Impact of systematic variations in hematocrit and platelet count on thrombelastometry tissue factor activated assay parameters.

BACKGROUND: Thromboelastogram testing is increasingly being used to manage patients with massive bleeding. An earlier study found that the test results were influenced by the hematocrit (Hct) and platelet (PLT) concentrations. This study sought to determine if these factors confounded the results of a different manufacturer's thromboelastography testing. METHODS: Using freshly collected whole blood from volunteers and stored red blood cells (RBC) and plasma, the whole blood was manipulated to achieve different Hct values and PLT concentrations. Each reconstituted whole blood sample was tested in triplicate on the ROTEM Delta device and the ExTEM results were recorded. RESULTS: Many of the ExTEM results varied according to the Hct and PLT concentration. In particular, the ExTEM clot formation time (CFT) was abnormally long when the Hct was 45% and the PLT concentration was ≤75 × 109/L, normalizing only when the PLT count was ≥100 × 109/L. CFT samples with Hct 25% and 35% were also abnormal with low PLT concentrations but normalized at lower PLT concentrations compared to the Hct 45% samples. The ExTEM angle also demonstrated abnormal results when the Hct was 45% and the PLT concentration was ≤50 × 109/L. The ExTEM A10 and maximum clot firmness (MCF) tests tended to also be abnormal when the Hct was between 25% and 45% and the platelet concentrations were below 75 × 109/L. CONCLUSION: While thromboelastogram testing is gaining popularity for managing bleeding patients, clinicians should be aware of these confounding factors when making transfusion decisions based on their results.

The precision of ROTEM EXTEM is decreased in hypocoagulable blood: a prospective observational study.

BACKGROUND: The use of viscoelastic tests is becoming increasingly popular. There is a paucity of validation of the reproducibility of varying coagulation states. Therefore, we aimed to study the coefficient of variation (CV) for the ROTEM EXTEM parameters clotting time (CT), clot formation time (CFT), alpha-angle and maximum clot firmness (MCF) in blood with varying degrees of coagulation strength. The hypothesis was that CV increases in states of hypocoagulability. METHODS: Critically ill patients and patients subjected to neurosurgery at a university hospital during three separate periods were included. Each blood sample was tested in eight parallel channels, yielding the CVs for the tested variables. In 25 patients, the blood samples were analysed both at baseline and after dilution with albumin 5%, as well as after being spiked with fibrinogen, simulating weak and strong coagulation. RESULTS: In total, 225 unique blood samples were collected from 91 patients. All samples were analysed in eight parallel ROTEM channels, resulting in 1,800 measurements. In hypocoagulable samples, defined as those with values outside the normal reference range, the CV of CT was higher (median (interquartile range)) (6.3% (5.1-9.5)) than for normocoagulable samples (5.1% (3.6-7.5)), p < 0.001. CFT showed no difference (p = 0.14), while the CV of alpha-angle was higher in hypocoagulable samples (3.6% (2.5-4.6)) than in normocoagulable samples (1.1% (0.8-1.6), p < 0.001. The CV of MCF was higher in hypocoagulable samples (1.8% (1.3-2.6)) than in normocoagulable samples (1.2% (0.9-1.7)), p < 0.001. The CV ranges for the different variables were as follows: CT: 1.2%-37%, CFT: 1.7%-30%, alpha-angle: 0.0%-17% and MCF: 0.0%-8.1%. CONCLUSIONS: CVs for the EXTEM ROTEM parameters CT, alpha-angle, and MCF increased in hypocoagulable blood compared to blood with normal coagulation, confirming the hypothesis for CT, alpha-angle, and MCF but not for CFT. Furthermore, the CVs for CT and CFT were much higher than those for alpha-angle and MCF. The results demonstrate that EXTEM ROTEM results from patients with weak coagulation should be interpreted with the notion of limited precision and that procoagulative treatment, based only on ROTEM EXTEM, should be given with some caution.

Assessment of agreement between EXTEM and NATEM thromboelastometry measurement assays in critically ill neonates.

