I. Origin and Principle
Thromboelastography was invented in 1948 by Harter from Germany. It is a testing method that simulates the dynamic changes of blood coagulation in the human body in vitro (including the formation rate of fibrin, the lysis state, and the strength and elasticity of the clot). It began to be widely used clinically in the 1980s to guide intraoperative blood transfusion, achieving good results. It has now become the most important indicator for monitoring perioperative coagulation function and is also a vital tool for managing blood products. As a new type of blood viscoelastic testing system suitable for point-of-care testing, thromboelastography uses whole blood samples to monitor the entire process of blood coagulation and fibrinolysis, effectively compensating for the shortcomings of traditional coagulation tests.
The Thromboelastogram (TEG) monitors the physical properties of a blood clot based on the following principle: A specially designed stationary cylindrical cup containing the blood sample rotates through an angle of 4°45', with each rotation cycle lasting 10 seconds. The movement of the blood sample is monitored by a pin suspended by a torsion wire and immersed in the sample. Once fibrin-platelet complexes bond the cup and pin together, the rotational force generated by the cup is transmitted to the pin within the blood sample. The strength of the fibrin-platelet complex influences the amplitude of the pin's movement; a firm clot causes the pin to move in synchrony with the cup's rotation. The rotation of the pin is converted into an electrical signal by an electromechanical transducer, and this signal can be monitored using a computer.
II. Clinical Value
(1) Assisting in Perioperative Coagulation Function Analysis and Management
Correctly assessing the perioperative coagulation function of patients with potential massive hemorrhage and providing rational blood transfusion are directly related to the patient's life. Numerous literature reports have demonstrated the benefits of using thromboelastography for perioperative coagulation management. Coagulation dysfunction during the perioperative period makes blood transfusion an important and necessary treatment measure and is also an independent risk factor for perioperative patient mortality. However, the value of traditional coagulation tests in predicting perioperative coagulation disorders and treatment effects is very limited. For instance, tests like PT and APTT use plasma samples and only reflect the initial coagulation stage involving clotting factors in plasma. They do not account for the contribution of platelets to the coagulation process and cannot provide functional information about the fibrinolytic system.
Causes of perioperative coagulation dysfunction include:
Pre-existing coagulation abnormalities in the primary disease, such as reduced platelet count or insufficient function.
Loss and consumption of blood cells and various clotting factors due to bleeding during surgery.
Congenital or acquired clotting factor deficiencies.
Massive transfusion of stored red blood cell suspensions; factors include high potassium, low calcium, and decreased pH in stored blood.
Effects of factors like hypothermia, leading to coagulation dysfunction in patients.
Primary or secondary hyperfibrinolysis.
(2) Guiding Personalized Blood Transfusion with Thromboelastography
Thromboelastography first demonstrated its advantages in transfusion management during cardiac surgery. As early as 1999, surgeons and anesthesiologists at Mount Sinai Medical Center in New York, USA, published an article pioneering the use of TEG to guide perioperative transfusion in cardiac surgery. The TEG-guided group consumed significantly fewer red blood cells, plasma, and platelet products. Compared to traditional coagulation tests, using TEG for perioperative coagulation management allows earlier detection of coagulation abnormalities, effectively predicts intraoperative blood loss, and using it to guide transfusion can save 20% to 50% of blood products. In cases of massive hemorrhage, it may even reduce mortality.
(3) Monitoring Hemostasis/Thrombolytic Therapy Process
Heparin-based drugs are among the most widely used anticoagulants, offering good antithrombotic efficacy. However, they carry side effects such as thrombocytopenia and bleeding, necessitating close monitoring of drug efficacy during use. The TEG heparinase comparison test significantly improves the detection limit, especially when monitoring low concentrations of unfractionated heparin (UFH).
Besides heparin-based drugs, antiplatelet drugs are also essential for clinical treatment of thrombotic diseases. Aspirin and clopidogrel are the most commonly used antiplatelet drugs clinically. However, overtreatment (bleeding) and treatment failure (thrombosis) occasionally occur clinically. The diversity and complexity of platelets themselves are significant contributing factors. The Platelet Mapping assay in TEG provides clinicians with a personalized testing method based on platelet reactivity.
III. Clinical Applications of Thromboelastography
1. Citrated Kaolin (CK) and RapidTEG (CRT) Assay Reports
The CK assay activates the intrinsic coagulation pathway, causing citrated blood samples to clot upon recalcification with CaCl2, and this process is depicted as a coagulation curve.
