Rotational Thromboelastometry Parameters Research Articles

Hypocoagulability in severe yellow fever infection is associated with bleeding: results from a cohort study

BackgroundSevere yellow fever infection (YFI) may be complicated by a hemorrhagic diathesis. However, the hemostasis profile of YFI has rarely been reported. ObjectivesThe aim of this study was to characterize the hemostatic features of YFI by using a rotational thromboelastometry (ROTEM). MethodsWe evaluated clinical, laboratory, and ROTEM parameters in adults with severe YFI and their correlation with hemostatic variables according to bleeding and death. ResultsA total of 35 patients were included (median age, 49 years). ROTEM was performed in 22 patients, of whom 21 (96%) presented bleeding and 4 (18%) died. All patients who died had major bleeding. Patients who died presented prolonged clotting time (CT; median, 2326 minutes; IQR, 1898-2986 minutes) and reduced alpha angle (median, 12°; IQR, 12°-15°) in comparison with patients who had minor (median CT, 644 minutes; IQR, 552-845 minutes and alpha angle, 47°; IQR, 28°-65°) and major (median CT, 719 minutes; IQR, 368-1114 minutes and alpha angle, 43°; IQR, 32°-64°) bleeding who survived. In patients who had bleeding, CT showed a strong negative correlation with factor (F)V (r = −.68), FIX (r = −.84), and FX (r = −.63) as well as alpha angle showed a strong negative correlation with FIX (r = −.92). In patients who died, the correlations were even stronger. A total of 19/21 (90%) patients presented hypocoagulability assessed by ROTEM. ConclusionHypocoagulabitity is the hallmark of the bleeding diathesis of severe YFI. Abnormal CT and alpha angle associated with death and could be used as potential predictors of adverse outcome in severe YFI.

Rotational Thromboelastometry as a Diagnostic Tool for Persistent Infection in Two-Stage Exchange Arthroplasty.

Background/Objectives: There is a lack of reliable biomarkers for diagnosis of infection eradication prior to second-stage reimplantation in two-stage exchange arthroplasty for periprosthetic joint infections (PJIs). The aim of this study was to assess the diagnostic accuracy of rotational thromboelastometry (ROTEM) for persistent infection in two-stage exchange arthroplasties. Methods: A pilot, retrospective analysis was performed including 70 patients who underwent a two-stage exchange arthroplasty for PJI. They were categorized as patients without (n = 64) or patients with persistent infection (n = 6) prior to reimplantation. Definition of persistent infection prior to reimplantation was based on the 2018 ICM criteria. Conventional coagulation biomarkers and ROTEM parameters were compared between groups. Results: Higher FIBTEM MCF values were associated with persistent infection (odds ratio [OR], 1.30, 95% confidence interval [CI], 1.04-1.63; p = 0.020), and FIBTEM MCF had the highest diagnostic accuracy for persistent infection prior to second-stage reimplantation (AUC, 0.907; 95% CI, 0.812-1.000). A cut-off value ≥ 18 mm for FIBTEM MCF was found to have 100.0% sensitivity and 73.4% specificity for diagnosing persistent infection prior to second-stage reimplantation. Moreover, the diagnostic accuracy of FIBTEM MCF was higher than that of fibrinogen levels (p = 0.036) and D-dimer (p = 0.006). Conclusions: Our findings indicate that ROTEM parameters have the potential to identify persistent infections before reimplantation in two-stage exchange arthroplasties for PJI. Such coagulation biomarkers could provide guidance regarding the optimal timing for reimplantation. Further studies in larger populations are warranted to validate the diagnostic accuracy of ROTEM parameters for persistent PJI.

Increased blood coagulation is associated with poor neurological outcome in aneurysmal subarachnoid hemorrhage

