In vitro evaluation of a new viscoelastometry-based point-of-care analyzer.

INTRODUCTION: The VCM is a point-of-care analyzer using a new viscoelastometry technique for rapid assessment of hemostasis on fresh whole blood. Its characteristics would make it suitable for use in austere environments. The purpose of this study was to evaluate the VCM in terms of repeatability, reproducibility and interanalyzer correlation, reference values in our population, correlation with standard coagulation assays and platelet count, correlation with the TEG5000 analyzer and resistance to stress conditions mimicking an austere environment. METHODS: Repeatability, reproducibility, and interanalyzer correlation were performed on quality control samples (n = 10). Reference values were determined from blood donor samples (n = 60). Correlations with standard biological assays were assessed from ICU patients (n = 30) and blood donors (n = 60) samples. Correlation with the TEG5000 was assessed from blood donor samples. Evaluation of vibration resistance was performed on blood donor (n = 5) and quality control (n = 5) samples. RESULTS: The CVs for repeatability and reproducibility ranged from 0% to 11%. Interanalyzer correlation found correlation coefficients (r2) ranging from 0.927 to 0.997. Our reference values were consistent with those provided by the manufacturer. No robust correlation was found with conventional coagulation tests. The correlation with the TEG5000 was excellent with r2 ranging from 0.75 to 0.92. Resistance to stress conditions was excellent. CONCLUSION: The VCM analyzer is a reliable, easy-to-use instrument that correlates well with the TEG5000. Despite some logistical constraints, the results suggest that it can be used in austere environments. Further studies are required before its implementation.

Temporal dynamics of in vitro hemostatic function in platelets cryopreserved using a novel approach for rapid issuance.

BACKGROUND: Current procedures for thawing and issuing of cryopreserved platelets (CPPs) are laborious and have remained challenging in emergency settings such as blood banks and military operations. In this prospective study, a novel processing method designed to facilitate the rapid issuance of CPPs with no postthaw handling required was developed and functionally characterized in parallel with standard CPPs manufactured. STUDY DESIGN AND METHODS: Double-dose plateletpheresis units (n = 42) were cryopreserved at -80°C in 5%-6% dimethyl sulfoxide to produce matched pairs thawed successively over a 27-month period for comparison between two processing arms. In contrast to the standard CPPs manufactured as standalone units, platelets were frozen in tandem with resuspending plasma in a distinct partition as a single unit in the novel method, herein referred to as tandem CPPs. Postthaw (PT) CPPs from both arms were assessed at PT0-, 12-, and 24-h to measure platelet recovery, R-time (time to clot initiation; min), and maximum amplitude (MA; clot strength; mm) using thromboelastography. RESULTS: In the overall dataset, mean platelet recovery was higher (p < .0005) for tandem CPPs (83.9%) compared with standard CPPs (73.3%) at PT0; mean R-times were faster (p < .0005) for tandem CPPs (2.5-3.6 min) compared with standard CPPs (3.0-3.8 min); mean MA was higher for tandem CPPs (57.8-59.5 mm) compared with standard CPPs (52.1-55.8 mm) at each postthaw time point (p < .05). CONCLUSION: Robust temporal dynamics of superior hemostatic functionality were established for tandem CPPs over extended cryopreservation up to 27 months and 24 h of postthaw storage.

The role of viscoelastic hemostatic assays for postpartum hemorrhage management and bedside intrapartum care.

Viscoelastic hemostatic assays are point-of-care devices that assess coagulation and fibrinolysis in whole blood samples. These technologies provide numeric and visual information of clot initiation, clot strength, and clot lysis under low-shear conditions, and have been used in a variety of clinical settings and subpopulations, including trauma, cardiac surgery, and obstetrics. Emerging data indicate that these devices are useful for detecting important coagulation defects during major postpartum hemorrhage (especially low plasma fibrinogen concentration [hypofibrinogenemia]) and informing clinical decision-making for blood product use. Data from observational studies suggest that, compared with traditional formulaic approaches to transfusion management, targeted or goal-directed transfusion approaches using data from viscoelastic hemostatic assays are associated with reduced hemorrhage-related morbidity and lower blood product requirement. Viscoelastic hemostatic assays can also be used to identify and treat coagulation defects in patients with inherited or acquired coagulation disorders, such as factor XI deficiency or immune-mediated thrombocytopenia, and to assess hemostatic profiles of patients prescribed anticoagulant medications to mitigate the risk of epidural hematoma after neuraxial anesthesia and postpartum hemorrhage after delivery.

