Tooth acellular extrinsic fibre cementum incremental lines in humans are formed by parallel branched Sharpey's fibres and not by its mineral phase.

In humans, the growth pattern of the acellular extrinsic fibre cementum (AEFC) has been useful to estimate the age-at-death. However, the structural organization behind such a pattern remains poorly understood. In this study tooth cementum from seven individuals from a Mexican modern skeletal series were analyzed with the aim of unveiling the AEFC collagenous and mineral structure using multimodal imaging approaches. The organization of collagen fibres was first determined using: light microscopy, transmission electron microscopy (TEM), electron tomography, and plasma FIB scanning electron microscopy (PFIB-SEM) tomography. The mineral properties were then investigated using: synchrotron small-angle X-ray scattering (SAXS) for T-parameter (correlation length between mineral particles); synchrotron X-ray diffraction (XRD) for L-parameter (mineral crystalline domain size estimation), alignment parameter (crystals preferred orientation) and lattice parameters a and c; as well as synchrotron X-ray fluorescence for spatial distribution of calcium, phosphorus and zinc. Results show that Sharpey's fibres branched out fibres that cover and uncover other collagen bundles forming aligned arched structures that are joined by these same fibres but in a parallel fashion. The parallel fibres are not set as a continuum on the same plane and when they are superimposed project the AEFC incremental lines due to the collagen birefringence. The orientation of the apatite crystallites is subject to the arrangement of the collagen fibres, and the obtained parameter values along with the elemental distribution maps, revealed this mineral tissue as relatively homogeneous. Therefore, no intrinsic characteristics of the mineral phase could be associated with the alternating AEFC incremental pattern.

The FIBTEM paradox: Do coronary artery bypass grafting patients with high baseline FIBTEM clot firmness need more allogeneic blood transfusion?

BACKGROUND: Fibrinogen thromboelastometry (FIBTEM) test is clinically used for rotational thromboelastometry as a surrogate measure of fibrinogen. Elevated fibrinogen might confer protection against bleeding after major surgery. This single-center study was conducted to assess any relationship between baseline FIBTEM value and exposure to allogeneic transfusion in patients undergoing coronary artery bypass grafting (CABG). STUDY DESIGN AND METHODS: Data were obtained retrospectively from local FIBTEM data and the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database between 2016 and 2019. Preoperative FIBTEM 10-min amplitude (A10) was categorized as low (≤ 18 mm), intermediate (19-23 mm), or high (≥24 mm). The primary outcome was any transfusion during the hospitalization, including red blood cells (RBCs), platelets, plasma, and cryoprecipitate. A multivariable regression model was used to adjust for confounders and calculate an odds ratio (OR) for any transfusion. RESULTS: The high FIBTEM group included more female and African-American patients, as well as urgent surgery. The STS predicted risks of morbidity and mortality were greater, and anemia was most prevalent with high FIBTEM. Unadjusted blood transfusion rates were increased with high FIBTEM due to RBC transfusion, but non-RBC transfusion was highest with low FIBTEM. After adjustments, a lower OR for transfusion was associated with high FIBTEM (0.426; 95% confidence interval, 0.199-0.914) compared to low FIBTEM. CONCLUSION: The high FIBTEM group frequently presented with anemia and comorbidities, and received more RBCs but not non-RBC products. Postoperative blood loss was less with high FIBTEM, and after adjustments, it conferred protection against any transfusion.

Clinical value of early viscoelastometric point-of-care testing during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: To evaluate rotational fibrin-based thromboelastometry (ROTEM® FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to severe postpartum hemorrhage, and compare its predictive value with that of fibrinogen. MATERIAL AND METHODS: Prospective cohort study in the Netherlands including women with 800-1500 ml of blood loss within 24 h following birth. Blood loss was quantitatively measured by weighing blood-soaked items and using a fluid collector bag in the operating room. Both FIBTEM A5 values and fibrinogen concentrations (Clauss method) were measured between 800 and 1500  ml of blood loss. Predictive accuracy of both biomarkers for the progression to severe postpartum hemorrhage was measured by area under the receiver operating curves (AUC). Severe postpartum hemorrhage was defined as a composite endpoint of (1) total blood loss >2000 ml, (2) transfusion of ≥4 packed cells, and/or (3) need for an invasive intervention to cease bleeding. RESULTS: Of the 391 women included, 72 (18%) developed severe postpartum hemorrhage. Median (IQR) volume of blood loss at blood sampling was 1100 ml (1000-1300) with a median (interquartile range [IQR]) fibrinogen concentration of 3.9 g/L (3.4-4.6) and FIBTEM A5 value of 17 mm (13-20). The AUC for progression to severe postpartum hemorrhage was 0.53 (95% confidence interval [CI] 0.46-0.61) for FIBTEM A5 and 0.58 (95% CI 0.50-0.65) for fibrinogen. Positive predictive values for progression to severe postpartum hemorrhage for FIBTEM A5 ≤12 mm was 22.5% (95% CI 14-33) and 50% (95% CI 25-75) for fibrinogen ≤2 g/L. CONCLUSIONS: The predictive value of FIBTEM A5 compared to fibrinogen concentrations measured between 800 and 1500 ml of blood loss following childbirth was poor to discriminate between women with and without progression towards severe postpartum hemorrhage.

