Thromboelastography Measurements Research Articles

Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial

BackgroundTranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in...

Anticoagulation with Intravenous Direct Thrombin Inhibitors in Pediatric Extracorporeal Membrane Oxygenation: A Systematic Review of the Literature.

Although intravenous (IV) direct thrombin inhibitors (DTI) have gained interest in pediatric extracorporeal membrane oxygenation (ECMO), dosing and safety information is limited. The objective of this systematic review was to characterize DTI types, dosing, monitoring, and outcomes (bleeding and thromboembolic) in pediatric ECMO patients managed with IV DTIs. We conducted searches of MEDLINE (Ovid) and Embase (Elsevier) from inception through December 2022. Case reports, retrospective studies, and prospective studies providing per-patients or summary data for patient(s) <18 years of age receiving IV DTI for ECMO anticoagulation were included. Study selection and data extraction were conducted independently by two reviewers. A total of 28 studies: 14 case reports, 13 retrospective studies, and 1 prospective study were included, totaling 329 patients. Bivalirudin was utilized in 318 (96.7%), argatroban in 9 (2.7%), and lepirudin in 2 (0.6%) patients. Infusion dosing included: bivalirudin 0.14 ± 0.37 mg/kg, argatroban 0.69 ± 0.73 µg/kg/min, lepirudin 0.14 ± 0.02 mg/kg/h. Laboratory monitoring tests utilized were the activated clotting time, activated partial thromboplastin time (aPTT), diluted thrombin time, and thromboelastography measures. The aPTT was utilized in most patients (95%). Thromboembolism, bleeding, or death were observed in 17%, 17%, and 23% of bivalirudin, argatroban, and lepirudin patients, respectively. Bivalirudin appears to be the most frequently used DTI in pediatric ECMO. Dosing and laboratory monitoring varied, and bleeding and thromboembolic events were reported in 17% of patients. Prospective studies are warranted to establish dosing, monitoring, safety, and efficacy of bivalirudin and other IV DTI in pediatric ECMO.

Effect of 10-Day Treatment with 50 mg Prednisolone Once-Daily on Haemostasis in Healthy Men-A Randomised Placebo-Controlled Trial.

Synthetic corticosteroids are widely used due to their anti-inflammatory and immunosuppressant effects. Their use has been associated with venous thromboembolism, but it is unknown whether thromboembolism has a causal relationship with corticosteroid treatment. In a randomised, double-blind, placebo-controlled trial in normal to overweight healthy men, the effect of the corticosteroid prednisolone on haemostasis using either 50 mg prednisolone or matching placebo once daily for ten days was investigated. The primary outcome was a change from baseline in the viscoelastic measurement maximal amplitude of clot in kaolin-activated thromboelastography (TEG). Changes from baseline in other TEG measurements, D-dimer, von Willebrand factor (VWF) antigen, and ristocetin cofactor activity (RCo), antithrombin, protein C, prothrombin, fibrinogen, INR, APTT, and platelet count were secondary outcomes. Thirty-four men participated in this study. Compared to placebo, prednisolone treatment did not affect maximal amplitude of clot (difference -0.77 (95% confidence interval (CI) -2.48, 0.94) mm, p = 0.37, missing: n = 2), but it altered VWF antigen (28%, p = 0.0004), VWF:RCo (19%, p = 0.0006), prothrombin (5%, p = 0.05), protein C (31%, p < 0.0001), antithrombin (5%, p = 0.013), and fibrinogen (-15%, p = 0.004). Thus, prednisolone treatment did not alter TEG-assessed maximal amplitude of clot, despite that it affected prothrombotic markers (increased prothrombin, VWF antigen, VWF:RCo, prothrombin, and decreased fibrinogen) and increased antithrombotic markers (protein C and antithrombin).

Combining Serum Procalcitonin Level, Thromboelastography, and Platelet Count to Predict Short-term Development of Septic Shock in Intensive Care Unit.