The CRT assay activates both the intrinsic and extrinsic coagulation pathways simultaneously, causing rapid clotting of the blood sample upon CaCl2 addition, and this process is also depicted as a coagulation curve. The Activated Clotting Time (ACT) parameter from this assay can be used to monitor the effect of heparin therapy.
Clinically, the CRT assay is generally used for rapid assessment of coagulation status in critically ill patients, such as monitoring coagulation status and heparin anticoagulant effect during and after thromboembolic diseases, cardiovascular surgeries, trauma, and cardiac surgeries. The CK assay is typically used for a comprehensive evaluation of coagulation, determining the coagulation state. It can guide component transfusion in transfusion medicine, differentiate between primary and secondary hyperfibrinolysis, assess the efficacy of procoagulant and anticoagulant drugs, and evaluate the risk of thrombosis for prevention.
2. Heparinase (CKH) Comparison Assay
Heparin-based drugs enhance the activity of antithrombin in the blood, exerting an anticoagulant effect. The addition of heparinase degrades heparin in the blood, neutralizing its anticoagulant effect and allowing the sample to clot. When testing blood samples containing residual heparin using the standard CK assay, the clotting time is often prolonged due to heparin interference. Therefore, by superimposing the TEG curves of the CK assay and the CKH assay, if the clotting time (R time) of the CKH assay is shorter than that of the CK assay, it indicates residual heparin in the sample. If the times are the same, it indicates no residual heparin.
Generally, clinically, the R value from CK is compared with the R value from CKH.
① No difference in R values suggests: No heparin present (or no effect).
② If the CK R value is 2-3 times the CKH R value and CK R < 20 min, it indicates a good heparin effect.
③ If the CK R value is more than 3 times the CKH R value or CK R > 20 min, it indicates the presence of heparin and possible heparin overdose. Protamine sulfate should be administered to neutralize the heparin until neutralization is complete.
3. Platelet Mapping Assay
The Platelet Mapping assay simultaneously generates three curves from the same whole blood sample: the standard coagulation curve (CK or Kaolin), the curve with fibrin activation only (activated with reptilase and factor XIIIa, representing the fibrin contribution), and the curve after inhibition by antiplatelet drugs (representing the uninhibited platelet function). It records the maximum amplitude (MA) for each curve. By determining the clot strength attributable to fibrin (MAfibrin), the assay calculates the difference in clot strength between normal blood and blood affected by antiplatelet drugs, thereby computing the inhibition rate of the specific drug on the patient's platelets.
An inhibition rate less than 20% indicates non-response; 20%-50% indicates minimal response; 50%-75% indicates response; greater than 75% indicates good inhibition. Based on the efficacy, the dose can be increased, or the drug can be changed for targeted therapy.
Note: The MA value for fibrin (MAfibrin, from the ADP or AA channel's fibrin contribution) should not exceed 20mm. Exceeding 20mm suggests high fibrinogen activity posing a thrombotic risk, independent of high platelet activity. Even with high platelet inhibition, a thrombotic risk may still exist in this scenario, requiring management to reduce fibrinogen activity.
4. Functional Fibrinogen Assay
This assay is used to assess clinical conditions in patients during and after cardiovascular surgery, liver transplantation, trauma, and cardiac surgery, such as postoperative bleeding or thrombosis. It aids in managing cryoprecipitate transfusion doses for subjects and detects fibrinogen function. It can distinguish the respective functions of fibrinogen and platelets in the coagulation process, enhancing the monitoring and diagnosis of hemostasis and thrombosis.
【Explanation of Test Results】
① R time is the reaction time of coagulation proteins, reflecting the activity of clotting factors in the intrinsic pathway and the effect of anticoagulant used.
② MA value (Maximum Amplitude) directly reflects the cross-linking strength of the fibrin network, representing the contribution of fibrinogen to the coagulation process.
③ FLEV is the functional fibrinogen activity level, calculated from the MA value via a formula, reflecting the fibrinogen content in the blood.
IV. Summary
Thromboelastography is the most important method for monitoring coagulation function during surgery and has become a key tool for blood product management in developed countries worldwide. Transfusion guidelines explicitly state that using TEG can save 20% to 50% of blood products. In China, the thromboelastography test has been included in the "National Catalogue of Clinical Laboratory Test Items" and the "National Specification for Medical Service Price Items (Trial 2001 Edition)."
Currently, our main reagent types include seven: CK (Citrated Kaolin) assay, CRT (RapidTEG) assay, Heparinase (CKH) comparison assay, Platelet Mapping assay (including AA, ADP, and AA+ADP combination types), and Functional Fibrinogen assay.