Ananya Datta Mitra, MD
Denis M. Dwyre, MD

Thromboelastography (TEG) was first described by Dr. Hartert in Germany almost 60 years ago. However, it came to clinical practice almost 25 years following its discovery [1]. This test measures the viscoelastic changes associated with the entire coagulation process and provides a global assessment of the hemostatic function. It was initially used in 1980s for monitoring coagulation in orthotopic liver transplantation. Over the following decades, technological advances have resulted in significant improvements in the test leading to its current use as a point-of-care device, however, keeping the basic principles unchanged. There are multiple applications of TEG in clinical care including but not limited to surgical and trauma patients, liver transplantation, acute and chronic liver disease, optimal blood utilization, coagulopathies (like hemophilia), cardiac bypass, sepsis, pregnancy and postpartum hemorrhage, neonatal care, veterinary medicine and drug monitoring [2]. Although TEG has been used widely to guide hemostatic therapies, and some consider it to be superior to conventional laboratory assays, many clinicians and authors claim that these tests are not completely validated. In this blog, we are going to review TEG as a viscoelastic global tool regulating hemostatic therapies and its optimal utilization in current clinical practice.

General principles of TEG

In traditional kaolin activated TEG, whole blood at 37 degrees centigrade is placed into a sample cup in which a pin is suspended by a torsion wire. The cup then rotates either clockwise or anticlockwise. As the blood clots, platelets and fibrin forming in the cup adhere to the pin which is measured as torque via a torsion wire. Results are graphically displayed in real-time. TEG with platelet mapping is a modality to measure platelet function, especially in patients taking antiplatelet medications. It consists of three components: arachidonic acid (AA), which is sensitive to aspirin, adenosine diphosphate (ADP), which is sensitive to clopidogrel, and an activator substituting for thrombin, used for comparison to calculate percent inhibition. For TEG platelet mapping, results show underlying hemostasis but also shows receptor-specific platelet function and inhibition. However, TEG has not been shown to consistently predict total bleeding risk.

Current indications of TEG [3]:

  1. Express the function of and identify dysfunction in the patient's hemostasis system
  2. Reduce the use of unnecessary blood products and reduce thrombotic complications
  3. Distinguish between anatomical (surgical) and coagulopathic bleeding
  4. Differentiate primary from secondary fibrinolysis, including the consumptive phase
  5. Provide a personalized platelet function and inhibition assessment for patients known to be on anti-platelet medications

General limitations of TEG:

In this modern era of personalized healthcare, an ideal test on blood coagulation still does not exist. Although TEG has been in clinical use and has convincingly demonstrated its usefulness to help improve outcomes in cardiac surgery, Cochrane database systematic review of 9 RCTs with a total of 776 participants, found a decreased amount of bleeding when TEG were utilized but without a decrease in morbidity or mortality [4].

Blood coagulation is a complex process and involves the interactions between the tissue factor and the endothelium with other components like blood flow, vessel size, and local vessel wall biology that determine the quantity and functional activity of the membrane-bound pro- and anticoagulation factors, which cannot be quantified in vitro. The main principle behind TEG is measuring blood coagulation in vitro, with or without an additional activator, rather than flow within an endothelialized vasculature. Thus, the TEG tracing is not reflective of the role of endothelium to coagulation. Inherently the test is a poor predictor of platelet adhesion and von Willebrand’s disease related bleeding diathesis.

Moreover, an abnormal TEG in a patient lacking clinically relevant bleeding does not require transfusion of blood components. A single test or patient-related factor seldom guides the decision to transfuse blood components or initiate/correct antithrombotic therapy. Studies have also shown that preoperative TEG data are poor predictors of postoperative bleeding. Furthermore, the TEG results do not correlate the effects of hypothermia during surgeries, especially in cardiac cases as TEG is performed at 37°C [5,6].

TEG has a low sensitivity and specificity, which significantly varies in different populations. Patients taking anticoagulants and antiplatelet agents are a major concern in the trauma setting. Recently in a cohort study, it was noted that TEG was normal despite high international normalized ratio (INR) values in a large percentage of patients receiving warfarin. This might be related to the use of kaolin as a part of TEG procedure. Kaolin activates the intrinsic coagulation cascade, which cannot effectively detect alterations in the extrinsic coagulation cascade caused by warfarin [7]. This is a good example of how TEG may miss a potentially clinically significant coagulopathy. Hence, INR is still the gold standard of monitoring warfarin therapy. Several important blood tests also cannot be currently replaced by TEG, such as P2Y12 platelet function assay to guide clopidogrel therapy, D-Dimer to exclude venous thrombo-embolism (VTE) in low-risk outpatients, and advanced thrombophilia diagnostic tests.

Coagulopathies in massive trauma is related to the activation of the fibrinolytic system and is a major cause of increased mortality from traumatic hemorrhage [8]. In such settings, TEG is useful in detecting the fibrinolysis process. However, there are limitations in using TEG over conventional plasma biomarkers of fibrinolytic activation, e.g. plasmin-α2-antiplasmin (PAP) complex. Studies have shown that using PAP as a biomarker for fibrinolysis has detected fibrinolytic activation in over 80% of severely injured patients [9], whereas TEG detected hyperfibrinolysis in only 5–18% of the cases. This occurred due the that fact that TEG detects fibrinolysis only when the tPA (tissue plasminogen activator) levels are five times the normal. Moreover, rapid inhibition of tPA by plasminogen activator inhibitor (PAI)-1 may result in false negative rates of detection of fibrinolysis by TEG [9,10]. Thus, antifibrinolytic therapies with tranexamic acid (TXA) cannot be optimized in these patients based on TEG data [11]. Also, there is conflicting evidence for TEG usefulness in trauma patients. A recent Cochrane database systematic review found inadequate data to compare the accuracy of TEG versus PT/INR in the diagnosis of trauma-induced coagulopathy.[12] The review concluded that these tests are still in the phase of clinical research. Moreover, recent studies have shown that the use of platelet mapping with TEG appears to be limited by its nonspecific findings of platelet receptor inhibition in determining anti-platelet therapy in certain patient populations [13].