Despite the recent advances in diagnosis and treatment, sepsis continues to lead to high morbidity and mortality. Early diagnosis and prompt treatment are essential to save lives. However, most biomarkers can only help to diagnose sepsis, but cannot predict the development of septic shock in high-risk patients. The present study determined whether the combined measurement of procalcitonin (PCT), thromboelastography (TEG) and platelet (PLT) count can predict the development of septic shock. A retrospective study was conducted on 175 septic patients who were admitted to the intensive care unit between January 2017 and February 2021. These patients were divided into two groups: 73 patients who developed septic shock were assigned to the septic shock group, while the remaining 102 patients were assigned to the sepsis group. Then, the demographic, clinical and laboratory data were recorded, and the predictive values of PCT, TEG and PLT count for the development of septic shock were analyzed. Compared to the sepsis group, the septic shock group had statistically lower PLT count and TEG measurements in the R value, K value, α angle, maximum amplitude, and coagulation index, but had longer prothrombin time (DT), longer activated partial thromboplastin time (APTT), and higher PCT levels. Furthermore, the Sequential Organ Failure Assessment (SOFA) score was higher in the septic shock group. The multivariate logistic regression analysis revealed that PCT, TEG and PLT count were associated with the development of septic shock. The area under the curve analysis revealed that the combined measurement of PCT, TEG and PLT count can be used to predict the development of septic shock with higher accuracy, when compared to individual measurements. The combined measurement of PCT, TEG and PLT count is a novel approach to predict the development of septic shock in high-risk patients.

Preoperative thromboelastography in the prediction of post-tonsillectomy hemorrhage by coblation tonsillectomy: a post-hoc analysis.

Post-tonsillectomy hemorrhage (PTH) affects around 4% of patients after tonsillectomy. We hypothesized that preoperative thromboelastography (TEG) might identify patients at higher risk of PTH. Investigate whether evaluation of coagulation function by preoperative TEG might help to predict PTH after tonsillectomy by coblation tonsillectomy (TE). Post-hoc analysis of randomized controlled study. Otolaryngology Department between January 2017 and August 2019. This post-hoc analysis included adults who underwent coblation TE for benign tonsillar disorders. Routine blood tests and TEG were performed preoperatively. The TEG parameters evaluated included coagulation reaction time (R) and maximum thrombus amplitude (MA). The main outcome was PTH during the 4-week postoperative period. 284 RESULTS: The 19 patients (6.7%) that experienced PTH had a higher prevalence of diabetes mellitus, lower use of intraoperative suturing, fewer patients with grade I and II tonsillar enlargement, a higher white blood cell count, lower platelet count, lower fibrinogen level, lower R value, and a lower MA value than patients without PTH (all P<.05). Multivariate logistic regression revealed that diabetes mellitus (P<.053), fibrinogen level ≤2.735 g/L (P<.027), R≤6.55 min (P<.011) and MA≤59.15 mm (P<.012) were independently associated with PTH. A regression model incorporating these four factors predicted PTH with a sensitivity of 73.7% and specificity of 83.8%. Preoperative evaluation of diabetes mellitus history, fibrinogen level, and TEG parameters might help to identify patients at higher risk of PTH after coblation TE. Single-center study with a small sample size; possibly underpowered statistically. TEG measurements might not accurately reflect coagulation function, and a validation cohort was unavailable. None. CHINESE CLINICAL TRIAL REGISTRY NUMBER OF STUDY USED IN THIS ANALYSIS: ChiCTR2000032171. http://www.chictr.org.cn/showprojen.aspx?proj=52553.

