Thromboelastography (TEG) is a point-of-care viscoelastic hemostasis assay that evaluates the dynamic process of whole blood coagulation, from initial fibrin formation to clot strength and eventual fibrinolysis, providing a graphical representation of hemostatic function to guide transfusion therapy and identify coagulopathy.[1][2]Developed in 1948 by German physiologist Helmut Hartert, TEG was initially designed to monitor blood clotting during surgery and gained widespread clinical adoption in the 1980s, particularly for liver transplantation where it helped reduce unnecessary blood product transfusions.[1][3] TEG measures the viscoelastic properties of whole blood during coagulation. Traditional devices use a rotating cup with a suspended pin to measure torque resistance as the clot forms and strengthens, while modern cartridge-based systems like the TEG 6s employ resonance frequency technology to detect changes in blood vibration, producing a characteristic trace that reflects the interplay of clotting factors, platelets, fibrinogen, and fibrinolysis.[1][2] Unlike traditional coagulation tests such as prothrombin time (PT) or activated partial thromboplastin time (aPTT), which assess isolated plasma components in a static manner, TEG provides a holistic, real-time evaluation of whole blood under near-physiological conditions, often yielding results within 5-10 minutes.[2][3]The TEG trace yields several key parameters that quantify different phases of hemostasis: R time (reaction time), the latency from test initiation to initial fibrin formation (normal range: 4-8 minutes), indicating clotting factor activity; K time (kinetics), the time to reach a clot amplitude of 20 mm (normal: 1-4 minutes), reflecting fibrinogen and platelet function; α angle, the slope of the trace measuring fibrin polymerization speed (normal: 45-75 degrees); MA (maximum amplitude), the peak clot strength (normal: 50-70 mm), primarily determined by platelet aggregation and fibrinogen levels; and LY30 (lysis at 30 minutes), the percentage of clot breakdown (normal: <8%), assessing fibrinolysis activity.[1][2] These parameters allow for targeted interventions, such as cryoprecipitate for low α angle or platelets for reduced MA.[3]Clinically, TEG is most established in high-bleeding-risk settings like trauma, cardiac surgery, and liver transplantation, where studies have shown it can decrease allogeneic blood transfusions by up to 30%; a 2016 randomized controlled trial in trauma patients demonstrated improved survival rates.[1][3] More recently, as of 2024, the EACTS/EACTAIC Guidelines have recommended TEG and similar assays for transfusion guidance in adult cardiac surgery.[4] Emerging applications include obstetrics, sepsis, extracorporeal membrane oxygenation (ECMO), and monitoring anticoagulation in conditions like COVID-19-associated coagulopathy, though evidence remains limited outside surgical contexts.[3] Advantages include its ability to detect hyperfibrinolysis (present in 2-5% of severe trauma cases with up to 80% mortality) and hypocoagulable states not captured by conventional tests, potentially reducing transfusion-related complications.[2][3] However, limitations persist, such as variability due to sample handling, lack of standardization between TEG and similar assays like rotational thromboelastometry (ROTEM), and insufficient validation for routine preoperative screening or non-bleeding patients.[1][2]
History and Development
Invention and Early Applications
Thromboelastography was invented in 1948 by Helmut Hartert at the University of Heidelberg in Germany, where he developed it as a point-of-care method to monitor the viscoelastic properties of blood coagulation in real time during surgical procedures.[5] Hartert's innovation aimed to provide a dynamic assessment of clot formation and lysis using whole blood samples, addressing limitations of traditional static coagulation tests.[6]The initial apparatus featured a small rotating cup (approximately 8 mm in diameter) that held the blood sample, oscillated at a low shear rate to mimic venous flow, with a pin suspended via a thin torsion wire connected to a transducer for detecting rotational resistance as the clot formed and imparted elasticity.[6] This mechanical setup recorded the clot's strength on a graphical trace, enabling qualitative and quantitative evaluation of hemostasis without the need for plasma separation.[7]In its early clinical applications during the 1950s and 1960s, thromboelastography was employed in anesthesiology and cardiac surgery to detect hypercoagulable states and optimize heparin dosing, particularly in patients undergoing procedures with high bleeding risk, such as those involving cardiopulmonary bypass.[5] The technique's first reported clinical application occurred during the Vietnam War era, where it guided blood product transfusions for trauma patients by identifying coagulopathy patterns at the bedside.[5]The first commercial thromboelastography device, the TEG system, was introduced in the 1970s by Haemoscope Corporation, marking the transition from laboratory prototypes to accessible clinical tools and facilitating broader adoption in perioperative settings.[8]
