Thromboelastography: Clinical Applications and Utility for Physicians
Dr Neeraj Manikath ,Claude.ai
Abstract
Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are viscoelastic hemostatic assays that provide comprehensive assessments of the entire clotting process, from initial fibrin formation to clot stability and eventual fibrinolysis. Unlike conventional coagulation tests that evaluate isolated components of the coagulation cascade, these viscoelastic methods offer a holistic, dynamic evaluation of clot formation and dissolution. This review explores the principles, methodology, interpretation, and diverse clinical applications of TEG/ROTEM across various medical specialties. We discuss their utility in perioperative management, trauma care, cardiovascular surgery, obstetrics, critical illness, and chronic liver disease. Additionally, we address the limitations of these technologies and provide a perspective on their future applications. By understanding the capabilities and constraints of viscoelastic testing, physicians can better leverage these tools to guide targeted hemostatic interventions, optimize transfusion management, and improve patient outcomes in scenarios involving complex coagulopathies.
Introduction
Blood coagulation is a complex, dynamic process involving multiple interacting components, including platelets, coagulation factors, and fibrinolytic enzymes. Traditional laboratory coagulation tests such as prothrombin time (PT), partial thromboplastin time (PTT), International Normalized Ratio (INR), fibrinogen levels, and platelet counts provide valuable but limited information about specific aspects of the coagulation process. These conventional tests are performed on platelet-poor plasma under static conditions, removing the cellular elements that significantly contribute to in vivo clot formation.^1,2^
Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) represent significant advances in coagulation monitoring by providing a comprehensive assessment of the viscoelastic properties of whole blood during clot formation and subsequent fibrinolysis. These technologies measure the viscoelastic changes that occur during coagulation, providing information on clot initiation, formation, strength, stability, and dissolution in real-time.^3,4^
First described by Hartert in 1948, thromboelastography has evolved significantly over decades.^5^ Modern TEG and ROTEM systems offer point-of-care capabilities with relatively rapid results compared to conventional laboratory tests, making them particularly valuable in acute care settings where timely decision-making is critical.^6^ This review aims to provide physicians with a comprehensive understanding of TEG/ROTEM principles, interpretation, and clinical applications across various medical specialties.
Technical Principles and Methodology
Basic Principles
Both TEG and ROTEM utilize similar principles to assess the viscoelastic properties of clot formation, though they differ in mechanical design and some nomenclature. In TEG, a blood sample is placed in a heated cup that oscillates through a small angle. A pin suspended in the blood is connected to a torsion wire that transmits the motion to a mechanical-electrical transducer. As coagulation occurs, increasing viscosity of the sample transfers more cup motion to the pin, which is detected and recorded.^7^
In ROTEM, the cup remains stationary while the pin rotates. The resistance to rotation as the blood clots is measured optically. Both systems record the changing viscoelastic properties during clotting, generating characteristic curves that reflect the different phases of coagulation.^8^
Key Parameters and Their Interpretation
TEG and ROTEM provide several parameters that correspond to different aspects of the coagulation process:^9,10^
Clot Initiation:
- TEG: Reaction time (R) - Time from test initiation until initial fibrin formation (normal: 3-8 minutes)
- ROTEM: Clotting time (CT) - Similar to R time (normal values vary by reagent used)
Clot Formation Kinetics:
- TEG: Kinetics (K) - Time from beginning of clot formation until a predetermined clot strength (normal: 1-3 minutes)
- TEG: Alpha angle (α) - Speed of fibrin build-up and cross-linking (normal: 55-78 degrees)
- ROTEM: Clot formation time (CFT) and alpha angle - Similar to TEG parameters
Clot Strength:
- TEG: Maximum amplitude (MA) - Maximum strength of the developed clot (normal: 51-69 mm)
- ROTEM: Maximum clot firmness (MCF) - Similar to MA (normal values vary by reagent)
Fibrinolysis:
- TEG: Lysis at 30 minutes (LY30) - Percentage decrease in amplitude 30 minutes after MA (normal: 0-8%)
- ROTEM: Maximum lysis (ML) - Percentage decrease from MCF during measurement
Assay Modifications and Reagents
Various modifications and reagents can be employed to emphasize specific aspects of coagulation:^11,12^