Background and purposePatients with aneurysmal subarachnoid hemorrhage (aSAH) have demonstrated increased blood coagulation which is thought to contribute to delayed cerebral ischemia (DCI) and to a worse outcome. Therefore, we sought to determine whether this increased blood coagulation, detectable with rotational thromboelastometry (ROTEM), was associated with DCI and neurological outcome. MethodsWe conducted a prospective observational study of 60 consecutive adult aSAH patients. ROTEM's EXTEM and FIBTEM assays and D-dimer were analyzed at admission and post-bleed days (PBDs) 2–3, 4–5, 7–8, and 11–12. ROTEM's clot formation time (CFT) represents the stabilization of the clot, and the maximum clot firmness (MCF) the maximum clot strength. Glasgow Outcome Scale extended (GOSe) at three months determined the neurological outcome. ResultsDCI incidence was 41.7%. EXTEM-CFT was significantly shorter in patients with unfavorable neurological outcome (GOSe 1–4) on PBDs 4–5 and 7–8, p < 0.05, respectively. FIBTEM-MCF was significantly higher in patients with unfavorable neurological outcomes on PBD 4–5 (p < 0.05), PBD 7–8 (p < 0.05), and PBD 11–12 (p < 0.05). EXTEM-CFT decreased, and FIBTEM-MCF rose during the study period in all patients. Patients with unfavorable neurological outcome had a higher D-dimer at all studied time points, p < 0.05. No difference was found in the ROTEM parameters or D-dimer when assessing patients with and without DCI. ConclusionsPatients were in a state of increased blood coagulation after aSAH, with those with unfavorable neurological outcome being more coagulable than those with favorable outcome. However, increased blood coagulation was not associated with DCI.ClinicalTrials.gov, NCT03985176

Rotational Thromboelastometry and Clot Waveform Analysis as Point-of-Care Tests for Diagnosis of Disseminated Intravascular Coagulation in Critically Ill Children in Thailand.

This study aimed to determine the test performances of rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-based clot waveform analysis (aPTT-CWA) compared with the International Society on Thrombosis and Hemostasis disseminated intravascular coagulation (ISTH-DIC) score for diagnosis of overt disseminated intravascular coagulation (ODIC) in critically ill children. Prognostic indicators of DIC complications were also evaluated. A prospective cross-sectional observational study was conducted. ROTEM and aPTT-CWA were assessed alongside standard parameters based on the ISTH-DIC score and natural anticoagulants. Both conventional and global hemostatic tests were repeated on days 3-5 for nonovert DIC. PICU of the Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Infants and children who were admitted to PICU with underlying diseases predisposed to DIC, such as sepsis, malignancy, major surgery, trauma, or severe illness, were included in the study between July 1, 2021, and November 30, 2022. None. Sixty-four children were enrolled in this study. The prevalence of ODIC was 20.3%. Regarding ROTEM parameters, using EXTEM clot formation time (CFT) cutoff of greater than 102 seconds provided sensitivity and specificity of 90.9% and 80.9%, respectively, for diagnosing ODIC, with the area under the curve (AUC) of 0.86. In the case of aPTT-CWA performance, no biphasic waveform was observed, whereas both maximum coagulation acceleration (Min2) of less than 0.35%/s 2 and maximum coagulation deceleration of less than 0.25%/s 2 demonstrated identical sensitivities of 76.9% and specificities of 79.6%. Combining two global hemostatic tests significantly improved the diagnostic performance (INTEM CFT + EXTEM CFT + Min2 AUC 0.92 [95% CI, 0.80-1.00] vs. EXTEM CFT AUC 0.86 [95% CI, 0.75-0.96], p = 0.034). Bleeding was the most common consequence. In multivariable logistic regression analysis, Min2 of less than 0.36%/s 2 was an independent risk factor for bleeding complications, with an adjusted odds ratio of 15.08 (95% CI, 1.08-211.15, p = 0.044). ROTEM and aPTT-CWA were valuable diagnostic tools in critically ill children who might require point-of-care tests. Min2 showed significant clinical implications for predicting bleeding events in this population.

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.

P204 Utility of Rotational Thrombo-Elastometry as an Objective Measure of Hypercoagulability in Patients with Ulcerative Colitis-A Prospective Case Control Study