Thromboelastography-Guided Antiplatelet Therapy for Patients with Ischemic Cerebrocardiovascular Diseases: A Systematic Review and Meta-Analysis.

INTRODUCTION: The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. METHODS: Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. RESULTS: Ten studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR: 0.45, 95% CI: 0.27-0.75, p = 0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR: 0.26, 95% CI: 0.19-0.37; p < 0.00001), ischemic events (OR: 0.28, 95% CI: 0.19-0.41; p < 0.00001), and bleeding events (OR: 0.31, 95% CI: 0.16-0.62; p = 0.0009) in patients with IS or CAD. CONCLUSION: TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.

Rotational thromboelastometry predicts future bleeding events in patients with cirrhosis.

BACKGROUND AND AIMS: Patients with cirrhosis of the liver are in a delicate state of rebalanced haemostasis and are at risk of developing both bleeding and thrombotic complications. Conventional haemostatic tests are unable to predict bleeding and thrombosis in these patients. We aimed to explore the role of Rotational Thromboelastometry (ROTEM) in predicting bleeding and thrombotic events in patients with cirrhosis. METHODS: We conducted a prospective cohort study of patients with cirrhosis at two metropolitan hospitals. All patients underwent ROTEM analysis and were then followed to record any bleeding and thrombotic events. Univariate and multivariate logistic regression analyses were performed to explore associations with bleeding and thrombotic events. RESULTS: Nineteen of the 162 patients recruited experienced a bleeding event within one year of ROTEM analysis. On univariate analysis, maximum clot firmness (MCF) using both EXTEM and INTEM tests was significantly reduced in patients who had a bleeding event, compared to those who did not (50 mm vs. 57 mm, p < 0.01 and 48 mm vs. 54 mm, p < 0.01, respectively). In addition, on univariate analysis, clotting time (CT) in the INTEM test was prolonged in the bleeding group (214 s vs. 198 s, p = 0.01). On multivariate analysis, only MCFEX was a significant predictor of bleeding events. In contrast, there was no association found between ROTEM parameters and development of thrombosis within a one-year period. CONCLUSIONS: ROTEM may provide a useful tool in predicting future bleeding events in patients with cirrhosis. Larger studies are required to further validate this finding and explore its application in clinical practice.

The Influence of Diabetes on Thrombotic Profiles and Outcomes on Patients with Peripheral Artery Disease.

BACKGROUND: Elevated glycated hemoglobin (HbA1c) is associated with vascular complications, including arterial thrombosis post-revascularization. However, the objective relationship between levels of HbA1c and coagulation profiles has not been established. This study aims to determine the association between specific coagulation parameters and variations in HbA1c in patients undergoing lower extremity revascularization. METHODS: Patients with Peripheral Artery Disease (PAD) undergoing revascularization were prospectively evaluated between December 2020 and July 2023. Patients were categorized based on their HbA1c levels, and their thromboelastography with platelet mapping (TEG-PM) results were compared at baseline, post-operatively day 1, 1 month, 3 months and 6 months. The parameters included Maximum Amplitude (MA) with both adenosine diphosphate (ADP) and arachidonic acid (AA), as well as ADP and AA percent aggregation indicating clot strength. The study further assessed the differences in these parameters between groups with varying HbA1c levels through the use of unpaired Student t test for pairwise analysis and Mann-Whitney U tests. RESULTS: Among 830 samples, those with HbA1c above 6.5 demonstrated a significant increase in ADP MA (52.6 vs. 43.5, p<0.01), AA MA (36.6 vs. 29.65, p<0.05), clot strength without platelets ActF MA (activator F: 13.10 vs. 10.80, p<0.01), and heparin neutralized uninhibited clot strength from thrombin activation HKH MA (heparinized kaolin with heparinase: 61.10 vs. 57.70, p<0.01) values at baseline. Post-operatively, patients with HbA1c levels greater than 6.5 had higher median functional fibrinogen CFF FLEV levels (citrated functional fibrinogen: 40.95 vs. 371.35, p<0.05) and higher formation of fibrin in response to stimulation of thrombin by tissue factor CFF MA values (22.90 vs. 20.40, p<0.05) when measured within 36 hours of intervention, with these trends staying consistent during the 1-month follow-up visit. The trend analysis revealed a progressive increase in ADP MA values with rising HbA1c values, indicating a unit increase in the thrombotic risk relationship. Regression analysis showed a positive relationship between HbA1c and both ADP MA (a 2.261 unit increase for each unit increase in HbA1c) and AA MA. The R-square values indicate that HbA1c only explains a small percentage of the variance in these parameters, suggesting the confounding influence of other factors contributing to thrombosis. CONCLUSION: Elevated HbA1c levels appear to be associated with pro-thrombotic tendencies in clot dynamics as measured by TEG-PM, particularly in parameters related to platelet function. HbA1c explains a limited proportion of the variability in these measures, emphasizing the need for a comprehensive approach to evaluating clotting profiles in patients. This study lays the groundwork for further investigation into personalized antithrombotic strategies for patients with varying HbA1c levels.