TEG Assays:
- Kaolin TEG: Standard activator for routine assessment
- Rapid TEG: Uses tissue factor and kaolin for accelerated results
- Heparinase TEG: Contains heparinase to neutralize heparin
- Functional fibrinogen TEG: Uses a platelet inhibitor to isolate fibrinogen contribution
- Platelet mapping: Assesses platelet function and response to antiplatelet medications
ROTEM Assays:
- EXTEM: Uses tissue factor activation to assess extrinsic pathway
- INTEM: Uses contact activation to assess intrinsic pathway
- FIBTEM: Contains platelet inhibitor to isolate fibrinogen contribution
- HEPTEM: Contains heparinase to neutralize heparin
- APTEM: Contains aprotinin to inhibit fibrinolysis
- ECATEM: For direct thrombin inhibitor (DTI) monitoring
These modifications allow for targeted assessment of specific aspects of hemostasis and can help identify the underlying causes of coagulopathies.^13^
Clinical Applications
Perioperative and Surgical Management
TEG/ROTEM has found significant utility in perioperative settings, particularly in complex surgeries associated with substantial blood loss and coagulation disturbances.^14^
Cardiac Surgery: Cardiac surgery involving cardiopulmonary bypass (CPB) introduces multiple hemostatic challenges, including hemodilution, hypothermia, consumption of coagulation factors, platelet dysfunction, and fibrinolysis. TEG/ROTEM has become an integral component of hemostatic management in this setting.^15^ Studies have demonstrated that TEG/ROTEM-guided therapy reduces blood product utilization, reoperation rates for bleeding, and potentially mortality compared to standard laboratory-based approaches.^16,17^
A meta-analysis by Deppe et al. encompassing 17 studies and 8,332 cardiac surgery patients showed that viscoelastic testing-guided hemotherapy significantly reduced transfusion requirements, thromboembolic events, and costs compared to conventional coagulation testing.^18^ The 2019 European Association of Cardiothoracic Anaesthesiology (EACTA)/European Association of Cardiothoracic Surgery (EACTS) guidelines strongly recommend viscoelastic testing for managing perioperative hemostasis in cardiac surgery (Class I recommendation, Level B evidence).^19^
Liver Transplantation: Orthotopic liver transplantation (OLT) presents complex hemostatic challenges due to the liver's central role in the synthesis of most coagulation factors, natural anticoagulants, and fibrinolytic proteins.^20^ The procedure typically progresses through phases with distinct coagulation profiles: preanhepatic (characterized by baseline abnormalities from liver disease), anhepatic (marked by decreasing coagulation factors), reperfusion (often accompanied by fibrinolysis), and postreperfusion (gradual recovery of synthetic function).^21^
TEG/ROTEM provides valuable real-time information throughout these phases, helping guide appropriate component therapy.^22^ Multiple studies have demonstrated that TEG/ROTEM-guided transfusion protocols during liver transplantation reduce blood product utilization and may improve outcomes.^23,24^ A prospective randomized trial by Wang et al. found that TEG-guided transfusion in liver transplantation reduced transfusion of fresh frozen plasma by 66% and platelets by 34% compared to conventional coagulation test-guided transfusion.^25^
Major Orthopedic Surgery: In major orthopedic procedures such as spine surgery and joint arthroplasty, TEG/ROTEM can help manage the substantial bleeding risk and detect hyperfibrinolysis.^26^ These surgeries often involve elderly patients with multiple comorbidities and concomitant anticoagulant or antiplatelet therapy, complicating perioperative hemostatic management.^27^
Additionally, TEG/ROTEM may help identify patients at increased risk for thromboembolic complications following orthopedic surgery. Rafee et al. demonstrated that hypercoagulable TEG parameters on postoperative day 1 after total hip arthroplasty were associated with an increased risk of venous thromboembolism.^28^
Trauma and Critical Care
Trauma-Induced Coagulopathy: Trauma-induced coagulopathy (TIC) is a complex, multifactorial condition associated with increased mortality. It involves tissue injury, shock, hemodilution, hypothermia, acidosis, and hyperfibrinolysis.^29^ Conventional coagulation tests have limited utility in this setting due to their long turnaround times and inability to assess important components of TIC such as hyperfibrinolysis.^30^
TEG/ROTEM has emerged as a valuable tool for rapidly diagnosing and characterizing TIC. A prospective study by Davenport et al. found that ROTEM parameters could identify TIC within 5 minutes of test initiation, significantly faster than conventional tests.^31^ The rapid availability of results allows for earlier, targeted hemostatic interventions.