Abstract Background Inflammatory bowel disease (IBD) has an increased risk of venous thromboembolism (VTE) with factors like hospitalization and surgery increasing this risk. Although few recent guidelines recommend anticoagulation thromboprophylaxis for hospitalised IBD patients, there is wide variation in reported practices for VTE prophylaxis. This study was aimed to evaluate Rotational Thrombo-Elastometry (ROTEM) for assessing blood coagulation status in ulcerative colitis (UC) and to evaluate the relationship between ROTEM, disease severity and response to treatment. Methods This was a prospective age- and sex-matched study with 60 patients each in UC and irritable bowel syndrome (IBS) groups, latter being controls. Clinical details, blood investigations including ROTEM and D-dimer were collected and analysed after taking informed consent. Hypercoagulable state was defined using Kaufmann’s classification. ROTEM parameters [clotting time (CT), clot formation time (CFT), alpha angle (AA), maximum clot firmness (MCF), maximum lysis (ML)] and D-dimer levels were compared between the two groups. Results Of the 60 UC patients (age: 38.6±11.64 years, 44 males); 15(25%) were in remission, 18(30%), 17(28.3%) and 10(16.7%) had mild, moderate, and severe disease respectively. The UC group had significantly more hypercoagulable ROTEM than the control group (66.7% vs. 36.7%, p=0.001). Hypercoagulable ROTEM was found in 9(60%), 8(44.4%), 14(82.3%) and 9(90%) of those in remission, with mild, moderate and severe UC respectively. Compared to controls; CT [292.36±70.45 vs 337.56±77.89, p=0.001], CFT [103.15±30.31 vs 128.61±40.18, p=0.0001], AA [69.88±5.19 vs 65.36±6.4, p=0.00004], MCF [65.75±5.64 vs 63.25±4.43, p=0.008] and D-dimer levels [329(63-2358) vs 145.5(54-1304), p=0.00001) were significantly abnormal in UC group. Among UC patients with mild, moderate and severe disease; only CFT, AA and D-dimer were significantly different between the groups. There was no significant difference in ROTEM values and D-dimer level in patients with severe UC after one week of treatment. On univariate analysis; partial Mayo score [OR: 1.49, 95% CI: 1.04-2.12, p=0.028], serum albumin [OR: 0.32, 95% CI: 0.10-0.98, p=0.04], hemoglobin [OR: 0.59, 95% CI: 0.40-0.86, p=0.007], and platelets [OR: 1, 95% CI: 1.01-1.02, p=0.035], were predictors of hypercoagulable state in active UC. On multivariate analysis; only haemoglobin [OR: 0.61, 95% CI: 0.38-0.98, p=0.04] was found to be significant independent predictor. Conclusion UC patients had hypercoagulable ROTEM regardless of activity of inflammatory process. The degree of hypercoagulability increased with disease activity. Low haemoglobin was found to predictive of hypercoagulable state in active UC patients.

Diagnostic value of clot formation parameters determined by rotational thromboelastometry in 63 patients with congenital dysfibrinogenemia.

Rotational thromboelastometry (ROTEM) is a global hemostasis assay. The diagnosis added value of ROTEM in congenital dysfibrinogenemia remains to be established. The aim of this study was to analyze clot formation by ROTEM in a cohort of dysfibrinogenemic patients and to establish correlations with genotype, clinical features, and coagulation parameters. The study included genetically confirmed congenital dysfibrinogenemia cases (n = 63) and healthy controls ( n = 50). EXTEM, INTEM, FIBTEM tests were used to measure ROTEM parameters, that is, clotting time (CT), clot formation time (CFT), maximal clot firmness (MCF) and amplitude 10 min after CT (A10). The ISTH bleeding assessment tool was used to determine bleeding episodes. CT (INTEM) was statistically significantly shorter in congenital dysfibrinogenemia patients compared to controls while CFT (EXTEM) was prolonged. Patients's MCF in EXTEM, INTEM, and FIBTEM were similar to controls while A10 (FIBTEM) was statistically significantly lower. Fibrinogen activity was positively correlated with fibrinogen antigen, A10 and MCF in all three assays. Bleeding phenotypes were observed in 23 (36.5%) patients. Only CFT in EXTEM and CT in INTEM were statistically different in patients with bleeding phenotype versus controls. Carriers of the FGA mutation p.Arg35His had a CT (EXTEM) slightly prolonged and a reduced A10 (FIBTEM) compared to controls. Some ROTEM parameters were able to distinguish congenital dysfibrinogenemia patients from controls, and patients with a bleeding phenotype. Prolonged CFT in EXTEM were associated with congenital dysfibrinogenemia and bleeding phenotype. Bleeding episodes in most patients were generally mild and prevalence of thrombosis was very low.

Group B or not group B? An association between ABO, early mortality, and organ dysfunction in major trauma patients with shock

