|Year : 2017 | Volume
| Issue : 1 | Page : 8-18
Thromboelastography as a novel viscoelastic method for hemostasis monitoring: Its methodology, applications, and constraints
Anupam Verma1, Hemlata2
1 Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Anaesthesiology, King George's Medical University, Lucknow, Uttar Pradesh, India
|Date of Web Publication||22-Mar-2017|
Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Thromboelastography (TEG) is a novel viscoelastic method which provides a comprehensive assessment of hemostasis from clot initiation and development to fibrinolysis involving both cellular and plasmatic components of hemostatic system. Apart from surgery its role is expanding into medical specialties with increasing integration into laboratory settings. TEG complements the conventional coagulation tests in assessment of bleeding disorders. Further hemotherapy based on TEG results has been shown to reduce transfusion requirements in varied clinical settings besides helping in identifying coagulopathies in patients with major bleedings. This review article addresses briefly the methodology, clinical applications, interpretation of TEG results including authors' own experience of TEG in different clinical scenarios and limitations of TEG. Overall, this technique seems to be helpful for evaluation of hypercoagulable state and in detecting fibrinolysis which are difficult to be detected with conventional coagulation tests. Kaolin activated citrated blood samples analyzed within 30-60 min of sampling can provide reliable results in a laboratory setting. However, multiple assays using different activators or modifiers may be required for accurate results in selected cases. The operator should be aware about the various preanalytical and analytical variables which can affect the results including limitations of this technique. The tracing of the thromboelastography should be interpreted cautiously taking into consideration the clinical picture of the patient and results of other laboratory tests. With improved model and availability of more assays it is hoped that TEG and other such hemostasis analyzers would bring in the paradigm shift in the hemostasis monitoring and treatment of patients in future.
Keywords: Conventional coagulation tests, hemostasis monitoring, thromboelastography, viscoelastic tests
|How to cite this article:|
Verma A, Hemlata. Thromboelastography as a novel viscoelastic method for hemostasis monitoring: Its methodology, applications, and constraints. Glob J Transfus Med 2017;2:8-18
|How to cite this URL:|
Verma A, Hemlata. Thromboelastography as a novel viscoelastic method for hemostasis monitoring: Its methodology, applications, and constraints. Glob J Transfus Med [serial online] 2017 [cited 2017 Dec 11];2:8-18. Available from: http://www.gjtmonline.com/text.asp?2017/2/1/8/202714
| Introduction|| |
Hemostasis is a complex dynamic process involving bleeding and thrombosis as two extreme ends. Traditionally, plasma-based coagulation assays, namely prothrombin time (PT) and the activated partial thromboplastin time (APTT) and other laboratory tests are utilized to assess hemostasis which provide little information about the dynamics of the clot formation or the quality of clot. However, with our better understanding about cell-based model of coagulation as opposed to separate intrinsic and extrinsic coagulation pathways, focus is gradually shifting from these conventional coagulation assays which work in isolation.
Viscoelastic point-of-care (POC) devices provide in vitro assessment of global coagulation in the whole blood sample, from beginning of clot formation to fibrinolysis. These are considered to provide a better picture of in vivo hemostasis due to interaction of all cellular and plasmatic components compared to conventional coagulation assays. There are three equipment currently being used: thrombelastograph Hemostasis Analyzer or TEG ® (Haemonetics Corporation, Niles, USA); rotational thromboelastometry or ROTEM ® (Tem International, GmbH, Munich, Germany); and Sonoclot ® (Sienco Inc., CO, USA). The methodology and principle of these three devices are slightly different with respect to each other; however, all these instruments are used to assess hemostasis and guide hemotherapy in varied clinical settings.
This review article addresses briefly the methodology, clinical applications, interpretation of TEG results including authors' own experience of TEG in different clinical scenarios, and limitations of TEG. This hemostasis monitoring device has been used mostly by the anesthesiologists worldwide as a POC test in the operating theater (OT); however, it is now becoming increasingly popular with transfusion medicine specialty as a part of laboratory coagulation testing.
Historically, it was Hartert in 1948 from Germany who first described the principle of TEG by measuring shear elastic modulus during clot formation in whole blood samples. The term “Coaguloelastograph” has been proposed for Hartert's device as the word thrombus is reserved for an in vivo clot., However, this device was not used in routine clinical settings until two decades ago due to technical and operational limitations, thus limiting its role as a research tool at most centers. With technical refinements in successive models coupled with the good number of research publications, recently a renewed interest in TEG has been shown worldwide as a rapid hemostasis analyzer capable of providing almost real-time monitoring of coagulation process.
| Methodology|| |
TEG is designed to measures the clot's physical property under low shear conditions using a cylindrical cup that holds the blood sample and oscillates through an angle of 4° 45' with each rotation cycle lasting 10 s. A pin connected to a torsion wire is suspended within a blood-filled cup. When clotting ensues, the formation of fibrin-platelet bonds between the wall of the cup and the pin causes an increased movement of the pin which is converted by a mechanical–electrical transducer to an electrical signal monitored by a computer displaying a graphical output over time. For laboratory-based TEG analysis, the sample required is 340 μL of sodium-citrated whole blood along with 20 μL of 0.2 mol/L of CaCl2, and test is required to be run within 30 min to maximum 2 h after sample collection (preferably within 1 h of sample collection). Whereas 360 μL of whole blood without anticoagulant is used for native sample in POC testing as in OT and time to test is within 4–6 min of phlebotomy. While whole blood is used mainly for thromboelastography in clinical practice, however, platelet-rich plasma or platelet-poor plasma samples can also be run on this analyzer.