Intrinsic or Nonintrinsic End-stage Liver Disease and Its Association With Thromboelastography-based Coagulation States in Patients Undergoing Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Perioperative coagulation management in liver transplantation recipients is challenging. Viscoelastic testing with rotational thromboelastography (TEG) can help quantify hemostatic profiles. The current work aimed to investigate whether the etiology of end-stage liver disease, pretransplant disease severity, or pretransplant thrombotic or bleeding complications are associated with specific TEG patterns. DESIGN: Retrospective cohort study. SETTING: Single quaternary care hospital. PARTICIPANTS: A total of 1,078 adult liver transplant patients. INTERVENTIONS: The primary exposure was the etiology of end-stage liver disease classified as either intrinsic or nonintrinsic (eg, biliary obstruction or cardiovascular). Secondary exposures were patients' preoperative Model for End-Stage Liver Disease (MELD) score, Child-Pugh class, presence of major preoperative thrombotic complications, and major bleeding complications. MEASUREMENTS AND MAIN RESULTS: Patients with intrinsic liver disease (84%) showed higher odds of hypocoagulable (odds ratio [OR]: 3.70, 95% confidence interval [CI]: 1.94-7.07, p < 0.0001) and mixed TEG patterns (OR: 4.59, 95% CI: 2.07-10.16, p = 0.0002) compared with those with nonintrinsic disease. Increasing MELD scores correlated with higher odds of hypocoagulable (OR: 1.14, 95% CI: 1.08-1.19, p < 0.0001) and mixed TEG patterns (OR: 1.08, 95% CI: 1.03-1.14, p = 0.0036). Child-Pugh class C was associated with higher odds of hypocoagulable (OR: 8.55, 95% CI: 3.26-22.42, p < 0.0001) and mixed patterns (OR: 12.48, 95% CI: 3.89-40.03, p < 0.0001). Major preoperative thrombotic complications were not associated with specific TEG patterns, although an interaction with liver disease severity was observed. CONCLUSIONS: Liver transplantation candidates with intrinsic liver disease tend to exhibit hypocoagulable TEG patterns, while nonintrinsic disease is associated with hypercoagulability. Increasing end-stage liver disease severity, as evidenced by increasing MELD scores and higher Child-Pugh classification, was also associated with hypocoagulable TEG patterns.

Optimizing platelet inhibition in peripheral artery disease: A comparison of mono-antiplatelet therapy and dual-antiplatelet therapy using thromboelastography.