BackgroundABO blood group alters coagulation profiles in the general population and may influence outcomes after trauma. The relationship between trauma-induced coagulopathy, severe injury with hemorrhagic shock, and survival with respect to ABO group is unknown. ObjectivesIn severe hemorrhagic trauma, we aimed to characterize the association of ABO group with admission coagulation profiles, mortality, and immune-mediated complications. MethodsClinical and laboratory variables were examined from severely injured adult patients enrolled in a perpetual observational cohort study at a UK Major Trauma Center. Univariate and multivariate analyses were performed to determine differences in clinical outcomes (mortality, organ dysfunction, and critical care support). In a shock subgroup, we performed an exploratory analysis of rotational thromboelastometry parameters and coagulation biomarkers. ResultsIn 1119 trauma patients, we found no difference in mortality between ABO groups. In patients with shock, 24-hour mortality was significantly lower in group B vs non-B groups (7% vs 16%, adjusted odds ratio [aOR], 0.19; P = .030), but there were increased rates of invasive ventilation (aOR, 3.34; P = .033), renal replacement therapy (aOR, 2.55; P = .037), and a trend for infection (aOR, 1.85; P = .067). Comparing patients with shock, group B vs non-B patients had 40% higher fibrinogen, 65% higher factor (F) VIII, 36% higher FIX, 20% higher FXIII, and 19% higher von Willebrand factor. ConclusionIn this observational study limited by single time-point sampling and subgroup analysis of trauma hemorrhage with shock, group B patients have enhanced hemostatic capability associated with early survival but with increased risk of immune-mediated complications.

Exploration of rotational thromboelastometry (ROTEM) to characterize the coagulation profiles of newly diagnosed pediatric leukemia patients

BackgroundViscoelastic testing has been used in adult hematologic malignancies in conjunction with conventional coagulation tests (CCTs) to predict coagulopathies and tailor blood product replacement. However, there is a paucity of similar pediatric studies. ObjectivesAnalyze and correlate leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCT’s and Rotational Thromboelastometry (ROTEM). MethodsPediatric patients with newly diagnosed acute leukemia underwent testing with ROTEM and CCTs on days 0, 15 and 29 of induction chemotherapy. ResultsSixty-two patients were enrolled. At presentation, 54.8 % of patients had platelets <50 K/μL, 73 % had prolonged PT, 1.6 % had fibrinogen <150 mg/dL. Fifteen patients (24.2 %) had WHO grade 1 bleeding and two patients (3 %) had WHO grade 4 bleeding. EXTEM/INTEM values at presentation (day 0) reflected hypocoagulability, however FIBTEM revealed hypercoagulability. Patients showed a progressive hypocoagulability in all ROTEM assays by day 15 (day 0 vs day 15, p < 0.001), with improvement by day 29 (day 15 vs day 29, p < 0.001). Day 0 ROTEM parameters were comparable to day 29. Fibrinogen strongly correlated with ROTEM at all three time points (p < 0.0001), along with platelet count with moderate correlations (p < 0.001). ConclusionFibrinogen and platelets appear to be the drivers of leukemia associated coagulopathy in the pediatric population, suggesting the utility of using CCTs and ROTEM in this population to better evaluate hemostatic function and guide blood product replacement.

A combination of clot formation abnormalities in thromboelastometry has a high prognostic value in patients with acute-on-chronic liver failure.

Global coagulation tests offer a better tool to assess procoagulant and anticoagulant pathways, fibrinolysis and clot firmness and evaluate more accurately coagulation defects compared to conventional coagulation tests. Their prognostic role in acute-on-chronic liver disease (ACLF) or acute decompensation (AD) has not been well established. To assess the properties and prognostic value of the coagulation profile measured by rotational thromboelastometry (ROTEM) in ACLF and AD. 84 consecutive patients (35 ACLF and 49 AD) were prospectively studied. Twenty healthy persons matched for age and gender were used as controls. 'Hypocoagulable' or 'hypercoagulable' profiles on admission were assessed based on nine ROTEM parameters and mortality was recorded at 30 and 90 days. Individual ROTEM parameters denoted significantly more hypocoagulability in patients compared to controls. 'Hypocoagulable' profile (defined as a composite of 4 or more ROTEM parameters outside the range) was associated with more severe liver disease assessed either as MELD or Child-Pugh scores ( P < 0.001 for both) and higher 30-day mortality (Log-rank P = 0.012). 'Hypocoagulable' profile (HR 3.160, 95% CI 1.003-9.957, P = 0.049) and ACLF status (HR 23.786, 95% CI 3.115-181.614, P = 0.002) were independent predictors of 30-day mortality, in multivariate model. A higher early mortality rate was shown in ACLF patients with 'hypocoagulable' phenotype compared to those without (Log-rank P = 0.017). 'Hypocoagulable' profile was not associated with mortality in AD. 'Hypocoagulable' profile was associated with more advanced liver disease and higher short-term mortality in patients with ACLF.

Thromboelastometry and prediction of in-hospital mortality in neonates with sepsis.

