Rotational Thromboelastometry Research Articles

Evaluation of fibrinogen concentration by clot firmness using a dielectric blood coagulation test system.

To determine if fibrinogen concentration can be evaluated by dielectric permittivity changes in dielectric blood coagulation testing (DBCM) during cardiovascular surgery with cardiopulmonary bypass (CPB). We performed a single-center prospective observational study at a university hospital. One hundred patients undergoing cardiovascular surgery with CPB were enrolled. Whole-blood samples were obtained after weaning from CPB, and dielectric clot strength (DCS) was measured by intrinsic pathway testing with or without heparinase in DBCM. The FIBTEM test was performed during rotational thromboelastometry using the same samples, and maximum clot firmness (MCF) was evaluated. Spearman's correlation analysis was performed, and receiver operating characteristics (ROC) curve analyses were used to evaluate the performance of hypofibrinogenemia detection. DCS showed a strong positive correlation with plasma fibrinogen concentration (Rs = 0.76, P < 0.0001). The area under the ROC curve for evaluating plasma fibrinogen concentration < 200mg/dL was 0.91 (95% confidence interval (CI) 0.85-0.97) for DCS, compared with 0.88 (95% CI 0.81-0.94) for FIBTEM MCF. The optimal cutoff value of DCS was 17.0 (sensitivity 94%, specificity 80%). DCS variables showed a significantly strong correlation with plasma fibrinogen concentration, and the diagnostic performance for hypofibrinogenemia was comparable to that for FIBTEM MCF. This novel methodology has the potential to provide a point-of-care test with sufficient accuracy for the detection of perioperative hypofibrinogenemia during cardiovascular surgery with CPB.

Role of Thromboelastography and Thromboelastometry in Predicting Risk of Hypercoagulability and Thrombosis in Critically Ill COVID-19 Patients: A Qualitative Systematic Review.

Thromboelastography and rotational thromboelastometry are the viscoelastic point of care devices that use whole blood samples to assess coagulation and fibrinolysis. These devices give information from initiation of the coagulation cascade, activation of clotting factors to fibrin cross-linking, and contribution of fibrinogen and platelet to clot strength and clot lysis. Viscoelastic point of care tests are well established in hypocoaguable states like trauma, cardiac surgery, liver transplantation, and their use in critical care settings with coronavirus disease 2019 (COVID-19) is not so well-known. We performed a systematic review of studies on thromboelastography and rotational thromboelastometry and their modifications to assess their role in critically ill patients with COVID-19. Inclusion criteria were any kind of studies using thromboelastography or rotational thromboelastometry during coronavirus disease critical illness published in English. Ninety-three articles, from December 1, 2019, to August 31, 2020, were identified in the initial search, out of which 12 articles (a total of 380 patients) satisfied the inclusion and exclusion criteria. Thromboelastography and rotational thromboelastometry were observed to detect the hypercoagulable changes and fibrinolysis shutdown associated with COVID-19. Hypercoagulability is associated with an increased risk of venous thrombosis and micro-thrombosis. This review identifies the role of thromboelastography and rotational thromboelastometry in studying the mechanisms contributing to coagulopathy and incidence of thrombosis in COVID-19.

Is ROTEM Diagnostic in Trauma Care Associated with Lower Mortality Rates in Bleeding Patients?-A Retrospective Analysis of 7461 Patients Derived from the TraumaRegister DGU®.

