Thrombelastography Parameters Research Articles

Thrombelastography and Conventional Coagulation Markers in Chronic Obstructive Pulmonary Disease: A Prospective Paired-Measurements Study Comparing Exacerbation and Stable Phases.

Chronic Obstructive Pulmonary Disease (COPD) exacerbation is known for its substantial impact on morbidity and mortality among affected patients, creating a significant healthcare burden worldwide. Coagulation abnormalities have emerged as potential contributors to exacerbation pathogenesis, raising concerns about increased thrombotic events during exacerbation. The aim of this study was to explore the differences in thrombelastography (TEG) parameters and coagulation markers in COPD patients during admission with exacerbation and at a follow-up after discharge. This was a multi-center cohort study. COPD patients were enrolled within 72 h of hospitalization. The baseline assessments were Kaolin-TEG and blood samples. Statistical analysis involved using descriptive statistics; the main analysis was a paired t-test comparing coagulation parameters between exacerbation and follow-up. One hundred patients participated, 66% of whom were female, with a median age of 78.5 years and comorbidities including atrial fibrillation (18%) and essential arterial hypertension (45%), and sixty-five individuals completed a follow-up after discharge. No significant variations were observed in Kaolin-TEG or conventional coagulation markers between exacerbation and follow-up. The Activated Partial Thromboplastin Clotting Time (APTT) results were near-significant, with p = 0.08. In conclusion, TEG parameters displayed no significant alterations between exacerbation and follow-up.

Increased clot strength following transcatheter aortic valve replacement

Abstract Background Patients treated with transcatheter aortic valve replacement (TAVR) are at high risk for bleeding and ischemic events. Thrombelastography (TEG) parameters are associated with thromboembolic and bleeding risk. TEG may be used to risk-stratify TAVR patients. The variability of TEG over time and the association of TEG parameters with antithrombotic medication in these patients has not been studied. Aim To assess the changes in platelet function and global hemostasis between periprocedural and long-term measurement in patients undergoing TAVR. Methods We performed a prospective, single center cohort study and included patients after TAVR. TEG was performed during the index hospitalization (T0) and 6 (± 2) months after TAVR (T1). TEG was used to determine the maximum blood clot strength as maximum amplitude (MA) after stimulation with kaolin + tissue factor (CRT) and kaolin + heparinase (CKH). Platelet count and thromboplastin time (INR) were determined as conventional coagulation parameters. At time of the measurements, patients were treated with acetylsalicylic acid (ASA), dual antiplatelet therapy (DAPT), oral anticoagulation (OAC) or a combination of these medications. We compared TEG parameters, thrombocytes and INR between measurements T0 and T1 and stratified patients according to the antithrombotic regimen. Results From December 2021 to April 2022, 64 patients were enrolled and measured after TAVR: T0 at median on day 4 (min. 2, max.17) and T1 at a median of 6 months (min. 4 max. 8). The median age was 81 years (interquartile range IQR 78-83) and 28 (47%) patients were male. 59 of 64 patients had no change in indication for anticoagulation between measurements T0 and T1, thus taking either OAC (28 of 59) or antiplatelet (AP) without OAC (31 of 59) at measurements T0 and T1. MA was higher in patients at T0 compared with T1 and was observed independently of antithrombotic therapy. OAC: [MA-CRT 66.5mm (IQR 64.5-69.1mm) vs. 63.8mm (IQR 59.7-66.0mm); p<0.0001] and [MA-CKH 64.5mm (61.3-68.0mm) vs. 60.1mm (56.4-64.7mm); p<0.0001)]. AP: [MA-CRT 66.8mm (IQR 63.75-69.9mm) vs 64.2mm (IQR 60.7.7-66.1mm); p<0.0001] and [MA-CKH 64.5mm (61.3-68.0mm) vs 60.1mm (56.4-64.7mm); p<0.0001]. Platelet count (Tc) was not significantly different at T0 vs. T1 in patients with OAC and those with AP. [Tc (OAC) 162.5103/µl (IQR 131.2-223.2 103/µl) vs.178tsd/µl (IQR 152-209.75103/µl); p=0.29] and [Tc (AP) 181tsd/µl (IQR 128-243103/µl) vs. 202tsd/µl (IQR 175-247103/µl), respectively; p=0.056, Figure 1]. Conclusion Compared with long-term measurements, clot strength measured during the index hospitalization after TAVR was significantly increased. The increased clot strength was independent of baseline antithrombotic therapy. Whether this corresponds to an early procoagulant state that favors the occurrence of valvular thrombosis or cardiovascular events needs to be investigated in prospective studies.

Factors influencing thrombelastography in pregnancy.

