Detection of Acute Traumatic Coagulopathy by Viscoelastic Haemostatic Assays Compared to Standard Laboratory Tests: A Systematic Review
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 2023;50(4):334-347
INTRODUCTION The aim of this systematic review was to investigate whether viscoelastic haemostatic assays (VHAs) offer comparative diagnostic ability of acute traumatic coagulopathy (ATC) compared to the standard laboratory coagulation tests (SLCT). ATC is a complication of major trauma characterized by dysfunctional blood clotting, leading to an increased bleeding risk. Additionally, we aimed to analyse the association of VHA with blood product use and health outcomes. METHODS The search protocol was pre-published and completed on December 2, 2020, assessing manuscripts from 2000 until the present. We searched MEDLINE, Embase, Cochrane Central, BIOSIS, Emcare, CINAHL, and additional online resources and referenced lists. Included were manuscripts that quantitatively reported the detection of ATC using VHAs and SLCTs. A meta-analysis was undertaken including observational studies that reported on patients with injuries to all body regions and results analysed using a random-effects model and reported using pooled odds ratio with 95% confidence intervals (CI). RESULTS There were 14 observational studies and one randomized control trial involving 2,715 participants that satisfied inclusion criteria. We observed significant heterogeneity in the definitions of ATC, study design, setting, and patient population. Among observational studies that reported on patients with injuries to all body regions, VHAs were associated with higher odds of diagnosing ATC compared to SLCT (pooled OR 2.4; 95% CI: 1.4-4.1). There was inadequate evidence to suggest VHAs were associated with reduced blood product usage or lower mortality. CONCLUSION VHAs detected more patients with ATC compared to SLCTs. However, the clinical significance and applicability of this finding remains unknown as translation to management was not adequately reported.
Assessment of Hemostatic Profile in Neonates with Intrauterine Growth Restriction: A Systematic Review of Literature
Seminars in thrombosis and hemostasis. 2023
Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.
Comparison of anticoagulation monitoring strategies for adults supported on extracorporeal membrane oxygenation: A systematic review
Heart & lung : the journal of critical care. 2023;61:72-83
BACKGROUND Anticoagulation is critical in patients supported on extracorporeal membrane oxygenation (ECMO). The appropriate monitoring strategies for heparin remain unclear. OBJECTIVES This systematic review aimed to compare the accuracy and safety of various monitoring strategies for patients supported on ECMO. METHODS The PubMed and Web of Science databases were searched for articles in March 2023 without restrictions on publication date. Anticoagulation monitoring strategies for adults supported on ECMO were compared across all included studies. The incidence of bleeding, thrombosis, mortality, blood transfusion, correlation between tests and heparin dose, and the discordance between different tests were discussed in the included studies. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane Collaboration's tool. RESULTS Twenty-six studies, including a total of 1,684 patients, met the inclusion criteria. The monitoring of anticoagulation by activated partial thromboplastin time (aPTT) resulted in less blood product transfusion than that by activated clotting time (ACT). Moreover, the monitoring of anticoagulation by anti-factor Xa (Anti-Xa) resulted in a more stable anticoagulation than that by aPTT. Anti-Xa and aPTT correlated with heparin dose better than ACT, and the discordance between different monitoring tests was common. Finally, combined monitoring showed some advantages in reducing mortality and blood product transfusion. CONCLUSION Anti-Xa and aPTT are more suitable for anticoagulation monitoring for patients supported on ECMO than ACT. Thromboelastography and combination strategies are less applied. Most of the studies were retrospective, and their sample sizes were relatively small; thus, more appropriate monitoring strategies and higher quality research are needed.