TEG/ROTEM parameters associated with poor outcomes in trauma include prolonged clot initiation, decreased clot strength, and hyperfibrinolysis. Hyperfibrinolysis, in particular, is strongly associated with mortality and is difficult to detect using conventional tests.^32^ A study by Chapman et al. demonstrated that LY30 > 3% was associated with a mortality rate of 76%, compared to 9% in patients without hyperfibrinolysis.^33^
Massive Transfusion Protocols: TEG/ROTEM can significantly refine massive transfusion protocols (MTPs) by providing specific information about coagulation deficits, allowing for targeted component therapy rather than fixed-ratio approaches.^34^
The PROPPR trial, which compared fixed-ratio transfusion strategies, found similar outcomes with 1:1:1 and 1:1:2 (plasma:platelets:RBCs) approaches.^35^ However, subsequent research suggests that viscoelastic testing-guided resuscitation may further optimize blood product utilization. A single-center study by Tapia et al. found that implementation of TEG-guided resuscitation was associated with improved survival compared to an MTP with fixed ratios.^36^
The 2016 European guidelines on management of major bleeding and coagulopathy following trauma recommend the use of viscoelastic methods to assist in characterizing coagulopathy and in guiding hemostatic treatment (Grade 1C recommendation).^37^
Critical Care: In critical care settings, TEG/ROTEM can help assess and manage coagulopathies associated with sepsis, disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS).^38^
Sepsis-induced coagulopathy can manifest as either a hypercoagulable state, potentially leading to microvascular thrombosis and organ dysfunction, or as an anticoagulant phase with bleeding complications.^39^ TEG/ROTEM can detect these patterns and guide appropriate interventions. Müller et al. demonstrated that hypercoagulability detected by ROTEM in septic patients was associated with increased mortality and development of multiple organ failure.^40^
In DIC, TEG/ROTEM typically shows a biphasic pattern with initial hypercoagulability followed by hypocoagulability as coagulation factors and platelets are consumed.^41^ These dynamic changes may not be adequately captured by conventional coagulation tests.
Obstetrics
Pregnancy and the peripartum period involve substantial hemostatic changes, including increases in most coagulation factors, decreased natural anticoagulant activity, and impaired fibrinolysis, resulting in a physiological hypercoagulable state.^42^ These normal changes, combined with the potential for severe obstetric hemorrhage, create unique challenges in hemostatic management.
Postpartum Hemorrhage: Postpartum hemorrhage (PPH) remains a leading cause of maternal mortality worldwide.^43^ Early identification of coagulopathy and targeted hemostatic interventions are crucial for reducing adverse outcomes. TEG/ROTEM can rapidly assess the specific coagulation deficits in PPH, which commonly include hypofibrinogenemia, platelet dysfunction, and, occasionally, hyperfibrinolysis.^44^
Collins et al. found that a FIBTEM A5 ≤ 12 mm (measured 5 minutes after clot initiation) had a positive predictive value of 85% for fibrinogen level < 2 g/L in women with PPH.^45^ Since results are available within minutes, targeted fibrinogen replacement can be initiated earlier than when guided by conventional fibrinogen assays.
The revised 2022 PPH guidelines from the UK acknowledge the potential value of viscoelastic testing in managing PPH, particularly when available as point-of-care.^46^
Pre-eclampsia: Pre-eclampsia is associated with complex hemostatic changes, including endothelial dysfunction, platelet activation, and alterations in the coagulation and fibrinolytic systems.^47^ While conventional tests may remain normal or show only mild thrombocytopenia, TEG/ROTEM may detect hypercoagulability before clinical manifestations become apparent.^48^
A study by Armstrong et al. demonstrated that women with pre-eclampsia had significantly increased clot strength and decreased fibrinolysis compared to normotensive pregnant women, despite similar conventional coagulation parameters.^49^ These findings suggest potential utility for TEG/ROTEM in risk stratification and management of pre-eclampsia.
Cardiovascular Disease
Anticoagulation Monitoring: TEG/ROTEM can provide valuable information about the effects of various anticoagulant medications, including unfractionated heparin, low-molecular-weight heparins, direct oral anticoagulants (DOACs), and vitamin K antagonists.^50^
For unfractionated heparin, the comparison between standard and heparinase-modified TEG/ROTEM provides a direct assessment of heparin effect.^51^ For DOACs, specific TEG/ROTEM parameters show characteristic changes: direct thrombin inhibitors primarily affect clot initiation (R time/CT), while factor Xa inhibitors may impact both clot initiation and formation kinetics.^52^
While viscoelastic testing should not replace specialized assays for DOAC monitoring, it may provide useful information in emergency situations when specific assays are unavailable.^53^
Antiplatelet Therapy: Modified TEG assays, particularly platelet mapping, can assess platelet function and the effects of antiplatelet medications.^54^ This may be valuable in patients undergoing cardiac procedures or those with acute coronary syndromes.