Modern Evolution and Standardization
Following the initial invention by Helmut Hartert in 1948, thromboelastography experienced renewed interest and commercialization in the 1980s and 1990s, driven by its demonstrated utility in high-bleeding-risk surgeries such as liver transplantation and cardiac procedures.[5]Haemoscope Corporation played a pivotal role in this phase, developing and marketing the TEG system as a point-of-care diagnostic tool for assessing whole-blood coagulation properties.[9] The TEG 5000 analyzer, a key commercial product from Haemoscope, was cleared by the U.S. Food and Drug Administration in 2000 as substantially equivalent to prior models for quantitative and qualitative evaluation of hemostasis.[10]Parallel advancements occurred with the introduction of rotational thromboelastometry (ROTEM) by TEM International in Munich, Germany, developed between 1995 and 1997 as a rotational variant designed for faster assay results through automated pipetting and simultaneous multi-channel testing.[11] This system addressed limitations in traditional thromboelastography by enhancing reproducibility and reducing operator variability, facilitating broader clinical adoption in perioperative settings.[12] These milestones marked the transition from research-oriented prototypes to standardized commercial devices, with ROTEM's 1995 development representing a significant evolution toward more efficient viscoelastic testing.[12]Efforts to standardize thromboelastography protocols and nomenclature intensified in the 2010s through international collaborations, including the TEG-ROTEM Working Group, which issued consensus recommendations in 2011 emphasizing the need for uniform reference ranges, quality control measures, and validation studies to improve inter-laboratory comparability.[13] These guidelines addressed variations in assay performance across devices and populations, promoting consistent interpretation of parameters like clotting time and maximum clot firmness for clinical decision-making.[14] Subsequent working group reports in the decade further refined quality assurance protocols, including operator training and reagent standardization, to mitigate discrepancies between TEG and ROTEM systems.[14]In the 2000s, the integration of computerized analysis revolutionized thromboelastography by enabling automated calculation of core parameters, such as reaction time and clot formation angle, directly from tracings in systems like the TEG 5000 and ROTEM.[9] This advancement, supported by dedicated software for real-time data processing and quality checks, reduced manual interpretation errors and enhanced the reliability of results in dynamic clinical environments.[15] By facilitating objective, reproducible outputs, computerized features solidified viscoelastic testing's role in goal-directed hemostatic management.[15]
Principles and Mechanics
Fundamental Principles
Thromboelastography evaluates the viscoelastic properties of whole blood during clot formation, which arise from the dynamic interplay between procoagulant elements—including coagulation factors, platelets, and fibrinogen—and counterbalancing processes such as fibrinolysis, all under low-shear conditions that preserve the integrity of cellular and plasma components.[5] This approach captures the evolving mechanical strength of the fibrin-platelet matrix as it transitions from a liquid to a solid state, providing insight into the overall balance of hemostasis without separating blood elements.[5]In contrast to conventional tests like prothrombin time (PT) and activated partial thromboplastin time (aPTT), which analyze isolated plasma fractions and focus on specific enzymatic pathways, thromboelastography assesses the complete hemostatic sequence—from clot initiation via thrombin burst to peak firmness and subsequent degradation—yielding a temporal profile of global coagulation function in native blood.[5] This comprehensive view reveals interactions often missed by plasma assays, such as the contributions of platelets and inhibitors to net clot dynamics.[5]The physiological foundation of these measurements lies in the clot's mechanical properties, which mirror thrombin generation as the trigger for fibrin formation, subsequent fibrin polymerization into a networked scaffold, and the reinforcement provided by platelet-fibrin cross-linking, culminating in a stable thrombus capable of resisting deformation.[15] These elements collectively determine clot resilience, with deficiencies or excesses in any component altering the viscoelastic response.[15]Unlike static or broad rheological techniques, thromboelastography incorporates dynamic oscillation to replicate the sluggish, low-flow environments of the venous system, such as stasis, thereby approximating in vivo conditions where shear forces are minimal and clot development proceeds unhindered by high arterial turbulence.[16]
Device Operation and Measurement Process