BACKGROUND: Antiplatelet therapy is used to prevent thrombosis in patients with peripheral artery disease (PAD) following revascularization. However, the current standard of care for these patients remains at the physician's discretion, varying from mono-antiplatelet therapy (MAPT) to dual-antiplatelet therapy (DAPT). Viscoelastic assays such as Thromboelastography with Platelet Mapping (TEG-PM) provide insight into individual coagulation profiles and measure real-time platelet function. This prospective, observational study looks at the differences in platelet function for patients on MAPT versus DAPT using TEG-PM. METHODS: Patients with PAD undergoing revascularization were prospectively evaluated between December 2020 and June 2023. TEG-PM analysis compared platelet function for patients prescribed MAPT (aspirin or clopidogrel) at the initial encounter and DAPT (aspirin and clopidogrel) at the next visit. Platelet function measured in percent inhibition was evaluated at these visits, and within-group t-tests were performed. RESULTS: Of the 195 patients enrolled, 486 samples were analyzed by TEG-PM. Sixty-four patients met the study criteria. At the initial visit, 52 patients had been prescribed aspirin, and 12 patients had been prescribed clopidogrel. For patients initially prescribed aspirin MAPT, an increase of 96.8%in the mean ADP platelet inhibition was exhibited when transitioning to DAPT [22.0% vs. 43.3%, p < .01], as well as an increase of 34.6%in the mean AA platelet inhibition when transitioning to DAPT [60.9% vs. 82.0%, p < .01]. For patients prescribed initial clopidogrel MAPT, an increase of 100% in AA platelet inhibition was exhibited on DAPT compared to the MAPT state [42.3% vs. 84.6%, p < .01]. CONCLUSIONS: Patients on DAPT showed a significant increase in platelet inhibition when compared to initial aspirin MAPT. A significant difference in AA %platelet inhibition was shown for patients on DAPT when compared to initial clopidogrel MAPT. The results show that patients may benefit from DAPT post-revascularization. Personalizing antiplatelet therapy with objective viscoelastic testing to confirm adequate treatment may be the next step in optimizing patient outcomes to reduce thrombosis in PAD patients.

Agreement between the thromboelastography reaction time parameter using fresh and citrated whole blood during extracorporeal membrane oxygenation with Teg®5000 and Teg®6s.

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.

The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure.

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-1ß, 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.

Thromboelastography versus thromboelastometry for unfractionated heparin monitoring in adult patients on extracorporeal membrane oxygenation.

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, seven of which were on veno-arterial (VA) ECMO and two of which were on veno-venous (VV) ECMO.Results: Under institutional standard operating practice, when TEG and/or activated partial thromboplastin time (aPTT) were considered therapeutic, intrinsic thromboelastometry clotting time (INTEM CT) was only 1.2 times higher than the normal range. TEG based monitoring compared to aPTT based monitoring tended to result in lower anti-Xa levels and less intensive anticoagulation. For the total cohort, bleeding events, driven by the need for blood transfusions, were more common compared to ischemic events (77% vs 11%; p = 0.02).Conclusion: INTEM CT tended to be less sensitive to lower doses of UFH with a value of 1.2 times higher than the normal range when aPTT and/or TEG were considered therapeutic. Due to the relative insensitivity of ROTEM, our institution decided to continue to use TEG instead of ROTEM. Larger, multicenter trials may be helpful to validate these findings.

Perioperative ROTEM® evaluation in a patient affected by severe VII factor deficiency undergoing microvascular decompression craniotomy for hemifacial spasm.

The potential use of TEG/ROTEM® in evaluating the bleeding risk for rare coagulation disorders needs to be assessed, considering the common mismatch among laboratory tests and the clinical manifestations. As a result, there is currently no published data on the use of viscoelastic tests to assess coagulation in FVII deficient patients undergoing elective neurosurgery. We describe the case of a patient affected by severe FVII deficiency who underwent microvascular decompression (MVD) craniotomy for hemifacial spasm (HFS). The ROTEM® did not show a significant coagulopathy according to the normal ranges, before and after the preoperative administration of the recombinant activated FVII, but a substantial reduction in EXTEM and FIBTEM Clotting Times was noted. The values of coagulation in standard tests, on the contrary, were indicative of a coagulopathy, which was corrected by the administration of replacement therapy. Whether this difference between ROTEM® and standard tests is due to the inadequacy of thromboelastographic normal ranges in this setting, or to the absence of clinically significant coagulopathy, has yet to be clarified. Neurosurgery is a typical high bleeding risk surgery; additional data is required to clarify the potential role for thromboelastographic tests in the perioperative evaluation of the FVII deficient neurosurgical patients.