Studies have demonstrated that TEG platelet mapping can identify patients with high platelet reactivity despite standard antiplatelet therapy ("non-responders"), potentially informing therapeutic adjustments.^55^ Tantry et al. found that TEG platelet mapping results correlated well with light transmission aggregometry for assessing platelet inhibition in patients on dual antiplatelet therapy.^56^
Mechanical Circulatory Support: Patients with ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) face complex hemostatic challenges, including bleeding due to surgical trauma, anticoagulation, and acquired von Willebrand syndrome, as well as thrombotic risks from device-related activation of coagulation.^57^
TEG/ROTEM may help optimize the delicate balance between bleeding and thrombosis in these patients. Ryerson et al. demonstrated that using TEG parameters to guide anticoagulation in VAD patients resulted in improved clinical outcomes compared to conventional aPTT-based protocols.^58^
Liver Disease and Cirrhosis
Chronic liver disease presents a complex hemostatic scenario characterized by concurrent reductions in procoagulant factors, anticoagulant proteins, and fibrinolytic system components, resulting in a precarious "rebalanced" coagulation system that can tip toward either bleeding or thrombosis.^59^ Conventional coagulation tests, particularly PT/INR, often overestimate bleeding risk in these patients by only reflecting deficiencies in procoagulant factors without accounting for concomitant decreases in anticoagulants.^60^
TEG/ROTEM provides a more comprehensive assessment of this rebalanced hemostasis. Despite prolonged conventional coagulation tests, many patients with cirrhosis demonstrate normal or even hypercoagulable TEG/ROTEM profiles, reflecting the balanced reduction in pro- and anticoagulant systems.^61^
A prospective study by Stravitz et al. found that maximum amplitude (MA) on kaolin-activated TEG was normal in 86% of patients with acute liver failure despite significantly elevated INR values, challenging the traditional view of severe coagulopathy in these patients.^62^ Similar findings have been reported in patients with chronic liver disease.^63^
This information has important implications for invasive procedures in cirrhotic patients. Prophylactic plasma transfusion based solely on elevated INR may not be beneficial and might even be harmful. A randomized trial by De Pietri et al. demonstrated that TEG-guided transfusion strategy in cirrhotic patients undergoing invasive procedures significantly reduced blood product usage without increasing bleeding complications compared to conventional coagulation test-guided strategy.^64^
TEG/ROTEM may also have prognostic value in liver disease. Hypocoagulable parameters, particularly decreased MA/MCF, have been associated with increased mortality in patients with cirrhosis.^65^ A study by Hugenholtz et al. found that ROTEM parameters were independent predictors of 30-day mortality in patients with cirrhosis and acute decompensation.^66^
Oncology and Hematologic Disorders
Cancer-Associated Thrombosis: Malignancy is associated with a hypercoagulable state that increases the risk of venous thromboembolism (VTE) and may contribute to tumor progression.^67^ Conventional coagulation tests typically remain normal in these patients despite their prothrombotic state. TEG/ROTEM may detect this cancer-associated hypercoagulability, potentially identifying patients at higher thrombotic risk.^68^
A prospective study by Ay et al. found that elevated TEG parameters of clot strength were associated with increased risk of VTE in cancer patients.^69^ Similarly, Königsbrügge et al. demonstrated that hypercoagulable ROTEM parameters correlated with development of VTE during chemotherapy.^70^
TEG/ROTEM may also help guide anticoagulation management in cancer patients, who face higher risks of both thrombosis and bleeding compared to the general population. In particular, these assays may be valuable for monitoring the effects of low-molecular-weight heparins, which remain mainstays of cancer-associated thrombosis treatment.^71^
Hematologic Malignancies: Patients with hematologic malignancies often have complex coagulation abnormalities due to disease effects, treatments, and complications such as sepsis.^72^ TEG/ROTEM can help characterize these abnormalities and guide management.
In acute leukemia, both hypercoagulable and hypocoagulable patterns may be observed depending on disease characteristics and treatment phase.^73^ During induction chemotherapy, severe thrombocytopenia may lead to increased bleeding risk, while asparaginase therapy in acute lymphoblastic leukemia can cause hypofibrinogenemia.^74^ TEG/ROTEM can detect these specific deficits and guide targeted replacement therapy.
Hemophilia and Other Bleeding Disorders: In patients with hemophilia and other heritable coagulation factor deficiencies, TEG/ROTEM can provide valuable information beyond factor levels alone.^75^ These assays may be particularly useful for monitoring response to factor replacement therapy and bypassing agents.