OBJECTIVES: To investigate the agreement between the EXTEM and NATEM measurements. METHODS: In this retrospective observational study, EXTEM and NATEM analyses were performed on blood samples from 162 ill neonates, providing 324 paired measurements. The agreement between EXTEM and NATEM measurements was evaluated by the nonparametric spearman's rank correlation to assess the correlation between the paired measurements, by the Bland-Altman analysis for the graphical presentation of the agreement, and by the Deming regression model to assess the significance of the agreement. The agreement between the two methods for the detection of bleeding events was determined by kappa statistic. RESULTS: Strong correlations were found between EXTEM and NATEM measurements for A10, MCF. The Bland-Altman plots showed good agreement for A10, MCF, LI60, and alpha angle parameters, while CT showed a nearly linear slope indicating that bias increased with the mean. The highest agreement for bleeding events was found for the A10 parameter (κ = 0.70, p < .001), while the lowest for the CT parameter (κ = 0.36, p = .94). CONCLUSIONS: NATEM parameters that reflect clot firmness and fibrinolytic activity are strongly correlated with the corresponding EXTEM measurements with a good agreement between them, indicating that these two methods could be used interchangeably.

A prospective study on the correlation between thromboelastometry and standard laboratory tests - influence of type of surgery and perioperative sampling times.

This prospective study aimed at investigating the influence of surgery type and perioperative sampling times on the correlations between rotational thromboelastometry (ROTEM) parameters and standard laboratory coagulation tests assessing comparable coagulation phases. Patients undergoing glioblastoma multiforme resection (GBR group, n = 60) or laparoscopic colon cancer resection (CCR group, n = 40) were prospectively included. Blood samples for ROTEM and laboratory assessments were consecutively drawn within 24-hours prior to surgery (baseline), and at 2, 24 and 48-hours after surgery. Correlations between perioperative ExTEM clotting-time (CT-exTEM) and prothrombin time (PT), and between FibTEM maximum clot firmness (MCF-fibTEM) with and plasma fibrinogen (pFB) concentration (Clauss method), were evaluated using the Spearman's rho test. The efficiency of recommended cut-offs of CT-exTEM (>75 s) and MCF-fibTEM (<10 mm) for predicting a prolonged PT (>15 s) or a low pFB (<2 g/L), respectively, was assessed using Receiver-Operator Characteristic curves. Correlations between CT-exTEM and PT were weak in GBR (rho = 0.25 [0.12-0.38], p < .01), and very weak in CCR (rho = 0.06 [-0.12-0.27]). Those between MCF-fibTEM and pFB, were strong in both GBR (rho = 0.69 [0.61-0.76], p < .01) and CCR (rho = 0.70 [0.60-0.78], p < .01). These correlations remained largely unchanged over the studied perioperative period in both groups. Recommended CT-exTEM and MCF-fibTEM cut-offs had poor sensitivity for predicting a prolonged PT (17% [8-31]) or a low pFB (46% [32-62]), without group-related differences. Neither the type of surgery nor the perioperative sampling times had a significant influence on the correlations between ROTEM parameters and standard laboratory tests. ClinicalTrials.gov ID: NCT02652897.

Rotational thromboelastometry-guided transfusion during lumbar pedicle subtraction osteotomy for adult spinal deformity: preliminary findings from a matched cohort study.

OBJECTIVESignificant blood loss and coagulopathy are often encountered during adult spinal deformity (ASD) surgery, and the optimal intraoperative transfusion algorithm is debatable. Rotational thromboelastometry (ROTEM), a functional viscoelastometric method for real-time hemostasis testing, may allow early identification of coagulopathy and improve transfusion practices. The objective of this study was to investigate the effect of ROTEM-guided blood product management on perioperative blood loss and transfusion requirements in ASD patients undergoing correction with pedicle subtraction osteotomy (PSO).METHODSThe authors retrospectively reviewed patients with ASD who underwent single-level lumbar PSO at the University of Virginia Health System. All patients who received ROTEM-guided blood product transfusion between 2015 and 2017 were matched in a 1:1 ratio to a historical cohort treated using conventional laboratory testing (control group). Co-primary outcomes were intraoperative estimated blood loss (EBL) and total blood product transfusion volume. Secondary outcomes were perioperative transfusion requirements and postoperative subfascial drain output.RESULTSThe matched groups (ROTEM and control) comprised 17 patients each. Comparison of matched group baseline characteristics demonstrated differences in female sex and total intraoperative dose of intravenous tranexamic acid (TXA). Although EBL was comparable between ROTEM versus control (3200.00 ± 2106.24 ml vs 3874.12 ± 2224.22 ml, p = 0.36), there was a small to medium effect size (Cohen's d = 0.31) on EBL reduction with ROTEM. The ROTEM group had less total blood product transfusion volume (1624.18 ± 1774.79 ml vs 2810.88 ± 1847.46 ml, p = 0.02), and the effect size was medium to large (Cohen's d = 0.66). This difference was no longer significant after adjusting for TXA (ß = -0.18, 95% confidence interval [CI] -1995.78 to 671.64, p = 0.32). More cryoprecipitate and less fresh frozen plasma (FFP) were transfused in the ROTEM group patients (cryoprecipitate units: 1.24 ± 1.20 vs 0.53 ± 1.01, p = 0.03; FFP volume: 119.76 ± 230.82 ml vs 673.06 ± 627.08 ml, p < 0.01), and this remained significant after adjusting for TXA (cryoprecipitate units: ß = 0.39, 95% CI 0.05 to 1.73, p = 0.04; FFP volume: ß = -0.41, 95% CI -772.55 to -76.30, p = 0.02). Drain output was lower in the ROTEM group and remained significant after adjusting for TXA.CONCLUSIONSFor ASD patients treated using lumbar PSO, more cryoprecipitate and less FFP were transfused in the ROTEM group compared to the control group. These preliminary findings suggest ROTEM-guided therapy may allow early identification of hypofibrinogenemia, and aggressive management of this may reduce blood loss and total blood product transfusion volume. Additional prospective studies of larger cohorts are warranted to identify the appropriate subset of ASD patients who may benefit from intraoperative ROTEM analysis.