The number of gestational women has been increased in recent years, resulting in more adverse pregnancy outcomes. It is crucial to assess the coagulation function of pregnant women and to intervene in a timely manner. This study aims to analyze the influencing factors on thrombelastography (TEG) and explore the evaluation of TEG for gestational women. A retrospective study was conducted on 449 pregnant women who were hospitalized in the obstetrics department in Xiangya Hospital of Central South University from 2018 to 2020. We compared the changes on the TEG parameters among normal pregnant women between different age groups, different ingravidation groups, and different stages of pregnancy groups. The influence on TEG of hypertensive disorders in pregnancy (HDP) and gestational diabetes mellitus (GDM) as well as two diseases synchronization was explored. Compared with the normal second trimester women, the R values and K values of TEG were increased, and α angle, CI values and LY30 values were decreased in third trimester women (all P<0.05). Compared with normal group, the R values and CI values of TEG of the HDP group have significant difference (both P<0.05). There were no significant difference of TEG between the GDM group, the HDP combined with GDM group and the normal group (all P>0.05). Multiple linear regression analysis showed that the influencing factors for R value in TEG were weeks of gestation (P<0.001) and mode of conception (P<0.05), for α angle was weeks of gestation (P<0.05), for MA value was mode of conception (P<0.05), and for CI value was weeks of gestation (P<0.05). The analysis of correlation between TEG with platelet (PLT) and coagulation routines represented that there was a correlation between TEG R values and activated partial thromboplastin time (APTT) (P<0.01), and negative correlation between TEG CI values and APTT (P<0.05). There was a negative correlation between TEG K values and FIB (P<0.05). The correlation of α angle (P<0.05), MA values (P<0.01) and CI values (P<0.05) with FIB were positive respectively. The TEG parameters of 3 stages of pregnancy were different. The different ingravidation approach has effect on TEG. The TEG parameters were consistent with conventional coagulation indicators. The TEG can be used to screen the coagulation status of gestational women, recognize the abnormalities of coagulation and prevent the severe complication timely.

Hypofibrinolysis in Pediatric Patients with Veno-Occlusive Disease in Hematopoietic Stem Cell Transplantation

Background Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplantation (HSCT) with a high incidence in pediatric patients (11-27%). In clinical practice, VOD is diagnosed with criteria including weight gain, ascites, hepatomegaly, hyperbilirubinemia, and refractory thrombocytopenia. To date, there are no established markers for an earlier diagnosis of VOD. The aspect of assessing hypofibrinolysis, which plays a role in VOD pathogenesis, has not been elucidated. This study aimed to detect signs of hypofibrinolysis in HSCT and VOD patients using thrombelastography parameters and to discover correlations between alterations of these parameters and established symptoms of VOD. Patients and Methods Patients admitted for HSCT to the pediatric HSCT ward at the University Children's Hospital Tübingen, Germany, between May 2020 and November 2021 were prospectively enrolled (study group). Patients who underwent minor surgical procedures or follow-up blood tests years after recovering from oncological diseases and who were otherwise healthy, were recruited as a control group. Blood samples for thrombelastography (EX and TPA test, including the coagulation time (CT), clot formation time (CFT), clot amplitude after 5 minutes (A05), maximum clot firmness (MCF), maximum lysis (ML), α-angle, and lysis time (LT)) were taken once to twice weekly in addition to daily routine blood tests in patients undergoing HSCT. Routine testing included blood counts, coagulation parameters, d-dimers, and bilirubin. VOD symptoms were monitored daily and body weight was measured twice a day. Ultrasound screenings for ascites, progredient hepatomegaly, and portal venous flow velocity were performed in case of suspected VOD. All patients received intravenous anticoagulation with 100 IU/kg and day of unfractionated heparin. Of the control group patients, 6 ml blood was collected once per patient for routine coagulation testing and thrombelastography. Results A total of 51 patients with a median age of 7.8 years were recruited in the study group. Of these patients, five (9.8%) developed VOD and received defibrotide treatment. The VOD was graded moderate (n=2; 4%), severe (n=1; 2%) or very severe (n=2; 4%). Defibrotide treatment was initiated for 4 weeks or until the resolution of symptoms in standard dosing (25 milligrams per kilogram per day (mg/kg/d)) in four doses over 2 hours). The control group consisted of 55 patients with a median age of 6.7 years. A significant difference in thrombelastographic measurements was observed when comparing the VOD to the HSCT group. The lysis time after activation of fibrinolysis in the TPA test was prolonged in the VOD group at 3 weeks after HSCT (d+14 to +21: VOD: 330±67 seconds, HSCT: 246±53 seconds, p=0.0106). Additionally, a significant difference between the VOD and control groups was observed in days +14 to +21 (control: LT 234±50 seconds, p=0.0299). For the time points of day 0 to +6 and day +7 and +13 after HSCT lysis time was also prolonged in VOD patients, but without statistical significance (LT: d0 to +6: VOD: 304±57 seconds; HSCT: 251±67 seconds, p=0.06; d+7 to +13: VOD: 278±34 seconds; HSCT: 255±70 seconds, p=0.12). It was observed that LT correlated positively with weight gain (>5%), progredient hepatomegaly, right upper quadrant pain and reduced portal venous flow velocity (d0 to d+6: weight gain: r=0.31, p=0.0351; pain: r=0.44, p=0.0018; hepatomegaly: r=0.37, p=0.0108; d+7 to +13: pain: r=0.35, p=0.0143; hepatomegaly: r=0.39, p=0.0058; d+14 to d+21: weight gain: r=0.42, p=0.0035; pain: r=0.37, p=0.0103; hepatomegaly: r=0.44, p=0.0020; reduced portal venous flow velocity: r=0.35, p= 0.0167). Conclusions The results suggest that HSCT patients and patients diagnosed with VOD show signs of hypofibrinolysis. Fibrinolysis can be assessed in a rapid and accessible way via thrombelastography. Therefore, thrombelastography might be a useful tool to facilitate early diagnosis of VOD and to identify high-risk patients. Larger studies are needed to determine specific cut-off-values. Stefanie Hammer and Michaela Döring contributed equally to this work.

Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa.

IntroductionAndexanet alfa (andexanet) is an approved antidote used to reverse the bleeding effects of Direct Oral Anticoagulant (Direct-Xa agents) agents because it reverses anti-Xa activity. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit anti-Xa activity. The purpose is to investigate the neutralization of UFH and LMWH by andexanet in activated clotting time (ACT), thrombelastography (TEG), and anti-Xa due to the protamine sulfate shortage.MethodsUFH and LMWH were studied with andexanet, PS, or saline as potential reversal agents/controls at varying concentrations in ACT, TEG, and anti-Xa and compared to each other.ResultsAndexanet partially neutralized both drugs several TEG parameters at high andexanet concentrations, but it was not as effective as protamine sulfate in any of the assays used. Most TEG parameters were correlated with andexanet concentration. In ACT, significant neutralization was demonstrated at many andexanet concentrations for UFH, but not LMWH. UFH was completely neutralized by PS in ACT, while LMWH was partially neutralized by PS in ACT. Andexanet alfa was a less effective neutralization agent than the protamine sulfate as it only partially neutralized UFH in ACT and was ineffective at neutralizing LMWH when tested at the same concentration as PS (10 ug/mL).ConclusionAndexanet partially neutralized UFH and LMWH with variability between assays, necessitating investigation into assay-dependent differences.

Evolution of Platelet Function and Bleeding in Children and Adults with Chronic Immune Trombocytopenia on Romiplostim Treatment

INTRODUCTION. Platelets in immune thrombocytopenia (ITP) are not only reduced in quantity, but were also reported to have impaired function. There is evidence that this might be the mechanism behind the clinically established fact that severity of bleeding in ITP does not correllate well with the degree of thrombocytopenia. However, there are no established methods or guidelines to predict bleeding risks based on the platelet function tests, and little information about the effects of thrombopoietin mimetics on platelet function.MATERIALS. We studied evolution of platelet function and clinical bleeding symptoms in 32 adult and 44 pediatric patients with chronic ITP 32 over six months of romiplostim treatment using flow cytometry and thrombelastography (TEG). As controls, samples of 20 healthy donors were used. The median age of adult patients was 62 (19-80 years), that of pediatric patients was 10 (1-18 years). All had previous history of treatment (one to three lines of therapy). Platelet function was characterized by flow cytometry before and after activation with SFLLRN plus collagen-related peptide. Levels of CD42b, CD61, CD62P, PAC1, annexin V binding, and mepacrine uptake and release were evaluated. Bleeding score was determined using a standardized consensus-based ITP-specific bleeding assessment tool developed by the International Working Group on ITP. Thrombelastography (TEG) was employed to characterize integral hemostasis function. Investigations were performed in accordance with the Declaration of Helsinki under a protocol approved by the NSPC CHOI Ethical Committee, and written informed consent was obtained from all donors and patients. Comparisons between groups were performed using Mann-Whitney non-parametric test.RESULTS. Bleeding before the start of therapy was observed in 10 adults and 25 children. There was no significant difference in platelet count between the bleeding and non-bleeding adults (median 25 versus 23, respectively). For children, it was significantly (median 19 versus 83, p<0.05) lower for those with bleeding. Both adult's and children's platelets were significantly pre-activated by all parameters (PAC1, CD62p, annexin V) and increased in size (forward scatter, CD42b, CD61, mepacrine uptake) compared with normal ones. The TEG lag time parameters R and K were significantly increased in the ITP patients, while α angle and MA were decreased. Platelet pre-activation, size, and TEG parameter changes were significantly greater (by 50-100%) in the adult patients with bleeding phenotype compared with those who had no hemorrhage. Evaluation of their predictive capabilities with regard to bleeding risks using ROC analysis produced AUC values between 0.78 and 0.91, allowing design of a risk calculator. The results for children were similar when adjusted for the platelet count difference in the bleeding and non-bleeding groups. Romiplostim treatment led to a rapid (<1 month) decrease of procoagulant annexin V-positive platelets in the circulation to the normal level, followed by a more gradual normalization of platelet size and decrease of PAC1-positive platelets over several months. In some adult and pediatric patients, disappearance of clinical bleeding syndromes on romiplostim was associated with normalization of platelet function parameters in the absence of platelet count increase.CONCLUSIONS. Our data indicate that: a) platelets in chronic ITP are pre-activated, large and slowly reacting; b) these changes are associated with bleeding independently of platelet count, and can be used for risk stratification; c) romiplostim treatment decreases platelet size and pre-activation. DisclosuresPanteleev:Amgen: Research Funding.

Pulmonary arterial hypertension patients display normal kinetics of clot formation using thrombelastography.

