort-Persistence of Hypercoagulability and Hypofibrinolysis Despite Anticoagulation.

Background: Coronavirus Disease 2019 (COVID-19) patients often present with thromboembolic events. In COVID-19 patients, routine hemostatic assays cannot correctly identify patients at risk for thromboembolic events. Viscoelastic testing with rotational thromboelastometry (ROTEM) might improve the characterization of COVID-19-associated coagulopathy.Objective: To unravel underlying coagulopathy and fibrinolysis over time as measured by serial assessment heparin-independent (FIBTEM and EXTEM) and fibrinolysis illustrating (tissue plasminogen activator; tPA) ROTEM assays.Patients/Methods: Between April 23 and June 12, consecutive adult patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included, and a comprehensive set of clinical, physiological, pharmaceutical, and laboratory variables were collected daily. Twice per week, EXTEM, FIBTEM, and tPA ROTEM were performed. Clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT) were determined to assess clot development and breakdown and were compared to routine hemostatic assays.Results: In 36 patients, 96 EXTEM/FIBTEM and 87 tPA ROTEM tests were performed during a 6-week follow-up. CT prolongation was present in 54% of EXTEM measurements, which were not matched by prothrombin time (PT) in 37%. Respectively, 81 and 99% of all EXTEM and FIBTEM MCF values were above the reference range, and median MCF remained elevated during follow-up. The ROTEM fibrinolysis parameters remained prolonged with median LOT consequently >49 min and unmeasurable LT in 56% of measurements, suggesting a severe hypofibrinolytic phenotype.Conclusion: ROTEM tests in COVID-19 ICU patients show hypercoagulability and severe hypofibrinolysis persisting over at least 6 weeks.

ROTEM in the setting of liver transplant surgery reduces frozen plasma transfusion

BackgroundINR is traditionally used as a marker of clinical coagulopathy, but is suboptimal in liver disease patients due to rebalanced hemostasis and its ineffectiveness to predict bleeding. Rotational thromboelastometry (ROTEM) testing evaluates whole blood hemostasis, which may provide more accurate assessments with the EXTEM CT parameter than INR. Thus, in end-stage liver disease (ESLD) patients, we hypothesized that elevated INRs are associated with normal EXTEM CT values. MethodsA retrospective study assessing adult (>18) patients with ESLD and elevated INRs undergoing liver transplantation, was performed to assess correlations between INR and EXTEM CT. This included patients post-ROTEM implementation where all had pre-operative ROTEM testing; and patients up to one year pre-ROTEM implementation to compare transfusion utilization. Data abstracted also included patient demographics, coagulation testing results, liver disease etiology, and MELD score. ResultsThe study included 138 patients in the post-ROTEM group and 59 patients in the pre-ROTEM group. Normal EXTEM CT was observed in 95.3 % and 93 % of patients with INR of 1.3–1.8 and up to 3 respectively. There was no correlation between INR of 1.3–1.8 and EXTEM CT (⍴ = 0.239), and only moderate correlation was observed with higher INRs (⍴ = 0.617 with INRs >1.8). ROTEM-guided transfusion in liver transplant surgeries was associated with reduced plasma transfusion (OR 0.27, 95 % CI 0.12−0.58, p = 0.001) after adjusting for red cell utilization and coagulation testing. ConclusionOur study suggests ROTEM may be advantageous for evaluating coagulopathy in patients with liver disease and ROTEM-guided transfusion reduces plasma transfusion.

Whole Blood miR-210, miR-122, miR-223 Expression Levels and Their Relationship With Iron Status Parameters and Hypercoagulability Indices in Children With Iron Deficiency Anemia.

MicroRNAs have the potential to regulate systemic and cellular iron homeostasis at multiple points. In iron deficiency anemia (IDA), hypoxia, platelet reactivity, and potentially microRNAs play a role in the development of hypercoagulability. A total of 57 children diagnosed with IDA between October 2016 and October 2017 and 48 healthy children were included in this cross-sectional study. Blood count parameters, serum iron, transferrin saturation, ferritin level, maximum clot firmness (MCF), and clot formation time index, which are indicators of hypercoagulability in rotational thromboelastometry test, of the IDA and control groups obtained in our previous study were recorded. miR-210, miR-122, and miR-223 levels were analyzed. There was no difference in the miR-210, miR-122, and miR-223 levels between the IDA and control groups. Patients with hemoglobin (Hb) <8 g/dL had higher miR-210 levels than patients with Hb>8 g/dL (P<0.05). There was a negative correlation between miR-210 and Hb and ferritin levels, a positive correlation between miR-122 and ferritin levels, and a negative correlation between miR-223 and MCF index. In IDA, there is a close relationship between the severity of anemia and miR-210, and miR-210 expression is slightly increased in those with severe anemia. miR-210 and miR-122 collectively play a role in maintaining the iron balance. The correlation between miR-223, a platelet function regulator, and the MCF index, suggested that miR-223 has a role in the development of hypercoagulability in IDA.

Minimal invasive extracorporeal circulation preserves coagulation integrity.

Coagulopathy after cardiac surgery is a serious multifactorial complication that results in postoperative bleeding requiring transfusion of red blood cells and procoagulant products. Use of cardiopulmonary bypass represents the major contributing factor affecting coagulation. We sought to prospectively investigate the effect of contemporary minimal invasive extracorporeal circulation (MiECC) on coagulation parameters using point-of-care (POC) rotational thromboelastometry and the relation to postoperative bleeding. Patients undergoing elective cardiac surgery on MiECC were prospectively recruited. Anticoagulation strategy was based on individualized heparin management and heparin level-guided protamine titration. Rotational thromboelastometry testing was performed before induction of anesthesia and after aortic cross-clamp release. A strict POC-guided transfusion protocol was implemented. The primary endpoint was the assessment of viscoelastic properties of the coagulating blood at the end of surgery compared to preoperative values and the relation to postoperative bleeding and 24-hour transfusion requirements. Fifty patients were included in the study with a significant proportion having complex surgery. Thirteen patients (26%) required blood transfusion (mean rate: 0.5 ± 1 units per patient), 5/50 (10%) received coagulation factors while no patient received fresh frozen plasma, platelets or fibrinogen. Thromboelastometry analysis showed that the major derangement was CT EXTEM > 100 seconds in 28/50 (56%) and A10 EXTEM < 40 mm in one (2%) patient without clinical significance. Platelet function was preserved throughout surgery. A10-FIBTEM was found predictive of postoperative bleeding at 12 hours. MiECC preserves clot quality throughout surgery acting in both key determinants of clot strength; fibrinogen and platelets. This is clinically translated into minimal postoperative bleeding and restricted use of blood products and coagulation factors.