Introduction: Death from uncontrolled trauma haemorrhage and subsequent trauma-induced coagulopathy (TIC) is potentially preventable. Point-of-care devices such as rotational thromboelastometry (ROTEM®) are advocated to detect haemostatic derangements more rapidly than conventional laboratory diagnostics. Regarding reductions in RBC transfusion, the use of ROTEM has been described as being efficient and associated with positive outcomes in several studies. Objective: The effect of ROTEM use was assessed on three different outcome variables: (i) administration of haemostatics, (ii) rate of RBC transfusions and (iii) mortality in severely injured patients. Methods and Material: A retrospective analysis of a large data set of severely injured patients collected into the TraumaRegister DGU® between 2009 and 2016 was conducted. The data of 7461 patients corresponded to the inclusion criteria and were subdivided into ROTEM-using and ROTEM-non-using groups. Both groups were analysed regarding (i) administration of haemostatics, (ii) rate of RBC transfusions and (iii) mortality. Results: A lower mortality rate in ROTEM-using groups was observed (p = 0.043). Furthermore, more patients received haemostatic medication when ROTEM was used. In ROTEM-using groups, there was a statistically relevant higher application of massive transfusion. Conclusions: In this retrospective study, the use of ROTEM was associated with reduced mortality and an increased application of haemostatics and RBC transfusions. Prospective evidence is needed for further evidence-based recommendations.

Role of Fibrinolysis in the Management of Patients with COVID-19 and Thromboembolic Complications: A Review.

An impaired fibrinolytic process has been demonstrated in patients infected with SARS-CoV-2, including those in severe or critical condition. Disruption of fibrinolysis leads to fibrin deposition, which exacerbates inflammation and fibrosis and damages the pulmonary surfactant. Numerous authors point out the different course of coagulopathy in patients with COVID-19. It is reported that they may have a state of secondary hyperfibrinolysis, which may explain, at least in part, the increased incidence of venous thromboembolism, even among those patients already receiving appropriate anticoagulant treatment. This raises the question of whether current guidelines for the prevention and treatment of embolic–thrombotic complications, among patients with severe COVID-19, are sufficient. Some studies show evidence of clinical improvement in patients who have received fibrinolytic therapy, beyond the current indications for its implementation. However, when considering the inclusion of systemic fibrinolytic therapy, the benefits of such treatment should always be weighed over the risk of adverse effects. Thromboelastography and rotational thromboelastometry can be helpful in making such decisions. The purpose of this study was to review the current knowledge regarding fibrinolysis and its role in the treatment of patients with severe COVID-19, including those with thromboembolic complications.

A comparison of the ClotPro system with rotational thromboelastometry in cardiac surgery: a prospective observational study

Viscoelastic coagulation tests have been increasingly used for hemostasis management in cardiac surgery. The ClotPro system is a novel viscoelastic device based on principles of rotational thromboelastometry. We aimed to compare ClotPro with ROTEM and plasma coagulation assays in cardiopulmonary bypass (CPB) patients. Blood samples were collected from 25 CPB patients at (1) baseline, (2) start of CPB, (3) end of CPB, and (4) end of surgery. The EX-test, IN-test, HI-test, FIB-test parameters on ClotPro were compared with corresponding ROTEM assay (EXTEM, INTEM, HEPTEM, and FIBTEM). Standard plasma coagulation assays and endogenous thrombin generation (TG) were simultaneously evaluated. Pearson correlation analyses showed moderate correlations between clotting times (CTs) (r = 0.63–0.67; p < 0.001, respectively), and strong correlations with maximal clot firmness (MCF) (r = 0.93–0.98; p < 0.001, respectively) between ClotPro and ROTEM. EX-test and IN-test MCF parameters were interchangeable with acceptable percentage errors (EX-test MCF: 7.3%, IN-test MCF: 8.3%), but FIB-test MCF (27.0%) and CT results were not (EX-test CT: 44.7%, IN-test CT: 31.4%). The correlations of PT/INR or peak TG with EX-test CTs were higher than with EXTEM CTs (PT/INR: r = 0.80 and 0.41, peak TG: 0.43 and 0.18, respectively). FIB-test MCF has strong correlation with plasma fibrinogen and factor XIII level (r = 0.84 and 0.66, respectively). ROC analyses showed that ClotPro was capable of emulating well-established ROTEM thresholds (area under curves: 0.83–1.00). ClotPro demonstrated strong correlations in MCF parameters of ROTEM in CPB patients. It may be reasonable to modify ROTEM-based transfusion algorithm pertaining to MCF parameters to establish cut-off values for ClotPro device.

