Baseline Thromboelastography Research Articles

Utility of thromboelastography to assess the effect of anticoagulation reversal in intracranial hemorrhage.

Intracranial hemorrhage (ICH) is a serious complication associated with oral anticoagulant use and is associated with significant morbidity and mortality. Although anticoagulation reversal agents are utilized as standard of care, practitioners are limited in their ability to assess degree of anticoagulation reversal for direct oral anticoagulants (DOACs). There is a clinical need identify biomarkers to assess anticoagulation status in patients with DOAC-associated ICH to ensure hemostatic efficacy of anticoagulation reversal agents in the acute setting. The purpose of this study was to assess the utility of thromboelastography (TEG) to assess the impact of anticoagulation reversal in patients presenting to the emergency department (ED) with DOAC-associated ICH. We conducted a prospective, observational cohort study in adult patients presenting to the ED with acute DOAC-associated ICH. Patients were excluded if last DOAC dose was >48 hours prior to hospital arrival, if they experienced polytrauma, were pregnant, incarcerated, had a history of hepatic failure or coagulopathy, or received anticoagulation reversal with products other than prothrombin complex concentrates (PCCs). We collected baseline TEG samples from participants prior to anticoagulation reversal, as well as 30-minutes, 12-hours, and 24-hours post-reversal. TEG samples were also collected from participants who transferred to our facility after reversal at ED presentation, as well as 12- and 24-hours post-reversal. Pre-reversal TEG was collected on 10 participants prior to DOAC reversal. A significant decrease in TEG R-time was observed at 30 minutes post-reversal. R-time increased at 12- and 24-hours to baseline levels. Significant changes were not observed in K-time, clot strength, maximum amplitude, or coagulation index. TEG R-time may be able to detect a change in anticoagulation activity of DOACs in ICH after anticoagulation reversal. R-time decreases acutely after anticoagulation reversal and rebounds at 12- and 24-hours post-reversal.

Abstract WP169: Thromboelastography as a Biomarker of Emergent Direct-Acting Oral Anticoagulant Reversal With Prothrombin Complex Concentrates for Intracranial Hemorrhage

Prothrombin complex concentrates (PCCs) are used to emergently reverse direct-acting oral anticoagulant (DOAC) activity. PCCs are recommended as an alternative to recombinant coagulation factor-Xa to reverse anticoagulation activity of apixaban or rivaroxaban. Measuring the degree of anticoagulation reversal in this population is limited. Thromboelastography (TEG) has been used to detect the presence of DOAC plasma levels in patients chronically taking a DOAC but has not been utilized to measure the effect on anticoagulant activity after PCC administration. We aimed to determine whether TEG R-time is useful in detecting the impact of PCC administration on anticoagulation activity in patients with anti-factor Xa-associated intracranial hemorrhage (ICH). We prospectively evaluated the utility of TEG to assess anticoagulation activity after factor Xa inhibitor reversal with 4-factor PCC. Adults with ICH taking apixaban or rivaroxaban were included. Patients were excluded if their last known dose of anticoagulation was >48 hours prior to arrival, had known apixaban or rivaroxaban blood levels <20 ng/mL, or had the following comorbidities: hepatic failure, hereditary disorders of hemostasis, polytrauma, or pregnancy. TEG samples were collected before PCC administration (if available), and 0.5, 12, and 24 hours after PCC administration. Thirty-one patients were enrolled between November 2022 and August 2023. The median PCC dose was 24.5 units/kg (IQR 20.3-26.9 units/kg; n=29). Nine patients received anticoagulation reversal after baseline TEG collection; the remainder received anticoagulation reversal at transferring facilities. Baseline R-time was negatively correlated with time since last dose of DOAC (n=9). A median decrease in R-time of 0.8 minutes after PCC (IQR -1.6 - 0.3; n=8) was found in patients with baseline TEG collection. R-time rebounded by a median of 0.75 minutes (IQR 0.2-2.0; n=8) from 0.5 hours to 12 hours after PCC administration (n=8). TEG R-time, a measure that inversely correlates with the degree of anticoagulant effect, rapidly decreases after PCC in patients taking DOACs that present with acute ICH. TEG R-time rebounds 12 hours after PCC administration. TEG-R time may be a useful biomarker in DOAC reversal with PCC.