Thrombelastography (TEG(®) 6s) early amplitudes predict maximum amplitude in severely injured trauma patients
Scandinavian journal of clinical and laboratory investigation. 2022;:1-5
Severely injured trauma patients are often coagulopathic and early hemostatic resuscitation is essential. Previous studies have revealed linear relationships between thrombelastography (TEG(®)) five- and ten-min amplitudes (A5 and A10), and maximum amplitude (MA), using TEG(®) 5000 technology. We aimed to investigate the performance of A5 and A10 in predicting low MA in severely injured trauma patients and identify optimal cut-off values for hemostatic intervention based on early amplitudes, using the cartridge-based TEG(®) 6s technology. Adult trauma patients with hemorrhagic shock were included in the iTACTIC randomized controlled trial at six European Level I trauma centers between 2016 and 2018. After admission, patients were randomized to hemostatic therapy guided by conventional coagulation tests (CCT) or viscoelastic hemostatic assays (VHA). Patients with available admission-TEG(®) 6s data were included in the analysis, regardless of treatment allocation. Low MA was defined as <55 mm for Kaolin TEG(®) and RapidTEG(®), and <17 mm for TEG(®) functional fibrinogen (FF). One hundred eighty-seven patients were included. Median time to MA was 20 (Kaolin TEG(®)), 21 (RapidTEG(®)) and 12 (TEG(®) FF) min. For Kaolin TEG(®), the optimal Youden index (YI) was at A5 < 36 mm (100/93% sensitivity/specificity) and A10 < 47 mm (100/96% sensitivity/specificity). RapidTEG(®) optimal YI was at A5 < 34 mm (98/92% sensitivity/specificity) and A10 < 45 mm (96/95% sensitivity/specificity). TEG(®) FF optimal YI was at A5 < 12 mm (97/93% sensitivity/specificity) and A10 < 15 mm (97/99% sensitivity/specificity). In summary, we found that TEG(®) 6s early amplitudes were sensitive and specific predictors of MA in severely injured trauma patients. Intervening on early amplitudes can save valuable time in hemostatic resuscitation.
Adult trauma patients with haemorrhagic shock enrolled in the iTACTIC study at six European trauma centers (n= 187).
Haemostatic therapy guided by conventional coagulation tests (CCT).
Viscoelastic haemostatic assays (VHA).
The study aimed to investigate the performance of A5 and A10 in predicting low maximum amplitude (MA), and to identify optimal cut-off values for haemostatic intervention based on early amplitudes, using the cartridge-based TEG® 6s technology. Patients with available admission-TEG® 6s data were included in the analysis, regardless of treatment allocation. Low MA was defined as <55 mm for Kaolin TEG® and RapidTEG®, and <17 mm for TEG® functional fibrinogen (FF). Median time to MA was 20 (Kaolin TEG®), 21 (RapidTEG®) and 12 (TEG® FF) min. For Kaolin TEG®, the optimal Youden index (YI) was at A5 < 36 mm (100/93% sensitivity/specificity) and A10 < 47 mm (100/96% sensitivity/specificity). RapidTEG® optimal YI was at A5 < 34 mm (98/92% sensitivity/specificity) and A10 < 45 mm (96/95% sensitivity/specificity). TEG® FF optimal YI was at A5 < 12 mm (97/93% sensitivity/specificity) and A10 < 15 mm (97/99% sensitivity/specificity).
Utility of viscoelastic hemostatic assay to guide hemostatic resuscitation in trauma patients: a systematic review
World Journal of Emergency Surgery : Wjes. 2022;17(1):48
OBJECTIVE Viscoelastic 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. METHODS The 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. RESULTS Of 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. CONCLUSION Although 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.
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.
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.
The Role of TEG and ROTEM in Damage Control Resuscitation
Shock (Augusta, Ga.). 2021;56(1s):52-61
Trauma-induced coagulopathy is associated with very high mortality, and hemorrhage remains the leading preventable cause of death after injury. Directed methods to combat coagulopathy and attain hemostasis are needed. The available literature regarding viscoelastic testing, including thrombelastography (TEG) and rotational thromboelastometry (ROTEM), was reviewed to provide clinically relevant guidance for emergency resuscitation. These tests predict massive transfusion and developing coagulopathy earlier than conventional coagulation testing, within 15 min using rapid testing. They can guide resuscitation after trauma, as well. TEG and ROTEM direct early transfusion of fresh frozen plasma when clinical gestalt has not activated a massive transfusion protocol. Reaction time and clotting time via these tests can also detect clinically significant levels of direct oral anticoagulants. Slowed clot kinetics suggest the need for transfusion of fibrinogen via concentrates or cryoprecipitate. Lowered clot strength can be corrected with platelets and fibrinogen. Finally, viscoelastic tests identify fibrinolysis, a finding associated with significantly increased mortality yet one that no conventional coagulation test can reliably detect. Using these parameters, guided resuscitation begins within minutes of a patient's arrival. A growing body of evidence suggests this approach may improve survival while reducing volumes of blood products transfused.