Young et al. demonstrated that TEG parameters improved with increasing factor VIII levels in hemophilia A patients receiving replacement therapy, providing a functional assessment of hemostasis.^76^ Similarly, ROTEM has been used to monitor the efficacy of bypassing agents in patients with inhibitors.^77^
TEG/ROTEM may also help identify patients with milder forms of bleeding disorders who have normal conventional coagulation parameters but abnormal clot formation or stability.^78^
Implementation and Interpretation Challenges
Pre-analytical Variables
TEG/ROTEM results can be affected by various pre-analytical factors that require standardization for reliable results:^79^
Sample Collection and Processing:
- Venipuncture technique: Traumatic venipuncture can activate coagulation
- Blood sampling site: Central venous versus peripheral samples may differ
- Anticoagulant used: Citrate is standard, but concentration matters
- Time from collection to analysis: Ideally within 4 hours for citrated samples
- Sample temperature: Should be warmed to 37°C prior to analysis
Patient-Related Factors:
- Recent meals: Postprandial lipemia may affect results
- Circadian variations in coagulation parameters
- Medications affecting coagulation
- Comorbidities influencing baseline hemostasis
Quality Control and Standardization
Despite technological advancements, TEG/ROTEM faces challenges in standardization across instruments, reagents, and institutions:^80^
Standardization Issues:
- Variation between TEG and ROTEM platforms
- Different activators and reagents yield different reference ranges
- Limited external quality assessment programs
- Operator-dependent variability in sample processing
Quality Control Recommendations:
- Regular electronic and biological control testing
- Standardized operating procedures
- Operator training and competency assessment
- Participation in external quality assessment programs when available
Interpretation in Complex Clinical Scenarios
Interpreting TEG/ROTEM requires understanding the integrated nature of the coagulation process and the specific clinical context:^81^
Interpretation Challenges:
- Distinguishing primary from secondary fibrinolysis
- Effects of hypothermia and acidosis on test results
- Interpretation in patients with multiple hemostatic defects
- Integration with conventional coagulation tests and clinical findings
Educational Needs:
- Interdisciplinary education about TEG/ROTEM principles
- Development of institution-specific protocols and algorithms
- Regular case reviews to enhance interpretation skills
- Collaboration between laboratory medicine, anesthesiology, critical care, and other specialties
Limitations and Considerations
While TEG/ROTEM offers valuable insights into the coagulation process, several limitations should be acknowledged:^82^
Technical Limitations:
- Limited sensitivity to platelet dysfunction unless modified assays are used
- Poor sensitivity for mild factor deficiencies
- Variable sensitivity to DOACs without specific modifications
- Limited detection of von Willebrand disease
Clinical Limitations:
- Limited evidence from large randomized controlled trials in some applications
- Threshold values for interventions not well established in all clinical scenarios
- Cost considerations for device acquisition and maintenance
- Need for 24/7 availability and trained personnel in acute care settings
Integration with Other Testing:
- Often most valuable when combined with conventional tests
- May complement point-of-care platelet function testing
- Should be interpreted in clinical context rather than in isolation
Future Directions
The field of viscoelastic hemostatic assays continues to evolve with several promising developments:^83,84^
Technical Advancements:
- Fully automated systems reducing operator variability
- Modified assays to detect effects of novel anticoagulants
- Enhanced sensitivity for specific coagulation abnormalities
- Cartridge-based systems for easier point-of-care implementation
Emerging Clinical Applications:
- Risk stratification for thrombotic events in various patient populations
- Personalized anticoagulation and antiplatelet therapy management
- TEG/ROTEM-guided protocols in novel clinical settings
- Applications in precision medicine approaches to hemostatic management
Ongoing Research Priorities:
- Large multicenter randomized trials evaluating clinical outcomes
- Cost-effectiveness studies across different healthcare settings
- Standardization of testing protocols and reference ranges
- Development of machine learning algorithms to enhance interpretation
Conclusion
Thromboelastography and rotational thromboelastometry represent significant advances in hemostatic testing by providing a comprehensive, dynamic assessment of the coagulation process. Their ability to generate rapid results at the point of care makes them particularly valuable in acute settings requiring timely decision-making.
The clinical utility of TEG/ROTEM spans multiple specialties, including trauma care, perioperative management of complex surgeries, critical care, obstetrics, and management of chronic liver disease. In these settings, viscoelastic testing can guide targeted hemostatic interventions, potentially improving outcomes while optimizing blood product utilization.
Despite their advantages, TEG/ROTEM face challenges in standardization and require careful attention to pre-analytical variables and operator training. Additionally, these technologies should complement rather than replace conventional coagulation tests, with interpretation always occurring within the specific clinical context.
As research continues to refine the applications and limitations of viscoelastic testing, TEG/ROTEM are likely to play an increasingly important role in personalized approaches to hemostasis management across the spectrum of medical and surgical care.
References
Ganter MT, Hofer CK. Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg. 2008;106(5):1366-1375.
Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev. 2012;26(1):1-13.
Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol. 2014;89(2):228-232.
Hartert H. Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin Wochenschr. 1948;26(37-38):577-583.
Karon BS. Why is everyone so excited about thromboelastrography (TEG)? Clin Chim Acta. 2014;436:143-148.