Pulmonary arterial hypertension is characterized by endothelial dysfunction and microthrombi formation. The role of anticoagulation remains controversial, with studies demonstrating inconsistent effects on pulmonary arterial hypertension mortality. Clinical anticoagulation practices are currently heterogeneous, reflecting physician preference. This study uses thrombelastography and hematology markers to evaluate whether clot formation and fibrinolysis are abnormal in pulmonary arterial hypertension patients. Venous blood was collected from healthy volunteers (n = 20) and patients with pulmonary arterial hypertension (n = 20) on stable medical therapy for thrombelastography analysis. Individual thrombelastography parameters and a calculated coagulation index were used for comparison. In addition, hematologic markers, including fibrinogen, factor VIII activity, von Willebrand factor activity, von Willebrand factor antigen, and alpha2-antiplasmin, were measured in pulmonary arterial hypertension patients and compared to healthy volunteers. Between group differences were analyzed using t tests and linear mixed models, accounting for repeated measures when applicable. Although the degree of fibrinolysis (LY30) was significantly lower in pulmonary arterial hypertension patients compared to healthy volunteers (0.3% ± 0.6 versus 1.3% ± 1.1, p = 0.04), all values were within the normal reference range (0–8%). All other thrombelastography parameters were not significantly different between pulmonary arterial hypertension patients and healthy volunteers (p ≥ 0.15 for all). Similarly, alpha2-antiplasmin activity levels were higher in pulmonary arterial hypertension patients compared to healthy volunteers (103.7% ± 13.6 versus 82.6% ± 9.5, p < 0.0001), but all individual values were within the normal range (75–132%). There were no other significant differences in hematologic markers between pulmonary arterial hypertension patients and healthy volunteers (p ≥ 0.07 for all). Sub-group analysis comparing thrombelastography results in patients treated with or without prostacyclin pathway targeted therapies were also non-significant. In conclusion, treated pulmonary arterial hypertension patients do not demonstrate abnormal clotting kinetics or fibrinolysis by thrombelastography.

Identification of hypercoagulability with thrombelastography in patients with hip fracture receiving thromboprophylaxis.

Background:Venous thromboembolism (VTE) is the second most common complication after hip fracture surgery. We used thrombelastography (TEG), a wholeblood, point-of-care test that can provide an overview of the clotting process, to determine the duration of hypercoagulability after hip fracture surgery.Methods:In this prospective study, consecutive patients aged 51 years or more with hip fractures (trochanteric region or neck) amenable to surgical treatment who presented to the emergency department were eligible for enrolment. Thrombelastography, including calculation of the coagulation index (CI) (combination of 4 TEG parameters for an overall assessment of coagulation) was performed daily from admission until 5 days postoperatively, and at 2 and 6 weeks postoperatively. All patients received 28 days of thromboprophylaxis. We used single-sample t tests to compare mean maximal amplitude (MA) values (a measure of clot strength) to the hypercoagulable threshold of greater than 65 mm, a predictor of in-hospital VTE.Results:Of the 35 patients enrolled, 11 (31%) were hypercoagulable on admission based on an MA value greater than 65 mm, and 29 (83%) were hypercoagulable based on a CI value greater than 3.0; the corresponding values at 6 weeks were 23 (66%) and 34 (97%). All patients had an MA value greater than 65 mm at 2 weeks. Patients demonstrated normal coagulation on admission (mean MA value 62.2 mm [standard deviation (SD) 6.3 mm], p = 0.01) but became significantly hypercoagulable at 2 weeks (mean 71.6 mm [SD 2.6 mm], p < 0.001). There was a trend toward persistent hypercoagulability at 6 weeks (mean MA value 66.2 mm [SD 3.8 mm], p = 0.06).Conclusion:More than 50% of patients remained hypercoagulable 6 weeks after fracture despite thromboprophylaxis. Thrombelastography MA thresholds or a change in MA over time may help predict VTE risk; however, further study is needed.

Hypercoagulability as Measured by Thrombelastography May Be Associated with the Size of Acute Ischemic Infarct-A Pilot Study.

Background: Thromboelastography (TEG®) measures coagulation function in venous blood. Previous studies have reported that this device providing an integrated data on dynamics of clot formation may be useful for predicting clinical outcome in ischemic stroke. We investigated whether a hypercoagulability detected by thrombelastography may be associated with larger size of acute ischemic infarct. Methods: We included 40 ischemic stroke subjects with large artery atherosclerosis or small-vessel disease to a cross-sectional pilot study. Thrombelastography parameters related to time of clot formation (R- reaction time, K-clot kinetics), clot growth and strengthening (angle-alpha and MA-maximum amplitude) and lysis (Ly30) were performed within first 24 h after the onset of stroke. A volume of ischemic infarct was assessed on the basis of diffusion-weighted imaging (DWI) sequence of magnetic resonance imaging. Results: In the entire group, we reported that subjects with a large ischemic focus (>2 cm3) had a higher diameter of a clot (measured as MA) than subjects with a small ischemic focus (p = 0.0168). In the large artery atherosclerosis subgroup, we showed a significant correlation between MA and size of acute infarct (R = 0.64, p = 0.0138), between angle (alpha) and size of acute infarct (R = 0.55, p = 0.0428) and stroke subjects with hypercoagulability (MA > 69 mm) had significantly higher probability of a larger size of acute ischemic focus compared to normalcoagulable subjects (5.45 cm3 vs. 1.35 cm3; p = 0.0298). In multivariate logistic regression hypercoagulability was a predictor of a large size of ischemic infarct (Odds ratio OR = 59.5; 95% confidence interval (CI) 1.08–3558.8; p = 0.0488). Conclusions: We emphasized that thrombelastography, based on the parameters related to clot strength, may have clinical utility to identify the risk of the extensive ischemic infarct.