Thromboelastography (TEG) devices measure the viscoelastic properties of whole blood during clot formation and lysis using a mechanical system consisting of a rotating cup and a suspended pin. A standard sample of 0.36 mL citrated whole blood is pipetted into a disposable plastic cup with an inner clearance of approximately 1 mm around the pin, and the assembly is heated to 37°C to simulate physiological conditions.[5][6] The cup then oscillates at 0.1 Hz through an arc of 4°45', creating low shear stress that mimics venous flow while allowing fibrin strands to form between the cup wall and the pin.[17][18]The pin is suspended from a torsion wire connected to a transducer, which detects rotational torque as the developing clot transmits motion from the oscillating cup to the pin. This mechanical resistance increases with clot strength, and the resulting signal is converted to an electrical output by the device software, generating a real-time graphical tracing (thromboelastogram) over 30 to 60 minutes.[5][3] The tracing plots amplitude (representing clot firmness) against time, providing a continuous profile of hemostatic function without requiring plasma separation.[19]To initiate clotting, the citrated blood sample is first activated and recalcified. Common activators include kaolin to stimulate the intrinsic pathway or tissue factor for the extrinsic pathway, with celite used in some rapid assays to accelerate contact activation.[5][20] The procedural steps typically involve: mixing 0.36 mL of citrated blood with 20 µL of activator (e.g., kaolin); pipetting the mixture into the preheated cup; adding 20 µL of 0.2 M calcium chloride to reverse citrate anticoagulation; inserting the pin assembly; and starting the oscillation to produce the tracing via computer interface.[5][21] This process enables point-of-care assessment, with initial results available in 10 to 15 minutes.[19]
Parameters and Tracings
Core Parameters
Thromboelastography (TEG) tracings capture the viscoelastic properties of blood clotting through a series of characteristic parameters that reflect distinct phases of hemostasis, from initiation to fibrinolysis. These core parameters are derived from the amplitude-time curve generated during the assay, where a rotating cup and pin detect clot formation in whole blood. The primary measurements include reaction time, kinetic time, alpha angle, maximum amplitude, and clot lysis at 30 minutes, each corresponding to physiological aspects of coagulation.The reaction time (R) represents the latency phase from the addition of an activator to the initial formation of fibrin strands, typically measured as the time until the tracing reaches a 2 mm amplitude from baseline. This parameter primarily reflects the activity of plasma clotting factors, such as factors VII and X in the extrinsic pathway or factors XII and VIII in the intrinsic pathway, indicating the speed of thrombin generation and early fibrin polymerization. Normal R values range from 4 to 8 minutes in standard assays.[17]The kinetic time (K) measures the time elapsed from the end of R to when the clot amplitude reaches 20 mm, capturing the amplification and propagation phases of clot development. It assesses the rate of fibrin cross-linking and buildup, influenced by fibrinogen levels and the efficiency of thrombin-mediated conversion of fibrinogen to fibrin. A normal K range is 1 to 4 minutes, highlighting the dynamics of clot strengthening shortly after initiation.[17]The alpha angle (α) quantifies the slope of the tangent to the curve at the midpoint between R and K, often defined as the angle from the baseline to the line intersecting the 20 mm amplitude point. This parameter evaluates the kinetics of fibrin formation and platelet-fibrinogen interactions, serving as an indicator of fibrinogen function and overall clot formation speed during the propagation phase. Typical normal values fall between 47° and 74°.[17]The maximum amplitude (MA) denotes the peak height of the tracing, corresponding to the ultimate strength and stability of the formed clot. It primarily reflects the mechanical properties arising from platelet aggregation and fibrin-platelet interactions, with platelets contributing approximately 80% and fibrinogen 20% to this clot firmness. Normal MA values are 55 to 73 mm, providing a measure of the clot's resistance to shear forces.[17]The clot lysis at 30 minutes (LY30) indicates the extent of clot degradation, calculated as the percentage reduction in amplitude 30 minutes after achieving MA. This parameter assesses the activity of the fibrinolytic system, including plasmin-mediated breakdown of fibrin strands, which helps maintain vascular patency post-hemostasis. Normal LY30 values are 0% to 8%, signifying minimal spontaneous lysis in healthy coagulation.[17]
Derived Measurements and Calculations