Individualized antiplatelet therapy for non-cardiogenic ischemic stroke.

OBJECTIVE: This research aims to investigate the impact of individualized antiplatelet therapy guided by thromboelastography with platelet mapping (TEG-PM) on the clinical outcomes of patients with non-cardiogenic ischemic stroke. METHODS: Among a total of 1264 patients, 684 individuals diagnosed with non-cardiogenic ischemic stroke underwent TEG-PM testing. Based on the adjustment of antiplatelet medication, these patients were divided into individual and control groups. Within the individual group, in accordance with the TEG-PM test results, a Maximum amplitude (MA) value greater than 47mm was defined as high residual platelet reactivity (HRPR), while an MA value less than 31mm was defined as low residual platelet reactivity (LRPR). Patients with arachidonic acid (AA) less than 50% and adenosine diphosphate (ADP) less than 30% were classified as aspirin-resistant or clopidogrel-resistant. Treatment strategies for antiplatelet medication were subsequently adjusted accordingly, encompassing increment, decrement, or replacement of drugs. Meanwhile, the control group maintained their original medication regimen without alterations. RESULTS: The individual group included 487 patients, while the control group had 197. In the individual group, approximately 175 patients (35.9%) were treated with increased medication dosages, 89 patients (18.3%) with reduced dosages, and 223 patients (45.8%) switched medications. The results showed that the incidence rate of ischemic events in the individual group was lower than that of the control group (5.54% vs. 12.6%, P = 0.001), but no significant difference was observed in bleeding events. Cox regression analysis revealed age (hazard ratio, 1.043; 95% CI, 1.01-1.078; P = 0.011) and coronary heart disease (hazard ratio, 1.902; 95% CI, 1.147-3.153; P = 0.013) as significant risk factors for adverse events. CONCLUSION: Individualized antiplatelet therapy based on TEG-PM results can reduce the risk of ischemic events in patients with non-cardiogenic ischemic stroke without increasing the risk of bleeding events or mortality. Advanced age and coronary heart disease were identified as risk factors affecting the outcomes of individualized antiplatelet therapy.

Amplitude at 10 min in thromboelastography predicts maximum amplitude: a single-center observational study.

Thromboelastography is a quantitative test widely used to measure the efficiency of blood clotting. However, awaiting the results of maximum amplitude (MA) is necessary for determining the need for platelet- and fibrinogen-containing products. A more rapid prediction of MA could facilitate faster preparation and administration of blood transfusion products, thereby resulting in coagulation improvement. In this retrospective study, we hypothesized that early amplitude at 10 min (A10) could be a predictor of MA. Therefore, we investigated whether MA can be rapidly inferred from thromboelastographic 6 s (TEG6s) measurements and evaluated its correlation with A10. We extracted TEG6s measurements obtained in operating rooms and intensive care units of our hospital between January 2018 and December 2022. The correlation of MA with display items of TEG6s results, including reaction time, kinetics, α angle, activated clotting time, and A10, was evaluated. The relationship between citrated rapid TEG (CRT)-A10 and CRT-MA, as well as between citrated functional fibrinogen (CFF)-A10 and CFF-MA, were evaluated if A10 and MA showed a good correlation. The results showed good correlations between CRT-A10 and CRT-MA, as well as between CFF-A10 and CFF-MA. Therefore, evaluating A10 using TEG6s could predict MA.

Association of clopidogrel resistance and ABCD-GENE score with long-term clinical prognosis in patients with ischemic stroke or TIA.