This study aimed at evaluating the role of rotational thromboelastometry (ROTEM) assays in the prediction of in-hospital mortality of neonates with sepsis. Over a 6-year period, 129 neonates with confirmed sepsis, hospitalized in our neonatal intensive care unit (NICU) were included in the study. Demographics, clinical, and laboratory data were recorded at the sepsis onset and ROTEM assays were performed. Modified neonatal multiple organ dysfunction (NEOMOD) and neonatal sequential organ failure assessment (nSOFA) were calculated simultaneously. Mortality during in-hospital stay was the main outcome measure. In-hospital mortality was associated with patient intense hypocoagulability expressed by lower ROTEM MCF in the INTEM assay. The INTEM MCF demonstrated the best prognostic performance for NICU mortality in septic neonates among the other ROTEM parameters but without statistical significance (area under the curve [AUC] = 0.731; 95% confidence interval [CI]: 0.593-0.869). Our results indicate that ROTEM INTEM MCF parameter has good predictive capacity for in-hospital mortality of septic neonates, similar to that of modified NEOMOD score, nSOFA score, and platelet count, highlighting the integral role of coagulation in sepsis pathophysiology. Hence, ROTEM could serve as a valuable monitoring tool to identify neonates at risk.

Prospective assessment of platelet function in patients undergoing elective resection of glioblastoma multiforme

This prospective study was aimed to test changes in hemostasis in patients with GBM, occurring at baseline (before surgery, time 0, T0) and 2 (T2), 24 (T24), and 48-hour (T48) after surgery. We enrolled consecutive patients subjected to GBM resection (GBR group; N = 60), laparoscopic colon cancer resection (comparative CCR group; N = 40), and healthy blood donors (HBD group; N = 40). We performed 1. conventional coagulation tests 2. ROTEM (rotational thromboelastometry) parameters and 3. platelet function tests, including PFA-200 closure time when stimulated by collagen/epinephrine (COL-EPI) and ROTEM platelet, using three different activators (arachnoid acid in ARATEM, adenosine diphosphate in ADPTEM, and thrombin receptor-activating peptide-6 in TRAPTEM). Variables associated with unfavorable 1-year clinical outcome were investigated, too. We observed in GBR patients that platelet aggregometry, as assessed by ROTEM platelet parameters, was significantly impaired along with a shortened closure time. These changes were evident from T0 to T48. A decreased area under the aggregation curve in TRAPTEM was associated with improved survival (adjusted odd ratio (95% CI), 1.03 (1.01–1.06)). This study suggests that patients with GBM presented a decreased platelet aggregation from before surgery and thorough the postoperative period. Decreased platelet aggregation improved clinical outcome.

Thromboelastometry for predicting hemostasis disorders after cardiopulmonary bypass during cardiac surgery

Introduction. Assessment of the state of the hemostasis system in cardioanesthesiology is carried out both clinically and using standard laboratory tests — thromboelastography (TEG), rotational thromboelastometry (ROTEM), or a combination of both. Both TEG and ROTEM are designed to detect disorders in the hemostasis system in real time. Aim – to evaluate the informativeness of ROTEM performed at the stage of cardiopulmonary bypass (CPB) before neutralization of heparin with protamine and to study the prognostic value of this study in assessing the risk of postoperative bleeding during cardiac surgery with a high risk of bleeding. Materials and methods. The assessment of the diagnostic significance of ROTEM studies at the CPB stage is based on the observation of 31 patients operated on from July to October 2018. The median age of these patients was 55 years (31–72 years). The criteria for inclusion of patients in the study were the performance of planned cardiac surgery with a high risk of bleeding: operations on the aorta, combined operations (coronary bypass surgery and/or surgery on the valve(s), multivalve correction), including repeated. Methods of descriptive statistics, correlation and comparative analyses, and ROC-analysis were used to assess the diagnostic and prognostic capabilities of ROTEM research during CPB against the back=-ground of high doses of heparin. Results. A statistically significant linear correlation was noted between A5 and MCF indicators in EXTEM, FIBTEM and PLTEM tests performed both during and after CPB. The results obtained indicate that determining the cause of bleeding and deciding on the choice of therapy is possible significantly earlier than the MCF indicator is determined, namely 5 minutes after the start of blood clotting in the ROTEM study. The informative value of ROTEM studies performed during CPB is shown, however, when interpreting the results, it is necessary to focus not only on the reference intervals, but also on the obtained cut-off levels for ROTEM parameters during CPB for early detection of hypofibrinogenemia or thrombocytopenia after CPB. Conclusion. ROTEM performed with the use of high doses of heparin during CPB is informative for the choice of pathogenetically justified therapy for possible bleeding.