Comunicação breve: Rotational thromboelastometry and thromboelastography for patients undergoing surgical procedures: an indirect meta-analysis

Background: There is no consensus in the literature on the superiority between viscoelastic haemostatic assay (VHA) devices and several authors have performed meta-analyzes including them within the same group, assuming that their effects are similar. Objective: The objective of this study is to compare the efficacy of the protocols guided by rotational thromboelastometry with the protocols guided by thromboelastography for the control of the coagulation on patients undergoing surgical procedures. Methods: An indirect meta-analysis was conducted under a frequentist approach. Weights were calculated using the inverse variance method and adjusted using the DerSimonian and Laird random effects model. The measure of association used was the Odds Ratio (OR). All analyzes were performed in R. Results: No significant difference was observed between ROTEM® and TEG® in the indirect meta-analysis for the outcomes mortality (OR=0.6482, 95%CI=0.2213- 1.8984), acute kidney injury (OR=0.5282, 95%CI=0.0858-3.2522), thromboembolic events (OR=0.2759, 95%CI=0.0051-14.9529), reoperation for bleeding (OR=1.0719, 95%CI=0.3589-3.2013), risk of RBC transfusion (OR=1.0044, 95%CI=0.5346 to 1.8872), FFP (OR=0.6964, 95%CI=0.1258-3.8554), or platelets (OR=1.1956, 95%CI=0.4524 to 3.1597), or volume of RBC transfusion (MD=-0.0847, 95%CI=-3.6879 to 3.5185). Conclusion: No difference was observed between thromboelastography and rotational thromboelastometry in any of the outcomes included. This result suggest that they might be combined into a single meta-analysis. Nevertheless, there is much imprecision in the data for a robust conclusion.

Commentary on “The suboptimal fibrinolytic response in COVID‐19 is dictated by high PAI‐1”

Commentary on “The suboptimal fibrinolytic response in COVID‐19 is dictated by high PAI‐1”

Platelet preservation in cardiac surgery using minimally invasive extracorporeal circulation versus optimized cardiopulmonary bypass.

Minimally invasive extracorporeal circulation (MiECC) is employed as a strategy to attenuate the physiologic disturbance caused by cardiopulmonary bypass. The aim of this study was to compare the coagulation profile of MiECC to an optimized conventional extracorporeal circuit (OpECC) with regards to platelet function, rotational thromboelastometry and blood product usage. A retrospective analysis of coronary artery bypass grafting operations using either MiECC or OpECC was performed at a single institution. A total of 112 patients were included, with 61 receiving MiECC and 51 OpECC patients. OpECC patients had a significantly larger BSA (1.95+/- 0.22m2 vs 1.88 +/- 0.18m2, p = 0.034), than those who received MiECC. No difference between groups was observed regarding red blood cell, plasma, and platelet transfusions. Functional platelet count during the warming phase of cardiopulmonary bypass was found to be higher in the MiECC group ((136 (102-171) x109/L vs 109 (94-136) x109/L), p = 0.027), as were functional platelets as a percent of total platelet count ((86 (77-91)% vs 76 (63-82)%), p = 0.003). There were no significant differences between other outcomes such as operative mortality, incidence of stroke, and intensive care unit length of stay. While we did not see a difference in blood transfusions, MiECC resulted in a statistically significant advantage over OpECC with regards to preservation of functional platelets.

Peri-operative hemostatic management of tooth extraction in patients with hemophilia A, with and without inhibitors, receiving emicizumab prophylaxis.