Chitlur M, Sorensen B, Rivard GE, et al. Standardization of thromboelastography: a report from the TEG-ROTEM working group. Haemophilia. 2011;17(3):532-537.
Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol. 2005;27(2):81-90.
Görlinger K, Dirkmann D, Solomon C, Hanke AA. Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability. Br J Anaesth. 2013;110(2):222-230.
Hans GA, Besser MW. The place of viscoelastic testing in clinical practice. Br J Haematol. 2016;173(1):37-48.
Dias JD, Norem K, Doorneweerd DD, Thurer RL, Popovsky MA, Gibbs VA. Use of thromboelastography (TEG) for detection of new oral anticoagulants. Arch Pathol Lab Med. 2015;139(5):665-673.
Solomon C, Ranucci M, Hochleitner G, Schöchl H, Schlimp CJ. Assessing the methodology for calculating platelet contribution to clot strength (platelet component) in thromboelastometry and thrombelastography. Anesth Analg. 2015;121(4):868-878.
Wikkelsø A, Wetterslev J, Møller AM, Afshari A. Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to monitor haemostatic treatment in bleeding patients: a systematic review with meta-analysis and trial sequential analysis. Anaesthesia. 2017;72(4):519-531.
Serraino GF, Murphy GJ. Routine use of viscoelastic blood tests for diagnosis and treatment of coagulopathic bleeding in cardiac surgery: updated systematic review and meta-analysis. Br J Anaesth. 2017;118(6):823-833.
Deppe AC, Weber C, Zimmermann J, et al. Point-of-care thromboelastography/thromboelastometry-based coagulation management in cardiac surgery: a meta-analysis of 8332 patients. J Surg Res. 2016;203(2):424-433.
Raphael J, Mazer CD, Subramani S, et al. Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients. Anesth Analg. 2019;129(5):1209-1221.
Pagano D, Milojevic M, Meesters MI, et al. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. Eur J Cardiothorac Surg. 2018;53(1):79-111.
Hartmann M, Szalai C, Saner FH. Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment. World J Gastroenterol. 2016;22(4):1541-1550.
Krzanicki D, Sugavanam A, Mallett S. Intraoperative hypercoagulability during liver transplantation as demonstrated by thromboelastography. Liver Transpl. 2013;19(8):852-861.
Roullet S, Pillot J, Freyburger G, et al. Rotation thromboelastometry detects thrombocytopenia and hypofibrinogenaemia during orthotopic liver transplantation. Br J Anaesth. 2010;104(4):422-428.
Wang SC, Shieh JF, Chang KY, et al. Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplant Proc. 2010;42(7):2590-2593.
Naik BI, Pajewski TN, Bogdonoff DI, et al. Rotational thromboelastometry-guided blood product management in major spine surgery. J Neurosurg Spine. 2015;23(2):239-249.
Fenger-Eriksen C, Jensen TM, Kristensen BS, et al. Fibrinogen substitution improves whole blood clot firmness after dilution with hydroxyethyl starch in bleeding patients undergoing radical cystectomy: a randomized, placebo-controlled clinical trial. J Thromb Haemost. 2009;7(5):795-802.
Rafee A, Herlikar D, Gilbert R, et al. Thromboelastography in the prediction of risk of venous thromboembolism in patients with hip fractures: a prospective cohort study. Bone Joint J. 2019;101-B(12):1524-1529.
Brohi K, Cohen MJ, Davenport RA. Acute coagulopathy of trauma: mechanism, identification and effect. Curr Opin Crit Care. 2007;13(6):680-685.
Davenport R, Manson J, De'Ath H, et al. Functional definition and characterization of acute traumatic coagulopathy. Crit Care Med. 2011;39(12):2652-2658.
Holcomb JB, Minei KM, Scerbo ML, et al. Admission rapid thrombelastography can replace conventional coagulation tests in the emergency department: experience with 1974 consecutive trauma patients. Ann Surg. 2012;256(3):476-486.
Chapman MP, Moore EE, Ramos CR, et al. Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy. J Trauma Acute Care Surg. 2013;75(6):961-967.
Nardi G, Agostini V, Rondinelli B, et al. Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs. Crit Care. 2015;19(1):83.
Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471-482.
Tapia NM, Chang A, Norman M, et al. TEG-guided resuscitation is superior to standardized MTP resuscitation in massively transfused penetrating trauma patients. J Trauma Acute Care Surg. 2013;74(2):378-386.
Spahn DR, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23(1):98.
Müller MC, Meijers JC, Vroom MB, Juffermans NP. Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review. Crit Care. 2014;18(1):R30.
Brenner T, Schmidt K, Delang M, et al. Viscoelastic and aggregometric point-of-care testing in patients with septic shock - cross-links between inflammation and haemostasis. Acta Anaesthesiol Scand. 2012;56(10):1277-1290.