Patients with infective endocarditis undergoing cardiac surgery have distinct ROTEM profiles and more bleeding complications compared to patients without infective endocarditis.

The coagulation system is crucial in the pathogenesis of infective endocarditis and undergoes significant changes during course of the disease. However, little is known about the implications of those changes in the perioperative period. Aim of the present study was to delineate the specific coagulation patterns and their clinical consequence in patients undergoing cardiac surgery due to infective endocarditis. In this single-centre, exploratory, prospective observational study, we investigated the incidence and degree of coagulopathy in patients with (n = 31) and without infective endocarditis (n = 39) undergoing cardiac valve surgery. The primary outcome was the differences between these two groups in rotational thromboelastometry (ROTEM) results before, during and after surgery. The secondary outcomes were the differences between the groups in heparin sensitivity, bleeding complications, and transfusion requirements. Most ROTEM parameters in EXTEM, INTEM and FIBTEM assays were significantly altered in patients with infective endocarditis. Clotting time in the EXTEM assay was significantly prolonged in the endocarditis group at all time-points, while all clot firmness parameters (A5, A10 and MCF) were significantly increased. The heparin sensitivity index was significantly lower in the endocarditis group (median index 0.99 vs 1.17s. IU-1.kg-1, p = .008), indicating increased heparin resistance. Patients with infective endocarditis had more bleeding complications as assessed by the universal definition of perioperative bleeding score (OR 3.0, p = .018), and more patients with endocarditis underwent early re-exploration (p = .018). The findings of this exploratory investigation show significantly altered coagulation profiles in patients with infective endocarditis, with concomitant hyper- and hypocoagulability. Furthermore, the incidence of bleeding complications and transfusion requirements were increased in patients with endocarditis. These results show the potential of ROTEM to detect coagulation abnormalities in patients with infective endocarditis. Existing point-of-care coagulation testing guided algorithms for optimizing perioperative coagulation management possibly need to be adjusted for these high-risk patients undergoing cardiac surgery.

Fibrinolysis shutdown and elevated D-dimer levels have high prognostic capacity for postoperative thromboembolic complications in patients with bone tumors.

Surgical resection of malignant bone tumors is associated with a high risk of venous thromboembolism (VTE). The purpose of this study was to evaluate the association between rotational thromboelastometry (ROTEM) parameters and VTE following oncologic resections, and to evaluate their prognostic capacity for this complication. A prospective observational study was conducted including 113 patients who underwent surgical resection of malignant bone tumors. ROTEM analysis and conventional coagulation studies were performed preoperatively and on the 2nd postoperative day, while patients were followed for the development of VTE. Logistic regression was used to assess the association between ROTEM parameters and occurrence of VTE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated as measures of discrimination and predictive accuracy. Fourteen patients (12.4%) developed symptomatic VTE. Development of VTE was associated with shortened INTEM CFT (Odds Ratio [OR] 0.90, 95% Confidence Interval [CI] 0.84 - 0.96, p = 0.004), higher INTEM A10 (OR 1.21, 95% CI 1.07 - 1.36, p = 0.002), higher INTEM MCF (OR 1.22, 95% CI 1.08 - 1.37, p = 0.001) and higher INTEM LI60 (OR 2.10, 95% CI 1.38 - 3.21, p = 0.001). An INTEM LI60 value indicative of fibrinolysis shutdown (≥ 98%) had the best predictive accuracy for VTE (AUC = 0.887, 95% CI 0.824 - 0.951, sensitivity = 100%, specificity = 67.0%), higher than that of D-dimer levels (p = 0.028). ROTEM parameters were promising predictors of symptomatic VTE. Fibrinolysis shutdown as reflected by ROTEM LI60 and high D-dimer levels can aid the identification of high-risk patients. Future studies should evaluate whether the addition of ROTEM findings to an expanded risk-assessing model can improve the predictive capacity and provide better guidance in thromboprophylaxis.