Derived measurements in thromboelastography extend beyond primary tracing parameters by applying mathematical transformations to quantify aspects of clot kinetics and strength more precisely, aiding in targeted clinical interventions such as transfusion decisions. These calculations often derive from the velocity curve of the thromboelastogram, which represents the first derivative of the amplitude tracing, providing insights into the speed and efficiency of thrombus formation.[22]The maximum rate of thrombus generation (MRTG) measures the peak velocity of clot formation, calculated as the maximum slope of the rising phase in the velocity curve, typically expressed in dynes/cm² per second. This parameter reflects the overall rate of enzymatic and polymerization processes driving clot assembly, with higher values indicating faster thrombus generation often seen in hypercoagulable states. Clinically, MRTG helps assess the urgency of clot formation in trauma or surgical settings, where reduced MRTG may signal hypofibrinogenemia or platelet dysfunction requiring fibrinogen or platelet supplementation.[23][24]Time to maximum rate of thrombus generation (TMRTG) is the temporal point at which MRTG occurs, derived from the velocity curve and indicating the latency to peak clot-building speed. Prolonged TMRTG suggests delays in thrombin burst or fibrin polymerization, correlating with anticoagulant effects or factor deficiencies. This metric enhances diagnostic precision in perioperative monitoring, guiding the timing of hemostatic therapies to prevent excessive bleeding.[22][25]The G-value, or clot firmness, quantifies the shear elastic modulus of the formed clot, calculated using the formula:G = \frac{5000 \times \mathrm{MA}}{100 - \mathrm{MA}}where MA is the maximum amplitude in millimeters, yielding units in dynes/cm². Normal G-values range from 5300 to 12400 dynes/cm², with values below this threshold signaling inadequate clot strength due to low platelet count or function. In practice, a G-value less than approximately 6000 dynes/cm² often serves as a transfusion threshold for platelets, as it predicts poor resistance to shear stress and higher bleeding risk in critically ill patients.[26][27][28][29]Clot elasticity, sometimes denoted as CE in related viscoelastic assays, provides a measure of overall hemostatic balance by evaluating the interplay between clot kinetics and strength, though specific derivations vary by system. In thromboelastography contexts, it aligns closely with G-value assessments, emphasizing the elastic properties for transfusion guidance in coagulopathic scenarios.[26]
Interpretation and Diagnostics
Normal Ranges and Abnormal Patterns
Normal reference ranges for thromboelastography (TEG) parameters vary based on the activator (e.g., kaolin or native), patient factors such as age and sex, and assay-specific protocols, with values typically established from large cohorts of healthy volunteers. For kaolin-activated TEG using citrated blood in 118 healthy adults, the 95% reference ranges are reaction time (R) of 3.8–9.8 minutes, coagulation time (K) of 0.7–3.4 minutes, alpha angle (α) of 47.8–77.7 degrees, maximum amplitude (MA) of 49.7–72.7 mm, and 30-minute lysis (LY30) of -2.3–5.77%.[30] Women in this cohort exhibited slightly more hypercoagulable profiles than men, while age and ethnicity showed no significant associations with coagulability.[30] In a larger 2022 study of 17,708 healthy Chinese adults using a matched activated reagent, adjusted ranges included R of 5.1–10 minutes, K of 1.3–3.8 minutes, α of 44.9–70.2 degrees, and MA of 50.4–71 mm, with narrower intervals in younger groups (20–59 years) compared to the elderly.[31]Hypercoagulable patterns on TEG tracings are characterized by shortened R and K times, a steepened α angle greater than 78 degrees, and elevated MA exceeding 69 mm, reflecting accelerated clot initiation and enhanced clot strength due to excessive thrombin generation or platelet hyperactivity.[17] These features are commonly observed in early disseminated intravascular coagulation (DIC) or acute trauma, where up to 62% of patients may show R below 3.7 minutes on admission, indicating a prothrombotic state that can progress to consumption coagulopathy.[32]In contrast, hypocoagulable patterns display prolonged R (>9.8 minutes) and K (>3.4 minutes), a flattened α angle below 47.8 degrees, and reduced MA (<49.7 mm), signifying delayed fibrin formation and weak clot stability often from dilutional effects or clotting factor depletion.[17] Such tracings are typical in dilutional coagulopathy following massive fluid resuscitation in trauma or surgical bleeding.[33]Fibrinolytic abnormalities are identified by elevated LY30 greater than 8%, where the tracing shows progressive clot breakdown after peak MA, denoting hyperfibrinolysis that impairs hemostasis.[17] This pattern occurs in approximately 25% of severe trauma cases and serves as an independent predictor of 24-hour mortality.[34]Distinct tracing morphologies highlight specific deficiencies: a flat-line pattern, with minimal amplitude rise and no defined MA, indicates severe hypofibrinogenemia and absent fibrin polymerization, as seen in congenital afibrinogenemia or massive hemorrhage.[35] Factor deficiencies, such as in hemophilia, typically produce asymmetric or prolonged initiation phases with extended R time, underscoring isolated delays in the intrinsic coagulation pathway.[36]
Clinical Decision-Making Guidelines