PROGNOSIS AND PREVENTION OF UTERUS BLEEDINGS IN EARLY POSTPARTUM PERIOD FOR WOMEN WITH IDIOPATHIC ARTERIAL HYPOTENSION

The aim: To establish the effectiveness of thromboelastography (TEG) and tranexamic acid (TXA) for prognosis and prevention of early postpartum period bleedings (PPB) for postpartum women with idiopathic arterial hypotension (IAH). Materials and methods: Coagulogical research was conducted (coaugologram screening, dynamic function of platelets under the influence of adenosine diphosphate (ADP) (visual assessment), measurement of soluble fibrin-monomer complexes (FMC) and TEG of 36 in parturient women during the I chilbirth period with arterial hypotension. 14 parturient women with normal fibrinolysis were included into the first observation group; The second group includes 22 parturient women with TEG results which show signs of hyperfibrinolysis. Further, in cases when stronger fibrinolysis was detected during the late pushing phase of childbirth period, the TXA by amount of 1,0 g IV (bolus) was injected due to bleeding prevention. TEG was repeated during early postpartum period. Results: the inhibition of platelet aggregation activity with ADP was observed in every parturient woman with IAH in the first partum period. In 61,1% cases with TEG hyperfibrinolysis were shown, which was accompanied by significant increase in FMC levels in blood. The use of TXA as PPB prevention for parturient women with IAH and hyperfibrinolysis during TEG was fully oppressing the fibrinolytic activity and was not affecting the coagulation part of hemostasis. Conclusions: hemostasis testing during childbirth based on TEG gives the ability to prognose the hemorrhagic complications in parturient women with IAH and administer their prophylaxy using TXA.

Prognostic value of repeated thromboelastography measurement for favorable neurologic outcome during targeted temperature management in out-of-hospital cardiac arrest survivors

BackgroundCardiac arrest can activate blood coagulation, which clinically manifests as obstruction of the microcirculation and multiple organ dysfunction. Thromboelastography (TEG) provides a rapid and comprehensive assessment of hemostatic processes, but there are limited data on the use of sequential TEG values during targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA) survivors. The aim of this study was to investigate the prognostic value of coagulopathy assessed by repeated TEG to predict neurologically intact survival. MethodsA prospective cohort of consecutive non-trauma OHCA patients who were successfully resuscitated and treated with TTM. Patients with a target temperature of 36 ℃, no TEG data, and who declined appropriate treatment were excluded. TEG was measured at three time points of TTM (initial phase, target phase, and rewarming phase). The primary outcome was 28 day favorable neurologic function, defined as a Cerebral Performance Category of 1 or 2. ResultsA total of 125 patients (mean age, 61 years; 63.2% male) were analyzed. A favorable neurologic outcome at 28 days was seen in 40 patients (32.0%). TEG values of R and LY30 in the initial phase were significantly lower in the favorable neurologic outcome group than in the unfavorable group (5.8 vs. 8.1 and 0.1 vs. 0.7, respectively; p < 0.01). TEG values of R < 5 or LY30 < 7.5 in the initial phase were more frequently seen in the favorable outcomes group than in the unfavorable group (37.5% vs. 12.9%, p = 0.002 and 95.0% vs. 72.9%, p = 0.004, respectively). However, no significant differences were seen between the two groups in other TEG values (R, K, alpha, and MA) in the target and rewarming phases (p > 0.05 for all). Univariate analysis showed higher D-dimer levels, prothrombin time, and activated partial thromboplastin time in the unfavorable outcome group. In the multivariable analysis, TEG values of combination of R < 5 and LY30 < 7.5 in the initial phase were the only coagulation profiles seen to be independently associated with favorable neurologic outcome (OR, 4.508, 95% CI, 1.254–16.210). ConclusionTEG results are available within minutes, and shorted R values or the absence of prolonged LY30 values in the initial phase are an early predictor of neurologically intact survival in successfully resuscitated OHCA patients.

Fibrinolysis Shutdown Correlation with Thromboembolic Events in Severe COVID-19 Infection

BackgroundCOVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement. The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.Study DesignPatients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied. Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.ResultsForty-four patients with COVID-19 were included in the analysis. Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes. A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021). A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005). Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).ConclusionsFibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19. Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.

Comparison of Thromboelastography and Conventional Coagulation Tests in Patients With Severe Liver Disease.