Elevated levels of soluble glycoprotein V - The plasma marker of platelet activation by thrombin in patients with early stage primary biliary cholangitis (PBC)

PurposeThere is a growing body of evidence for a prothrombotic tendency in patients with primary biliary cholangitis (PBC). The aim of the study was to evaluate coagulation disorders in patients with early stage PBC compared to healthy controls and evaluation of their relationship with clinical data, with particular emphasis on minimal hepatic encephalopathy (MHE). Patients and methodsFifty-one participants (PBC group – 38 patients, all patients but one Child-Pugh A; control group – 13 healthy controls) were included in our prospective, single center study. We assessed the plasma levels of sGPV, plasma procoagulant phospholipids (PPL) and rotational thromboelastometry (ROTEM) profiles in all study participants. Porto-systemic encephalopathy syndrome test was used to assess MHE. ResultsThe sGPV levels were higher in the PBC group compared to the controls: 36.07 ​± ​11.32 ​ng/mL vs 27.04 ​± ​11.72 ​ng/mL, p ​= ​0.031. The PPL level was lower in the PBC group compared to controls resulting in increased clotting time in a factor Xa-based coagulation assay: 54.65 (47.83–58.83) sec. vs 45.90 (43.3–50.5) sec., p ​= ​0.0065. PPL levels were correlated with platelet count (rho ​= ​−0.46, p ​= ​0.001). ROTEM parameters did not differ significantly between groups. Coagulation parameters did not differ significantly between patients with and without MHE. ConclusionsWe have showed increased levels of sGPV - a plasma marker of platelet activation by thrombin in patients with early stage PBC compared to healthy controls. We found no relationship between the coagulation disorders and the occurrence of MHE. The PPL level was lower in the PBC group.

P542 Short term efficacy, safety and thromboembolic risk of tofacitinib in moderate to severe Ulcerative Colitis

Abstract Background Tofacitinib is a small oral molecule approved to treat moderate to severe ulcerative colitis (UC), which effectiveness and safety is still poorly known in UC patients. Recent concerns have been raised regarding its administration at high dosage in UC patients because of a likely higher incidence of drug-related thromboembolic events. Methods The aim of this study was to evaluate short-term effectiveness and safety of tofacitinib. As secondary aim, we analyzed the state of blood coagulation at baseline in order to evaluate whether it could predict thromboembolic events in relation to demographic, clinical and biochemical characteristics. A multicenter, retrospective, observational study was conducted, including patients from March 2021 to October 2022; a prospective single-centre sub-study concerning the thromboembolic risk was performed. At baseline, demographic, clinical, biochemical and endoscopic data, and previous therapies were recorded; quality of life was evaluated through IBD-Disability Index (IBD-DI) and Pittsburgh Sleep Quality Index (PSQI). In a subgroup of patients, a thrombophilic screening and a Rotational Thromboelastometry (ROTEM) were performed at baseline. Patients were reassessed after 8 weeks, 6 months and 1 year, evaluating for each timepoint clinical and biochemical characteristics, IBD-DI and PSQI, and reporting adverse events (AEs) and discontinuation of therapy. The following clinical outcomes were considered: benefit, steroid-free remission and response. Results 44 adult patients were enrolled. The overall clinical benefit was 54.2%, summing up 45.8% of subjects in steroid-free clinical remission and 8.3% with clinical response; significant short-term improvement of IBD-DI and PSQI scores (p=0.000 in both cases after 6 months of therapy) was observed. Patients previously treated with less than two different biological therapies had major rates of clinical benefit at 6 months (p=0.045). Ten AEs, including one venous thrombosis, were reported; global therapy failure rate was 31.4%. In the subgroup with additional data on coagulation (17 patients), we did not observe significant alterations of coagulating factors or inhibitors, nor of ROTEM parameters, although some coagulation features were significantly increased in obese patients (FII, p=0.030; FIX, p=0.000; FX, p=0.000; fibrinogen blood levels, p=0.030) and subjects older than 40 years old (FVIII, p=0.020). We did not find significant correlation with gender, smoking habit, concomitant steroid therapy, CRP, fecal calprotectin. Conclusion Our data confirm literature ones on effectiveness and safety of tofacitinib in UC patients, while the risk of thrombosis needs to be better evaluated in larger longitudinal studies.

High levels of factor VIII activity in patients with acquired hemophilia A in remission are associated with unusually low coagulation potentials.