Thromboelastography (TEG) facilitates goal-directed hemostatic therapy by providing real-time assessment of coagulation dynamics, enabling clinicians to tailor interventions based on specific parameter abnormalities rather than empiric protocols.[37] In established algorithms, prolonged reaction time (R >10 minutes) indicates delayed clot initiation due to factor deficiencies, prompting administration of fresh frozen plasma (FFP) to replenish clotting factors.[1] Similarly, low maximum amplitude (MA <50 mm) reflects reduced clot strength from platelet dysfunction or hypofibrinogenemia, guiding transfusion of platelets or cryoprecipitate to enhance platelet function and fibrinogen levels.[37]For hyperfibrinolysis indicated by lysis at 30 minutes (LY30 >10%), antifibrinolytic agents such as tranexamic acid are recommended to stabilize the clot and prevent excessive breakdown.[38] Goal-directed targets in hemostatic resuscitation often include achieving an MA >55 mm to ensure adequate clot firmness during high-risk procedures, with repeated TEG assessments to monitor response and adjust therapy.[38] Additionally, a maximum clot elasticity (G <5.3 dynes/cm²) signals profound hypofibrinogenemia, warranting fibrinogen replacement via cryoprecipitate or concentrate to restore fibrin cross-linking.[39] Prolonged R times may also prompt use of prothrombin complex concentrate (PCC) when FFP is unavailable or in cases of rapid factor depletion, particularly if fibrinogen is normalized.[40]
Major anesthesiology and trauma societies endorse TEG integration into massive transfusion protocols for improved outcomes. The American Society of Anesthesiologists (ASA) guidelines highlight TEG-guided therapy to reduce blood product transfusions and transfusion rates in perioperative settings.[41] The European guideline on major bleeding and coagulopathy following trauma recommends viscoelastic methods like TEG for early identification of coagulopathy and targeted resuscitation in massive transfusion scenarios.[37] These protocols emphasize serial TEG testing to dynamically guide therapy, minimizing over-transfusion while addressing specific deficits.
Assay Variants
Standard Assays
Standard assays in thromboelastography (TEG) encompass the foundational protocols for evaluating whole bloodcoagulation dynamics in routine clinical settings, primarily through variations in activation methods to target intrinsic, extrinsic, or overall pathways. These assays utilize citrated or native blood samples processed on devices like the TEG 5000 analyzer, where a small volume of blood is placed in a rotating cup with a torsion wire to detect clot formation viscoelastic changes.[5] The core protocol involves adding 340 μL of blood to a preheated cup (37°C) containing 20 μL of 0.2 M calcium chloride to reverse citrate anticoagulation, followed by the specific activator if applicable; assays typically run for up to 60 minutes or until the trace stabilizes, with quality control ensured by verifying calcium reversal and periodic external proficiency testing.[42][5]Kaolin-activated TEG (KA-TEG) serves as the standard assay for assessing overall coagulation status, activating the intrinsic pathway via contact activation with kaolin reagent. In this protocol, the TEG cup is preloaded with 20 μL of kaolin solution, to which the 340 μL blood and 20 μL calcium chloride mixture is added, initiating clot formation within 5-10 minutes as reflected in the reaction time (R) parameter.[5][42] This assay provides a comprehensive profile of clot initiation, formation, and strength, making it suitable for routine monitoring in perioperative and critical care environments.[5]Native TEG, in contrast, employs no exogenous activator and uses non-citrated whole blood drawn directly into the analyzer to evaluate spontaneous intrinsic coagulation, offering a closer approximation to in vivo conditions. The protocol follows the same volume and calcium addition as KA-TEG but omits the activator, resulting in a longer activation phase of 20-30 minutes before detectable clot formation begins.[5][43] Due to its extended run time and sensitivity to pre-analytic variables like sample handling, native TEG is less commonly used in high-volume settings but remains valuable for baseline assessments without artificial pathway stimulation.[5]Tissue factor-activated TEG (TF-TEG) is designed for expedited evaluation of the extrinsic pathway, particularly in emergencies, by adding 20 μL of tissue factor reagent to the cup prior to blood and calcium introduction. This activation mimics tissue injury-induced coagulation, yielding results in approximately 10-15 minutes for initial parameters, which facilitates quicker decision-making compared to other standards.[5][42] Like KA-TEG, it supports broad routine testing but emphasizes rapid turnaround for time-sensitive scenarios such as trauma.[5]
Specialized and Functional Assays