Usually, kaolin is used as an activator of coagulation (intrinsic pathway of clotting cascade) in the standard TEG, whereas tissue factor is utilized as an activator for extrinsic pathway in addition to kaolin for rapid analysis of hemostasis (rapid-TEG). [Figure 1]a and [Figure 1]b shows the TEG analyzer along with two types of cups – clear (plain) and blue (heparinase), the latter is used if sample contains heparin. Furthermore, to assess the contribution of fibrinogen and platelets in the clot strength “functional fibrinogen assay” is now available. [Table 1] shows the various assays currently available with TEG. Moreover, with the recent development, the newer model of TEG (6s) has been introduced which works with cartridge system without the complicated test preparation process unlike the present model (TEG ® 5000) which utilizes cups [Figure 1]c.
|Figure 1: Device and its basic principle (TEG 5000 model); (b) plain and heparinase cups of thromboelastograph; (c) new model thromboelastograph 6s|
Click here to view
Important parameters of thromboelastography tracing
A normal TEG tracing along with main parameters is shown with quantitative and qualitative data in [Figure 2]. Importantly, R, K, Angle, maximum amplitude (MA), coagulation index (CI), and LY30 values are described besides other less commonly used parameters.
- R value is time (in min) from the beginning of the trace until amplitude of 2 mm is reached. This denotes the time taken from the placement of the blood sample in the cup until the significant level of clot formation. A prolonged value represents a deficiency in coagulation factors, effects of heparin, and/or hemodilution. The treatment with fresh frozen plasma is advisable depending on the clinical picture. Conversely, a shortening in the R value (<2 min) would indicate a hypercoagulable picture
- K is the time (in min) from the end of R until a fixed level of clot firmness is reached, i.e., amplitude of the trace is 20 mm. A low value may indicate hypercoagulability and a high value usually indicates the need for fibrinogen concentrates or cryoprecipitate administration
- Angle (α) – It is the angle (in degree) of the trace formed by tangential line drawn to the curve starting from split point of trace or R. Both K and α angle measure speed of clot formation or clot kinetics; however, latter is considered more important as K may not be defined in some cases of coagulopathy
- MA – It is a measure of maximum strength (in mm) of the developed clot and assesses the platelets (mainly) and fibrinogen. A low MA value can result from decreased platelet number or function or low fibrinogen level. Transfusing platelets may improve hemostatic condition
- CI is the linear combinations of R, K, α, and MA values. Normal values of CI are from −3 to +3 (normocoagulable), values <−3 represent hypocoagulable picture, and >+3 represent hypercoagulable profile. CI is not calculated when MA or K values are very less
- LY30 is percent decrease in area under the TEG tracing from MA over 30 min. It represents the rate of fibrinolysis.
In addition to above parameters, G is often used as the actual measure of clot firmness (shear elastic modulus strength) and is measured in dyne/cm 2. G increases exponentially in proportion to the amplitude of the tracing. Estimated percent lysis (EPL) is also used besides LY30 to evaluate clot lysis which gives an idea about the percent lysis at 30 min after MA. The normal value of EPL is 0%–15%. Apart from these variables, other lesser used parameters describing thrombus formation and lysis are also generated known as velocity ( first derivative) parameters, namely, maximum rate of thrombus generation (TG), time to maximum rate of TG, total TG, and time to maximum rate of lysis. Thus, all these parameters are used to assess the kinetics, strength, and stability of a coagulum in the whole blood sample.
TEG results are affected by sample characteristics, use of activators, and sample handling procedures.,, Johansson et al. have supported the routine use of TEG in the laboratory setting by demonstrating an acceptable technical day-to-day and intra-assay variation. Further, authors recommended immediate analysis of sample based on their results, wherein storage of citrated sample for up to 30 min did not, except for R, affect clot formation variables. The normal values of TEG differ between the coagulated and anticoagulated blood samples leading to divergent results. The normal ranges for each parameter may differ between arterial and venous blood samples. Gender, age, alcohol, and ethnicity have also been observed to affect the TEG parameters. The normal values of TEG provided by the manufacturer using recalcified citrated blood for laboratory-based TEG analysis have been shown in [Table 2].
|Table 2: Normal values of TEG parameters (kaolin activated citrated sample)|
Click here to view
Comparison of thromboelastography to conventional coagulation tests in clinical settings
The PT and APTT assess only initial plasmatic events in hemostasis, and they correspond to R time of TEG which is the end point of these conventional coagulation assays. Whereas TEG has multiple end points and each parameter of TEG represents a different aspect of physical properties of the clot. The shape of the tracing allows overall qualitative assessment of hemostatic profile. Thus, TEG can overcome several limitations of routine coagulation tests. Inconsistent data are observed in literature on comparing TEG with conventional coagulation tests. A weak correlation for R with PT and APTT has been found which is ascribed to different preanalytic factors and different specimens used. The R time has been observed to be more sensitive to coagulation factor deficiencies or the presence of heparin as compared to PT/APTT. Another study found that the agreement between two methods of tests for hypocoagulation was 100%, but the agreement with the overall TEG analysis was poor with a sensitivity of 33% and a specificity of 95%. Similarly, Pekelharing et al. in a study on 107 pediatric patients observed that TEG did not show a better correlation with postoperative bleeding than conventional clotting tests. However, MA was found to be correlated with platelet count and fibrinogen. Furthermore, in a recent study by Gatt et al., MA showed an excellent correlation with the platelet count (r = 0.91, P< 0.0001). Here, MA was reduced in the majority of cases of hematological malignancies although 25% still had normal values despite platelet counts <20 × 109/L. The authors proposed that as TEG is a global coagulation assay, it is affected by all other blood components that could compensate for thrombocytopenia. MA values were also found to be increased after platelet transfusions as observed by the authors. The strong correlation of platelet count with MA may partly be explained by the fact that low platelet count primarily affects MA; however, platelets also affect the initiation phase of plasmatic coagulation (R, K) as well as the speed of thrombin generation (α).