Elevated factor VIII activity (FVIII:C) is often observed in patients with acquired hemophilia A (PwAHA) in remission. However, comprehensive coagulation potentials in this patient group remain to be investigated. To evaluate comprehensive coagulation potentials in PwAHA. We investigated coagulation function in eleven PwAHA with high FVIII:C (> 150IU/dL) using thrombin generation assay (TGA) and/or rotational thromboelastometry (ROTEM), and compared findings with results obtained from contrived samples generated by spiking recombinant FVIII. The median FVIII:C and FVIII inhibitor titers during remission in enrolled PwAHA were 206IU/dL and 0.44 BU/mL, respectively. In all patients, lag time and time to peak were either prolonged or normal compared to contrived samples corresponding to their FVIII:C. However, higher values of peak thrombin and endogenous thrombin potentials compared to contrived samples were observed in two patients. ROTEM parameters were within normal ranges in all cases. One patient (FVIII:C 171IU/dL) developed venous thrombosis and pulmonary embolism, but TGA parameters showed low or normal coagulation potential compared to contrived samples corresponding to his FVIII:C. PwAHA with high FVIII:C could exhibit lower coagulation potentials than those corresponding to their FVIII:C.

The use of rotational thromboelastometry parameters in understanding the coagulopathy following hump-nosed viper (Hypnale spp) bites: a preliminary study

BackgroundHump-nosed vipers (HNV; Hypnale spp) are one of the medically important venomous snakes in Sri Lanka and South-Western regions of India. The haemostatic dysfunction due to HNV bites is poorly characterized by standard diagnostic tests performed to identify coagulopathy. We aimed to determine the usefulness of rotational thromboelastometry (ROTEM) parameters compared to 20-minute whole blood clotting test (WBCT20) and prothrombin time (PT) in understanding the coagulopathy of HNV bites.MethodsTwenty-three HNV snakebite patients in a prospective study of 127 consecutive snakebites were recruited. After recording details of the clinical presentation, PT/international normalized ratio (INR), WBCT20 and ROTEM delta were performed at presentation.ResultsIn this preliminary study, none of the patients had clinically apparent bleeding. Coagulopathy was detected by either WBCT20, INR or ROTEM in 13 HNV patients. Eleven had a coagulopathy detectable by ROTEM (either abnormal EXTEM-CT, INTEM-CT or FIBTEM-MCF) but with negative WBCT20. Of them, only two had prolonged INR values. Two patients had positive WBCT20 but with normal ROTEM and INR values. The remaining 10 patients did not show any coagulopathy either by INR, ROTEM or WBCT20.ConclusionIn this preliminary study with small number of sample size, ROTEM parameters appeared to be more sensitive to subtle changes in coagulation compared to WBCT20. The clinical utility of detecting these changes and their usefulness in managing snakebite should be explored further in a larger study.

Evaluating the Association Between Fibrinogen and Rotational Thromboelastometry and the Progression to Severe Obstetric Hemorrhage.

This study aims to investigate the ability of fibrinogen and rotational thromboelastometry (ROTEM) parameters measured at obstetric hemorrhage protocol initiation to predict severe hemorrhage. In this retrospective study we included patients whose hemorrhage was managed with an obstetric massive transfusion protocol. Fibrinogen and ROTEM parameters EXTEM clotting time (CT), clot formation time (CFT), alpha angle, A10, A20, lysis index 30 min after CT (LI30), FIBTEM A10, A20, were measured at initiation of the protocol with transfusion based on a predefined algorithm. Patients were grouped into either severe or nonsevere hemorrhage based on: peripartum fall in hemoglobin ≥4 g/dL, transfusion of ≥4 units of blood product, invasive procedures for hemorrhage control, intensive care unit admission, or death. Of the 155 patients included, 108 (70%) progressed to severe hemorrhage. Fibrinogen, EXTEM alpha angle, A10, A20, FIBTEM A10, A20 were significantly lower in the severe hemorrhage group while the CFT was significantly prolonged in the severe hemorrhage group. In univariate analysis, predicted progression to severe hemorrhage yielded areas under the receiver operating characteristic curve (95% confidence interval [CI]) of: fibrinogen: 0.683 (0.591-0.776), CFT: 0.671 (0.553, 0.789), EXTEM alpha angle: 0.690 (0.577-0.803), A10: 0.693 (0.570-0.815), A20: 0.678 (0.563-0.793), FIBTEM A10: 0.726 (0.605-0.847), and A20: 0.709 (0.594-0.824). In a multivariable model, fibrinogen was independently associated with severe hemorrhage (odds ratio [95% CI] = 1.037 [1.009-1.066]) for every 50 mg/dL decrease in fibrinogen drawn at obstetric hemorrhage massive transfusion protocol initiation. Both fibrinogen and ROTEM parameters measured at the initiation of an obstetric hemorrhage protocol are useful parameters for predicting severe hemorrhage.