BACKGROUND: Clopidogrel resistance (CR) is associated with adverse clinical outcomes in acute ischemic stroke or transient ischemic attack (TIA) patients. However, whether CR affects the long-term clinical prognosis remains to be clarified. The ABCD-GENE score is a novel risk model that identifies CR in cardiovascular disease patients; its diagnostic ability and application in ischemic stroke or TIA remain to be studied. This study aimed to investigate the diagnostic ability of the ABCD-GENE score for CR and analyze the relationship between CR and long-term clinical prognosis in patients with ischemic stroke or TIA. METHODS: From January 2018 to January 2021, 251 ischemic stroke or TIA patients who were treated with clopidogrel for more than three months after onset and maintained the medication until the follow-up time were enrolled, and platelet reactivity was detected by thromboelastography. CYP2C19 gene analysis was performed. Adverse clinical outcomes were recorded from 3months after onset. The median follow-up time was 878days. RESULTS: The prevalence of CR was 33.9%. The proportion of CYP2C19 loss-of-function carriers was 62.2%. The ABCD-GENE score≥10 was independently associated with CR (OR=1.82, 95% CI: 1.02-3.24, P=0.041), and the C-statistic value of the score (as a binary and integer variable) on CR was 0.58 and 0.63, respectively. The risk of long-term adverse clinical outcomes was not significantly different between CR and clopidogrel sensitive groups (12.94% vs. 11.44%, HR=1.22, 95% CI: 0.57-2.62, P=0.603). A similar result was observed between ABCD-GENE score≥10 and ABCD-GENE score<10 groups (10.38% vs. 12.64%, HR=1.19, 95% CI: 0.55-2.60, P=0.666). CONCLUSIONS: In ischemic stroke or TIA patients, the ABCD-GENE score could identify the risk of CR. CR was not associated with long-term adverse clinical outcomes.

Prognostic Role of Initial Thromboelastography in Emergency Department Patients with Primary Postpartum Hemorrhage: Association with Massive Transfusion.

BACKGROUND: The early prediction of the need for massive transfusions (MTs) and the preparation of blood products are essential for managing patients with primary postpartum hemorrhage (PPH). Thromboelastography (TEG) enables a thorough evaluation of coagulation status and is useful for guiding the treatment of hemorrhagic events in various diseases. We investigated the role of TEG in predicting the need for MT in patients with primary PPH. METHODS: A retrospective observational study was conducted in the emergency department (ED) of a university-affiliated, tertiary referral center between November 2015 and August 2023. TEG was performed upon admission. We defined MT as the requirement for transfusion of more than 10 units of packed red blood cells within the first 24 h. The primary outcome was the need for MT. RESULTS: Among the 184 patients with initial TEG, 34 (18.5%) required MT. Except for lysis after 30 min, the MT and non-MT groups had significantly different TEG values. Based on multivariate analysis, an angle < 60 was an independent predictor of MT (odds ratio (OR) 7.769; 95% confidence interval (CI), 2.736-22.062), along with lactate (OR, 1.674; 95% CI, 1.218-2.300) and shock index > 0.9 (OR, 4.638; 95% CI, 1.784-12.056). Alpha angle < 60 degrees indicated the need for MT with 73.5% sensitivity, 72.0% specificity, and 92.3% negative predictive value. CONCLUSIONS: Point-of-care testing of TEG has the potential to be a useful tool in accurately predicting the necessity for MT in ED patients with primary PPH at an early stage.

Constitutive hypercoagulability in pediatric sickle cell disease patients with hemoglobin SS genotype.

Background: Constitutive inflammation and hemostatic activation have been identified as key contributors to the pathophysiology of sickle cell disease (SCD), leading to clinical consequences such as vaso-occlusive crises and stroke. Patients with hemoglobin SS (HbSS) and hemoglobin SC (HbSC) genotypes are reported to have different symptoms, as do patients in steady-state and crisis situations. Differences among these groups remain unclear in pediatric patients. Objectives: To compare hemostatic activity in HbSS and HbSC pediatric patients during steady state, in crisis, and in clinical follow-up and compare HbSS and HbSC patients with normal healthy children. Methods: Whole-blood coagulation assay thromboelastography (TEG) was used to assess hemostatic activity. In parallel, flow cytometry was used to assess procoagulant surface expression of platelets and red blood cells. Results: TEG results indicated no significant differences in clotting onset (R time), clot maximum amplitude, or maximum rate of thrombus generation among steady-state, crisis, and follow-up subgroups of HbSS and HbSC patients. TEG parameters did not differ significantly between HbSC patients and healthy children, while HbSS patients showed significantly shorter R time and greater maximum amplitude and maximum rate of thrombus generation, all indicative of a constitutive hypercoagulable state. Flow cytometry results did not detect increased platelet integrin αIIbß3 activation or red blood cell procoagulant surface expression in SCD patients compared with unaffected children. Conclusion: Our results indicate that pediatric SCD patients with the HbSS genotype have constitutively activated hemostasis relative to HbSC patients and healthy children. It remains to be determined how treatments that improve clinical outcomes in SCD patients affect this constitutively hypercoagulable state.