Pneumatic tube transport of blood samples affects global hemostasis and platelet function assays.

Pneumatic tube systems (PTS) are frequently used for rapid and cost-effective transportation of blood samples to the clinical laboratory. The impact of PTS transport on platelet function measured by the Multiplate system and global hemostasis measured by the TEG 5000 was evaluated. Paired samples from healthy adult individuals were obtained at two study sites: Rigshospitalet (RH) and Nordsjaellands Hospital (NOH). One sample was transported by PTS and one manually (non-PTS). Platelet function was assessed by platelet aggregation (Multiplate) and global hemostasis was assessed by a variety of thrombelastography (TEG) assays. Multiplate (n=39) and TEG (n=32) analysis was performed at site RH, and Multiplate (n=28) analysis was performed at site NOH. A significant higher agonist-induced platelet aggregation was found for PTS samples compared to manual transport at site NOH (P<.02, all agonists). No significant difference was found at site RH (P>.05, all agonists). For Kaolin TEG, samples transported by PTS showed a significant lower R-time and higher Angle (P<.001). No significant differences in MA and LY30 was found (P>.05). ACT of RapidTEG was significantly reduced (P=.001) and MA of Functional Fibrinogen TEG was significantly increased (P<.001) after PTS transport. No significant impact of PTS was observed for TEG assays with heparinase (P>.05). Depending on the type of PTS, transportation by PTS affected platelet aggregation measured by Multiplate. Furthermore, PTS alters TEG parameters possibly reflecting coagulation factors. Clinical laboratories should evaluate the effect of the local PTS on Multiplate and TEG results.

Prevention of postoperative bleeding after complex pediatric cardiac surgery by early administration of fibrinogen, prothrombin complex and platelets: a prospective observational study

BackgroundPostoperative bleeding is a major problem in children undergoing complex pediatric cardiac surgery. The primary aim of this prospective observational study was to evaluate the effect of an institutional approach consisting of early preventive fibrinogen, prothrombin complex and platelets administration on coagulation parameters and postoperative bleeding in children. The secondary aim was to study the rate of re-intervention and postoperative transfusion, the occurrence of thrombosis, length of mechanical ventilation, ICU stay and mortality.MethodsIn fifty children (age 0–6 years) with one or more predefined risk factors for bleeding after cardiopulmonary bypass (CPB), thrombelastography (TEG) and standard coagulation parameters were measured at baseline (T1), after CPB and reversal of heparin (T2), at sternal closure (T3) and after 12 h in the ICU (T4). Clinical bleeding was evaluated by the surgeon at T2 and T3 using a numeric rating scale (NRS, 0–10).ResultsAfter CPB and early administration of fibrinogen, prothrombin complex and platelets, the clinical bleeding evaluation score decreased from a mean value of 6.2 ± 1.9 (NRS) at T2 to a mean value of 2.1 ± 0.8 at T3 (NRS; P < 0.001). Reaction time (R), kinetic time (K), maximum amplitude (MA) and maximum amplitude of fibrinogen (MA-fib) improved significantly (P < 0.001 for all), and MA-fib correlated significantly with the clinical bleeding evaluation (r = 0.70, P < 0.001). The administered total amount of fibrinogen (mg kg− 1) correlated significantly with weight (r = − 0.42, P = 0.002), priming volume as percentage of estimated blood volume (r = 0.30, P = 0.034), minimum CPB temperature (r = − 0.30, P = 0.033) and the change in clinical bleeding evaluation from T2 to T3 (r = 0.71, P < 0.001). The incidence of postoperative bleeding (> 10% of estimated blood volume) was 8%. No child required a surgical re-intervention, and no cases of thrombosis were observed. Hospital mortality was 0%.ConclusionIn this observational study of children with an increased risk of bleeding after CPB, an early preventive therapy with fibrinogen, prothrombin complex and platelets guided by clinical bleeding evaluation and TEG reduced bleeding and improved TEG and standard coagulation parameters significantly, with no occurrence of thrombosis or need for re-operation.Trial registrationGerman Clinical Trials Register DRKS00018109 (retrospectively registered 27th August 2019).

Admission thrombelastography does not guide dose adjustment of enoxaparin in trauma patients

BackgroundEnoxaparin is used as chemoprophylaxis to reduce incidence of venous thromboembolism and its complications following trauma. Serum anti-Xa monitoring is used to assess efficacy but requires several doses to be administered. Thrombelastography assesses hypercoagulability and may have utility identifying high-risk patients for venous thromboembolism. The objective was to evaluate whether thrombelastography parameters could identify trauma patients requiring enoxaparin dose adjustment earlier than serum anti-Xa concentrations. MethodsA single-center, retrospective medical record review evaluated patients admitted to a regional level I trauma center that received an admission thrombelastography and a dose of enoxaparin with a serum trough anti-Xa concentration drawn. Patients were divided into standard-dose or dose-adjusted enoxaparin. Venous thromboembolism incidence between groups and risk factors for enoxaparin dose adjustment and venous thromboembolism development were evaluated. ResultsA total of 204 patients were included. Differences observed between groups included age (standard-dose enoxaparin, 48.5 [29.3–72] vs dose-adjusted enoxaparin, 38.5 [25–55.7] years; P = .005), admission creatinine clearance (standard-dose enoxaparin, 92.9 [67.4–113.4] vs dose-adjusted enoxaparin, 102.1 [83.8–129.2] mL/min; P = .017), and time to venous thromboembolism prophylaxis initiation (standard-dose enoxaparin, 23.8 [11.2–36.4] vs dose-adjusted enoxaparin, 34.5 [18.3–52.7] hours; P = .004). No differences in thrombelastography parameters or venous thromboembolism incidence were observed. No independent risk factors for enoxaparin dose adjustment were identified; however, risk assessment profile score > 10 was an independent risk factor for venous thromboembolism development. ConclusionNo relationship between admission thrombelastography and need for enoxaparin dose adjustment in trauma patients was observed. As thrombelastography continues growing in clinical use, it is prudent to investigate other potential applications. Currently, thrombelastography should not be used to guide enoxaparin dosing.