Thromboelastography is a Marker for Clinically Significant Progressive Hemorrhagic Injury in Severe Traumatic Brain Injury.

Coagulopathy in traumatic brain injury (TBI) is associated with increased risk of poor outcomes, but accurate prediction of clinically significant progressive hemorrhagic injury (PHI) in patients with severe TBI remains a challenge. Thromboelastography (TEG) is a real-time test of whole blood coagulation that provides dynamic information about global hemostasis. This study aimed to identify differences in TEG values between patients with severe TBI who did or did not experience clinically significant PHI. This was a single-center retrospective cohort study of adult patients with severe TBI. Patients were eligible for inclusion if initial Glasgow coma scale (GCS) was ≤ 8 and baseline head computed tomography (CT) imaging and TEG were available. Exclusion criteria included receipt of hemostatic agents prior to TEG. PHI was defined as bleeding expansion on CT within 24h associated with 2-point drop in GCS, neurosurgical intervention, or mortality within 24h. The primary endpoint was TEG value differences between patients with and without PHI. Secondary endpoints included differences in conventional coagulation tests (CCTs) between groups. Of the 526 patients evaluated, 141 met inclusion criteria. The most common reason for exclusion was lack of baseline TEG and receipt of reversal product prior to TEG. Sixty-four patients experienced PHI in the first 24h after presentation. K time (2.03min vs. 1.33min, P = 0.035) and alpha angle (65° vs. 69°, P = 0.015) were found to be significantly different in patients experiencing PHI. R time (5.25min vs. 4.71min), maximum amplitude (61mm vs. 63mm), and clot lysis at 30min after maximum clot strength (3.5% vs. 1.7%) were not significantly different between groups. Of the CCTs, only activated partial thromboplastin time (30.3s vs. 27.6s, P = 0.014) was found to be different in patients with PHI. Prolonged K time and narrower alpha angle were found to be associated with developing clinically significant PHI in patients with severe TBI. Despite differences detected in alpha angle, median values in both groups were within normal reference ranges. These abnormalities may reflect pathologic hypoactivity of fibrinogen, and further study is warranted to evaluate TEG-guided cryoprecipitate administration in this patient population.

Orthopedic Injury‐Induced Hypercoagulability in Rats

Trauma‐associated hypercoagulability is estimated to occur in 28% of injured patients, leading to thromboembolic complications such as deep venous thrombosis and pulmonary embolism. Orthopedic injury accounts for >45% of injuries requiring hospitalization. However, few clinically relevant models exist to examine the specific mechanisms underlying orthopedic injury‐induced hypercoagulability. Therefore, the aim of this study was to establish a novel rodent model of hypercoagulability after bilateral hindlimb injury mimicking the hypercoagulability found in trauma patients. For this purpose, 16‐week‐old male Wistar rats (n=5, mean body weight=381±21 g) were anesthetized; had carotid catheters placed for serial blood sampling; and were subjected to bilateral hindlimb fibula fracture with controlled soft tissue and muscular crush injury followed by injection of bone homogenate, mimicking injuries sustained with bilateral femur fracture. Blood samples were drawn into 4% sodium citrate, incubated for 30 min at room temperature while rocking, and analyzed by native thromboelastography (TEG) at 3, 6, 12, and 24 h post‐injury. TEG is a viscoelastic assay that allows for comprehensive assessment of clot formation and degradation in whole blood which, unlike standard clinical coagulation tests, can detect hypercoagulability. Baseline TEG studies were performed in triplicate immediately after catheter placement. Compared to baseline measurements, mean TEG parameters did not significantly differ at 3 and 6 h time points. However, significant hypercoagulability was noted at 12 h in maximal amplitude of clot firmness (1.2‐fold increase, p=0.002), overall clot strength (TEG ‘G’ value, 2.1‐fold increase, p=0.003), and thrombin generation (1.2‐fold increase, p=0.003); these parameters remained persistently elevated at 24 h (1.3, 2.5, and 1.2‐fold higher than baseline, respectively; all p<0.003). There were no significant differences compared to baseline at any time points in the TEG parameters R (reflecting time to clot initiation), K or angle (reflecting fibrin polymerization kinetics), or lysis index (reflecting fibrinolysis; all p>0.05). In summary, a rodent model of bilateral hindlimb orthopedic injury recapitulates post‐injury hypercoagulability identified in human trauma patients, as identified by TEG. Hypercoagulability is specifically manifested as increased clot strength and thrombin generation, with no changes alterations in time to clot formation, fibrin polymerization kinetics, or fibrinolysis. We propose that this model will allow for investigation of mechanisms mediating injury‐induced hypercoagulability to assist in identifying novel strategies for thromboprophylaxis.Support or Funding InformationNIH HL105324, NIH HL130577, NIH TR001417, and NIH GM115428This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fibrinolysis Shutdown Is Associated With Thrombotic and Hemorrhagic Complications and Poorer Outcomes After Liver Transplantation.