Objective:Thromboelastography (TEG) may provide rapid and clinically important coagulation information in acutely ill patients with chronic liver disease (CLD). Our objective was to describe the relationship between TEG and conventional coagulation tests (CCTs), which has not been previously explored in this population.Methods:In acutely ill patients with severe CLD (Child-Pugh score > 9, category C), we conducted a prospective observational study investigating coagulation assessment as measured by both CCTs and TEG. We used quantile regression to explore 30 associations between TEG parameters and corresponding CCTs. We compared TEG and CCT measures of coagulation initiation, clot formation, clot strength, and fibrinolysis.Results:We studied 34 patients on a total of 109 occasions. We observed inconsistent associations between TEG and CCT measures of coagulation initiation: TEG (citrated kaolin [CK] assay) standard reaction time and international normalized ratio: R 2 = 0.117 (P = .044). Conversely, there were strong and consistent associations between tests of clot formation: TEG (CK) kinetics time and fibrinogen: R 2 = 0.202 (P < .0001) and TEG (CK) α angle and fibrinogen 0.263 (P < .0001). We also observed strong associations between tests of clot strength, specifically TEG MA and conventional fibrinogen levels, across all TEG assays: MA (CK) and fibrinogen: R 2 = 0.485 (P < .0001). There were no associations between TEG and D-dimer levels.Conclusions:In acutely ill patients with CLD, there are strong and consistent associations between TEG measures of clot formation and clot strength and conventional fibrinogen levels. There are weak and/or inconsistent associations between TEG and all other conventional measures of coagulation.

Comparison of thromboelastography versus conventional coagulation tests in simulated Crotalus atrox envenomation using human blood

IntroductionPit viper bites are a source of significant morbidity and mortality. Pit viper bites can cause venom-induced consumptive coagulopathy (VICC), typically evaluated with laboratory-based conventional coagulation tests (CCTs). However, CCTs require a laboratory and average 1 h to conduct. Thromboelastography (TEG) provides real-time, point-of-care tests of coagulation that are fast and require no separate laboratory facilities, which could be advantageous in both hospital and austere settings. However, the relative efficacy of TEG versus CCTs was unclear, particularly at low venom concentrations. Therefore, the objectives of this study were to test human blood with various concentrations of pit viper venom using CCTs and TEG to determine dose-dependent changes, lowest observed effect concentration (LOEC), and sensitivity to detecting samples out of normal diagnostic range. MethodsBlood samples from 20 volunteers were mixed with varying concentrations of western diamond back rattlesnake (Crotalus atrox) venom based on the mouse LD50IV (none, 0.5%, 1%, 2%, 33%, 66%, and 100% LD50IV). Samples were split and assessed with both CCTs including prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), fibrinogen, and D-dimer, along with TEG measures of reaction time (R), kinetic time (K), rate of clot formation (α-angle), and clot strength (MA). Data were analyzed as dose-dependent concentration-based changes in raw values and in percent of samples exceeding diagnostic thresholds using ANOVA and nonparametric statistics at the p < .05 threshold. ResultsAll evaluations showed significant concentration-dependent changes, and 100% of samples exceeded diagnostic thresholds at 33%LD50IV and above, save D-dimer. At 0.5%LD50IV, R, K, α-angle, PT, and INR were significantly different from controls, and at 1%LD50IV, mean values exceeded diagnostic thresholds for R, K, α-angle, MA, PT, and INR, but not for PTT, D-dimer, or fibrinogen. At 2%LD50IV, 100% of samples were out of normal range for K, α-angle, and PT. ConclusionTEG is effective in coagulopathy evaluations of in vitro simulated pit viper envenomation. At low venom concentrations, TEG performed as well or better than the majority of CCTs. These findings provide empirical evidence supporting the use of TEG to rapidly and accurately evaluate VICC.

375 Is the Use of Thromboelastography in the Acute Young Trauma Patient Associated With Outcome and the Type and Amount of Blood Products Received?