FIBTEM clot firmness parameters correlate well with the fibrinogen concentration measured by the Clauss assay in patients and healthy subjects.

The Clauss assay is the assay most often used for measuring plasma fibrinogen levels. However, the FIBTEM-assay, determined using thromboelastometry (ROTEM) can also be used to estimate fibrinogen levels. A major advantage of the FIBTEM is that it can provide information about fibrinogen levels within minutes, while the Clauss assay needs 30-60 min before the result is available. The aim of this study was to investigate the correlation between fibrinogen levels measured by the Clauss assay and results from the FIBTEM-assay. We included 111 patients ≥18 years for whom both ROTEM analyses and a fibrinogen measurement using the Clauss assay were available. In addition, ROTEM and Clauss measurements from 75 healthy subjects were included. Spearman correlation was used to determine the association between the results of both assays. The patients included were mostly patients with major trauma or undergoing large surgery (e.g. cardiac surgery or liver transplantation). Strong correlations were found between FIBTEM clot firmness parameters and fibrinogen levels measured by the Clauss assay in patients (Spearman's correlation coefficients (rs) above 0.80 (p < .001) for all subgroups) and healthy subjects (rs = 0.66, p < .001). The correlation between early FIBTEM parameters (clot firmness at 5 or 10 min) and the maximum clot firmness was almost perfect (rs above 0.96). Also, the correlation between the α-angle and FIBTEM parameters was strong (rs above 0.7). In conclusion, strong correlations were found between early FIBTEM parameters and fibrinogen levels.

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.

Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment.

BACKGROUND: Thromboelastometry may reduce red blood cell (RBC) transfusion in liver transplantation (LT). Fibrinogen concentration is a primary determinant of FIBTEM maximum clot firmness (MCF), but several factors could affect the correlation between FIBTEM MCF and fibrinogen values. We aimed to investigate (1) the concordance between fibrinogen level and FIBTEM MCF and (2) the association of fibrinogen level and FIBTEM MCF with RBC transfusion during LT. METHODS: A post hoc analysis of data from a randomized, multicentre, double-blind, saline/fibrinogen trial was used (NCT01539057). A total of 86 adult patients were included. RESULTS: The Lin concordance coefficient (LCC) between FIBTEM MCF and fibrinogen levels with the model formula 1·3679 + 0·05414* FIBTEM MCF was poor overall (LLC [95% CI]: 0·387 [0·340 to 0·432]) and moderate for the preperfusion period (LLC [95% CI]: 0·789 [0·747 to 0·824]), but very poor for the postreperfusion period (LLC [95% CI] 0·170 [0·105 to 0·233]). The model assessed for RBC transfusion for FIBTEM MCF showed an area under the curve of 0·788 [0·745-0·832]. Patients with FIBTEM MCF values <8 mm had a significantly higher likelihood of receiving RBC than patients with higher values. (OR [95% CI]: 2·08 [1·30-3·33], P = 0·002). FIBTEM MCF values over 10 mm do not appear to reduce the likelihood of RBC transfusion. CONCLUSION: FIBTEM MCF is not a good indicator of plasma fibrinogen values after graft reperfusion. FIBTEM MCF >8 mm during the LT procedure is associated with less RBC transfusion. FIBTEM MCF values over 10 mm could lead to unnecessary fibrinogen administration.

Neurosurgical applications of viscoelastic hemostatic assays.