Moreover, sample collection and processing need to be standardized in TEG in order to reduce inter-observer variabilities between laboratories. There is a continuous requirement for adequate maintenance, quality control, and supervision of personnel performing the test when testing occurs away from the controlled environment of the laboratory, as when used as a point of care device. The instrument requires multiple daily calibrations which should be performed by trained personnel and under standardized techniques. Sometimes this can be more expensive, as well as more time consuming, than conventional coagulation testing in the lab. Lastly, excessive TEG testing impacts laboratory workflow by competing with other time sensitive coagulation assays and intraoperative TEG. Each TEG run generally takes 30 minutes to an hour to complete and only a few cases can run simultaneously, unlike conventional lab coagulation testing. Therefore, optimization of TEG use is an important concern in providing appropriate patient laboratory testing.

Lab Best Practices

TEG has been used in different clinical settings with different algorithms at UC Davis Health (UCDH). However, the rationale behind ordering platelet mapping with TEG has not been evaluated and needs to be evaluated in order to improve patient care and appropriate laboratory utilization. Optimizing resources with a goal of improving patient care begins with determining the justification for testing with TEG, with or without platelet mapping, in different UCDH clinical settings.

Although TEG is recommended by NICE (National Institute for Health and Care Excellence) guidelines to help detect, manage, and monitor hemostasis in cardiac surgery patients (NICE guidelines, 2014), current clinical guidelines do not strongly recommend TEG for use in additional settings due to the lack of high-quality evidence. Recently updated guidelines of the European Society of Anesthesiology recommended viscoelastic hemostatic assays (TEG) to guide the management of perioperative bleeding and severe peripartum hemorrhage even though with the low level of evidence [14].

Based on our preliminary evaluations on TEG ordering practices, the Laboratory has designed the following best practice algorithm to follow when ordering kaolin TEG and/or TEG with platelet mapping. The goal of this algorithm is to optimize TEG utilization for patients needing emergent coagulation/TEG testing and support on-label use of the platform.

 

Future directions:

Evaluation of TEG test ordering practices at UCDH need to be completed, and evaluation of adherence to guidelines analyzed. Adjustments to the algorithm will be made based upon the evaluation. Additionally, in the area of coagulation research, future studies may determine and refine the indications for TEG and evaluate if TEG can measure the effect of antiplatelet therapy, detect hyporesponsiveness, and predict the risk of bleeding or thromboembolic complications. The potential of TEG to improve the quality of antithrombotic therapy is a promising avenue for experimental and clinical research. The novel concept of personalized health care can be applied to the laboratory, including both anticoagulation and antiplatelet therapy monitoring.

Acknowledgements:

Dr. Nam Tran and Leslie Freeman.

References:

  1. Hartert H. [Not Available]. Klinische Wochenschrift 1948;26:577-583.
  2. Othman M, Kaur H. Thromboelastography (TEG). Methods in molecular biology 2017;1646:533-543.
  3. TEG® Hemostasis Analyzer, Model 5000, package insert
  4. Wikkelsø A, Wetterslev J, Møller AM, Afshari A. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding. Cochrane Database Syst Rev. 2016 Aug 22;(8):CD007871.
  5. Enriquez LJ, Shore-Lesserson L. Point-of-care coagulation testing and transfusion algorithms. British journal of anaesthesia 2009;103 Suppl 1:i14-22.
  6. Rhee AJ, Kahn RA. Laboratory point-of-care monitoring in the operating room. Current opinion in anaesthesiology 2010;23:741-748.
  7. Dunham CM, Rabel C, Hileman BM, et al. TEG(R) and RapidTEG(R) are unreliable for detecting warfarin-coagulopathy: a prospective cohort study. Thrombosis journal 2014;12:4.
  8. Gall LS, Davenport RA. Fibrinolysis and antifibrinolytic treatment in the trauma patient. Current opinion in anaesthesiology 2018;31:227-233.
  9. Raza I, Davenport R, Rourke C, et al. The incidence and magnitude of fibrinolytic activation in trauma patients. Journal of thrombosis and haemostasis : JTH 2013;11:307-314.
  10. Leebeek FW, Rijken DC. The Fibrinolytic Status in Liver Diseases. Seminars in thrombosis and hemostasis 2015;41:474-480.
  11. Cole E, Davenport R, Willett K, et al. Tranexamic acid use in severely injured civilian patients and the effects on outcomes: a prospective cohort study. Annals of surgery 2015;261:390-394.
  12. Nakayama Y, Nakajima Y, Tanaka KA, Sessler DI, Maeda S, Iida J, Ogawa S, Mizobe T. Thromboelastometry-guided intraoperative haemostatic management reduces bleeding and red cell transfusion after paediatric cardiac surgery. Br J Anaesth. 2015 Jan;114(1):91-102.
  13. Lam H, Katyal N, Parker C, Natteru P, Nattanamai P, Newey CR, Kraus CK. Thromboelastography With Platelet Mapping is Not an Effective Measure of Platelet Inhibition in Patients With Spontaneous Intracerebral Hemorrhage on Antiplatelet Therapy. Cureus. 2018 Apr 22;10(4):e2515.
  14. Roullet S, Pillot J, Freyburger G, Biais M, Quinart A, Rault A, Revel P, Sztark F. Rotation thromboelastometry detects thrombocytopenia and hypofibrinogenaemia during orthotopic liver transplantation. Br J Anaesth. 2010 Apr;104(4):422-8.