Specialized and functional assays in thromboelastography (TEG) and its rotational counterpart, thromboelastometry (ROTEM), extend the foundational evaluations by incorporating specific reagents to target anticoagulants, platelet function, or fibrinogen activity, enabling precise diagnostics in scenarios like heparin exposure or antiplatelet therapy.[3] These modifications allow for rapid, point-of-care assessment of targeted hemostatic components, distinguishing them from standard kaolin-activated TEG by focusing on niche pathways.[44]The heparinase TEG assay neutralizes heparin effects through the addition of heparinase enzyme, which enzymatically degrades heparin in the blood sample, permitting accurate monitoring of intrinsic coagulation without interference from residual anticoagulant during or after cardiopulmonary bypass (CPB).[45] This modification is particularly valuable in post-cardiac surgery settings, where it detects heparin contamination even when activated clotting time (ACT) is below 140 seconds and correlates post-protamine clot strength parameters (α-angle and maximum amplitude, MA) with pre-CPB baselines (r = 0.77-0.78, P < 0.001).[45] By reversing heparin's prolongation of reaction time without affecting heparin-free samples, heparinase TEG facilitates timely identification of coagulopathy and guides transfusion decisions in up to 50% of cases with borderline ACT values.[45]RapidTEG (r-TEG) combines tissue factor and kaolin activators to accelerate the clotting cascade, yielding reaction times under 5 minutes and overall results in 10-20 minutes, which is essential for early hemostatic resuscitation in trauma patients.[3] Unlike standard TEG, which relies solely on kaolin for intrinsic pathway activation, r-TEG integrates extrinsic pathway initiation via tissue factor, providing a broader profile akin to prothrombin time and activated partial thromboplastin time while detecting hyperfibrinolysis and coagulopathy faster than conventional tests (30-60 minutes).[3] Clinical studies demonstrate its efficacy in reducing mortality, with r-TEG-guided therapy linked to 19.6% 28-day mortality versus 36.4% with standard coagulation assays (P = 0.049).[3]The PlateletMapping assay evaluates antiplatelet drug effects by quantifying platelet inhibition through targeted activation of specific receptors, comparing maximum amplitude (MA) in agonist-stimulated samples to full thrombin-induced clot strength.[46] For aspirin, arachidonic acid activation measures thromboxane A2 pathway inhibition, while adenosine diphosphate (ADP) activation assesses clopidogrel's P2Y12 receptor blockade; inhibition percentage is derived as (MA_thrombin - MA_agonist) / (MA_thrombin - MA_fibrin) × 100.[46] This approach provides objective quantification of therapy responsiveness, aiding risk stratification in patients undergoing procedures like cardiac stenting where incomplete inhibition correlates with thrombotic events.[46]Functional fibrinogen (FF-TEG) isolates fibrinogen's contribution to clot firmness by incorporating tissue factor for coagulation initiation and abciximab, a glycoprotein IIb/IIIa inhibitor, to suppress platelet aggregation, ensuring MA reflects fibrinpolymerization alone.[47] Performed on citrated whole blood, this assay yields normal MA values of 10-25 mm, correlating with plasma fibrinogen levels and enabling prediction of transfusion needs in hypofibrinogenemic states.[47] By excluding platelet "noise," FF-TEG offers a functional measure superior to static Clauss methods for dynamic assessment during surgery or bleeding disorders.[47]ROTEM equivalents provide analogous specialized evaluations: INTEM activates the intrinsic pathway with ellagic acid or kaolin to assess factors VIII, IX, XI, and XII, mirroring activated partial thromboplastin time; EXTEM uses tissue factor for extrinsic pathway activation, evaluating factors VII and X alongside fibrinogen and platelets, similar to prothrombin time; and FIBTEM employs cytochalasin D to inhibit platelets, isolating fibrinogen function with normal maximum clot firmness of 9-25 mm.[44] These assays run concurrently for comprehensive profiling, with FIBTEM particularly sensitive for early fibrinogen deficiency detection in coagulopathies.[44]
Clinical Applications
Perioperative and Trauma Management
Thromboelastography provides real-time assessment of coagulation during high-risk surgeries, enabling intraoperative guidance for antifibrinolytic and blood product administration to mitigate bleeding. In cardiac surgery, TEG-guided algorithms titrate transfusions based on parameters like reaction time and maximum amplitude, reducing red blood cell transfusions by approximately 11% and platelet transfusions by 19% compared to conventional testing.[48] Similarly, in liver transplantation, TEG identifies hyperfibrinolysis early, allowing targeted use of tranexamic acid and fibrinogen concentrates, which decreases overall blood product requirements and reoperation rates for bleeding.[49]In trauma settings, thromboelastography facilitates goal-directed transfusion in patients with hemorrhagic shock, supporting reduced mortality through personalized hemostatic therapy. The PROPPR trial (2015), involving 680 patients with severe trauma, highlighted the benefits of balanced resuscitation protocols with a 1:1:1 plasma:platelet:red blood cell ratio, showing lower 24-hour mortality (9.2% vs 12.8%) and 30-day mortality (21.9% vs 26.7%) compared to 1:1:2.[50] A 2016 randomized controlled trial of TEG-guided resuscitation in trauma confirmed improved survival (odds ratio 0.55, 95% CI 0.33–0.92) and fewer transfusion requirements versus standard coagulation tests.