Emicizumab treatment may allow patients with hemophilia A without (PwHA) and with inhibitors (PwHA-I) to undergo some minor surgeries, such as tooth extraction, without peri-operative factor infusions. However, criteria for determining the necessity of factor infusions before minor surgeries are unknown. We report the peri-operative hemostatic management and outcomes of emicizumab-treated PwHA and PwHA-I cases who underwent tooth extractions using our institutional protocol. We retrospectively evaluated PwHA and PwHA-I who underwent tooth extraction with emicizumab prophylaxis at our institution. Local bleeding risk was assessed based on the method, number, and site of tooth extraction. Hemostasis was monitored peri-operatively by rotational thromboelastometry (ROTEM). Hemostatic agents and a mouth splint were used. Twenty-nine extractions (17 interventions) were performed in eight PwHA and two PwHA-I. Based on ROTEM, pre-operative factor infusions were used in ten PwHA and four PwHA-I interventions. Among nine low local bleeding risk interventions, three (33.3%) each received no infusions, one dose of factor infusion pre-operatively, and pre- and post-operative factor infusions. All eight high local bleeding risk interventions involved planned factor infusions. Absorbable hemostats were used in all extractions. A mouth splint was used in 21/25 (84.0%) PwHA and in 4/4 (100%) PwHA-I extractions. No post-extraction bleeding or thrombotic events occurred. Use of a systemic hemostatic treatment plan according to the local bleeding risk, peri-operative coagulation status assessment using ROTEM, filling the extraction socket with hemostats, and use of a mouth splint can achieve effective and safe hemostatic management in emicizumab-treated PwHA and PwHA-I.

The Supply Side of Coagulation: Fibrinogen and Bleeding in Liver Disease and Transplantation.

In this issue of Transplantation, Carrier et al1 describe a study that assesses the effect of preoperative fibrinogen levels on perioperative bleeding and outcomes. In 613 patients with end-stage liver disease who underwent liver transplantation between 2008 and 2019, preoperative low fibrinogen levels were associated with more blood loss but not worse 1-y survival in univariate and multivariate statistical models. This effect was most prominent when fibrinogen levels were below 3 g/L before surgery. In any model of coagulation, fibrinogen is the substrate required to create an effective clot and provide hemostasis. Like most components of hemostasis, fibrinogen is synthesized by the liver and reduced in severe liver disease. Additionally, and maybe more commonly‚ dysfibrinogenemia occurs in liver disease resulting in defects of the fibrinogen structure with undetermined effects on hemostasis.2 The coagulation abnormalities associated with liver disease result in dysbalanced hemostasis that can cause impaired clot formation or excessive thrombosis. Conventional coagulation tests cannot detect this dysbalanced hemostasis‚ as they measure only (a part of) the procoagulant side of hemostasis. Viscoelastic testing, now routinely used in many transplant centers‚ may provide a better assessment of all aspects of clot formation by creating a visual representation of changes in the viscosity of blood when a clot forms. Viscoelastic testing can guide transfusion management in many clinical scenarios‚ including liver transplantation‚ but possibly, more importantly, allows us to identify patients who are hypercoagulable even when the conventional coagulation tests are abnormally high. The results of Carrier et al suggest that low preoperative fibrinogen levels may be an indicator that a patient is at risk for increased intraoperative bleeding. This may be particularly useful if perioperative viscoelastic testing is not used or available as with the study center. This risk of bleeding increased when fibrinogen levels were below 3 g/L before surgery, a level that is far higher than what has traditionally been considered a concerning threshold. Most experts and societies, for example, the review on perioperative coagulation management in liver transplant recipients by Bezinover et al here in Transplantation in 2018,3 recommend fibrinogen concentrate and/or cryoprecipitate transfusion for fibrinogen levels below 1.5 to 2 g/L. Although raising new questions, the present study does not provide enough evidence to change this recommendation at this time. An association with bleeding (even in a multivariate model) does not necessarily mean that replacing fibrinogen with levels over 3 g/L will reduce the risk of bleeding. The assumption is that fibrinogen levels that are below 3 g/L before surgery may decrease more during transplantation to a level that actually impairs hemostasis. Excessive transfusion of cryoprecipitate (and, to a lesser degree, fibrinogen concentrates) is not without risk and may increase the risk of thromboembolic complications.4 The results by Carrier et al are raising new questions about fibrinogen thresholds and may provide the impetus for future (prospective) studies but should not necessarily change our current management. The Centre Hospitalier de L’Universite de Montreal (CHUM) has demonstrated for many years with great success what can be achieved with a concerted effort to reduce blood transfusion5: More than 70% of the patients in the present study did not receive any red blood cell transfusion at all! The center undertakes a number of interventions to achieve these remarkable results. For example, over 50% of the patients in this study underwent phlebotomy at the beginning of surgery. I am not aware of any other center that implemented such a vigorous and successful program to reduce blood transplantation. Unfortunately, this also limits the generalizability of the present study (and reduces the statistical power of the study). Furthermore, because viscoelastic testing was not used in this study, we do not know if lower preoperative fibrinogen levels result in deficient fibrinogen contribution to clot strength later during surgery (assessed, for example, using fibrinogen assays such as FIBTEM with rotational thromboelastometry, ROTEM). In summary, Carrier et al provide important insight into the role of fibrinogen in achieving hemostasis during and good outcomes after liver transplantation. Their data encourage us to check for fibrinogen levels whenever we measure conventional or viscoelastic coagulation tests and design future randomized trials of fibrinogen replacement in liver transplantation.