| Applications|| |
In the early 1980s, the TEG was used for hemostatic monitoring during liver transplant surgery. Over the years, use of TEG has been expanded in a diverse group of clinical settings including other solid organ transplantations, cardiac surgery, neurosurgery, obstetric, and trauma. Apart from surgical settings, its use has spread into medical branches also as a useful laboratory tool to monitor the balance of hemostasis, for example, in patients with chronic liver disease and patients admitted in intensive care unit [Table 3]. TEG has been used for monitoring heparin therapy in patients on heparin. Besides, it has also been used for monitoring recombinant FVIIa therapy in hemophilia patients with inhibitor and in predicting the severity of bleeding symptoms in hemophilia patients.
The ideal applications of TEG are in the patients undergoing liver transplant surgery (particularly orthotopic liver transplantation [OLT]), trauma, and cardiac surgery who have propensity toward major disturbances in hemostasis and TEG can rapidly and reliably detect hypocoagulable, thrombotic, and fibrinolytic states.
Derangement in hemostasis during OLT is due to multifactorial causes including preoperative (coagulopathy) and perioperative factors associated with different phases of transplant surgery. Impaired hemostasis during the anhepatic phase and immediately after reperfusion, wherein hyperfibrinolysis resulting from the accumulation of tissue plasminogen activator due to inadequate hepatic clearance and a release of exogenous heparin and endogenous heparinoids makes TEG highly desirable device., The new graft starts to function within 1 h of reperfusion with a decrease in fibrinolysis. Persistent coagulopathy indicates poorly functioning liver graft, whereas an improved TEG tracing is one of the surrogate markers of a functional graft [Figure 3]. Platelet count decreases after graft reperfusion and during postoperative period which usually takes up to 2 weeks to recover. TEG can differentiate between bleeding due to surgical etiology or bleeding arising from a hemostatic abnormality as in the former the TEG is normal. Moreover, a surgeon may also avoid the empirical transfusion of blood products in cases where normal TEG tracings are obtained. Further, TEG has been used to predict the need for antifibrinolytic therapy in patients receiving liver transplant  and to rationalize the usage of blood components. Apart from bleeding diathesis, thrombotic complications occurring postoperatively can be detected by TEG. A laboratory-based TEG analysis is possible even for liver transplant surgery, and TEG-based hemotherapy can also be provided with rapid turnaround. The authors follow serial monitoring of TEG in a liver transplant recipient by analyzing citrated blood samples at following points of time: at initial consultation, at induction of anesthesia; 60 min after induction; 5 min before anhepatic stage; 10 min into anhepatic; 5 min before reperfusion stage; 30 min after reperfusion; and 60–90 min after reperfusion, end of surgery, and postoperative day 1 and 3 (as indicated). Of note, results of conventional coagulation and other diagnostic tests should also be available to make any clinical decision.
|Figure 3: (a) TEG in a liver transplant recipient 5 min after reperfusion phase showing hyperfibrinolysis and almost a flat tracing. Prothrombin time >100 s, activated partial thromboplastin time >312 s; (b) TEG after 60 min of reperfusion phase showing marked improvement with no fibrinolysis. Prothrombin time 40 s, activated partial thromboplastin time 68 s|
Click here to view
TEG monitoring is also useful for donors of liver as in living donor liver transplantation (LDLT) as shown by Cerutti et al. who observed hypercoagulability in the majority of the participants after hepatectomy for LDLT. TEG monitoring could be useful in the perioperative management of liver donors to guide antithrombotic treatment and increase the safety of the procedure. In a systematic review, TEG has been found to offer particular advantages for liver surgery patient population, by allowing more timely and potentially more accurate decisions resulting into better clinical outcomes including mortality.
Patients undergoing cardiac surgery also have impaired hemostatic balance due to their intrinsic disease state, antiplatelet therapy, and the acquired coagulation disturbances induced by cardiopulmonary bypass (CPB). Increased fibrinolysis is seen in patients who undergo CPB due to endothelial activation and the action of tissue plasminogen activator. Heparin is given during surgery to inhibit clotting of the bypass circuit followed by reversal with protamine after surgical hemostasis. The activated clotting time is the most commonly used test for monitoring heparin anticoagulation during CPB which is affected by many variables. Analysis of blood sample with heparinase enables the TEG to show developing coagulation abnormalities while fully heparinized or the need for more protamine when reversing heparin after CPB. To predict bleeding after cardiac surgery, kaolin-activated TEG was demonstrated to be more useful than nonkaolin activated. However, studies evaluating the role of TEG as a predictor of excessive bleeding after CPB show conflicting reports, with some studies do not favor its usefulness , while others support its use., It is noteworthy that in large retrospective and prospective studies, incorporation of the transfusion algorithms based on TEG into clinical decision-making has resulted in decreased blood loss and transfusions.,,
On comparing the cost-effectiveness, a systematic review indicated that viscoelastic testing was cost saving and more effective than conventional laboratory testing. However, the same study did not find any improvement in clinical outcomes or length of hospital stay for cardiac surgery patients managed using such tests.
