TEG and Point of Care Evaluation of Sheila Ellis, MD University of Nebraska Medical Center

Hemostasis Primary: Formation of plug to stop bleeding from a vessel Platelet adhesion: adhere to the exposed subendothelial matrix of damaged endothelium (directly or indirectly via ). Platelet activation: Once platelets adhere, they then become activated and recruit (and activate) additional platelets to the injured site. Also, generated by the coagulation cascade is an extremely powerful platelet activator. Platelet plug formation: forms bridges between activated platelets to form the platelet plug.

Secondary: Formation of insoluble, cross-linked by activated coagulation factors, specifically thrombin. Fibrin stabilizes the primary platelet plug, particularly in larger blood vessels where the platelet plug is insufficient alone to stop hemorrhage.

Formation of fibrin by coagulation factors is usually initiated simultaneously (through exposure of tissue factor on subendothelial fibroblasts). Activated platelets promote fibrin formation and provide a physical scaffold on which fibrin formation proceeds.

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Ways to measure and evaluate hemostasis and coagulation One way is to obtain laboratory studies: Prothrombin time (PT), International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT), platelet count, platelet function, thrombin time, bleeding time, fibrinogen levels, factor assays…..

Some of these provide limited information, are done independently of each other, and only provide a static image of the coagulation status of the patient.

Thromboelastography (TEG) can measure the efficiency of the coagulation system. It was first developed in 1948 by Dr. Hellmut Hartet at the University of Heidelberg and provides real-time analysis of whole blood with a global assessment of hemostatic function.

Advantages of TEG Measures the viscoelastic properties and function of the hemostasis process all the way from initiation of the process to the end result of a clot (and potential breakdown of the clot)

Evaluates the coagulation process to determine the functional expression and allows for pinpoint determination of problems in hemostasis. The development, growth, strength, and stability of the clot can be assessed

Can provide substantive information on coagulation and hemostasis within 5-10 minutes, give most information within 30-45 minutes

Disadvantages May require specialized staff to perform and maintain quality controls on equipment May have variability between operators

Clinical Uses for TEG Trauma Massive transfusions Cardiac surgery Obstetrics Liver surgery including transplantation Assessment of platelet function (dialysis patients, platelet inhibiting drugs) Anticoagulants such a LMWH that are not able to be measured by traditional lab tests Hypercoagulable states Disseminated Intravascular Coagulation (DIC)

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Technique A small sample of blood (0.36 ml) is placed in the cup which oscillates. Development of fibrin strands causes the pin to be deflected with the movement of the cup, which is proportional to clot strength. Tension in the wire is detected and transmitted to create a tracing. This used to be done physically with a pen on paper (like an EEG tracing) but is now done electronically.

Sample preparation Addition of agents can modify and improve results Activator: Maximizes thrombin generation and speeds up clotting time Kaolin: Activates intrinsic pathway, used for normal TEG analysis Provides much faster response than non-activated whole blood Tissue factor: Specifically activates extrinsic pathway Heparinase: removes heparin from sample, allows assessment of underlying hemostatic profile of patient on heparin Platelet activators: Allows testing of antiplatelet agent efficacy

Measured Parameters R time= reaction time Time of latency from start of test to initial fibrin formation with amplitude of 2mm Normal time=5-10 minutes (all times noted with kaolin activation) Initiation K time=kinetics Time to achieve certain level of clot strength with an amplitude of 20 mm Normal time= 1-3 minutes Amplification Alpha angle=slope between R and K Measures speed at which fibrin build up and cross-linking takes place, assesses rate of clot formation Normal angle=53-67 degrees Thrombin burst MA=maximum amplitude Strength and stability of the fibrin clot, correlates with platelet function, direct function of maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa MA is 80% platelets, 20% fibrinogen Normal range=59-68mm Clot strength

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A30 or A60=amplitude at 30 or 60 minutes EPL=Estimated Percent Lysis Computer prediction of estimated rate of change in amplitude after MA is reached Earliest indicator of abnormal lysis as it can begin 30 second after MA LY30 (or LY60)=percentage decrease in amplitude 30 (or 60) minutes post MA Measures fibrinolysis Clot stability Primary fibrinolysis: Rapid breakdown of clot due to excess tissue plasminogen activator (tPA), diminished clot formation, presence of fibrin degradation products Secondary fibrinolysis: Associated with systemic hypercoagulability, commonly seen With disseminated intravascular coagulation (DIC) G: Measures the firmness of the clot (shear elastic modulus strength, SEMS) and overall platelet function. Is measured in dyn/cm2.

Coagulation Index: Linear combination of R, K, angle, and MA. Positive values (CI > +3.0) indicate the sample is hypercoagulable. Negative values (CI < -3.0) indicate that the sample is hypocoagulable. This represents the patient’s overall coagulation.

Interpretation of stages of coagulation 1. Clot formation: R and K times 2. Clot kinetics: R and K times, alpha angle, MA 3. Clot strength and stability: MA 4. Clot resolution: EPL, LY30/60

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Parameter changes Response Increased R time Factor deficiency FFP Factor dysfunction Anticoagulant reversal (e.g. protamine) Presence of anticoagulants Can consider cryoprecipitate or Severe hypofibrinogenemia platelets if severe Severe thrombocytopenia Increased K time Factor deficiency FFP Thrombocytopenia Platelets Platelet dysfunction Hypofibrinogenemia Decreased alpha angle Thrombocytopenia Platelets Hypofibrinogenemia Cryoprecipitate Decreased Maximum amplitude Thrombocytopenia Platelets, DDAVP Platelet dysfunction Cryoprecipitate Hypofibrinogenemia Increase in EPL or LY30, LY60 Primary fibrinolysis Antifibrinolytics like aminocaproic acid or tranexamic acid Secondary fibrinolysis Anticoagulate with heparin, treatment of DIC

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Algorithm for use of TEG in management of bleeding

Thakur, M, Ahmed AB. A Review of Thromboelastography. Int J Periop Ultrasound Appl Technol 2012;1(1):25-29

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Rotational Thromboelastometry (ROTEM) or TEM Similar to TEG except TEM has an immobile cup and the pin/wire transduction system oscillates Slightly different nomenclature for some parameters than TEG Clotting time (CT)=R value (reaction time) Clot formation time(CFT)=K value Maximum clot firmness (MCF)=Maximum amplitude (MA) Clot lysis=LY30 Uses different coagulation activators so results not directly comparable with TEG More resistant to mechanical shock and movement that TEG

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