Can prepartum thromboelastometry-derived parameters and fibrinogen levels really predict postpartum hemorrhage?

BACKGROUND: Decreased postpartum rotational thromboelastometric parameters of coagulation (ROTEM®) and fibrinogen levels have been associated with postpartum hemorrhage (PPH). However, the predictive power of prepartum ROTEM® parameters and fibrinogen levels (Fbgpre) for PPH remains unknown. METHODS: This prospective observational pilot study included 217 healthy pregnant women. Maximum clot firmness (FIBTEM-MCF), fibrinogen levels and standard coagulation parameters were measured upon admission to the delivery room for labor and within 1 h after vaginal delivery. Blood loss was measured with a calibrated collecting drape during the third stage of labor. PPH was defined as blood loss ≥500 mL. Predictors for bleeding were identified via receiver operating characteristic analyses and bivariate and multivariate regression analyses. RESULTS: Women with and without PPH did not differ in median FIBTEM-MCF [23 mm (25th percentile 20 mm, 75th percentile 26 mm) vs. 23 mm (19 mm, 26 mm), respectively; P=0.710] or mean Fbgpre (4.57±0.77 g/L vs. 4.45±0.86 g/L, respectively; P=0.431). Blood loss and prepartum coagulation parameters were not correlated (FIBTEM-MCF, rs=-0.055, P=0.431; Fbgpre, rs=-0.017, P=0.810). The areas under the curves (predictive power for PPH) for FIBTEM-MCF and Fbgpre and were 0.52 (0.41-0.64, P=0.699) and 0.53 [95% confidence interval (95% CI) 0.40-0.65, P=0.644], respectively. Neither FIBTEM-MCF nor Fbgpre was associated with PPH. However, primiparity [odds ratio (OR) 4.27, 95% CI 1.32-13.80, P=0.015) and urgent cesarean section (2.77, 1.00-7.67, P=0.050) were independent predictors of PPH. CONCLUSIONS: ROTEM® parameters, Fbgpre and postpartum blood loss were not associated, nor did these factors predict PPH. Sufficiently powered prospective studies are needed to confirm these results.

Evaluation of the Effect of Storage Time on ROTEM S® Parameters in Healthy and Ill Dogs.

Viscoelastic testing as a bedside test to assess global haemostasis has gained popularity in the past decade, with rotational thromboelastometry (ROTEM) and thromboelastography (TEG) being the two commonly used devices. TEG studies suggest analysis 30 min after blood sampling. However, the reproducibility of results over time for ROTEM analysis using lyophilized samples in dogs has not been established. In this study, we investigated the influence of time on viscoelastic testing, using 33 healthy staff-/client-owned dogs for blood sampling and repeated measurements of ROTEM tracings at three different time points after blood collection. Additionally, a group of 21 hospitalized patients with suspected coagulation disorders were included to investigate whether stability over time was comparable between healthy and ill dogs. We demonstrated a significant difference of ROTEM tracings over time, with a tendency towards hypocoagulability over time. These changes do have a clinical relevance as they exceed reference intervals and could therefore lead to erroneous conclusions about a patient's coagulation status. Therefore, time-specific reference intervals are proposed and presented in this publication.