Uncontrolled hemorrhage accounts for about 40% of early mortality in trauma, more so in patients who have a coagulopathy on arrival to the hospital. Therefore, early recognition of the acute coagulopathy of trauma is important, and TEG has been found useful in the identification and treatment of this condition. TEG has been emerging as the standard of care in the management of trauma patients as it has characteristics of an ideal coagulation test for use in early trauma resuscitation.,,,, Trauma is one of the areas where TEG should possibly be used as a POC test rather than laboratory-based test as rapidity to obtain results is of prime importance in such situations. In a study on trauma patients, a hypocoagulable status on TEG was reported to be the strongest predictor of any blood component transfusion. Similarly, the presence of hyperfibrinolysis was the strongest predictor of mortality., These findings prompted the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage trial to support the potential benefit of empirical antifibrinolytic therapy in injured patients. Contrary to these reports of excessive fibrinolysis (bleeding) in trauma, more recent studies have reported fibrinolysis shutdown (organ failure) as a more common response to injury.
TEG has been used to predict early transfusion requirements of trauma patients. Tissue factor-activated TEG (rapid TEG) was found useful as an early hemostasis analyzer in trauma patients with suspected coagulopathies. Furthermore, TEG has been found to be more sensitive than conventional coagulation tests in detecting hypercoagulable states in trauma patients., Similar to cardiac surgery, transfusion algorithms for trauma have recently been proposed.,
Evaluation of hypercoagulable and fibrinolytic states by thromboelastography
TEG has been reported to be useful in identifying thrombotic (hypercoagulable) conditions and hyperfibrinolysis or premature clot lysis states which are difficult to be identified by plasma-based coagulation assays.
Major surgery has been implicated to induce a hypercoagulable state in the postoperative period, leading to the development of postoperative thrombotic complications including deep vein thrombosis, pulmonary embolism, myocardial infarction, and vascular graft thrombosis., Similarly, hypercoagulable state may occur in pregnancy, cancer, sepsis, prolonged immobilization, nephrotic syndrome, hyperviscosity syndromes, vasculitis, and many other hematological abnormalities.,, Identifying hypercoagulability with conventional laboratory tests is difficult unless the platelet count or fibrinogen level is very high. Shortening of PT/APTT is rare and is often ascribed to sampling errors. TEG has been found useful in assessing coagulation status, including prothrombotic stage in critically ill patients.,, There is some evidence to suggest that increased MA may predict postoperative thrombotic complications as MA is mostly dependent on platelet function and fibrinogen concentration.
Thus, TEG analysis of patients without a history of thromboembolic complications can detect deranged coagulation parameters [Figure 4]. It is postulated that surgery, sepsis, and other pro-inflammatory states increase platelet adhesiveness and decrease fibrinolysis, resulting in a prothrombotic state., Investigators have reported that existing global assays have a potential to be an important tool of hypercoagulation diagnostics for both physiological and pathological hypercoagulable states.,
|Figure 4: (a) Hypercoagulable tracing showing decreased R value (plasmatic component); (b) Hypercoagulable tracing in a patient with sepsis showing increased maximum amplitude (platelet component), correlated with increased platelet count and evidence of thrombosis on Doppler|
Click here to view
The conventional diagnostic tests for fibrinolytic system notably clot lysis time, euglobulin lysis time, d-dimer, and fibrin degradation products assays are cumbersome and time consuming. LY30/ELT on TEG can provide useful information regarding the increased fibrinolysis. Hyperfibrinolysis should be differentiated from clot retraction as both these conditions present with LY30 >8%. A smooth decrease of the amplitude is observed after reaching MA when fibrinolysis takes place in the sample, whereas there is a sudden fall of amplitude due to loss of adhesion of the clot to the cup in clot retraction. This clot retraction is usually associated with high platelet count. Similarly, it is important to differentiate between secondary fibrinolysis and primary fibrinolysis. Secondary hyperfibrinolysis (±hypercoagulable TEG) seen in disseminated intravascular coagulopathy (DIC) is a physiological response of the body as fibrinolytic activation prevents permanent end-organ damage as a result of microvascular fibrin deposition unlike pathological response in primary hyperfibrinolysis where antifibrinolytic therapy is indicated.. CI and LY30 parameters are used to differentiate between primary and secondary hyperfibrinolysis [Figure 5]. In the former, CI is <−3 and LY30 is >8% while latter usually presents with CI >+3 and LY 30 >8%. In overt DIC, a severe hypocoagulable tracing on TEG is present [Figure 6].
|Figure 5: Examples of primary and secondary hyperfibrinolysis on thromboelastograph (top-primary, bottom-secondary fibrinolysis). Analysis was done using different thromboelastograph reference ranges|
Click here to view
|Figure 6: Thromboelastograph from a patient with overt disseminated intravascular coagulopathy during her Intensive Care Unit stay showing prolonged R and K times, very low angle and low maximum amplitude|
Click here to view
Thromboelastography in quality control of platelets and plasma
Of late, TEG has been used for a functional quality check of blood components., In a study, authors demonstrated that TEG was able to monitor the hemostatic effects of platelet transfusion with comparable hemostatic properties of transfused stored platelets compared to native circulating platelets. In terms of hemostasis, TEG analysis on PRP sample produces the tracing which is broadly similar to whole blood TEG tracing. Platelets have the major influence on clot strength, and the MA is significantly altered by changes in platelet number or function. However, its integration into blood banking to assess the quality of blood products will take time.
