Viscoelastic Hemostatic Assays and Outcomes in Traumatic Brain Injury: A Systematic Literature Review
World neurosurgery. 2021
BACKGROUND Coagulopathy in Traumatic brain injury (TBI) occurs frequently and is associated with poor outcomes. Conventional coagulation assays (CCA) traditionally used to diagnose coagulopathy are often not time sensitive and do not assess complete hemostatic function. Viscoelastic hemostatic assays (VHA) including thromboelastography (TEG) and rotational thromboelastography (ROTEM) provide a useful rapid and comprehensive point-of-care alternative for identifying coagulopathy, which is of significant consequence in TBI patients with intracranial hemorrhage. METHODS A systematic review was performed in accordance with guidelines for the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to identify studies comparing VHA to CCA in adult TBI patients. The following differences in outcomes were assessed based on ability to diagnose coagulopathy: mortality, need for neurosurgical intervention, and progression of traumatic intracranial hemorrhage (tICH). RESULTS Abnormal R-time, MA, and K value were associated with increased mortality in certain studies but not all studies. This association was reflected across studies utilizing different statistical parameters with different outcome definitions. An abnormal R-time was the only VHA parameter found to be associated with the need for neurosurgical intervention in one study. An abnormal R time was also the only VHA parameter associated with progression of tICH. Overall, many studies also demonstrated abnormal CCAs, mainly activated partial thromboplastin time (aPPT) to be associated with poor outcomes. CONCLUSION Given the heterogenous nature of the available evidence including methodology and study outcomes, the comparative difference between VHA and CCA in predicting rates of neurosurgical intervention, tICH progression, or mortality in TBI patients remains inconclusive.
Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis
Critical care explorations. 2021;3(9):e0526
Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy, Switzerland) provide rapid coagulopathy assessment and may be particularly useful for goal-directed treatment of traumatic brain injury patients. We conducted a systematic review to assess thromboelastography in the evaluation and management of coagulopathy in traumatic brain injury patients. DATA SOURCES MEDLINE, PubMed Central, Embase, and CENTRAL. STUDY SELECTION Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021. DATA EXTRACTION Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison. DATA SYNTHESIS Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; p = 0.030). CONCLUSIONS Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.
A systematic review on the rotational thrombelastometry (ROTEM(R)) values for the diagnosis of coagulopathy, prediction and guidance of blood transfusion and prediction of mortality in trauma patients
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2016;24((1)):114.
INTRODUCTION Viscoelastic assays have been promoted as an improvement over traditional coagulation tests in the management of trauma patients. Rotational thromboelastometry (ROTEM(R)) has been used to diagnose coagulopathy and guide hemostatic therapy in trauma. This systematic review of clinical studies in trauma investigates the ROTEM(R) parameters thresholds used for the diagnosing coagulopathy, predicting and guiding transfusion and predicting mortality. METHODS Systematic literature search was performed using MEDLINE, EMBASE and Cochrane databases. We included studies without restricting year of publication, language or geographic location. Original studies reporting the thresholds of ROTEM(R) parameters in the diagnosis or management of coagulopathy in trauma patients were included. Data on patient demographics, measures of coagulopathy, transfusion and mortality were extracted. We reported our findings according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Quality assessment and risk of bias were performed using Newcastle Ottawa Scale (NOS) and the quality assessment of diagnostic accuracy studies (QUADAS-2) tools, respectively. RESULTS A total of 13 observational studies involving 2835 adult trauma patients met the inclusion criteria. Nine studies were prospective and four were retrospective. There were no randomized controlled trials. The quality of the included studies was moderate (mean NOS 5.92, standard deviation 0.26). Using QUADAS-2, only 1 study (7.6 %) had low risk of bias in all domains, and 9 studies (69.2 %) had low risk of applicability concerns. Outcomes from 13 studies were grouped into three categories: diagnosis of coagulopathy (n = 10), prediction of massive transfusion or transfusion guidance (n = 6) and prediction of mortality (n = 6). Overall, specific ROTEM(R) parameters measured (clot amplitude and lysis) in the extrinsically activated test (EXTEM) and the fibrin-based extrinsically activated test (FIBTEM) were consistently associated with the diagnosis of coagulopathy, increased risk of bleeding and massive transfusion, and prediction of mortality. Presence of hyperfibrinolysis by ROTEM(R) was associated with increased mortality. CONCLUSIONS Most of the evidence indicates that abnormal EXTEM and FIBTEM clot amplitude (CA5, CA10) or maximal clot firmness (MCF) diagnose coagulopathy, and predict blood transfusion and mortality. The presence of fibrinolysis (abnormal lysis index [LI30] or maximum lysis [ML]) was also associated with mortality. ROTEM(R) thus, may be of value in the early management of trauma patients.
Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays
Annals of Surgery. 2016;263((6)):1051-9.