Correlation of rotational thromboelastometry (ROTEM) parameters with platelet count and their ability to predict thrombocytopenia in dogs.

The study objectivs were to evaluate the correlation between platelet count (PLT) and rotational thromboelastometry (ROTEM) parameters and to determine ROTEM cut-off values for identification of thrombocytopenia in dogs. Medical records of 113 dogs with concurrent EXTEM (ROTEM activated by proprietary tissue factor), FIBTEM (EXTEM with added cytochalasin D) analysis and PLT were retrospectively reviewed. Signalment, treatment prior to analysis, hematocrit (HCT), EXTEM/FIBTEM maximum clot firmness (MCFEXTEM, MCFFIBTEM), EXTEM/FIBTEM maximum clot elasticity (MCEEXTEM, MCEFIBTEM) and EXTEM maximum lysis (MLEXTEM) were extracted from patient records and ROTEM database. Delta (Δ) MCF was calculated as MCFEXTEM-MCFFIBTEM and ΔMCE as MCEEXTEM-MCEFIBTEM. The PLT was correlated to MCFEXTEM, MCEEXTEM, ΔMCF and ΔMCE using Spearman-Rho analysis. Correlations were further analyzed in thrombocytopenic dogs. The ability to predict thrombocytopenia was evaluated with receiver operating characteristics (ROC). Thirty-seven samples (32.7%) showed thrombocytopenia (<130 × 109/L) and 19 samples (17%) severe thrombocytopenia (<60* x 109/L). The PLT significantly correlated with MCFEXTEM (r = 0.545, P < .001), MCEEXTEM (r = 0.547, P < .001), ΔMCF (r = 0.441, P < .001) and ΔMCE (r = 0.559, P < .001). MCFEXTEM < 49 mm, MCEEXTEM < 93, ΔMCF <42 mm and ΔMCE <90 predicted thrombocytopenia <60 × 109/L with a sensitivity of 90% and a specificity of 78% with a negative predictive value >97% for all 4 parameters. In conclusion, PLT in dogs correlated moderately but significantly with all evaluated ROTEM parameters. All parameters were able to rule out thrombocytopenia <60 × 109/L with a high negative predictive value, while the sensitivity to predict thrombocytopenia was only moderate and the positive predictive value was low.

Correlation of early ROTEM parameters with conventional coagulation tests in patients with chronic liver disease undergoing liver transplant.

BACKGROUND AND AIMS: Viscoelastic tests such as rotational thromboelastometry (ROTEM) provide a quick and holistic assessment of coagulation status to guide transfusion during liver transplant (LT). Conventional coagulation tests (CCTs) measure single parameters in isolation, and also the results are delayed hampering management of patients during surgery. We evaluated the correlation of early ROTEM-derived parameters with CCTs and also assessed the ability of ROTEM-derived parameters to predict thrombocytopaenia and hypofibrinogenaemia during LT in patients with end-stage liver disease (ESLD). METHODS: This retrospective study was carried out in 100 patients with decompensated ESLD undergoing LT. Correlation between CCTs and ROTEM parameters was analyzed. Receiver operating characteristic curves with area under the curve were used to determine the cut-off values of A5 andA10 on EXTEM and FIBTEM. RESULTS: The values of A5EXTEM and A10EXTEM highly correlated with fibrinogen levels and platelet count, whereas A5FIBTEM and A10FIBTEM correlated well with fibrinogen levels. A5EXTEM<21 mm and A10EXTEM<28 mm correlated with a platelet count <75,000 mm-3, whereas A5EXTEM<18 mm and A10EXTEM<25 mm correlated with a platelet count <50,000 mm-3. Fibrinogen levels <100 mg/dL better correlated with A5FIBTEM<5 mm, A10FIBTEM<6 mm, A5EXTEM<21 mm and A10EXTEM<30 mm. CONCLUSION: Early ROTEM parameters A5 and A10 of both EXTEM and FIBTEM had an excellent correlation with thrombocytopaenia and hypofibrinogenaemia and may potentially guide early transfusion of relevant blood products during LT.

Evaluation of Thromboelastometry in Sepsis in Correlation With Bleeding During Invasive Procedures.