Monitoring antiplatelet therapy by Platelet Mapping
Platelet mapping which is an extension of TEG technology, in addition to providing information on clot formation and lysis of whole blood samples, quantifies the contribution of fibrin, adenosine diphosphate (ADP) receptor, and thromboxane A2 (TxA2) receptor in clot strength. The citrated and heparinized blood samples of a patient are used with the platelet mapping kits. The TEG platelet mapping assay measures the percent platelet inhibition relative to the individual's maximum uninhibited platelet function. This information allows monitoring of effectiveness of antiplatelet medications, for example, aspirin and clopidogrel, through inhibition of TxA2 and ADP receptors.
As illustrated in [Figure 7] apart from MA-thrombin (maximum possible clot strength), it also measures MA-fibrin (clot strength by fibrin alone), MA-ADP (clot strength under ADP receptor inhibition by clopidogrel), MA-AA (clot strength under TxA2 receptor inhibition by aspirin), and thereafter the percentage (%) platelet inhibition is calculated. Thus, platelet mapping measures platelet inhibition along with total platelet function as a reference point, thereby assessing the effect of antiplatelet agents more objectively.
|Figure 7: Thromboelastograph-platelet mapping shows hyporesponsiveness to clopidogrel (inhibition 44.6%) in a cardiac patient taking antiplatelets|
Click here to view
The existence of a high level of individual variability in platelet responsiveness to antiplatelet therapy and on-treatment platelet reactivity have been confirmed in the majority of clinical studies examining antiplatelet therapy efficacy in patients undergoing percutaneous coronary intervention. This POC test was found to be well correlated with the gold standard optical aggregometry. The readers can refer to published literature for detailed information about the platelet mapping.,, There is an evidence of baseline inhibition of platelet receptors in patients not taking any antiplatelet medications with mean TxA2 receptor inhibition of 1.2% (range 0%–10%) and ADP receptor inhibition of 18.6% (0%–58%). This can potentially lead to clinically significant overestimation of ADP and AA inhibition. Nonetheless, the method has been shown to be reliable with low analytical variation. However, further robust studies with appropriate power are required to define the possible role of these devices in routine monitoring of antiplatelet therapy.
| Constraints|| |
As with other diagnostic tests, TEG also has certain limitations. First, the methodology is still not standardized which results into significant intra- and inter-laboratory variability as demonstrated by the TEG-ROTEM Working Group. However, another study by Quarterman et al. showed good reproducibility with citrated samples. The manual pipetting and mixing of reagents and other operator-dependent factors can be responsible for variability in the outcomes of TEG. Second, vibration of surface on which TEG is placed may lead to erroneous results or introduce artifacts., A trained person can differentiate between the accurate TEG result and an artifact arising from various preanalytical or analytical factors [Figure 8]. One should not feel tempted to go with the interpretation of TEG result by the computer which is usually displayed graphically along with probable diagnosis. Third, it has a limited comparability with established plasma-based coagulation assays; however, this is expected as principles of both types of assays are different. With proper training and with daily calibration of device, better results can be obtained. Fourth, citrated blood samples for laboratory-based TEG analysis are required to be rested for a fixed time before analysis which can delay the decision-making during surgery. Furthermore, hypercoagulable tracings from citrated recalcified samples have been reported. However, kaolin-activated citrate samples generate results which are similar to those obtained from noncitrated, fresh samples. Fifth, results are affected by age, gender, hematocrit (hypocoagulable in increased hematocrit and hypercoagulable tracing in decreased hematocrit),, platelet count, and infusion of colloids or crystalloid., Mixing of blood with kaolin has been postulated as a critical step responsible for inadequate reproducibility in TEG results. TEG results need to be carefully interpreted in the presence of severe anemia, thrombocytopenia, and hemodilution as these conditions can variably affect the test results. Further, standard TEG is not sensitive to the diagnosis of Von Willebrand disease syndrome and mild disorders of primary hemostasis., Moreover, normal TEG values proposed by the manufacturer may not be appropriate for different populations; thus separate reference ranges should be prepared for males, females, and parturients in the target population. Finally, the increased cost of running multiple tests for a patient, especially for platelet mapping may act a constraint and be partly responsible for making this method out of reach for resource-constrained hospitals.
|Figure 8: (a) The premature splitting of R giving rise to low angle. The correct tangent line is shown in red color which provides accurate angle measurement. (b) Pin slippage during analysis giving rise to an artifact|
Click here to view
The diagnosis and management of hemostasis impairment should not be based on a single coagulation test (conventional/viscoelastic test), rather patient's history, physical examination, and results of other laboratory/diagnostic tests are also needed. The user manual for TEG also reiterates that the results from the TEG analyzer should not be the sole basis for a patient diagnosis, and TEG interpretations should be considered along with a clinical assessment of the patient's condition and other coagulation tests.
| Conclusion|| |
TEG is useful for a rapid assessment of hemostasis and for goal-directed transfusion/drug therapy in a variety of clinical settings. However, TEG is not a substitute for conventional coagulation assays rather it complements the results of conventional coagulation tests. The handling, maintenance, and quality checks of laboratory equipment come naturally to laboratory personnel. There are compelling reasons for this tool to be adopted by the transfusion medicine specialty as these experts can monitor hemostasis and guide specific hemotherapy along with appropriate dosages of blood components based on TEG results in varied clinical settings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hoffman M, Monroe DM 3rd
. A cell-based model of hemostasis. Thromb Haemost 2001;85:958-65.