Evaluation of coagulopathy in cirrhotic patients: A scoping review of the utility of viscoelastic testing.

BACKGROUND: Cirrhosis causes significant coagulopathy. Traditional coagulation tests may not accurately measure coagulopathy in well-compensated patients with cirrhosis. Viscoelastic tests are functional tests that may better assess coagulopathy in cirrhotic patients. METHODS: We searched PubMed, ScienceDirect, Google Scholar, and grey literature using terms meaning viscoelastic testing and cirrhosis. After reviewing over 500 titles and abstracts, 40 full-text papers met inclusion criteria. RESULTS: Twenty-two papers found viscoelastic testing was a better indicator of baseline coagulation than traditional testing in cirrhosis. Nineteen additional papers evaluated the utility of peri-procedural viscoelastic testing and found they led to a reduction in blood product administration without increasing risk of hemorrhage, thrombotic events, or other complications. CONCLUSIONS: The usage of viscoelastic testing in patients with cirrhosis allows for better assessment of coagulopathy, resulting in improved outcomes. Educating physicians to optimize care of this high-risk group is necessary to further improve their treatment.

Impact of coagulopathy assessment with thromboelastography and thromboelastometry on transfusion requirements in critically ill cirrhosis with nonvariceal bleeding: A prospective observational study.

Background: Viscoelastic tests are now routinely used for coagulopathy correction in patients with cirrhosis. Thromboelastography (TEG®) and rotational thromboelastometry (RoTEM®) are the most widely studied tests in this population. However, they have not been compared with each other in critically ill patients with liver disease presenting with nonvariceal bleed. Hence, we aimed to compare these tests for coagulopathy correction in patients with liver disease presenting with nonvariceal bleeding. Methods: Sixty adult patients with liver cirrhosis presented to the liver intensive care unit, presenting with a nonvariceal upper gastrointestinal (GI) bleed (diagnosed by doing upper GI endoscopy which revealed bleeding from a nonvariceal source) oral or nasal bleed were enrolled. The patients were allocated to the TEG® group (Group T) or RoTEM® group (Group R) depending on the immediate availability of the viscoelastic test. Coagulopathy correction was done in each group as per established protocols and the results were compared. Results: There was a significant difference in the fresh frozen plasma (FFP) transfusion between the groups. The TEG® group received more FFP when compared to the RoTEM® group (P = 0.001). Conclusion: RoTEM®-based coagulopathy correction leads to lesser use of blood products with similar control of bleeding when compared to TEG, in critically ill patients with cirrhosis.

Does the Use of Viscoelastic Hemostatic Assays for Periprocedural Hemostasis Management in Liver Disease Improve Clinical Outcomes?

Routine hemostasis parameters such as prothrombin time and fibrinogen are frequently abnormal in patients with chronic liver disease and have been demonstrated to be poor predictors for periprocedural bleeding. Alterations in procoagulant and anticoagulant factors in this population result in a state of rebalanced hemostasis, which is not reflected by routine hemostatic measures. Viscoelastic hemostatic assays (VHA) present a point of care measure of global hemostasis with an emerging role in guiding transfusion in the liver transplant setting. The potential role for VHA in guiding periprocedural transfusion is unknown. Here we critically appraise the available limited evidence on the use of VHA to guide prophylactic treatment in patients with cirrhosis undergoing procedures. We assess whether the impact of a VHA-guided approach improves clinical outcomes. Suggested areas for future research with a focus on clinically relevant outcomes, particularly periprocedural bleeding, are highlighted.