Fibrinolysis in Dogs with Intracavitary Effusion: A Review.

Simple SummaryIn blood vessels there is a balance between clot formation and its dissolution. Fibrinolysis normally allows the breakdown of blood clots during the healing of injured blood vessels. This process is mediated by the activation of a blood enzyme (plasmin) which breaks down a meshed protein (fibrin) which holds blood clots at the site of the vessel injury. In some diseases, the activation of plasmin becomes excessive, leading to bleeding tendencies (hyperfibrinolysis). Under normal conditions, abdominal and thoracic cavities are filled with a small amount of fluid deriving from the blood. The results of recent studies have shown that, in dogs, all types of pathologic intracavitary fluids have an increased fibrinolytic activity. This increased fibrinolytic activity is also present in their blood, in some cases reaching a hyperfibrinolytic state. Hyperfibrinolysis and bleeding tendencies have also been documented in cardiopathic dogs with ascites. The latter result is surprising considering that thrombotic events are commonly documented in humans and cats with some cardiac diseases.Physiologic fibrinolysis is a localized process in which stable fibrin strands are broken down by plasmin in response to thrombosis. Plasmin activation can also take place separately from the coagulation process, resulting in pathologic fibrinolysis. When plasmin activation exceeds the neutralizing capacity of plasmin inhibitors, severe bleeding can potentially take place. Although the processes which regulate coagulation and fibrinolysis in the blood are well known, it is less clear as to what extent the same processes take place in the body cavities and whether they influence systemic hemostasis. The results of the studies herein cited demonstrate that coagulation followed by fibrinogenolytic/fibrinolytic activity takes place in all kinds of canine ascitic and pleural fluids. Moreover, systemic clotting abnormalities suggesting primary fibrinolysis/primary hyperfibrinolysis (i.e., elevated plasma fibrin/fibrinogen degradation products [FDPs] and normal D-dimer concentrations with fibrinogen concentrations ≤ 100 mg/dL or above this cut-off, respectively) occur in dogs with intracavitary effusion. Enhanced fibrinolytic activity in dogs with intracavitary effusion can also be detected using rotational thromboelastometry (ROTEM), although the degree of agreement between ROTEM and FDPs, D-dimer and fibrinogen concentrations is poor. Finally, contrary to the thrombotic events commonly documented in some humans and cats with cardiac diseases, bleeding tendencies due to primary fibrinolysis/primary hyperfibrinolysis have been documented in dogs with cardiogenic ascites.

Utility of viscoelastic hemostatic assay to guide hemostatic resuscitation in trauma patients: a systematic review