Patients taking antithrombotic agents are very common in neurosurgical practice. The perioperative management of these patients can be extremely challenging especially as newer agents, with poorly defined laboratory monitoring and reversal strategies, become more prevalent. This is especially true with emergent cases in which rapid reversal of anticoagulation is required and the patient's exact medical history is not available. With an aging patient population and the associated increase in diseases such as atrial fibrillation, it is expected that the use of these agents will continue to rise in coming years. Furthermore, thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and myocardial infarction are common complications of major surgery. These trends, in conjunction with a growing understanding of the hemostatic process and its contribution to the pathophysiology of disease, stress the importance of the complete evaluation of a patient's hemostatic profile in guiding management decisions. Viscoelastic hemostatic assays (VHAs), such as thromboelastography and rotational thromboelastometry, are global assessments of coagulation that account for the cellular and plasma components of coagulation. This FDA-approved technology has been available for decades and has been widely used in cardiac surgery and liver transplantation. Although VHAs were cumbersome in the past, advances in software and design have made them more accurate, reliable, and accessible to the neurosurgeon. VHAs have demonstrated utility in guiding intraoperative blood product transfusion, identifying coagulopathy in trauma, and managing postoperative thromboprophylaxis. The first half of this review aims to evaluate and assess VHAs, while the latter half seeks to appraise the evidence supporting their use in neurosurgical populations.

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.

Validity of Thromboelastometry for Rapid Assessment of Fibrinogen Levels in Heparinized Samples During Cardiac Surgery: A Retrospective, Single-center, Observational Study.

OBJECTIVE: To assess the validity of fibrinogen assay of rotational thromboelastometry (FIBTEM)-derived estimates of fibrinogen in samples collected during cardiopulmonary bypass in cardiac surgical patients by comparison to Clauss method fibrinogen concentration. DESIGN: Retrospective observational study. SETTING: Single university hospital center. PARTICIPANTS: Human participants. INTERVENTIONS: Retrospectively obtained laboratory assays including rotational thromboelastometry (ROTEM) and Clauss fibrinogen assay. MEASUREMENTS AND MAIN RESULTS: A retrospective review was performed of anesthesia records at a single university teaching hospital during a 1-year period. From paired samples taken near the end of cardiopulmonary bypass, fibrinogen concentrations (Clauss method) were compared with FIBTEM-derived measures of maximal clot firmness (MCF) and clot amplitude at 10 minutes (A10) using Spearman's rank correlation, linear regression, and receiver operating characteristic curve analysis. The study included 1,077 patients. Clauss fibrinogen was correlated strongly with FIBTEM amplitudes (r = 0.78 for MCF and A10; p<0.01). The correlation was related inversely to hemoglobin concentration (p<0.01). The area under the receiver operating characteristic curve was 0.95; the optimal FIBTEM A10 cutoff for diagnosis of a fibrinogen concentration of<1.5 g/L was ≤8 mm. CONCLUSIONS: The FIBTEM was a valid point-of-care method for estimating the fibrinogen concentration during cardiopulmonary bypass and may be used for prediction of hypofibrinogenemia before separation from the extracorporeal circuit.

Fibrinogen in trauma, an evaluation of thrombelastography and rotational thromboelastometry fibrinogen assays.

BACKGROUND: Identifying hypofibrinogenemia in trauma is important. The optimal method of fibrinogen determination is unknown. We therefore evaluated fibrinogen levels determined by two whole blood viscoelastic hemostatic assays, thrombelastography functional fibrinogen (FF) and rotational thromboelastometry FIBTEM in trauma patients and compared these with the plasma-based Clauss method. MATERIALS AND METHODS: Prospective study of consecutive adult trauma patients admitted to a level I trauma center. Levels of fibrinogen were analyzed by Clauss, FF, and FIBTEM on arrival. These methods were compared, and we then investigated whether specific cutoffs of fibrinogen levels were indicative for an increased risk of receiving a transfusion within the initial 6 h. RESULTS: A total of 182 patients with an Injury Severity Score of 17 (9-26) were enrolled. Functional fibrinogen maximum amplitude (FF MA) and FIBTEM maximum clot firmness (MCF) had identical correlation coefficients when compared with those of Clauss fibrinogen (both ρ = 0.64, P < 0.001), and FF MA and FIBTEM MCF correlated with each other (ρ = 0.71, P < 0.001). By logistic regression, the following cutoffs of fibrinogen levels were associated with increased odds of receiving a transfusion, red blood cell concentrates: Clauss <2.5 g/L, FF MA <14.9 mm, FIBTEM MCF <10 mm; fresh frozen plasma and platelets: Clauss <2.5 g/L, FF MA <16.9 mm, FIBTEM MCF <14 mm. CONCLUSIONS: The viscoelastic hemostatic assays for determining fibrinogen levels, FIBTEM and FF, are both correlated with the Clauss fibrinogen level, and there are no differences in the strength of these correlations. In this study, specific fibrinogen levels at arrival to the emergency department were indicative, although not necessarily causal, of increased odds of receiving a transfusion.

Administration of fibrinogen concentrate for refractory bleeding in massively transfused, non-trauma patients with coagulopathy: a retrospective study with comparator group.