Tormey CA, Smith BR. The transfusion medicine specialist as a coagulation consultant: A new variant of therapeutic pathology. Transfusion 2013;53:2086-93.
Hartert H. Blutgerinnungsstudien mit der Thrombelastographie; einem neuen Untersuchungs verfahren. Klin Wochenschr 1948;26:577-83.
Hartert H. Thrombelastography: Physical and physiological aspects. In: Copley AL, Stainsby G, editors. Flow Properties of Blood and Other Biological Systems. Oxford, UK: Pergamon; 1960. p. 186-98.
Evans PA, Hawkins K, Williams PR. Rheometry for blood coagulation studies. Rheol Rev 2006:255-91.
Scarpelini S, Rhind SG, Nascimento B, Tien H, Shek PN, Peng HT, et al.
Normal range values for thromboelastography in healthy adult volunteers. Braz J Med Biol Res 2009;42:1210-7.
TEG 5000 haemostasis analyser: User manual. Niles, IL, USA: Haemoscope Corporation; 2008.
Harr JN, Moore EE, Ghasabyan A, Chin TL, Sauaia A, Banerjee A, et al.
Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma. Shock 2013;39:45-9.
Gurbel PA, Bliden KP, Tantry US, Monroe AL, Muresan AA, Brunner NE, et al.
First report of the point-of-care TEG: A technical validation study of the TEG-6S system. Platelets 2016;27:642-9.
Zambruni A, Thalheimer U, Leandro G, Perry D, Burroughs AK. Thromboelastography with citrated blood: Comparability with native blood, stability of citrate storage and effect of repeated sampling. Blood Coagul Fibrinolysis 2004;15:103-7.
Roeloffzen WW, Kluin-Nelemans HC, Mulder AB, de Wolf JT. Thrombocytopenia affects plasmatic coagulation as measured by thrombelastography. Blood Coagul Fibrinolysis 2010;21:389-97.
Johansson PI, Bochsen L, Andersen S, Viuff D. Investigation of the effect of kaolin and tissue-factor-activated citrated whole blood, on clot-forming variables, as evaluated by thromboelastography. Transfusion 2008;48:2377-83.
Frumento RJ, Hirsh AL, Parides MK, Bennett-Guerrero E. Differences in arterial and venous thromboelastography parameters: Potential roles of shear stress and oxygen content. J Cardiothorac Vasc Anesth 2002;16:551-4.
Alexander DC, Butt WW, Best JD, Donath SM, Monagle PT, Shekerdemian LS. Correlation of thromboelastography with standard tests of anticoagulation in paediatric patients receiving extracorporeal life support. Thromb Res 2010;125:387-92.
Karon BS. Why is everyone so excited about thromboelastrography (TEG)? Clin Chim Acta 2014;436:143-8.
Ågren A, Wikman AT, Holmström M, Östlund A, Edgren G. Thromboelastography (TEG ®
) compared to conventional coagulation tests in surgical patients – a laboratory evaluation. Scand J Clin Lab Invest 2013;73:214-20.
Pekelharing J, Furck A, Banya W, Macrae D, Davidson SJ. Comparison between thromboelastography and conventional coagulation tests after cardiopulmonary bypass surgery in the paediatric Intensive Care Unit. Int J Lab Hematol 2014;36:465-71.
Gatt A, Bonello F, Buttigieg R, Debono S, Brincat P, Grima C, et al.
Flow cytometry and thromboelastography to assess platelet counts and coagulation in patients with haematological malignancies. Blood Transfus 2014;12:479-84.
Oshita K, Az-ma T, Osawa Y, Yuge O. Quantitative measurement of thromboelastography as a function of platelet count. Anesth Analg 1999;89:296-9.
Kang YG, Martin DJ, Marquez J, Lewis JH, Bontempo FA, Shaw BW Jr., et al.
Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg 1985;64:888-96.
Chitlur M, Sorensen B, Rivard GE, Young G, Ingerslev J, Othman M, et al.
Standardization of thromboelastography: A report from the TEG-ROTEM working group. Haemophilia 2011;17:532-7.
Agarwal S, Senzolo M, Melikian C, Burroughs A, Mallett SV. The prevalence of a heparin-like effect shown on the thromboelastograph in patients undergoing liver transplantation. Liver Transpl 2008;14:855-60.
Steib A, Gengenwin N, Freys G, Boudjema K, Levy S, Otteni JC. Predictive factors of hyperfibrinolytic activity during liver transplantation in cirrhotic patients. Br J Anaesth 1994;73:645-8.
Homatas J, Wasantapruek S, Von Kaulla E, Von Kaulla KN, Eiseman B. Clotting abnormalities following orthotopic and heterotopic transplantation of marginally preserved pig livers. Acta Hepatosplenol 1971;18:14-26.
Richards EM, Alexander GJ, Calne RY, Baglin TP. Thrombocytopenia following liver transplantation is associated with platelet consumption and thrombin generation. Br J Haematol 1997;98:315-21.
Ramsay MA, Randall HB, Burton EC. Intravascular thrombosis and thromboembolism during liver transplantation: Antifibrinolytic therapy implicated? Liver Transpl 2004;10:310-4.
Wang SC, Shieh JF, Chang KY, Chu YC, Liu CS, Loong CC, et al.
Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: Randomized clinical trial. Transplant Proc 2010;42:2590-3.