Thromboelastography (TEG) point-of-care systems allow for analysis of the sum of platelet function, coagulation proteases and inhibitors, and the fibrinolytic system within 30 minutes. This allows a clinician to guide transfusion more precisely with an appropriate type of blood product. Literature supports that TEG-guided resuscitation had lower mortality compared to standardized 1:1:1 (red blood cells (RBC), fresh-frozen plasma (FFP), and platelets) massive transfusion protocol (MTP) in penetrating trauma patients, but data has been sparse in examining the young trauma patient. The objective was to assess if TEG use was associated with the type and amount of blood products used and to compare outcomes between those that did and did not have TEG measured. The correlations between TEG and other measures of coagulation including prothrombin time, and international normalized ratio was assessed. A cross-sectional chart review study was performed with patients up to 30 years old seen with active bleeding resulting from trauma in two level one trauma centers serving children and utilizing the Florida Trauma registry from January 1, 2010 to June 26, 2018. Patients who met the standard for MTP retrospectively, but had not been placed on the MTP were also included. TEG use was evaluated in these patients. Blood products assessed included packed RBC, FFP, platelets, and cryoprecipitate. Outcomes included survival to hospital discharge, requiring surgery within 24 hours of arrival, receiving tranexamic acid (TXA), and receiving MTP. 258 patients were included in the analysis. The mean age was 21 years (SD5), 79% were male, 112 (43%) had penetrating trauma and 225 (87%) had polytrauma. MTP was instituted in 176 (69%) patients and 88 (34%) patients who had TEG measured. The mean TEG values were alpha 59 (56-61), kinetics 3.4 (2.5-4.2), maximum amplitude 51.8 (49.5-54.0), R-value 5.1 (4.5-5.7), and clot lysis time 141 (31-252). There were significant correlations between PTT and alpha (r=-0.46; p<0.001), PTT and Kinetics (r=0.53; p<0.001), and PTT and maximum amplitude (r=0.449; p<0.001). There were also significant correlations between PT and alpha (r=-0.29; p=0.008), and PT and maximum amplitude (r= -0.27; p=0.013). There was no significant correlation between TEG measures and INR. The associations between measurement of TEG and amount and type of blood product are described in Table 1. There was no significant association between no TEG and TEG measurement and survival to hospital discharge 62% vs 64% respectively (p=0.787). However, receiving TEG use had significant associations with requiring surgery within 24 hours 45% vs 61% (p=0.018), receiving TXA 20% vs 59% (p<0.001), and with receiving MTP 62% vs 83% (p=0.001), respectively. Measurement of TEG was associated with patients receiving TXA, MTP and more blood products. Components of TEG correlated with PT and PTT levels. Although there was no association with survival to hospital discharge, patients having TEG measured were more likely to undergo surgery within the first 24 hours of hospital arrival.

22 Thromboelastography Detects Coagulopathy Faster than Standard Coagulation Studies in Simulated Pit Viper Envenomation

Venomous snakebites pose a significant risk of morbidity and mortality in rural and austere environments, so it is not surprising that the World Health Organization recently set a goal of reducing snakebite deaths by half by 2030. Many of these envenomations are due to pit vipers, leading to severe hematologic derangements, such as venom-induced consumptive coagulopathy (VICC). Immediacy in detection of envenomations is crucial for ameliorating morbidity and mortality, but diagnosis of envenomization can be challenging, requiring access to clinical laboratory facilities. Further, the laboratory-based evaluations of coagulation function take more than an hour to conduct. In contrast, thromboelastography (TEG) is promising as a rapid, portable, bedside test of coagulation that produces meaningful results in less than 15 minutes. Therefore, the primary objective of this study was to assess the efficacy of TEG compared to standard lab tests in detecting pit viper venom at increasing concentrations. Blood samples drawn from 19 healthy adult volunteers were mixed with varying concentrations of western diamond back rattlesnake (Crotalus atrox) venom (none, 0.5%, 1%, 2%, 33%, 66%, and 100% of LD50), then assessed with standard laboratory-based tests of coagulation function (labs), including prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), D-dimer, and Fibrinogen, as well as with TEG measures of reaction time (R), amplification (K), rate of clot formation (Angle), and clot strength (MA). Data were analyzed as changes from baseline and categorized as percent of samples out of normal physiologic range, then analyzed using ANOVA and binomial statistics at the p<.05 threshold for statistical significance. TEG and standard labs were both excellent (100%) at detecting higher concentrations of venom (33%, 66%, 100%), save D-dimer. Importantly, at low venom concentration levels (0.5%, 1%, 2%), the TEG measures of R, K, alpha, and MA were similar to laboratory-based evaluations of PT and INR at detecting venom, and were significantly superior to PTT, D-dimer, and Fibrinogen. TEG provides a sensitive, real-time quantitative evaluation of coagulation derangements during simulated pit viper envenomation that is faster than standard laboratory tests. TEG was sensitive at low venom concentrations, outperforming multiple traditional laboratory evaluations of VICC. While the present study was limited to in vitro analyses, our findings suggest that TEG is a fast, effective, and portable point-of-care testing modality to assist the emergency physician community to rapidly and accurately diagnose patients stricken with venomous snake bites.