Detrimental consequences of hypofibrinolysis, also known as fibrinolysis shutdown (FS), have recently arisen, and its significance in liver transplantation (LT) remains unknown. To fill this gap, this retrospective study included 166 adults who received transplants between 2016 and 2018 for whom baseline thromboelastography was available. On the basis of percent of clot lysis 30minutes after maximal amplitude, patients were stratified into 3 fibrinolysis phenotypes: FS, physiologic fibrinolysis, and hyperfibrinolysis. FS occurred in 71.7% of recipients, followed by physiologic fibrinolysis in 19.9% and hyperfibrinolysis in 8.4%. Intraoperative and postoperative venous thrombosis events occurred exclusively in recipients with the FS phenotype. Intraoperative thrombosis occurred with an overall incidence of 4.8% and was associated with 25.0% in-hospital mortality. Incidence of postoperative venous thrombosis within the first month was deep venous thrombosis/pulmonary embolism (PE; 4.8%) and portal vein thrombosis/hepatic vein thrombosis (1.8%). Massive transfusion of ≥20units packed red blood cells was required in 11.8% of recipients with FS compared with none in the other 2 phenotype groups (P=0.01). Multivariate analysis identified 2 pretransplant risk factors for FS: platelet count and nonalcoholic steatohepatitis/cryptogenic cirrhosis. Recursive partitioning identified a critical platelet cutoff value of 50×109 /L to be associated with FS phenotype. The hyperfibrinolysis phenotype was associated with the lowest 1-year survival (85.7%), followed by FS (95.0%) and physiologic fibrinolysis (97.0%). Infection/multisystem organ failure was the predominant cause of death; in the FS group, 1 patient died of exsanguination, and 1 patient died of massive intraoperative PE. In conclusion, there is a strong association between FS and thrombohemorrhagic complications and poorer outcomes after LT.

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.

Thromboelastographic Characterization of the Activated Clotting System in Children with Sickle Cell Trait or Sickle Cell Disease

Background: Recent epidemiological evidence suggests sickle cell disease (SCD) and sickle cell trait (SCT) are risk factors for venous thromboembolism. The increased in vivo markers of thrombin generation support the notion that such patients are in a chronic hypercoagulable state. In an attempt to better understand the underlying mechanism, global hemostatic assays including thrombin generation assay (TGA) and thromboelastography (TEG) have been utilized by several groups, with inconsistent results either due to small sample size or technical differences. As opposed to the bleeding disorders, the traditional methods of TEG are not sensitive to hypercoagulability. Our group developed modified methods that prolonged the baseline TEG parameters to enhance this sensitivity. These altered TEG profiles were shown to be significantly shortened by increasing concentrations of thrombin in vitro.Objectives: Global hemostatic characterization of children with SCD or SCT by using TGA and modified TEG methods.Materials and methods: In this pilot study, we obtained hemostatic data including complete blood count with differential, reticulocyte count, fibrinogen, D-dimer, thrombin antithrombin complex and prothrombin fragment 1.2 on specimens from subjects with SCD in their usual state of health, subjects with SCT and healthy controls (NC). In addition global hemostatic assays including standard and modified thromboelastography methods as well as thrombin generation assays were performed.Results: Thirty-nine African-American subjects were recruited: 12 NC, 14 SCT and 13 SCD. The median ages for the groups were 12 (Range: 5-39), 19 (Range: 2-40) and 8 (Range: 2-14) years for NC, SCT, and SCD, respectively. Females represented 58% of the NC, 57% of the SCT subjects and 38% of the SCD subjects. In vivo markers of thrombin generation and activation of fibrinolysis including D-dimer and thrombin-antithrombin complexes were higher in SCD subjects as compared to SCT and NC (p=0.001; p=0.05 respectively). Reaction (R) time, and Kinetic (K) time with modified TEG methods was significantly shorter in SCD when compared to SCT and NC (p=0.014, p=0.038) respectively. Angle (alpha) and maximum amplitude (MA) did not show any significant differences between the groups. TGA profiles did not show any difference between the three groups either.Conclusion: The in vivo use of modified thromboelastography methods is able to detect the hypercoagulability known to occur in the sickle cell disease population but a larger sickle cell trait cohort needs to be studied to determine if this group also has hypercoagulability. Importantly, this study, the first to evaluate both TEG and TGA assays in SCD or SCT population demonstrates the importance of using whole blood to differentiate these groups as the TEG assay demonstrated differences the TGA could not detect. As SCD and SCT subjects have a highly complex physiology with not only alterations in almost all the components of the coagulation system, but also variation in the quantity and function of other blood components including white blood cells, platelets and red blood cells, TEG may prove a good tool in measuring a change in the activity of the coagulation system rather than a single baseline measurement. Our results support the need for further studies using thromboelastography in SCD and SCT population in order to better understand and triage this cohort of patients for risks of thrombotic complications. DisclosuresNo relevant conflicts of interest to declare.