ObjectiveViscoelastic hemostatic assay (VHA) provides a graphical representation of a clot’s lifespan and reflects the real time of coagulation. It has been used to guide trauma resuscitation; however, evidence of the effectiveness of VHAs is still limited. This systematic review aims to summarize the published evidence to evaluate the VHA-guided strategy in resuscitating trauma patients.MethodsThe PubMed, Embase, and Web of Science databases were searched from their inception to December 13, 2021. Randomized controlled trials (RCTs) or observational studies comparing VHA-guided transfusion to controls in resuscitating trauma patients were included in this systematic review.ResultsOf the 7743 records screened, ten studies, including two RCTs and eight observational studies, met the inclusion criteria. There was great heterogeneity concerning study design, enrollment criterion, VHA device, VHA-guided strategy, and control strategy. Thrombelastography (TEG) was used as a guiding tool for transfusion in eight studies, and rotational thromboelastometry (ROTEM), and TEG or ROTEM were used in the other two studies. The overall risk of bias assessment was severe or mild in RCTs and was severe or moderate in observational studies. The main outcomes reported from the included studies were blood transfusion (n = 10), mortality (n = 10), hospital length of stay (LOS) (n = 7), intensive care unit LOS (n = 7), and cost (n = 4). The effect of the VHA-guided strategy was not always superior to the control. Most of the studies did not find significant differences in the transfusion amount of red blood cells (n = 7), plasma (n = 5), platelet (n = 7), cryoprecipitate/fibrinogen (n = 7), and mortality (n = 8) between the VHA-guided group and control group. Notable, two RCTs showed that the VHA-guided strategy was superior or equal to the conventional coagulation test-guided strategy in reducing mortality, respectively.ConclusionAlthough some studies demonstrated VHA-guided strategy probable benefit in reducing the need for blood transfusion and mortality when resuscitating trauma patients, the evidence is still not robust. The quality of evidence was primarily downgraded by the limited number of included studies and great heterogeneity and severe risk of bias in these. Further studies are strongly recommended.

Traumatic Brain Injury Induces a Differential Immune Response in Polytrauma Patients; Prospective Analysis of CD69 Expression on T Cells and Platelet Expansion.

Background: Accidents and injuries are the leading causes of mortality in young people. CD4+ regulatory T cells (CD4+ Tregs), Th17 cells and platelets could be identified as key players in post-traumatic immunological dysfunction, which is a common cause of late mortality in trauma patients. The mechanisms of activation of these cell types and their interaction remain mostly unclear. Since CD69 is not only a leukocyte marker but has also immunoregulatory functions, we postulate a role for CD69 after trauma. The present study investigates the expression of CD69 on CD4+ Tregs and Th17 cells, as well as the posttraumatic expansion of platelets and hemostatic function. Subgroup analysis was performed to assess the differences between polytrauma patients with and without severe traumatic brain injury (TBI). Methods: In this non-interventional prospective clinical trial, we analyzed sequential blood samples over a period of 10 days from 30 patients after multiple traumas with an ISS ≥ 16. Platelet function was assessed by rotational thromboelastometry (ROTEM analysis). CD4+ Tregs and Th17 cells were stained with surface markers and analyzed by flow cytometry. Results: We were able to demonstrate a significantly increased expression of CD69 on CD4+ Tregs after trauma. Subgroup analysis revealed that the absence of severe TBI is associated with a significantly higher expression of CD69 on CD4+ Tregs and on Th17 cells. Platelets expanded and showed signs of dysfunction, while an overall tendency of posttraumatic hypercoagulation was detected. Conclusions: Our results support the concept of injury-specific immune responses and add to a further understanding of the complex pathophysiology of post-traumatic immune dysfunction.

Rotational thromboelastometry for the transfusion management of postpartum hemorrhage after cesarean or vaginal delivery: A single-center randomized controlled trial

Rotational thromboelastometry for the transfusion management of postpartum hemorrhage after cesarean or vaginal delivery: A single-center randomized controlled trial

The Utility of NATEM Assay in Predicting Bleeding Risk in Critically Ill Neonates.