Data-driven Development of ROTEM and TEG Algorithms for the Management of Trauma Hemorrhage: A Prospective Observational Multicenter Study.

Developing pragmatic data-driven algorithms for management of trauma induced coagulopathy (TIC) during trauma hemorrhage for viscoelastic hemostatic assays (VHAs). Admission data from conventional coagulation tests (CCT), rotational thrombelastometry (ROTEM) and thrombelastography (TEG) were collected prospectively at 6 European trauma centers during 2008 to 2013. To identify significant VHA parameters capable of detecting TIC (defined as INR > 1.2), hypofibrinogenemia (< 2.0 g/L), and thrombocytopenia (< 100 x10/L), univariate regression models were constructed. Area under the curve (AUC) was calculated, and threshold values for TEG and ROTEM parameters with 70% sensitivity were included in the algorithms. A total of, 2287 adult trauma patients (ROTEM: 2019 and TEG: 968) were enrolled. FIBTEM clot amplitude at 5 minutes (CA5) had the largest AUC and 10 mm detected hypofibrinogenemia with 70% sensitivity. The corresponding value for functional fibrinogen (FF) TEG maximum amplitude (MA) was 19 mm. Thrombocytopenia was similarly detected using the calculated threshold EXTEM-FIBTEM CA5 30 mm. The corresponding rTEG-FF TEG MA was 46 mm. TIC was identified by EXTEM CA5 41 mm, rTEG MA 64 mm (80% sensitivity). For hyperfibrinolysis, we examined the relationship between viscoelastic lysis parameters and clinical outcomes, with resulting threshold values of 85% for EXTEM Li30 and 10% for rTEG Ly30.Based on these analyses, we constructed algorithms for ROTEM, TEG, and CCTs to be used in addition to ratio driven transfusion and tranexamic acid. We describe a systematic approach to define threshold parameters for ROTEM and TEG. These parameters were incorporated into algorithms to support data-driven adjustments of resuscitation with therapeutics, to optimize damage control resuscitation practice in trauma.

Viscoelastic Signals for Optimal Resuscitation in Trauma: Kaolin Thrombelastography Cutoffs for Diagnosing Hypofibrinogenemia (VISOR Study).

Acute traumatic coagulopathy is common in trauma patients. Prompt diagnosis of hypofibrinogenemia allows for early treatment with cryoprecipitate or fibrinogen concentrate. At present, optimal cutoffs for diagnosing hypofibrinogenemia with kaolin thrombelastography (TEG) have not been established. We hypothesized that kaolin kaolin-TEG parameters, such as kinetic time (K-time), α-angle, and maximum amplitude (MA), would accurately diagnose hypofibrinogenemia (fibrinogen <200 mg/dL) and severe hypofibrinogenemia (fibrinogen <100 mg/dL). Adult trauma patients (injury severity score >15) presenting to our trauma center between October 2015 and October 2017 were identified retrospectively. All patients had a traditional plasma fibrinogen measurement and kaolin-TEG performed within 15 minutes of each other and within 1 hour of admission. Some patients had additional measurements after. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether K-time, α-angle, and MA could diagnose hypofibrinogenemia and severe hypofibrinogenemia. Area under the ROC curve (AUROC) was calculated for each TEG parameter with a bootstrapped 99% confidence interval (CI). Further, ROC analysis was used to estimate ideal cutoffs for diagnosing hypofibrinogenemia and severe hypofibrinogenemia by maximizing sensitivity and specificity. In addition, likelihood ratios were also calculated for different TEG variable cutoffs to diagnose hypofibrinogenemia and severe hypofibrinogenemia. Seven hundred twenty-two pairs of TEGs and traditional plasma fibrinogen measurements were performed in 623 patients with 99 patients having additional pairs of tests after the first hour. MA (AUROC = 0.84) and K-time (AUROC = 0.83) better diagnosed hypofibrinogenemia than α-angle (AUROC = 0.8; P = .03 and P < .001 for AUROC comparisons, respectively). AUROCs statistically improved for each parameter when severe hypofibrinogenemia was modeled as the outcome (P < .001). No differences were found between parameters for diagnosing severe hypofibrinogenemia (P > .05 for all comparisons). The estimated optimal cutoffs for diagnosing hypofibrinogenemia were 1.5 minutes for K-time (95% CI, 1.4-1.6), 70.0° for α-angle (95% CI, 69.8-71.0), and 60.9 mm for MA (95% CI, 59.2-61.8). The estimated optimal cutoffs for diagnosing severe hypofibrinogenemia were 2.4 minutes for K-time (95% CI, 1.7-2.8), 60.6° for α-angle (95% CI, 57.2-67.3), and 51.2 mm for MA (95% CI, 49.0-56.2). Currently recommended K-time and α-angle cutoffs from the American College of Surgeons had low sensitivity for diagnosing hypofibrinogenemia (3%-29%), but sensitivity improved to 74% when using optimal cutoffs. Kaolin-TEG parameters can accurately diagnose hypofibrinogenemia and severe hypofibrinogenemia in trauma patients. Currently recommended cutoffs for the treatment of hypofibrinogenemia are skewed toward high specificity and low sensitivity. Many patients are likely to be undertreated for hypofibrinogenemia using current national guidelines.