Thromboelastography (TEG) As a Global Assay to Elucidate Complex Nuances of Hemostasis in Pediatric Inhibitor Patients with High Titer Inhibitors

▪Background: Pediatric severe hemophilia A patients with high titer inhibitors are often reported to have inadequate control of acute bleeding episodes because they do not respond to bypassing agents as predictably as with FVIII therapy for non-inhibitor patients. Thromboelastography (TEG) is a global assay of hemostasis that has promising benefits for use in clinical care for hemophilia patients.Aims: This study was performed to determine in pediatric inhibitor patients: 1) if baseline TEG, specifically R or reaction time that corresponds to time to thrombin generation and clot formation, is stable over time in individual inhibitor patients; 2) if there are any predictors of baseline TEG R time; 3) to determine response to recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordisk, Copenhagen, Denmark); and 4) to determine predictors of TEG R time following rFVIIa.Methods: This analysis was conducted within a consented single institution prospective inceptional cohort study. Clinical data regarding healthy volunteers with no personal or family history of a bleeding or clotting disorder and pediatric hemophilia patients with and without inhibitors (assayed by Nijmegen modification of the Bethesda assay (BU)) were extracted from research records and electronic medical records. For this study, TEGs were performed in kaolin citrated samples with added TPA (final concentration 450 ng/mL). Descriptive data were presented as mean and SD. This report analyzed TEG R times, indicating time to clot formation and initial thrombin generation. Baseline TEGs were obtained at least five half-lives after the last infusion of each clotting factor or bypassing agent received. Post treatment TEGs were performed on patients 1 hour following a therapeutic treatment with rFVIIa.Results: R times on TEGs were obtained on 24 healthy adults, 23 healthy children, 15 children with severe hemophilia A without an inhibitor, and 12 children with severe hemophilia A and an inhibitor. 32 samples were obtained in the 12 children with inhibitors, with 1 to 11 samples from each child. Paired samples were obtained at baseline prior to and 1 hour following a dose (90-270 mg/kg) of rFVIIa. Mean TEG R times were 8.3 minutes (SD 1.4) for healthy adults, 7.7 minutes (SD 1.5) for healthy children, 20.2 minutes (SD 9.4) for children with severe hemophilia A and 102.1 minutes (SD 44.4) for children with severe hemophilia A and inhibitors. Healthy children did not differ from healthy adults (p=0.43), but children with hemophilia with inhibitors differed from healthy controls (p=0.046) and trended toward differences from children with hemophilia without inhibitors (p=0.08, however limited in sample number). Baseline R values in children with inhibitors did not correlate with age (r=-0.19) or inhibitor titer (r=0.23). Children studied on multiple occasions showed variability over time. TEG 1 hour following rFVIIa in a baseline state showed a mean R time of 25.1 minutes (SD 7.1). Post rFVIIa R time did not correlate with age (r=0.21) or inhibitor titer (r=-0.14), but showed considerable correlation with baseline TEG R time (Figure 1, r =0.65, p=0.013). Following infusion of rFVIIa, TEG R times of children with inhibitors never achieved the normal range. However, when rFVIIa was studied following multiple infusions without a washout, the mean TEG R was moderately, but non-significantly shorter at 20.6 minutes (SD 5.6).Conclusions: TEG R times in young children with severe hemophilia A with inhibitors are greatly prolonged compared to healthy children or adults, and moderately longer than that in children with severe hemophilia A without inhibitors. Baseline TEG R varies over time and cannot be predicted by age or inhibitor titer. Baseline TEG R time may be an important predictor of response to bypassing therapy and serial monitoring over time may be clinically useful to guide therapy. During the course of multiple infusions, moderately improved TEG R responses were determined compared with first infusions. This may, in part, explain our previously reported observation of longer duration of rFVIIa dosing in young children with inhibitors. Future studies employing TEG to help optimize response to bypassing agents are needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract W P58: Thromboelastography Can Detect the Anticoagulant Effect of Factor Xa Inhibitors in Patients Who Might Be Eligible for Tissue Plasminogen Activator Treatment for Acute Ischemic Stroke