Cerutti E, Stratta C, Romagnoli R, Schellino MM, Skurzak S, Rizzetto M, et al.
Thromboelastogram monitoring in the perioperative period of hepatectomy for adult living liver donation. Liver Transpl 2004;10:289-94.
McCrossin KE, Bramley DE, Hessian E, Hutcheon E, Imberger G. Viscoelastic testing for hepatic surgery: A systematic review with meta-analysis-a protocol. Syst Rev 2016;5:151.
Holloway DS, Summaria L, Sandesara J, Vagher JP, Alexander JC, Caprini JA. Decreased platelet number and function and increased fibrinolysis contribute to postoperative bleeding in cardiopulmonary bypass patients. Thromb Haemost 1988;59:62-7.
Shore-Lesserson L, Gravlee GP. Anticoagulation for cardiopulmonary bypass. In: Gravless GP, Davis RF, Kurusz M, et al
., editors. Cardiopulmonary Bypass Principles and Practice. Baltimore: Lippincott Williams and Wilkins; 2000. p. 435-72.
Welsby IJ, Jiao K, Ortel TL, Brudney CS, Roche AM, Bennett-Guerrero E, et al.
The kaolin-activated Thrombelastograph predicts bleeding after cardiac surgery. J Cardiothorac Vasc Anesth 2006;20:531-5.
Wang JS, Lin CY, Hung WT, O'Connor MF, Thisted RA, Lee BK, et al.
Thromboelastogram fails to predict postoperative hemorrhage in cardiac patients. Ann Thorac Surg 1992;53:435-9.
Nuttall GA, Oliver WC, Ereth MH, Santrach PJ. Coagulation tests predict bleeding after cardiopulmonary bypass. J Cardiothorac Vasc Anesth 1997;11:815-23.
Ti LK, Cheong KF, Chen FG. Prediction of excessive bleeding after coronary artery bypass graft surgery: The influence of timing and heparinase on thromboelastography. J Cardiothorac Vasc Anesth 2002;16:545-50.
Westbrook AJ, Olsen J, Bailey M, Bates J, Scully M, Salamonsen RF. Protocol based on thromboelastograph (TEG) out-performs physician preference using laboratory coagulation tests to guide blood replacement during and after cardiac surgery: A pilot study. Heart Lung Circ 2009;18:277-88.
Dorman BH, Spinale FG, Bailey MK, Kratz JM, Roy RC. Identification of patients at risk for excessive blood loss during coronary artery bypass surgery: Thromboelastography versus coagulation screen. Anesth Analg 1993;76:694-700.
Steiner ME, Despotis GJ. Transfusion algorithms and how they apply to blood conservation: The high-risk cardiac surgical patient. Hematol Oncol Clin North Am 2007;21:177-84.
Whiting P, Al M, Westwood M, Ramos IC, Ryder S, Armstrong N, et al.
Viscoelastic point-of-care testing to assist with the diagnosis, management and monitoring of haemostasis: A systematic review and cost-effectiveness analysis. Health Technol Assess 2015;19:1-228, v-vi.
Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R, Read RA, et al.
Epidemiology of trauma deaths: A reassessment. J Trauma 1995;38:185-93.
MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma 2003;55:39-44.
Park MS, Martini WZ, Dubick MA, Salinas J, Butenas S, Kheirabadi BS, et al.
Thromboelastography as a better indicator of hypercoagulable state after injury than prothrombin time or activated partial thromboplastin time. J Trauma 2009;67:266-75.
Plotkin AJ, Wade CE, Jenkins DH, Smith KA, Noe JC, Park MS, et al.
A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries. J Trauma 2008;64 2 Suppl: S64-8.
Martini WZ, Cortez DS, Dubick MA, Park MS, Holcomb JB. Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. J Trauma 2008;65:535-43.
da Luz LT, Nascimento B, Rizoli S. Thrombelastography (TEG ®
): Practical considerations on its clinical use in trauma resuscitation. Scand J Trauma Resusc Emerg Med 2013;21:29.
Ganter MT, Hofer CK. Coagulation monitoring: Current techniques and clinical use of viscoelastic point-of-care coagulation devices. Anesth Analg 2008;106:1366-75.
Cotton BA, Harvin JA, Kostousouv V, Minei KM, Radwan ZA, Schöchl H, et al.
Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration. J Trauma Acute Care Surg 2012;73:365-70.
Ives C, Inaba K, Branco BC, Okoye O, Schochl H, Talving P, et al.
Hyperfibrinolysis elicited via thromboelastography predicts mortality in trauma. J Am Coll Surg 2012;215:496-502.
CRASH-Trial Collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, et al.
Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): A randomised, placebo-controlled trial. Lancet 2010;376:23-32.
Moore HB, Moore EE, Gonzalez E, Chapman MP, Chin TL, Silliman CC, et al.
Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: The spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy. J Trauma Acute Care Surg 2014;77:811-7.
Kaufmann CR, Dwyer KM, Crews JD, Dols SJ, Trask AL. Usefulness of thrombelastography in assessment of trauma patient coagulation. J Trauma 1997;42:716-20.
Jeger V, Zimmermann H, Exadaktylos AK. Can RapidTEG accelerate the search for coagulopathies in the patient with multiple injuries? J Trauma 2009;66:1253-7.
Schreiber MA, Differding J, Thorborg P, Mayberry JC, Mullins RJ. Hypercoagulability is most prevalent early after injury and in female patients. J Trauma 2005;58:475-80.