Thromboelastography characterized CD36 null subjects as slow clot formation and indicative of hypocoagulability

BackgroundPlatelet CD36 is the receptor for oxidized low-density lipoprotein and collagen. The conventional platelet test cannot distinguish CD36-null subjects from normal expression subjects. Thromboelastography (TEG) testing can analyze global hemostasis. TEG testing data on CD36-null subjects are not available. MethodsOur subjects were 40 apheresis platelet donors, including 8 CD36-null individuals. We grouped the donors according to the platelet CD36 expression levels to assess the effects of platelet CD36 expression levels on TEG measurement variables. ResultsThe whole blood TEG test revealed that CD36-null subjects had prolonged reaction time of fibrin formation (TEG R time) and a slower rate to build up cross-linked fibrin (TEG α angle). The final maximal amplitudes of clot formation showed little difference between CD36-null individuals and normal expression individuals. Correlation analysis showed that CD36 expression levels were negatively correlated with TEG R time (r = −0.342, p = 0.031) and positively correlated with the TEG α angle (0.379, p = 0.016). TEG testing on apheresis platelet samples with diminished heterocellular interaction did not reveal differences between CD36-null and normal expression individuals. A subanalysis of the data of a group of healthy subjects showed that platelet CD36 levels correlated positively with platelet–monocyte aggregates (PMAs). Low PMA can diminish heterocellular interaction and likely explain the abnormal TEG results observed in CD36-null individuals. ConclusionTEG distinguishes CD36-null subjects from normal CD36 expression subjects as having a slower rate of fibrin formation and reassessment of TEG-based diagnostic monitoring is necessary for CD36 null subjects.

Thromboelastography Parameters Are Associated with Cirrhosis Severity.

Coagulopathy in cirrhosis represents complex coagulation derangements, and thromboelastography (TEG) measures these complex derangements. We sought to evaluate associations between TEG parameters and validated measures of cirrhosis severity, which have not been previously investigated. Adults with cirrhosis undergoing liver transplant (LT) were identified. Patients had TEG drawn immediately prior to LT. TEG parameters included reaction time (R), kinetic time (K), alpha angle (α), and maximum amplitude (MA). The validated measures of cirrhosis severity were MELD-Na and clinical stage of cirrhosis (classified using history of varices, variceal bleeding, or ascites). Multivariable linear and logistic regression analyses were conducted to evaluate the associations between TEG and stage of cirrhosis and MELD-Na. Among 164 patients with cirrhosis, advancing stage of cirrhosis was associated with more hypocoagulable TEG parameters including longer K-time (p = 0.05) and lower MA (p < 0.001). Similarly, with increasing MELD-Na quartiles, K-time was longer (p < 0.001), and both MA and α-angle decreased (p < 0.001, for both). Variceal bleeding within 6weeks prior to LT was associated with longer R-times (p = 0.02), longer K-times (p = 0.04), smaller α-angle (p = 0.03), and lower MA (p = 0.01). On multivariable analyses, decreasing MA remained statistically significantly associated with advancing stage of cirrhosis and increasing MELD-Na, after adjusting for multiple covariates including platelet count, (p = 0.02 and p < 0.0001, respectively). Hypocoagulable TEG measurements are associated with advancing stage of cirrhosis and increasing MELD-Na among patients with cirrhosis. These data indicate that TEG, as an informative measure of complex hemostatic function, may be a useful objective marker of liver disease severity in cirrhosis.

Epidural analgesia? A prospective analysis of perioperative coagulation in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BackgroundCytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is beneficial in peritoneal carcinomatosis. Epidurals provide excellent pain relief for laparotomies. Coagulopathy (platelet count <100 × 109/L, INR>1.5 or PTT >45) occurs with CRS and HIPEC, increasing risk for bleeding complications with epidurals. This prospective study characterizes clot kinetics with thromboelastography (TEG) to determine suitability for epidural analgesia. MethodsAfter Research Ethics approval, thirty consented patients had blood collected. Primary data collected included TEG and conventional coagulation measures (platelets, PTT and INR). Secondary data collected included demographics, disease, surgical, intraoperative factors and complications from epidural placement. ResultsOf 30 patients analyzed, two had incomplete data. Four developed abnormal coagulation between the second and fifth post-operative day. For all patients, TEG values remained normal. Postoperative INR was elevated until day 3 (all INR < 1.5). 17 patients received epidural analgesia, 3 demonstrated abnormal conventional coagulopathic criteria despite normal TEG. ConclusionsIn this study CRS and HIPEC do not contribute to the conventional definition of clinical coagulopathy. Clot kinetics indicate that epidural catheters may be recommended for post-operative analgesia.