Background: Factor Xa inhibitors are approved for stroke prevention in patients with atrial fibrillation. The management of such patients is challenging if they are candidates for intravenous tPA since there is no rapidly available test to detect their anticoagulant effect. Thromboelastography (TEG) analyzes the dynamics of coagulation (Figure 1) and has previously demonstrated a hypercoagulable state in acute stroke patients. We sought to determine whether TEG can detect the anticoagulation effect of Factor Xa inhibitors in stroke patients. Methods: Venous blood from seven subacute cardioembolic stroke patients prescribed Rivaroxaban was analyzed before (baseline) and 2, 4, 6 hours after drug administration with four patients also analyzed at 18 hours. Comparison of TEG parameters at various time intervals were assessed by repeated measures analysis of variance. Generalized Estimating Equations with an autoregressive correlation matrix was applied to account for the correlation within patients. Results: Baseline TEG results required approximately 11 minutes to obtain. Higher R values were seen from baseline upto 18 hours, along with increased K values lasting upto 6 hours. Lower G, MA, and alpha-angle values were seen from baseline till 4 hours (Table 2). Together these results indicate slower and less strong clotting, and that the anti-coagulation effects of the drug peak at about 4-6 hours, with a trend towards normalization by 18 hours. Conclusion: TEG can detect the anticoagulant effect of Factor Xa inhibitors in stroke patients, and might be useful for guiding emergency management of those eligible for tPA.

Abstract 105: Iodinated Contrast Does Not Alter Clotting Dynamics in Acute Ischemic Stroke as Measured by Thromboelastography

Introduction: Modern treatment of acute ischemic stroke (AIS) has increasingly incorporated multimodal CT imaging. Data illustrating that radiographic contrast agents alter fibrin fiber characteristics and decrease fibrinolysis by thrombolytic agents are potentially concerning. Thromboelastography (TEG) provides an integrated, dynamic view of coagulation and has recently been correlated with thrombolysis in AIS patients. This is the first study to examine the effects of contrast agents on tPA-induced clot lysis using TEG. We hypothesized that receiving computed tomography angiography (CTA) prior to tPA will impair thrombolysis as measured by TEG. Methods: AIS patients receiving 0.9 mg/kg tPA within 4.5 hours of symptom onset were enrolled. For CTA, iohexol dose was calculated using Medrad’s P3T software. Blood was drawn for TEG prior to CTA or tPA treatment and again 10-minutes after tPA bolus. TEG values, time of TEG draw and tPA administration, and CTA times were recorded. TEG values in patients having CTA prior to tPA were compared with patients in whom a CTA was performed either after tPA or not at all. Results were analyzed using Mann-Whitney U Test. Results: 100 AIS patients received tPA. Of these, 17 patients had CTA prior to TEG blood draws and tPA bolus. 57 patients had either CTA following tPA or no CTA. The median change in clot lysis (LY30) following tPA was 94.8% in the contrast group vs. 94.5% in controls (p = 0.84). The median reduction in clot strength (G) was -8.8 dyn/cm 2 in the contrast group vs. -8.6 dyn/cm 2 in controls (p = 0.51). Pre-tPA G appeared to be attenuated by contrast (7.7 vs. 5.9 dyn/cm 2 ) when corrected for platelet activity; however, this difference was not significant (p = 0.14). There was no effect of contrast on any other pre-tPA TEG value. Conclusion: The current data do not support any impairment of tPA-induced clot lysis by contrast agents. Baseline TEG also appears to be unaffected by contrast, but more patients are needed to better examine a possible interaction between clot strength and contrast agents.