[51]Within massive transfusion protocols for trauma-induced coagulopathy, TEG rapidly detects abnormalities, such as low maximum amplitude indicating platelet hypofunction or fibrinogen deficiency, affecting about 25% of severely injured patients on emergency department arrival.[52] This allows prompt intervention within 20 minutes of sampling, preventing progression of coagulopathy and optimizing component therapy over empirical approaches.[53]In orthopedic and obstetric surgery, TEG-guided management reduces blood product utilization, particularly in procedures like total joint arthroplasty and cesarean deliveries with postpartum hemorrhage, by avoiding unnecessary transfusions and lowering associated complications.[54] For instance, in obstetrics, viscoelastic testing protocols have decreased plasma and cryoprecipitate use while maintaining hemostasis.[55]
Critical Care and Other Settings
In intensive care units (ICUs), thromboelastography (TEG) serves as a valuable tool for monitoring coagulopathy in patients with sepsis, particularly for detecting disseminated intravascular coagulation (DIC). Prolonged reaction time (R) on TEG traces indicates delayed clot initiation due to factor deficiencies, while elevated lysis at 30 minutes (LY30) reflects hyperfibrinolysis, both hallmarks of DIC in septic patients.[56] These parameters enable early identification of hemostatic imbalances, with studies showing that TEG-guided interventions reduce transfusion requirements compared to conventional tests.[57] Additionally, TEG facilitates targeted anticoagulation reversal in sepsis-associated coagulopathy by quantifying clot strength and lysis, thereby minimizing bleeding risks in critically ill patients.[58]In obstetric settings, TEG and rotational thromboelastometry (ROTEM) are employed to manage postpartum hemorrhage, where rapid assessment of fibrinogen levels is crucial. Viscoelastic tests such as ROTEM's FIBTEM assay correlate strongly with plasma fibrinogen concentration, allowing for prompt fibrinogen concentrate administration in cases of hypofibrinogenemia, which reduces blood loss and transfusion needs.[47] In preeclampsia, TEG detects thrombocytopenia-related coagulation defects, guiding hemostatic therapy to prevent excessive bleeding during delivery.[59] These viscoelastic tests provide dynamic insights into clot formation, outperforming static assays in high-risk pregnancies.[60]During the COVID-19 pandemic (2020-2023), TEG and ROTEM revealed hypercoagulable patterns in severe cases, characterized by elevated maximum amplitude (MA), indicating increased clot firmness and thrombotic risk.[61] These findings informed intensified thromboprophylaxis strategies, with studies demonstrating that high MA values predicted venous thromboembolism in hospitalized patients, prompting escalated anticoagulation dosing.[62] Viscoelastic testing thus supported personalized management of COVID-19-associated coagulopathy, reducing thrombotic complications.[63]In liver disease, TEG assesses bleeding risk in cirrhosis complicated by portal hypertension, where conventional tests often overestimate coagulopathy due to rebalanced hemostasis.[64] TEG profiles in these patients typically show prolonged R and reduced MA, reflecting factor deficiencies, yet guide prophylactic transfusions more accurately than prothrombin time alone.[65] For pediatric applications, age-specific reference ranges are essential, as neonates exhibit accelerated clot formation compared to adults; adjusted TEG norms for term infants include shorter R times (around 4-7 minutes) to avoid misdiagnosis of hypercoagulability.[66] In preterm neonates, ROTEM parameters like clot formation time are prolonged, necessitating tailored interpretations for conditions such as neonatal sepsis.[67]Recent advances as of 2025 include the adoption of cartridge-based systems like the TEG6s for automated, rapid point-of-care testing, enhancing applications in critical care and neurology, where TEG predicts thrombosis risk in conditions like stroke.[68][69] Updated meta-analyses confirm TEG/ROTEM-guided strategies reduce mortality, bleeding volume, and transfusions across bleeding patients.[54]
Advantages, Limitations, and Advances
Evidence-Based Benefits
A 2020 review of clinical evidence, including meta-analyses of randomized controlled trials (RCTs), supports the use of thromboelastography (TEG) for guiding transfusions in bleeding patients, demonstrating reductions in mortality and blood product use.[3] A seminal 2016 Cochrane systematic review analyzed 17 RCTs involving 1,493 patients with severe bleeding and found that TEG-guided transfusion compared to standard care reduced overall mortality by an absolute 3.5% (from 7.4% to 3.9%; risk ratio 0.52, 95% CI 0.28-0.95; low-quality evidence) and decreased red blood cell transfusion volumes (moderate-quality evidence).[70] These findings indicate moderate evidence per GRADE assessments for TEG's role in optimizing transfusion guidance, particularly in reducing unnecessary blood product administration.