Prediction of bleeding by thromboelastography in ICU patients with haematological malignancy and severe sepsis

: ICU patients with haematological malignancy have an increased risk of bleeding. Recently, global haemostatic methods such as thromboelastography (TEG) have gained impact in evaluating coagulation. The aim of this study was to observe whether TEG could predict bleeding in haematological ICU patients with severe sepsis. Post-hoc single-centre analysis of patients with haematological malignancy included in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial. Clinical characteristics, TEG measurements and details regarding bleeding complications were retrieved from the 6S database. The association between TEG and bleeding were analysed by Cox regression and receiver operating characteristic curves. A total of 202 patients with severe sepsis were admitted to the ICU of Rigshospitalet, Copenhagen and included in the 6S trial. Forty-one had haematological malignancy and were analysed in the current study. During ICU stay, 20 patients (49%) had bleeding complications and 13 (32%) patients bled within the first 5 ICU days. We observed no associations between TEG and subsequent bleeding in Cox regression models. TEG variables at baseline had low predictive value for bleeding. Baseline TEG variables did not add value in identifying patients with high risk of bleeding in ICU patients with haematological malignancy and severe sepsis.

Effect of ABO blood group on haemostatic parameters in severe haemophilia A patients performing acute moderate-intensity exercise.

: The primary objective was to assess the effect of ABO blood group on von Willebrand factor (VWF) rise induced by four bouts of moderate-intensity physical activity, on pharmacokinetics of a B-domain-deleted recombinant FVIII (BDD-rFVIII), and haemostatic parameters in severe haemophilia A patients with a null mutation. The secondary objective was to compare the response to exercise according to infused product type in a subgroup of patients who previously participated to the same exercise protocol, while treated with a full length recombinant FVIII (FL-rFVIII). Twenty patients had two visits (rest and exercise). Blood samples were drawn before administration of BDD-rFVIII and at 6 time points, until 24 h postinfusion. FVIII activity increased transiently by 1.1-fold, but only after the first exercise session, as compared to rest. VWF:Ag and platelet count were significantly elevated after each session. Mean FVIII half-life and thromboelastography measurements were unchanged with exercise. However, 14 participants had a slight variation of FVIII half-life with exercise compared to rest (from -3.42 h to +2.51 h). Seven patients demonstrated a longer FVIII half-life (four with O blood group), whereas the remainders had a reduced half-life (three with O blood group). FVIII half-life correlated with baseline VWF:Ag at rest (r = 0.70, P < 0.001) and with exercise (r = 0.67, P < 0.002). Recovery was different between FL-rFVIII and BDD-rFVIII at rest (P = 0.032), but no significant differences were observed between half-life of products at rest and with exercise. ABO blood group and the type of rFVIII administered did not influence the response to exercise.

Thromboelastographic study of the snakebite-related coagulopathy in Djibouti.

: Hemostasis disorders are one of the major clinical conditions of snakebites and are because of mechanisms which may disrupt vessels, platelets, clotting factors and fibrinolysis. Thromboelastography (TEG) could help to understand these effects in the clinical practice. A retrospective study reports a series of patients presenting a snakebite-related coagulopathy, treated with antivenom and monitored with conventional tests and TEG in a French military treatment facility (Republic of Djibouti, East Africa) between August 2011 and September 2013. Conventional coagulation assays (platelets, prothrombin time, activated partial thromboplastin time, fibrinogen) and TEG measurements were taken on arrival and at various times during the first 72 h of hospitalization, at the discretion of the physician. The study included 14 patients (median age 28 years). Bleedings were present in five patients. All patients received antivenom. A coagulopathy was present in all patients and was detected by both conventional assays and TEG. None exhibited thrombocytopenia. Prothrombin time and fibrinogen remained abnormal for most of patients during the first 72 h. The TEG profiles of 11 patients (79%) showed incoagulability at admission (R-time > 60 min). TEG distinguished 10 patients with a generalized clotting factor deficiency and 4 patients with an isolated fibrinogen deficiency after an initial profile of incoagulability. Hyperfibrinolysis was evident for 12 patients (86%) after Hour 6. Snake envenomations in Djibouti involve a consumption coagulopathy in conjunction with delayed hyperfibrinolysis. TEG could improve medical management of the condition and assessment of additional therapeutics associated with the antivenom.