BACKGROUND Massive transfusion protocols (MTPs) have become standard of care in the management of bleeding injured patients, yet strategies to guide them vary widely. We conducted a pragmatic, randomized clinical trial (RCT) to test the hypothesis that an MTP goal directed by the viscoelastic assay thrombelastography (TEG) improves survival compared with an MTP guided by conventional coagulation assays (CCA). METHODS This RCT enrolled injured patients from an academic level-1 trauma center meeting criteria for MTP activation. Upon MTP activation, patients were randomized to be managed either by an MTP goal directed by TEG or by CCA (ie, international normalized ratio, fibrinogen, platelet count). Primary outcome was 28-day survival. RESULTS One hundred eleven patients were included in an intent-to-treat analysis (TEG = 56, CCA = 55). Survival in the TEG group was significantly higher than the CCA group (log-rank P = 0.032, Wilcoxon P = 0.027); 20 deaths in the CCA group (36.4%) compared with 11 in the TEG group (19.6%) (P = 0.049). Most deaths occurred within the first 6 hours from arrival (21.8% CCA group vs 7.1% TEG group) (P = 0.032). CCA patients required similar number of red blood cell units as the TEG patients [CCA: 5.0 (2-11), TEG: 4.5 (2-8)] (P = 0.317), but more plasma units [CCA: 2.0 (0-4), TEG: 0.0 (0-3)] (P = 0.022), and more platelets units [CCA: 0.0 (0-1), TEG: 0.0 (0-0)] (P = 0.041) in the first 2 hours of resuscitation. CONCLUSIONS Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by CCA and utilizes less plasma and platelet transfusions during the early phase of resuscitation.
Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma-induced coagulopathy in adult trauma patients with bleeding
Cochrane Database of Systematic Reviews. 2015;((2):):CD010438.
BACKGROUND Trauma-induced coagulopathy (TIC) is a disorder of the blood clotting process that occurs soon after trauma injury. A diagnosis of TIC on admission is associated with increased mortality rates, increased burdens of transfusion, greater risks of complications and longer stays in critical care. Current diagnostic testing follows local hospital processes and normally involves conventional coagulation tests including prothrombin time ratio/international normalized ratio (PTr/INR), activated partial prothrombin time and full blood count. In some centres, thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are standard tests, but in the UK they are more commonly used in research settings. OBJECTIVES The objective was to determine the diagnostic accuracy of thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for TIC in adult trauma patients with bleeding, using a reference standard of prothrombin time ratio and/or the international normalized ratio. SEARCH METHODS We ran the search on 4 March 2013. Searches ran from 1970 to current. We searched The Cochrane Library, MEDLINE (OvidSP), EMBASE Classic and EMBASE, eleven other databases, the web, and clinical trials registers. The Cochrane Injuries Group's specialised register was not searched for this review as it does not contain diagnostic test accuracy studies. We also screened reference lists, conducted forward citation searches and contacted authors. SELECTION CRITERIA We included all cross-sectional studies investigating the diagnostic test accuracy of TEG and ROTEM in patients with clinically suspected TIC, as well as case-control studies. Participants were adult trauma patients in both military and civilian settings. TIC was defined as a PTr/INR reading of 1.2 or greater, or 1.5 or greater. DATA COLLECTION AND ANALYSIS We piloted and performed all review stages in duplicate, including quality assessment using the QUADAS-2 tool, adhering to guidance in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. We analysed sensitivity and specificity of included studies narratively as there were insufficient studies to perform a meta-analysis. MAIN RESULTS Three studies were included in the final analysis. All three studies used ROTEM as the test of global haemostatic function, and none of the studies used TEG. Tissue factor-activated assay EXTEM clot amplitude (CA) was the focus of the accuracy measurements in blood samples taken near to the point of admission. These CAs were not taken at a uniform time after the start of the coagulopathic trace; the time varied from five minutes, to ten minutes and fifteen minutes. The three included studies were conducted in the UK, France and Afghanistan in both civilian and military trauma settings. In two studies, median Injury Severity Scores were 12, inter-quartile range (IQR) 4 to 24; and 22, IQR 12 to 34; and in one study the median New Injury Severity Score was 34, IQR 17 to 43.There were insufficient included studies examining each of the three ROTEM CAs at 5, 10 and 15 minutes to make meta-analysis and investigation of heterogeneity valid. The results of the included studies are thus reported narratively and illustrated by a forest plot and results plotted on the receiver operating characteristic (ROC) plane.For CA5 the accuracy results were sensitivity 70% (95% CI 47% to 87%) and specificity 86% (95% CI 82% to 90%) for one study, and sensitivity 96% (95% CI 88% to 100%) and specificity 58% (95% CI 44% to 72%) for the other.For CA10 the accuracy results were sensitivity 100% (95% CI 94% to 100%) and specificity 70% (95% CI 56% to 82%).For CA15 the accuracy results were sensitivity 88% (95% CI 69% to 97%) and specificity 100% (95% CI 94% to 100%).No uninterpretable ROTEM study results were mentioned in any of the included studies.Risk of bias and concerns around applicability of findings was low across all studies for the patient and flow and timing domains. However, risk of bias and concerns around applicability of findings for the index test domain was either high or unclear
What is known?