Fibrinogen levels are associated with bleeding in patients with primary immune thrombocytopenia

Bleeding is the most common clinical symptom and the leading cause of death in patients with primary immune thrombocytopenia (ITP). Our research intends to verify the role of fibrinogen levels as independent determinants of bleeding. We retrospectively analyzed the relationship between fibrinogen levels and bleeding events in 463 patients. Additionally, we confirmed the impact of fibrinogen level on clot firmness in 25 patients via thrombelastography (TEG). Fibrinogen levels (median and inter-quartile range, IQR) were significantly different (p < .001) between bleeding and non-bleeding patients [258(207–314) mg/dL vs. 315(262–407) mg/dL, respectively]. Further analyzes in three subgroups based on platelet (PLT) count showed that non-bleeding patients still had higher fibrinogen levels than bleeding patients. The optimal discriminant threshold of fibrinogen in bleeding was 288.5 mg/dL according to receiver operating characteristic (ROC) curves. Patients were divided into low (LF, 230[193–258] mg/dL) and high (HF, 349[313–424] mg/dL) fibrinogen groups based on this threshold. Bleeding event rates were significantly different (LF: 84.6% vs. HF: 60.4%, P < .001) between the two groups. Multivariable analyses further confirmed these differences. Moreover, TEG parameters showed elevated clot firmness in the HF group. Our data suggest that high fibrinogen levels are associated with reduced bleeding events.

Limited factor VIIa surface localization requirement of the factor VIIa–induced overall thrombin generation in platelet‐rich hemophilia A plasma

BackgroundThrombin generation assay (TGA) and thrombelastography (TEG) are increasingly employed, global, in vitro methods for assessment of the procoagulant potential of plasma/blood and possibly ideally suited tools to monitor, for example, therapy with recombinant factor VIIa (FVIIa). It remains controversial to what extent results obtained with spiked and postinfusion samples reflect the outcome in patients. ObjectiveTo characterize the TGA response to FVIIa in hemophilic plasma and compare with TEG data. MethodsHemophilia A (HA) was induced in platelet‐rich plasma (PRP) from healthy volunteers, followed by spiking with FVIIa, γ‐carboxyglutamic acid (Gla)‐domainless FVIIa or V158D/E296V/M298Q‐FVIIa (FVIIaDVQ). Samples were triggered with tissue factor and analyzed by TGA and TEG in parallel. ResultsAddition of 25 nmol L−1 FVIIa to HA PRP normalized TEG parameters angle and R time, as well as TGA lag time, but had poor effects on the thrombin peak height and velocity index. All parameters (at least) returned to normal levels either upon adding a much higher concentration of FVIIa (~1500 nmol L−1) or by using the superactive variant FVIIaDVQ. Surprisingly, Gla‐domainless derivatives of FVIIa and FVIIaDVQ also yielded considerable effects in HA PRP. ConclusionsThe good general responses to clinically effective concentrations of FVIIa (25 and 75 nmol L−1) seen in TEG analyses, as well as for TGA lag time, were accompanied by far‐from‐normal thrombin peaks. A near‐normal thrombin peak response required the presence of considerably higher FVIIa activity but, intriguingly, relied only marginally on a functional Gla domain (ie, on platelet surface localization).

Residual platelet reactivity is preferred over platelet inhibition rate in monitoring antiplatelet efficacy: insights using thrombelastography.

Although thrombelastography (TEG) has been widely implemented in the clinical setting of endovascular intervention, consensus on the optimal parameter for defining high ischemic risk patients is lacking due to the limited data about the relationship between various TEG parameters and clinical outcomes. In this article, we report a post hoc analysis of a prospective, single-center cohort study, including 447 patients with acute coronary syndrome (ACS). Arachidonic acid (AA)- or adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAAA or MAADP) was indicative of the net residual platelet reactivity after the treatment with aspirin or clopidogrel, respectively. AA% or ADP% was indices of the relative platelet inhibition rate on AA or ADP pathway. We found that each parameter alone was predictive of the risk of 6-month ischemic event, even after adjusting for confounding factors. However, the association between AA% and clinical outcome disappeared when further adjusted for MAAA. Likewise, inclusion of MAADP changed the significant relation between ADP% and clinical outcome. MAADP > 47.0 mm and MAAA > 15.1 mm were identified as the optimal cutoffs by receiver operating characteristic analysis. High MAAA (HR = 3.963; 95% CI: 1.152–13.632; P = 0.029) and high MAADP (HR = 5.185; 95% CI: 2.228–12.062; P < 0.001) were independent predictors when both were included in multivariable Cox regression hazards model. Interestingly, an even higher risk was found for the coexisting high MAAA and high MAADP (HR = 7.870; 95% CI: 3.462–17.899; P < 0.001). We conclude that when performing TEG to predict clinical efficacy, residual platelet reactivity has superiority over platelet inhibition rate as a measure of thrombotic risk in patients treated with aspirin and clopidogrel after ACS.