We aimed to investigate the hemostatic status of diseased neonates using nonactivated rotational thromboelastometry (ROTEM) assay (NATEM) assay and, in addition, to evaluate the discriminative power of NATEM parameters in predicting the risk of bleeding in critically ill neonates and compare it to that of EXTEM (extrinsically activated ROTEM) parameters. This cohort study included 158 consecutive, critically ill neonates with presumed sepsis, perinatal hypoxia, or respiratory distress syndrome. The EXTEM and NATEM assays were performed on the first day of disease onset. The neonatal bleeding assessment tool was used to record and assess clinical bleeding events on the day of ROTEM analysis. Several EXTEM and NATEM ROTEM parameters differed between neonates with and without clinical bleeding events, indicating a hypo-coagulable state in neonates with clinical bleeding. NATEM parameters had comparable predictive performance for clinical bleeding events with EXTEM parameters for clotting time, clot formation time (CFT), A10 (clot amplitude at 10minutes), maximum clot firmness, lysis index at 60minutes, and maximum clot elasticity (p>0.05). However, NATEM A20, A30, and α angle demonstrated better predictive ability than EXTEM A20, A30, and α angle, respectively (p<0.05). A NATEM CFT value ≥147seconds presented 95.2% sensitivity (95% confidence interval [CI]: 76.1-99.8%) and 65.6% specificity (95% CI: 57.1-73.5%) to detect neonates with clinical bleeding, while a NATEM A10 value ≤42mm had 80.8% sensitivity (95% CI: 71.8-85.9%) and 76.0% specificity (95% CI: 52.8-91.7%) to detect neonates with clinical bleeding events. The NATEM assay has shown remarkable sensitivity in predicting bleeding in critically ill neonates, exceeding EXTEM performance in some selected parameters. The incorporation of NATEM test parameters in predictive models for neonatal hemorrhage seems promising.

Importance of catecholamine signaling in the development of platelet exhaustion after traumatic injury

BackgroundImpaired ex vivo platelet aggregation is common in trauma patients. The mechanisms driving these impairments remain incompletely understood, but functional platelet exhaustion due to excessive in vivo activation is implicated. Given platelet adrenoreceptors and known catecholamine surges after injury, impaired ex vivo platelet aggregation in trauma patients may be linked to catecholamine‐induced functional platelet exhaustion. ObjectiveTo determine the relationship of catecholamines with platelet‐dependent hemostasis after injury and to model catecholamine‐induced functional platelet exhaustion in healthy donor platelets. Patients/MethodsWhole blood was collected from 67 trauma patients as part of a prospective cohort study. Platelet aggregometry and rotational thromboelastometry were performed, and plasma epinephrine (EPI) and norepinephrine (NE) concentrations were measured. The effect of catecholamines on healthy donor platelets was examined in a microfluidic model, with platelet aggregometry, and by flow cytometry examining surface markers of platelet activation. ResultsIn trauma patients, EPI and NE were associated with impaired platelet aggregation (both p < 0.05), and EPI was additionally associated with decreased viscoelastic clot strength, increased fibrinolysis, and mortality (all p < 0.05). In healthy donors, short duration incubation with EPI enhanced platelet aggregation, platelet adhesion under flow, and increased glycoprotein IIb/IIIa activation, while weaker effects were observed with NE. Compared with short incubation, longer incubation with EPI resulted in decreased platelet adhesion, platelet aggregation, and surface expression of glycoprotein IIb/IIIa. ConclusionsThese findings suggest sympathoadrenal activation in trauma patients contributes to impaired ex vivo platelet aggregation, which mechanistically may be explained by a functionally exhausted platelet phenotype under prolonged exposure to high plasma catecholamine levels.

Thromboelastometry as an Ancillary Tool for Evaluation of Coagulation Status after rFVIIa Therapy in a Pregnant Woman with Severe Hypoproconvertinemia-A Case Series and Review of the Literature.

Introduction: Factor VII (FVII) deficiency is a rare hemorrhagic diathesis. In females, heavy menstrual and postpartum bleeding can appear as a consequence of its deficiency. Supplementation of the recombinant FVIIa is widely accepted. The supplementation effect in FVII-deficient subjects is difficult to predict, and severe hemorrhage has been described even when FVII levels after supplementation were within normal ranges. The aim of this report is to present the application of thromboelastometry to control the coagulation status in a patient with severe FVII deficiency during pregnancy and delivery, supplemented by rFVIIa per protocol complicated with life-threatening venous thromboembolism. Methods: Rotational thromboelastometry (ROTEM) was performed in 16 pregnant women: in one 28 year old primigravida at 35 weeks of pregnancy with congenital FVII deficiency after rFVIIa administration and 15 healthy women at 38 gestational weeks. The results were compared. Results: The thromboelastometry results showed significant shortening of the clotting time in the extrinsic and the intrinsic pathway in the hypoproconvertinemia patient after rFVIIa administration in relation to healthy pregnant women. A significant reduction in maximum lysis of the clot after FVII supplementation was observed. Conclusions: The thromboelastometry results showed a significant hypercoagulable state with hypoproconvertinemia. Thrombotic complications after delivery might be prevented by the reduction in rFVIIa guided by thromboelastometry. Thromboelastometry performed on a pregnant woman with factor VII deficiency during the supplementation of rFVIIa in peripartum time might be helpful in order to determine an individual, effective dosage regimen of rFVIIa to ensure full correction of clotting disorders without the tendency to develop thrombosis, but further studies are needed.