Trauma induced coagulopathy (TIC) is an impairment of blood clotting that occurs soon after injury and has been reported to confer a mortality rate as high as 50%. TIC is associated with increased rates of transfusion, organ failure, sepsis and longer critical care stays. Early recognition of TIC may allow trauma teams to treat coagulopathy more rapidly and may lead to improved clinical outcomes. Historically, TIC has been defined using standard laboratory coagulation tests, most commonly the prothrombin time (PT) and the PT ratio (PTr) or INR. More recently, viscoelastic tests (VHA tests) are being used with increasing frequency, favoured by clinical teams for being both point-of-care tests and for the speed with which useful results can be obtained. There is a great deal of interest in the role that VHA tests can play in the diagnosis of TIC as well as how they can be used optimally to guide transfusion therapy.
What did this paper set out to examine?
This Cochrane review set out to determine how good TEG and ROTEM assessments were at diagnosing TIC in adult trauma patients with bleeding. This was a diagnostic test accuracy review and the accuracy of the TEG and ROTEM was compared against the PTr/INR which was used as the reference standard.
What did they show?
This paper included 3 cross-sectional studies (including 430 patients in total), with civilian and military patients. No RCTs were identified. All three studies compared ROTEM to standard clotting tests and no study was specifically designed to evaluate test accuracy. The included studies focussed on a single ROTEM measure -EXTEM clot amplitude (CA) to assess TIC, but the time points that CA values were reported varied i.e. CA5, CA10 and CA15 (result at 5, 10 or 15 minutes). The reference standard that the studies used also varied with 2 studies using a PTr > 1.5 and 1 study using a PTr > 1.2.
The authors found that the 3 studies provided very little evidence on the accuracy of ROTEM and no evidence for TEG in the diagnosis of TIC. 4 domains were evaluated for risk of bias, and bias was thought to be high for two domains: (a) the choice of index test (ie ROTEM) and (b) the choice of reference standard (ie PTr/INR). The authors highlighted that this raised concerns around the interpretation of sensitivity and specificity results of the 3 studies.
What are the implications for practice and for future work?
The conclusion from this review was that there were no high quality data to confirm the accuracy of TEG or ROTEM in the diagnosis of TIC and the authors recommended that VHA tests should be limited to the research setting only.
Future research will need to focus on several areas. Interventional studies looking at the effect of ROTEM/TEG guided algorithms for diagnosis or even treatment of TIC, when compared to standard treatment without a VHA device, may be required to fully evaluate the use of these devices. However, without consensus about which VHA (or indeed standard clotting test) parameter(s) diagnose TIC the value of these interventions will be limited.
Effect of thromboelastography (TEG) and rotational thromboelastometry (ROTEM) on diagnosis of coagulopathy, transfusion guidance and mortality in trauma: descriptive systematic review
Critical Care (London, England). 2014;18((5):):518.
INTRODUCTION The understanding of coagulopathies in trauma has increased interest in thromboelastography (TEG) and thromboelastometry (ROTEM), which promptly evaluate the entire clotting process and may guide blood product therapy. Our objective was to review the evidence for their role in diagnosing early coagulopathies, guiding blood transfusion, and reducing mortality in injured patients. METHODS We considered observational studies and randomized controlled trials (MEDLINE, EMBASE, and Cochrane databases) to February 2014 that examined TEG/ROTEM in adult trauma patients. We extracted data on demographics, diagnosis of early coagulopathies, blood transfusion, and mortality. We assessed methodologic quality by using the Newcastle-Ottawa scale (NOS) for observational studies and QUADAS-2 tool for diagnostic accuracy studies. RESULTS Fifty-five studies (12,489 patients) met inclusion criteria, including 38 prospective cohort studies, 15 retrospective cohort studies, two before-after studies, and no randomized trials. Methodologic quality was moderate (mean NOS score, 6.07; standard deviation, 0.49). With QUADAS-2, only three of 47 studies (6.4%) had a low risk of bias in all domains (patient selection, index test, reference standard and flow and timing); 37 of 47 studies (78.8%) had low concerns regarding applicability. Studies investigated TEG/ROTEM for diagnosis of early coagulopathies (n = 40) or for associations with blood-product transfusion (n = 25) or mortality (n = 24). Most (n = 52) were single-center studies. Techniques examined included rapid TEG (n =12), ROTEM (n = 18), TEG (n = 23), or both TEG and rapid TEG (n = 2). Many TEG/ROTEM measurements were associated with early coagulopathies, including some (hypercoagulability, hyperfibrinolysis, platelet dysfunction) not assessed by routine screening coagulation tests. Standard measures of diagnostic accuracy were inconsistently reported. Many abnormalities predicted the need for massive transfusion and death, but predictive performance was not consistently superior to routine tests. One observational study suggested that a ROTEM-based transfusion algorithm reduced blood-product transfusion, but TEG/ROTEM-based resuscitation was not associated with lower mortality in most studies. CONCLUSIONS Limited evidence from observational data suggest that TEG/ROTEM tests diagnose early trauma coagulopathy and may predict blood-product transfusion and mortality in trauma. Effects on blood-product transfusion, mortality, and other patient-important outcomes remain unproven in randomized trials.