Thromboelastography for Monitoring of Hemostatic Changes Following Factor Administration

AbstractAbstract 3373 Introduction:Monitoring therapy in children with hemophilia receiving factor replacement products is a major challenge. Measurement of factor levels following treatment is time consuming and not available in time to make changes to the treatment regimen. This study evaluates the use of thromboelastography (TEG), in monitoring the treatment with factor replacement products in children with severe hemophilia without inhibitors. Because of limitations of standard coagulation assays that test specific isolated end points of coagulation, thromboelastography has been used to assess hemostasis as a global process and can assess thrombin/fibrin generation potential of the whole blood. Materials and Methods:This is an ongoing study that has been approved by our University IRB. The aim of this study is to evaluate the haemostatic changes as demonstrated by TEG, following the administration of a single dose of replacement factor in pediatric patients with severe hemophilia A (SHA) or B (SHB) without inhibitors.Patients on prophylaxis or on-demand therapy, who had not received any replacement factor for a minimum of 72 hours were included on study. A baseline TEG and FVIII/IX activity was obtained in the non-bleeding state at the time of enrollment and subsequent samples were obtained at 15mins, 1, 4, 8, 24 and 48 hours post factor replacement. Results:24 patients with SHA (n=21) or SHB (n=3) have been enrolled to date. 1 patient had to be eliminated from the study as he was noted to have an inhibitor on the day of study enrolment. The mean age of our patients on study was 12.2 years with the range of 2–24 years. The mean factor activity at the time of enrollment was 1.2%. 3 patients who had FVIII or IX levels >2% at the time of enrollment were excluded from the analysis; 2 with SHB on prophylaxis 2–3 times per week (FIX activity= 2.44% and 5.12%); 1 with SHA on twice weekly prophylaxis (FVIII=13.9). This may be related to FIX having a longer half life, or non-compliance with 72 hour washout period.The mean Factor level prior to factor administration, after elimination of these subjects was 0.42%. The mean Factor level and R time at each time point of the study are presented in Table 1. The calculated half life of FVIII (t1/2) ranged from 5.89 to 14.52 hours. There was no significant difference in factor t1/2 for children below or above 10 years of age. The rate of rise in the R time at 8 hours and 48 hours correlated with the drop in factor activity following infusion of a single dose of factor and was statistically significant (p=0.05, shown in table 1). This indicates that a prolonged R time at 8 or 48 hours is associated with a significantly shorter t1/2.Table 1Draw timeMean R timeMean Factor activityRise in R time vs t1/2Pre Factor infusion38.730.42n/a15 minutes post factor infusion8.669.7n/a1 hour post factor infusion9.261.2n/a4 hours post factor infusion9.241.9n/a8 hours post factor infusion11.530.6P=0.05*24 hours post factor infusion13.79.8P=0.1148 hours post factor infusion28.72.95P=0.05*n/a: not applicable; * statistical significance. Conclusion:Thromboelastography has been used for monitoring the factor therapy in children with hemophilia. Our study indicates that this may be a potentially useful tool to predict the half life of Factor with a single blood draw at 8 hours. This is extremely important given the variability in half life seen from patient to patient in everyday practice and the difficulty in conducting a PK analysis at several time points especially in children. The TEG is a quick (less than 3 hours) and easy method to monitor and make necessary changes to ongoing therapy. Larger multicenter studies may help define the use of TEG parameters for this purpose more accurately. The small sample size was a major limitation of our study, and hence we were unable to make clinical correlations to bleeding rates. Disclosures:No relevant conflicts of interest to declare.