Pezold M, Moore EE, Wohlauer M, Sauaia A, Gonzalez E, Banerjee A, et al.
Viscoelastic clot strength predicts coagulation-related mortality within 15 minutes. Surgery 2012;151:48-54.
Kashuk JL, Moore EE, Wohlauer M, Johnson JL, Pezold M, Lawrence J, et al.
Initial experiences with point-of-care rapid thrombelastography for management of life-threatening postinjury coagulopathy. Transfusion 2012;52:23-33.
Salooja N, Perry DJ. Thrombelastography. Blood Coagul Fibrinolysis 2001;12:327-37.
McCrath DJ, Cerboni E, Frumento RJ, Hirsh AL, Bennett-Guerrero E. Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction. Anesth Analg 2005;100:1576-83.
Irish A. Hypercoagulability in renal transplant recipients. Identifying patients at risk of renal allograft thrombosis and evaluating strategies for prevention. Am J Cardiovasc Drugs 2004;4:139-49.
Mavrommatis AC, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S. Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med 2000;28:451-7.
Kiliç Y, Topçu I, Bambal H, Civi M. Thromboelastography in the evaluation of coagulation disorders in patients with sepsis. Turk J Med Sci 2014;44:267-72.
Lipets EN, Ataullakhanov FI. Global assays of hemostasis in the diagnostics of hypercoagulation and evaluation of thrombosis risk. Thromb J 2015;13:4.
Azim A, Muzaffar SN, Verma A, Baronia A. Thromboelastography evaluation for hemostatic dysfunction in severe sepsis and septic shock: An experience from tertiary care center in North India. J Crit Care 2015;30:849.
Mishra SB, Bhoyer J, Gurjar M, Muzaffar N, Verma A. Deep vein thrombosis of upper extremities due to reactive thrombocytosis in septic patients. Indian J Crit Care Med 2014;18:540-2.
] [Full text]
Stanworth SJ, Walsh TS. Fresh frozen plasma: Friend or faux pas in critical illness? Crit Care Med 2005;33:2714-6.
Priebe HJ. Triggers of perioperative myocardial ischaemia and infarction. Br J Anaesth 2004;93:9-20.
Sharma SK, Philip J, Wiley J. Thromboelastographic changes in healthy parturients and postpartum women. Anesth Analg 1997;85:94-8.
Bontekoe IJ, van der Meer PF, de Korte D. Determination of thromboelastographic responsiveness in stored single-donor platelet concentrates. Transfusion 2014;54:1610-8.
Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev 2012;26:1-13.
Hunt BJ, Segal H. Hyperfibrinolysis. J Clin Pathol 1996;49:958.
Svendsen MS, Rojkjaer R, Kristensen AT, Salado-Jimena JA, Kjalke M, Johansson PI. Impairment of the hemostatic potential of platelets during storage as evaluated by flow cytometry, thrombin generation, and thrombelastography under conditions promoting formation of coated platelets. Transfusion 2007;47:2057-65.
Verma A, Khetan D, Srivastava A, Elhence P, Katharia R. Thromboelastography as a tool for quality check of apheresis platelets. Asian J Transfus Sci 2016;10:111-2.
] [Full text]
Agarwal S, Coakley M, Reddy K, Riddell A, Mallett S. Quantifying the effect of antiplatelet therapy: A comparison of the platelet function analyzer (PFA-100) and modified thromboelastography (mTEG) with light transmission platelet aggregometry. Anesthesiology 2006;105:676-83.
Gurbel PA, Becker RC, Mann KG, Steinhubl SR, Michelson AD. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 2007;50:1822-34.
Craft RM, Chavez JJ, Snider CC, Muenchen RA, Carroll RC. Comparison of modified Thrombelastograph and Plateletworks whole blood assays to optical platelet aggregation for monitoring reversal of clopidogrel inhibition in elective surgery patients. J Lab Clin Med 2005;145:309-15.
Bliden KP, DiChiara J, Tantry US, Bassi AK, Chaganti SK, Gurbel PA. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: Is the current antiplatelet therapy adequate? J Am Coll Cardiol 2007;49:657-66.
Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, et al.
Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010;56:919-33.
Bochsen L, Wiinberg B, Kjelgaard-Hansen M, Steinbrüchel DA, Johansson PI. Evaluation of the TEG platelet mapping assay in blood donors. Thromb J 2007;5:3.
Quarterman C, Shaw M, Johnson I, Agarwal S. Intra- and inter-centre standardisation of thromboelastography (TEG ®
). Anaesthesia 2014;69:883-90.
Caprini JA, Traverso CI, Arcelus JI. Perspectives on thromboelastography. Semin Thromb Hemost 1995;21 Suppl 4:91-3.
Wasowicz M, Srinivas C, Meineri M, Banks B, McCluskey SA, Karkouti K. Technical report: Analysis of citrated blood with thromboelastography: Comparison with fresh blood samples. Can J Anaesth 2008;55:284-9.
Shibata J, Hasegawa J, Siemens HJ, Wolber E, Dibbelt L, Li D, et al.
Hemostasis and coagulation at a hematocrit level of 0.85: Functional consequences of erythrocytosis. Blood 2003;101:4416-22.
Oldenburg J, Ananyeva NM, Saenko EL. Molecular basis of haemophilia A. Haemophilia 2004;10 Suppl 4:133-9.
Lang T, von Depka M. Possibilities and limitations of thrombelastometry/-graphy. Hamostaseologie 2006;26 3 Suppl 1:S20-9.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2], [Table 3]