Thromboelastography for predicting bleeding in patients with aortic stenosis treated with transcatheter aortic valve implantation.

Bleeding complications are frequent and independently impact mortality after transcatheter aortic valve implantation (TAVI). Thromboelastography (TEG) measures viscoelastic properties of clot formation and is currently best known for perioperative management to reduce blood transfusion in cardiac surgery. We sought to determine whether TEG may be predictive of bleeding in patients treated with TAVI. Overall, 54 consecutive patients with severe aortic stenosis treated with TAVI were prospectively included. In all patients, two blood samples were obtained for TEG measurement (the first - 12 h prior to procedure tested with citrated kaolin [CK] TEG assay, and the second - immediately after prosthesis deployment tested with CK and citrated heparinised kaolin assay [CHK]). Major or life-threatening bleeding (MLTB) was diagnosed in 13 (24%) patients. In receiver-operating characteristic (ROC) curve analysis the only TEG parameters showing significant sensitivity and specific-ity for predicting MLTB were those obtained in the CK sample at the end of the procedure: R value (reaction time, time to initiation of clot formation) area under the curve (AUC) 0.69, 95% confidence interval (CI) 0.49-0.88, p = 0.04; angle (the rate of clot formation), AUC 0.75, 95% CI 0.59-0.92, p = 0.007, and maximum amplitude (MA, ultimate strength of fibrin clot), AUC 0.77, 95% CI 0.62-0.93, p = 0.003. After controlling for confounding factors on multivariate logistic regression, MA remained as the only TEG parameter that significantly correlated with bleeding after TAVI, both as a continuous variable (p = 0.004; 95% CI 0.92-0.98; odds ratio [OR] 0.95 per 1 mm increment) and after using the cut-off value derived from ROC analysis; MA < 46.6 mm (OR 10.4; 95% CI 2.1-51.8; p = 0.004). Low strength of fibrin clot measured by TEG immediately after TAVI may serve as an independent predictor of short-term major and life-threatening bleeding complications.

In-vitro assessment of the effect of dabigatran on thrombosis of adult and neonatal plasma: comparisons using thromboelastography and microscopic visualization of fibrin clot structure.

: Thromboelastography (TEG) is a global assay used for evaluating features of clot formation in vitro. Dabigatran is a reversible direct inhibitor of thrombin that has not been studied in neonates using a sophisticated global assay, such as TEG. Neonatal hemostasis differs from adult hemostasis in both quantitative and qualitative characteristics. Our aim was to compare the TEG clotting profile of neonatal and adult platelet-poor plasma when exposed to different concentrations of dabigatran. We used commercially collected adult pooled plasma and neonatal cord blood collected from placentas of healthy full term newborns. Platelet-poor plasma was isolated, pooled, and frozen. Prior to experiment, plasma was thawed and filtered. A reaction mixture of CaCl2, corn trypsin inhibitor, tissue factor, and dabigatran in imidazole buffer was mixed with plasma in a TEG cup. Time to clot initiation (R-time), speed of clot strengthening (α-angle), and maximum clot strength (maximal amplitude) were measured. Scanning electron microscopy was performed to evaluate fibrin clot structure. Without dabigatran, there was no significant difference in TEG measurements between neonatal and adult samples. However, neonatal plasma clotting with dabigatran had slower onset, slower speed, and weaker clots that were more porous with thicker fibers, compared with adult plasma clotting. Thus, neonatal plasma may be more sensitive to dabigatran as assessed by our in-vitro TEG study.