Application of thrombelastography in primary total knee and total hip replacement: a prospective 87 patients study.

: Thrombelastography (TEG) parameters and prothrombin time (PT), activated partial thromboplastin time (APTT) are compared and analysed. According to change of TEG parameters and assessment of haemostatic state of each patient, we try to explore the feasibility of individualized anticoagulant therapies. 87 people with hip or knee diseases awaiting arthroplasty were recruited. Haemoglobin levels and TEG parameters including R, K, α-angle, maximum amplitude, coagulation index were assessed in perioperative period. PT and APTT were assessed preoperatively. For 65 patients with normal TEG parameters, PT and APTT, we use tranexamic acid (TXA) to reduce blood loss during operation. As hypercoagulability group, 12 patients awaiting unilateral total knee arthroplasty with hypercoagulable state assessed by TEG parameters or risks for venous thromboembolism received daily 10-mg rivaroxaban until 24 h preoperatively and did not receive TXA during operation. All patients received intravenous administration of argatroban after 8 h postoperatively until day 3 and oral administration of rivaroxaban (10 mg) subsequently to prevent deep vein thrombosis or/and pulmonary embolism until 35 days postoperatively. TEG parameters have significant relationships with fibrinogen, platelet and APTT. The number of patients with abnormal haemostatic state assessed by TEG parameters is higher than that assessed by PT, APTT. TEG show hypercoagulability develops throughout perioperative period. There was no significant difference in haemoglobin concentration between hypercoagulability group and normal group in patients receiving unilateral total knee arthroplasty. TEG have higher sensitivity of perioperative abnormal haemostatic state than PT, APTT in primary arthroplasty. For patients with hypercoagulability, individualized anticoagulant therapies such as preoperative administration of rivaroxaban and not using TXA in operation is safe and effective.

Association of Thrombelastographic Parameters with Complications in Patients with Intracranial Aneurysm After Stent Placement

A prospective trial was conducted to investigate the platelet function and association between thrombelastographic (TEG) parameters and embolic or hemorrhagic complications in patients with intracranial aneurysm undergoing stent treatment. Between September 2013 and June 2016, we prospectively recruited patients with intracranial aneurysm who were treated with stent-assisted coiling. TEG parameters were used to assess the platelet function before stenting procedures. The primary study end point was the onset of ischemic stroke, transient ischemic attack, or silent ischemic events in the territory of the stented artery within 6 months after the procedure. The secondary end point was assessed by bleeding events. Four hundred and thirty-one patients with 453 intracranial aneurysms were enrolled. A total of 519 neurovascular stents were implanted. During the follow-up, a total of 70 primary end points (16.2%) and 59 secondary end points (13.7%) were detected. Thromboembolic complications such as symptomatic and slient ischemic complications were more frequently observed in patients with large aneurysms (>10 mm, P= 0.01), lower adenosine diphosphate (ADP) inhibition rate (P < 0.0001), and higher ADP-induced platelet-fibrin clot strength (maximum amplitude of adenosine diphosphate [MA-ADP]) (P < 0.0001). Besides, based on multivariate analysis, a higher ADP inhibition ratio was identified as a significant independent predictor of subsequent bleeding events (P < 0.0001). According to the receiver operating characteristic curve analysis, the safe range of the ADP inhibition ratio and MA-ADP of the TEG analysis were identified as 29.45%-55.4% and <46.15, respectively. The ADP inhibition ratio and MA-ADP of TEG analysis were associated with subsequent cerebral ischemic events and intracranial or extracranial bleeding events in patients with intracranial aneurysm after stent treatment.

Evaluation of the hypercoagulable state of gynecologic cancer patients by thromboelastography: a prospective pilot study and a review of the literature

Objective: Cancer patients are at risk for developing venous thromboembolism (VTE). The present authors assessed the value of using thrombelastography (TEG) to evaluate the coagulation state of women with various forms of gynecological disorders. Materials and Methods: Surgical patients with gynecological malignancy (study group, n = 65, 71%) were prospectively compared to patients with premalignant and benign disease (control group, n = 19, 29%). Routine blood tests and TEG results were collected one day prior to surgery. Clinical and laboratory data were collected from the medical charts. Univariate and multivariate analyses were performed to determine group differences. Results: The study patients included 15 (23%) women with endometrial, 22 (33.8%) with ovarian, and nine (13.8%) with uterine cervical cancer. They were significantly older, had a higher body mass index, and more comorbidities, all known risk factors to develop VTE, compared to the control group. Surprisingly, TEG parameters were similar for both groups except for the α angle (time of clot formation), that was wider in the study group (76.6 ± 3.43º vs. 74.66 ± 3.66º, p = 0.044, non-significant on multivariate analysis). Conclusions: The pre-surgical/basal TEG profile is similar for gynecological patients with malignant and benign disease and therefore does not differentiate between them in terms of greater risk of VTE.