BACKGROUND: This retrospective, single centre study was conducted to investigate the efficacy of fibrinogen concentrate (FBNc) in decreasing blood requirements and reaching optimal fibrinogen level, in non-trauma, massively transfused, bleeding patients with coagulopathy. METHODS: Over a 3-years period, all patients for whom a massive transfusion protocol was activated and had received ≥ 4 units of allogeneic blood components within a ≤ 4 h period, were included. Patients were classified according to whether they received FBNc or achieved an optimal fibrinogen level of ≥ 2 g/L within 24 h after FBNc administration. RESULTS: Seventy-one patients received 2 [2,4] g of FBNc (FBNc group) and 72 did not (comparator group). FBNc was administered after transfusing 5 [5,9] blood component units, 3 [2,6] hours after massive transfusion protocol activation. Linear regression analysis showed that SOFA (AOR 0.75 [95% CI:0.08-1.43]) and admission fibrinogen level (AOR -2.7 [95% CI:-4.68 - -0.78]), but not FBNc administration, were independently associated with total transfused units. There was a significant inverse relation between both admission and target fibrinogen levels, and total transfused components. Logistic regression showed a direct relationship between admission fibrinogen level and achieving a target level ≥ 2 g/L (AOR 3.29 [95% CI;1.95-5.56]). No thromboembolic events associated with FBNc were observed. CONCLUSIONS: In massively transfused, non-trauma patients with coagulopathy and refractory bleeding, late administration of low FBNc dosage was not associated with decreased blood transfusion or increased post-infusion fibrinogen level. Given that both fibrinogen upon admission and target fibrinogen levels were associated with decreased blood transfusion, earlier administration and higher doses of FBNc could be needed.

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.

Current perspective on fibrinogen concentrate in critical bleeding.

INTRODUCTION: . Massive hemorrhage continues to be a treatable cause of death. Its management varies from prefixed ratio-driven administration of blood components to goal-directed therapy based on point-of-care testing and administration of coagulation factor concentrates. AREAS COVERED: . We review the current role of fibrinogen concentrate (FC) for the management of massive hemorrhage, either administered without coagulation testing in life-threatening hemorrhage, or within an algorithm based on viscoelastic hemostatic assays and plasma fibrinogen level. We identified relevant guidelines, meta-analyzes, randomized controlled trials, and observational studies that included indications, dosage, and adverse effects of FC, especially thromboembolic events. EXPERT OPINION: . Moderate- to high-grade evidence supports the use of FC for the treatment of severe hemorrhage in trauma and cardiac surgery; a lower grade of evidence is available for its use in postpartum hemorrhage and end-stage liver disease. Pre-emptive FC administration in non-bleeding patients is not recommended. FC should be administered early, in a goal-directed manner, guided by early amplitude of clot firmness parameters (A5- or A10-FIBTEM) or hypofibrinogenemia. Further investigation is required into the early use of FC, as well as its potential advantages over cryoprecipitate, and whether or not its administration at high doses leads to a greater risk of adverse events.

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.

In vitro evaluation of the effect of haemodilution with dextran 40 on coagulation profile as measured by thromboelastometry and multiple electrode aggregometry.

We evaluated the effects of haemodilution with either dextran 40 or 0.9% normal saline on coagulation in vitro using rotational thromboelastometry (ROTEM®, Pentapharm Co., Munich, Germany) and multiple electrode aggregometry (Multiplate® Platelet Function Analyser, Dynabyte, Munich, Germany). Venous blood samples obtained from 20 healthy volunteers were diluted in vitro with dextran 40 or normal saline by 5%, 10% and 15%. Fibrinogen concentration, ROTEM-EXTEM® (screening test for the extrinsic coagulation pathway), FIBTEM® (an EXTEM-based assay of the fibrin component of clot) parameters including coagulation time, clot formation time, alpha angle, maximum clot firmness and lysis index were measured in the undiluted sample and at each level of haemodilution. Dextran 40 at 15% haemodilution significantly prolonged coagulation time, clot formation time and significantly decreased the alpha angle and maximal clot firmness (EXTEM amplitude at five minutes [A5] and ten minutes [A10]) compared with normal saline. The FIBTEM assay (maximal clot firmness and FIBTEM A5 and A10) showed a marked decrease in maximal clot firmness at all dilutions suggesting impaired fibrinogen activity and a risk of bleeding. Multiple electrode aggregometry did not demonstrate any platelet dysfunction. Haemodilution with dextran 40 causes significant impairment in clot formation and strength compared to saline haemodilution and undiluted blood. At the levels of in vitro haemodilution designed to reflect the clinical use of dextran infusions, no significant fibrinolysis or platelet inhibition was observed.

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.