Müller M, Balvers K, Binnekade JM, et al. Thromboelastometry and organ failure in trauma patients: a prospective cohort study. Crit Care. 2019;23(1):169.
Ostrowski SR, Windeløv NA, Ibsen M, Haase N, Perner A, Johansson PI. Consecutive thrombelastography clot strength profiles in patients with severe sepsis and their association with 28-day mortality: a prospective study. J Crit Care. 2013;28(3):317.e1-11.
Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003;29(2):125-130.
Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, et al. Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9947):980-1004.
Collins PW, Bell SF, de Lloyd L, Collis RE. Management of postpartum haemorrhage: from research into practice, a narrative review of the literature and the Cardiff experience. Int J Obstet Anesth. 2019;37:106-117.
Collins PW, Lilley G, Bruynseels D, et al. Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study. Blood. 2014;124(11):1727-1736.
Mavrides E, Allard S, Chandraharan E, et al. Prevention and management of postpartum haemorrhage. BJOG. 2022;129(5):e106-e149.
Thornton P, Douglas J. Coagulation in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2010;24(3):339-352.
Oudghiri M, Keita H, Kouamou E, et al. Reference values for rotation thromboelastometry (ROTEM) parameters following non-haemorrhagic deliveries. Correlations with standard haemostasis parameters. Thromb Haemost. 2011;106(1):176-178.
Armstrong S, Fernando R, Ashpole K, Simons R, Columb M. Assessment of coagulation in the obstetric population using ROTEM thromboelastometry. Int J Obstet Anesth. 2011;20(4):293-298.
Görlinger K, Shore-Lesserson L, Dirkmann D, Hanke AA, Rahe-Meyer N, Tanaka KA. Management of hemorrhage in cardiothoracic surgery. J Cardiothorac Vasc Anesth. 2013;27(4 Suppl):S20-S34.
Ellenberger C, Diaper J, Licker M, Cikirikcioglu M, Dulguerov P, Panos A. Transfusion and coagulation management in major orthopaedic surgery: role of viscoelastic testing. Blood Transfus. 2019;17(6):499-511.
Dias JD, Haney EI, Mathew BA, Lopez-Espina CG, Orr AW, Popovsky MA. New-generation thromboelastography: comprehensive evaluation of citrated and heparinized blood sample storage effect on clot-forming variables. Arch Pathol Lab Med. 2017;141(4):569-577.
Duceppe E, Parlow J, MacDonald P, et al. Canadian Cardiovascular Society guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery. Can J Cardiol. 2017;33(1):17-32.
Tantry US, Bliden KP, Gurbel PA. Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J Am Coll Cardiol. 2005;46(9):1705-1709.
Saini A, Hartman ME, Gage BF, et al. Incidence of platelet dysfunction by thromboelastography-platelet mapping in children supported with ECMO: A Pilot Retrospective Study. Front Pediatr. 2016;3:116.
Ryerson LM, Bruce AK, Lequez J, et al. Administration of antithrombin concentrate in infants and children on extracorporeal life support improves anticoagulation efficacy. ASAIO J. 2014;60(5):559-563.
Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood. 2010;116(6):878-885.
Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med. 2011;365(2):147-156.
Mallett SV, Chowdary P, Burroughs AK. Clinical utility of viscoelastic tests of coagulation in patients with liver disease. Liver Int. 2013;33(7):961-974.
Stravitz RT, Lisman T, Luketic VA, et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol. 2012;56(1):129-136.
Tripodi A, Primignani M, Chantarangkul V, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006;44(2):440-445.
De Pietri L, Bianchini M, Montalti R, et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial. Hepatology. 2016;63(2):566-573.
Stine JG, Niccum BA, Zimmet AN, et al. Increased risk of venous thromboembolism in hospitalized patients with cirrhosis due to non-alcoholic steatohepatitis. Clin Transl Gastroenterol. 2018;9(3):140.
Hugenholtz GCG, Adelmeijer J, Meijers JCM, Porte RJ, Stravitz RT, Lisman T. An unbalance between von Willebrand factor and ADAMTS13 in acute liver failure: implications for hemostasis and clinical outcome. Hepatology. 2013;58(2):752-761.
Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood. 2017;130(13):1499-1506.
Akay OM, Ustuner Z, Canturk Z, Mutlu FS, Gulbas Z. Laboratory investigation of hypercoagulability in cancer patients using rotation thrombelastography. Med Oncol. 2009;26(3):358-364.
Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: burden, mechanisms, and management. Thromb Haemost. 2017;117(2):219-230.