Prolongation of prothrombin time (PT) is often encountered in patients with sepsis. On the other hand, thromboelastometry as a global coagulation test might yield normal results. The aim of our study was to evaluate whether prolonged PT in the presence of normal thromboelastometry parameters is associated with severe bleeding in patients with sepsis undergoing invasive procedures. In patients with sepsis undergoing low-risk bleeding invasive procedures (central venous catheter placement, dialysis catheter insertion, drain insertion, and so on) or high-risk bleeding invasive procedures (surgical tracheostomy, surgical laparotomy, thoracotomy, and so on), coagulation was assessed by thromboelastometry using EXTEM test (test for evaluation of the extrinsic pathway of coagulation, contains activator of extrinsic pathway) and with PT. For period of years 2013 to 2016, we assessed occurrence of severe bleeding during those procedures and 24 hours later in patients with prolonged PT and normal thromboelastometry results. This retrospective study was performed at Department of Anaesthesiology and Intensive Care Medicine of Motol University Hospital in Prague. Data from 76 patients with sepsis were analyzed. Median value of international normalized ratio (INR) was 1.59 (min-1.3 and max-2.56), and median value of prothrombin ratio (PR) was 1.5 (min-1.23 and max-2.55) with normal thromboelastometry finding. Despite prolonged INR/PR, no severe bleeding was observed during invasive procedures. Our data show that sepsis may be accompanied by normal thromboelastometry results, despite prolonged values of PT, and invasive procedures were performed without severe bleeding. This approach to coagulation assessment in sepsis may reduce administration of fresh frozen plasma to the patients. The study was registered at Clinical Trials.gov with assigned number NCT02971111.

Rotational thromboelastometry-guided blood product management in major spine surgery.

OBJECT Major spinal surgery in adult patients is often associated with significant intraoperative blood loss. Rotational thromboelastometry (ROTEM) is a functional viscoelastometric method for real-time hemostasis testing. In this study, the authors sought to characterize the coagulation abnormalities encountered in spine surgery and determine whether a ROTEM-guided, protocol-based approach to transfusion reduced blood loss and blood product use and cost. METHODS A hospital database was used to identify patients who had undergone adult deformity correction spine surgery with ROTEM-guided therapy. All patients who received ROTEM-guided therapy (ROTEM group) were matched with historical cohorts whose coagulation status had not been evaluated with ROTEM but who were treated using a conventional clinical and point-of-care laboratory approach to transfusion (Conventional group). Both groups were subdivided into 2 groups based on whether they had received intraoperative tranexamic acid (TXA), the only coagulation-modifying medication administered intraoperatively during the study period. In the ROTEM group, 26 patients received TXA (ROTEM-TXA group) and 24 did not (ROTEM-nonTXA group). Demographic, surgical, laboratory, and perioperative transfusion data were recorded. Data were analyzed by rank permutation test, adapted for the 1:2 ROTEM-to-Conventional matching structure, with p < 0.05 considered significant. RESULTS Comparison of the 2 groups in which TXA was used showed significantly less fresh-frozen plasma (FFP) use in the ROTEM-TXA group than in the Conventional-TXA group (median 0 units [range 0-4 units] vs 2.5 units [range 0-13 units], p < 0.0002) but significantly more cryoprecipitate use (median 1 unit [range 0-4 units] in the ROTEM-TXA group vs 0 units [range 0-2 units] in the Conventional-TXA group, p < 0.05), with a nonsignificant reduction in blood loss (median 2.6 L [range 0.9-5.4 L] in the ROTEM-TXA group vs 2.9 L [0.7-7.0 L] in the Conventional-TXA group, p = 0.21). In the 2 groups in which TXA was not used, the ROTEM-nonTXA group showed significantly less blood loss than the Conventional-nonTXA group (median 1 L [range 0.2-6.0 L] vs 1.5 L [range 1.0-4.5 L], p = 0.0005), with a trend toward less transfusion of packed red blood cells (pRBC) (median 0 units [range 0-4 units] vs 1 unit [range 0-9 units], p = 0.09]. Cryoprecipitate use was increased and FFP use decreased in response to ROTEM analysis identifying hypofibrinogenemia as a major contributor to ongoing coagulopathy. CONCLUSIONS In major spine surgery, ROTEM-guided transfusion allows for standardization of transfusion practices and early identification and treatment of hypofibrinogenemia. Hypofibrinogenemia is an important cause of the coagulopathy encountered during these procedures and aggressive management of this complication is associated with less intraoperative blood loss, reduced transfusion requirements, and decreased transfusion-related cost.