Are thromboelastometric and thromboelastographic parameters associated with mortality in septic patients? A systematic review and meta-analysis
Journal of critical care. 2020;61:5-13
BACKGROUND Thromboelastometry/elastography (ROTEM/TEG) showed promising results for diagnosis of sepsis-induced coagulopathy, but their association with the outcome is unclear. Our aim was to assess any difference in ROTEM/TEG measurements between septic survivors and non-survivors. METHODS Pubmed, Web of Science, Embase and Cochrane Library databases were investigated. The research aimed to include any randomized or observational study: i) on septic adult patients admitted to Intensive Care Unit (ICU) or Emergency Department (ED); ii) including ROTEM/TEG; iii) assessing mortality. RESULTS Seven prospective and four retrospective observational studies (952 patients) were included. According to the INTEM/kaolin-assay, clotting time (CT)/R (standardized mean difference(SMD) -0.29, 95% CI -0.49 to -0.09, p = 0.004) and clot formation time (CFT)/K (SMD -0.42, 95% CI -0.78 to -0.06, p = 0.02) were shorter in survivors. According to the EXTEM-assay, CT was shorter (MD -11.66 s, 95% CI -22.59 to -0.73, p = 0.04), while MCF was higher (MD 3.49 mm, 95% CI 0.43 to 6.55, p = 0.03) in survivors. A hypocoagulable profile was more frequent in non-survivors (OR 0.31, 95%CI 0.18 to 0.55, p < 0.0001). Overall, the risk of bias of the included studies was moderate and the quality of evidence low. CONCLUSIONS Hypocoagulability and lower MCF in EXTEM may be associated with higher mortality in sepsis.
Thromboelastography and Rotational Thromboelastometry in Bleeding Patients with Coagulopathy: Practice Management Guideline from the Eastern Association for the Surgery of Trauma
The journal of trauma and acute care surgery. 2020
BACKGROUND Assessment of the immediate need for specific blood product transfusions in acutely bleeding patients is challenging. Clinical assessment and commonly used coagulation tests are inaccurate and time-consuming. The goal of this practice management guideline was to evaluate the role of the viscoelasticity tests: thromboelastography (TEG) and rotational thromboelastometry (ROTEM), in the management of acutely bleeding trauma, surgical and critically ill patients. METHODS Systematic review and meta-analyses of manuscripts comparing TEG/ROTEM to non-TEG/ROTEM-guided blood products transfusions strategies were performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the level of evidence and create recommendations for TEG/ROTEM-guided blood product transfusions in adult trauma, surgical, and critically ill patients. RESULTS Utilizing TEG/ROTEM-guided blood transfusions in acutely bleeding trauma, surgical, and critically ill patients was associated with a tendency to fewer blood product transfusions in all populations. TEG/ROTEM-guided transfusions were associated with a reduced number of additional invasive hemostatic interventions (angioembolic, endoscopic, or surgical) in surgical patients. TEG/ROTEM -guided transfusions were associated with a reduction in mortality in trauma patients. CONCLUSION In patients with ongoing hemorrhage and concern for coagulopathy, we conditionally recommend using TEG/ROTEM-guided transfusions, compared with traditional coagulation parameters, to guide blood component transfusions in each of the following three groups: adult trauma patients, adult surgical patients, and patients with critical illness. LEVEL OF EVIDENCE Level II TYPE OF STUDY Therapeutic.