Variability of thromboelastographic responses following the administration of rFVIIa to haemophilia A dogs supports the individualization of therapy with a global test of haemostasis

The efficacy of recombinant factor VIIa (rFVIIa) therapy in haemophilia A is challenged by the lack of a reliable monitoring tool for treatment response. This is further complicated by the significant inter-patient variability associated with this response. Thromboelastography (TEG), a real time global haemostatic test has shown superiority over conventional tests of haemostasis and has proven efficiency in the monitoring of bypass agents such as rFVIIa and FEIBA™. However, this evaluation has been limited to a few case studies or very small patient series. In this study, six severe haemophilia A dogs were treated with a clinically relevant single dose of rFVIIa, and therapy was monitored by thromboelastography predrug and at 15, 30 and 60 min postdrug administration using citrated whole blood samples activated with tissue factor and compared with non-tissue factor-activated samples. Despite the homogeneity of the tested dogs, a clear inter-individual variation was observed in the pre-and post-rFVIIa Thromboelastography analyzes. The improvement of global haemostatic parameters was seen as early as 15 min following drug administration, with a peak for factor VIIa activity in plasma at the same time. There is a significant correlation between plasma FVIIa and TEG parameters 15 min postinjection, and the baseline TEG profile influences the individual postdrug administration outcome. Together, these data support the value of TEG not only as an effective monitoring haemostatic test, but also as a tool for individualization of therapy to achieve the best haemostatic and cost effectiveness of rFVIIa therapy.

Evaluation of coagulation during cardiopulmonary bypass with a heparinase-modified thromboelastographic assay

Thromboelastography (TEG) is a useful method of assessing perioperative coagulation function in patients undergoing cardiac surgery. The presence of significant amounts of heparin in blood samples, however, prevents determination of changes in coagulation function by TEG or introduces artifactual error if samples contain heparin that is not present in vivo. For these reasons, whole blood coagulation function monitoring with TEG has not been feasible during cardiopulmonary bypass (CPS) with heparin anticoagulation. In this study, data obtained from 42 volunteers are presented to describe the effects of heparinase on TEG variables in the presence and absence of heparin. These data indicate that heparinase does not affect TEG parameters of whole blood not containing heparin and reverses the TEG effects of low levels of heparin contamination. Subsequently, 51 patients undergoing coronary artery surgery were studied using a modified TEG assay that incorporates in vitro application of heparinase to allow measurement of TEG parameters before, during, and after CPS. Heparinase-modified TEG assays facilitated diagnosis of heparin contamination in preoperative blood samples and permitted baseline TEG evaluation in patients receiving preoperative heparin infusions. Heparinase modified TEG assays revealed declines in α and MA values during CPS, which persisted and significantly correlated with values after protamine infusion ( α: r = 0.77, P = 0.001; MA: r = 0.78, P = 0.001). After CPS, heparinase-modified TEG assays revealed no evidence of residual heparin in 50% of 12 samples with activated clotting times (ACT) _ ̆ 140 seconds and that 21 of 39 patients had evidence of residual heparin despite ACT values < 140 seconds, consistent with the relative insensitivity of ACT and the greater sensitivity of TEG to very low levels of heparin. The use of heparinasemodified TEG assays during CPS also permitted detection of significant fibrinolysis in one patient before protamine administration. The data gathered in this study indicate the utility of the heparinase-modified TEG assay to monitor whole blood coagulation during CPB, identify the presence of heparin in TEG samples before systemic heparin therapy or protamine reversal, and evaluate platelet-fibrinogen interaction in patients receiving systemic heparin.

An assessment of the duration of cephapirin-induced coagulation abnormalities as measured by thromboelastography

Cephalosporin antibiotics are used prophylactically in cardiothoracic surgery to prevent postoperative infection. In 30 patients undergoing primary elective coronary artery bypass grafting, the whole blood coagulation system was prospectively evaluated before, and 10 and 30 minutes after administration of 1 g of cephapirin (Cefadyl, Bristol Laboratory, Evansville, IN). All patients had normal preoperative coagulation studies and had not received anticoagulant or antiplatelet therapy within 7 days of surgery. At 10 minutes after cephapirin administration, 23 of 30 patients had a significant change in all phases of whole blood coagulation as monitored by thromboelastography (TEG). Thirty minutes after cephapirin administration there was no statistical difference compared with the baseline TEG. It is concluded that cephapirin can cause a significant but transient change in the viscoelastic properties of blood. Coagulation parameters of the TEG should be measured prior to cephapirin administration to prevent errors in establishing baseline values prior to cardiopulmonary bypass.