[70]Key trials further illustrate these benefits in specific settings. The iTACTIC trial (2017-2018, published 2020), a multicenter RCT of 401 trauma patients with hemorrhagic shock, compared TEG-augmented protocols to conventional testing and showed faster time to hemostatic interventions (median 61 vs. 80 minutes; p<0.05), though overall transfusion volumes and 28-day mortality were similar; a subgroup with severe traumatic brain injury exhibited reduced mortality (44% vs. 74%; p=0.016). In cardiac surgery, a 2019 meta-analysis of 16 RCTs (n=3,332 patients) confirmed TEG-guided therapy reduced red blood cell transfusions by 1-2 units per patient, postoperative blood loss, and reoperation rates for bleeding, with a trend toward lower mortality.TEG's point-of-care nature provides results in 15-30 minutes, enabling rapid decision-making compared to conventional laboratory tests that often take 45-60 minutes or longer.[70] Economic analyses up to 2020 estimate cost savings in trauma and cardiac settings, primarily from lower transfusion requirements and reduced hospital length of stay.[71]
Known Limitations and Challenges
Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are sensitive to environmental factors such as vibration and temperature variations, which can lead to artifactual results and reduced test reliability.[18] Specifically, the TEG device requires placement on a stable, level surface to minimize vibration-induced noise, which manifests as spikes in the tracing, while temperature deviations from 37°C alter clot formation kinetics, mimicking hypothermic coagulopathy.[72][73] These assays also demand trained operators for accurate setup and interpretation, as interoperator variability can significantly affect reproducibility, with ROTEM generally showing lower variability than TEG in multiuser settings.[5][74] Additionally, inter-device variability between TEG and ROTEM platforms can reach up to 20% for certain parameters like reaction time and maximum amplitude, complicating direct comparisons across systems.[75]Interpretive challenges arise from the absence of universal reference ranges, which vary by device, activator, patient population, and assay conditions, hindering standardized clinical application.[76] Pre-analytical factors further complicate results; for instance, citrated blood samples are stable for only up to 2 hours at room temperature before factor degradation invalidates the trace, emphasizing the need for prompt analysis.[77]Evidentiary gaps persist due to the generally low quality of supporting trials, such as the 2020 iTACTIC randomized controlled trial, which was rated "very low" quality by the GRADE system for its traumatic brain injury subgroup owing to risks of bias, inconsistency, indirectness, and imprecision.[78] Moreover, while TEG/ROTEM may reduce transfusion needs in bleeding scenarios, randomized trials have shown no overall mortality benefit in some non-bleeding critical care contexts, limiting broader adoption.[79]Other barriers include substantial costs, with TEG devices priced around $25,000 plus ongoing maintenance and consumable expenses, and limited regulatory approval; for example, TEG is not FDA-cleared for monitoring in sepsis, restricting its use to specific indications like perioperativehemostasis assessment.[80][81]
Recent Developments and Future Directions
A 2023 systematic review and meta-analysis demonstrated the association between viscoelastic testing parameters, including those from thromboelastography (TEG), and increased mortality risk in COVID-19 patients, reinforcing its utility for confirming coagulopathy benefits in this population.[82] In 2024, advancements in artificial intelligence integration enabled automated interpretation of TEG traces, with software enhancements from manufacturers like Haemonetics improving diagnostic accuracy and reducing operator variability in real-time analysis.[83]By 2025, the TEG 6s system advanced as a portable, cartridge-based platform suitable for field use in trauma settings, offering rapid point-of-care assessment without traditional calibration needs and facilitating timely transfusion decisions in pre-hospital environments.[84] Concurrently, rotational thromboelastometry (ROTEM) expanded in extracorporeal membrane oxygenation (ECMO) monitoring, with studies validating its role in correlating clotting times to standard tests for precise anticoagulation adjustments in both adult and pediatric cases.[85]Looking ahead, ongoing standardization efforts, including a 2025 rapid update to guidelines on TEG and ROTEM, aim to harmonize reference ranges and protocols across devices to enhance interoperability and clinical adoption.[86] Future integrations may combine TEG with genomic profiling to enable personalized hemostasis management, as preliminary models predict clot dynamics from blood proteins and genetic markers for tailored therapies.[87] Emerging trials, such as the ThromboPredict study, are investigating ROTEM parameters as biomarkers for revascularization success in ischemic stroke and thrombectomy procedures.[88] In pediatric critical care, 2025 research highlights TEG-guided therapy's potential to optimize anticoagulation during ECMO, leading to improved management and reduced transfusion needs compared to conventional approaches.[89]