In seeking diagnostic tool for laboratory monitoring of FXII-targeting agents, could assessment of rotational thromboelastometry (ROTEM) in patients with factor XII deficiency be useful?

Introduction: Targeting factor XII (FXII) is a new concept for safe thrombosis prophylaxis. Global hemostasis tests offer promise in terms of the laboratory monitoring of FXII inhibition. The present study examines selected parameters of rotational thromboelastometry (ROTEM) in patients with FXII deficiency. The objective of this study was to assess the impact of FXII deficiency on selected parameters of ROTEM, which can be significant in the laboratory monitoring of FXII inhibition. Material and methods : The study included 20 patients with FXII deficiency ≤40% and 21 volunteers free of it. Clotting time (CT), clot formation time (CFT), alpha angle (α), maximum clot firmness (MCF), and maximum lysis (ML) were recorded in ROTEM. Results: For the INTEM test, CT and CFT readings were markedly higher in FXII deficient patients than in controls. No marked differences in relation to MCF and ML were found. Conclusion: The results of ROTEM show that FXII deficiency has a great impact on the initiation and amplification of coagulation. This was confirmed by a number of marked correlations between FXII activity and certain ROTEM parameters. ROTEM tests merit further investigation as treatment control strategies in the context of FXII inhibition.

A natural history study of coagulopathy in a porcine 40% total body surface area burn model reveals the time-dependent significance of functional assays

Various studies have reported discordant results on the magnitude and direction of burn-induced coagulopathy (BIC), which has recently been associated with multiple organ dysfunction syndrome (MODS) and death. The increased mechanistic understanding of BIC is due, in part, to novel assays that have expanded the armamentarium beyond traditional tests like PT and aPTT. Still, BIC is a dynamic process, and the progression is difficult to define in the thermally-injured. To this end, we aimed to enhance the understanding of burn-induced coagulation abnormalities by employing functional assessments of platelet aggregation, viscoelastic kinetics, and thrombin generation in an extensive burn model in swine. Anesthetized Yorkshire pigs sustained 40% total body surface area (TBSA) full-thickness contact burns and recovered in metabolic cages. Blood was collected at baseline (BL), as well as 6, 24, and 48 h after injury. A significant effect of burn (P < 0.0001) was seen on platelets, with mild thrombocytopenia apparent at 24 h. While slight decreases in aPTT were not significant, rotational thromboelastometry (ROTEM) analysis revealed hypercoagulation 6 and 24 h after burn by a decreased clotting time. Maximum clot firmness increased after burn, but was not statistically significant until 48 h. Hypercoagulation was not supported by platelet aggregation, as the response to ADP was greatly and persistently diminished, and the response to collagen was unchanged. Endogenous thrombin potential was significantly reduced at 6 and 24 h after burn (P < 0.0001), and also correlated with a number of ROTEM parameters and collagen-induced platelet aggregation. In contrast, PT was not correlated with other measured parameters. Taken together, novel coagulation parameters may be more sensitive than PT in characterizing coagulopathy in the setting of burns. The data presented herein makes initial strides to report the natural history of several of these variables over time in a large animal model of extensive burns, indicating early hypercoagulability followed by hypocoagulation. Future work will elucidate the effects of standard of care.

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

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). 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. 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. 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.