Königsbrügge O, Koder S, Riedl J, et al. A new measure for in vivo thrombin activity in comparison with in vitro thrombin generation potential in patients with hyper- and hypocoagulability. Clin Exp Med. 2017;17(2):251-256.
Napolitano M, Saccullo G, Marietta M, et al. Platelet cut-off for antiplatelet therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus. Blood Transfus. 2019;17(3):171-180.
Franchini M, Di Minno MN, Coppola A. Disseminated intravascular coagulation in hematologic malignancies. Semin Thromb Hemost. 2010;36(4):388-403.
Choudhry A, DeLoughery TG. Bleeding and thrombosis in acute promyelocytic leukemia. Am J Hematol. 2012;87(6):596-603.
Goyal J, Adamski J. L-Asparaginase-Induced Hypofibrinogenemia and Venous Thromboembolism in Acute Lymphoblastic Leukemia: Can Literature Review Spark New Studies and Drug Development? Clin Appl Thromb Hemost. 2020;26:1076029620943300.
Young G, Sørensen B, Dargaud Y, Negrier C, Brummel-Ziedins K, Key NS. Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: current state of art and future perspectives. Blood. 2013;121(11):1944-1950.
Young G, Mazaheri P, Perdue JJ, Suvannaset PC, Maahs JA, Tang RH. Differential effects of recombinant factor VIIa and activated prothrombin complex concentrate on thrombin generation in rare coagulopathies. Haemophilia. 2019;25(1):151-159.
Dargaud Y, Sorensen B, Shima M, et al. Global haemostasis and point of care testing. Haemophilia. 2012;18 Suppl 4:81-88.
Tarandovskiy ID, Balandina AN, Kopylov KG, et al. Investigation of the phenotype heterogeneity in severe hemophilia A using thromboelastography, thrombin generation, and thrombodynamics. Thromb Res. 2013;131(6):e274-280.
Kitchen DP, Jennings I, Kitchen S, Woods TA, Walker ID. Bridging the gap between point-of-care testing and laboratory testing in hemostasis. Semin Thromb Hemost. 2015;41(3):272-278.
Ebinger T, Ruland A, Lakner M, Schwaiger M. Validation, regulatory acceptance and future perspectives of thromboelastography and other viscoelastic haemostatic assays. Hamostaseologie. 2019;39(2):210-221.
Görlinger K, Pérez-Ferrer A, Dirkmann D, et al. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management. Korean J Anesthesiol. 2019;72(4):297-322.
Benes J, Zatloukal J, Kletecka J. Viscoelastic Methods of Blood Clotting Assessment - A Multidisciplinary Review. Front Med (Lausanne). 2015;2:62.
Saffer C, Olson J. Viscoelastic Coagulation Testing: Technology, Applications, and Limitations. Transfus Med Rev. 2016;30(4):200-206.
Haas T, Görlinger K, Grassetto A, et al. Thromboelastometry and impedance aggregometry based algorithm for coagulation management in pediatric liver transplantation. Paediatr Anaesth. 2018;28(12):1013-1023.
Crochemore T, Correa TD, Lance MD, et al. Thromboelastometry profile in critically ill patients: A single-center, retrospective, observational study. PLoS One. 2018;13(2):e0192965.
Veigas PV, Callum J, Rizoli S, Nascimento B, da Luz LT. A systematic review on the rotational thrombelastometry (ROTEM) values for the diagnosis of coagulopathy, prediction and guidance of blood transfusion and prediction of mortality in trauma patients. Scand J Trauma Resusc Emerg Med. 2016;24(1):114.
Winearls J, Reade M, Miles H, et al. Targeted coagulation management in severe trauma: the controversies and the evidence. Anesth Analg. 2016;123(4):910-924.
Shen L, Tabaie S, Ivascu N. Viscoelastic testing inside and beyond the operating room. J Thorac Dis. 2017;9(Suppl 4):S299-S308.
Görlinger K, Almutawah H, Almutawaa F, et al. The role of rotational thromboelastometry during the COVID-19 pandemic: a narrative review. Korean J Anesthesiol. 2021;74(2):91-102.
Chaudhary R, Kreutz RP, Bliden KP, Tantry US, Gurbel PA. Personalizing Antithrombotic Therapy in COVID-19: Role of Thromboelastography and Thromboelastometry. Thromb Haemost. 2020;120(11):1594-1596.
Görlinger K, Dirkmann D, Gandhi A, Simioni P. COVID-19-Associated Coagulopathy and Inflammatory Response: What Do We Know Already and What Are the Knowledge Gaps? Anesth Analg. 2020;131(5):1324-1333.
Pavoni V, Gianesello L, Pazzi M, Stera C, Meconi T, Frigieri FC. Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia. J Thromb Thrombolysis. 2020;50(2):281-286.
