Basic Clinician Training Module 2 TEG® Technology

Hemostasis monitoring Routine coagulation tests: PT, aPTT Based on cascade model of coagulation Measure coagulation factors interaction in solution (plasma) Determine if adequate levels of coagulation factors are present for clot formation Do not reflect the roles of cells or contributions of local vascular and tissue conditions Plasma-based assays miss the impact of platelets and platelet activation on thrombin generation. Plasma-based assays use static endpoints (e.g. fibrin formation) - miss impact of altered thrombin generation on platelet function and clot structure.

Hemostasis monitoring TEG analysis system Whole blood test Measures all phases of hemostasis: initiation through lysis Shows the net effect of hemostatic components on blood clotting process

The TEG analyzer Description TEG: point of care (POC) whole blood coagulation monitoring device Time to initial results: 4-8 minutes Time to completion (clot lysis): 45-60 minutes Uses activated blood to maximize thrombin generation and platelet activation in an in vitro environment Measures the hemostatic potential of the blood at a given point in time under optimal conditions of thrombin generation Demonstrates the contributions and interactions of hemostatic components during the clotting process.

TEG technology How it works

TEG sample preparation Blood samples can be “modified” by adding agents to the sample Activator – maximizes thrombin generation and speeds up clotting time Kaolin – activates intrinsic pathway, used for normal TEG analysis Tissue factor – specifically activates extrinsic pathway Heparinase – removes heparin from sample, allows view of the underlying hemostatic status of a patient on heparin. Platelet activators – allows testing antiplatelet agent responsiveness and efficacy. (Module 7)

TEG sample types Kaolin – used for normal TEG analysis Kaolin with heparinase – used for normal TEG analysis when patient on heparin Compared with Kaolin-only sample (run simultaneously) to determine reversal of heparin

Utility of the TEG Demonstrates all phases of hemostasis Initial fibrin formation Fibrin-platelet plug construction Clot lysis Identifies a balance or imbalance in the hemostatic system – between the clot forming and clot breakdown pathways Identifies likely cause(s) of bleeding Identifies likely cause(s) of thrombosis

What TEG analysis captures Time Amplitude of pin rotation What TEG analysis captures

Identification Definition TEG parameters Identification Definition

Thrombin formation The R parameter - identified Time Amplitude of pin rotation Initial fibrin formation Intrinsic, extrinsic, common pathways Pin is stationary Pin is engaged  Pin starts to rotate with cup Cup rotates, pin remains stationary

Fibrinogen The a (angle) parameter - identified Time Amplitude of pin rotation Fibrin increases Pin is engaged Amplitude of pin rotation increases as fibrin is generated and cross links are formed

Platelet function The MA parameter - identified Maximum amplitude (MA) of pin rotation Time Amplitude of pin rotation Amplitude of pin rotation

Platelet function The MA parameter - defined Maximum amplitude (MA) of pin rotation Amplitude of pin rotation Amplitude of pin rotation depends on clot strength Clot strength = 80% platelets + 20% fibrinogen Platelet function influences thrombin generation and fibrin formation  relationship between R, a, and MA

Coagulation index The CI parameter - defined Linear combination of kinetic parameters of clot development and clot strength (R, K, angle, MA) Provides a global index of hemostatic status CI < -3.0: hypocoagulable CI > +3.0: hypercoagulable

Fibrinolysis The LY30 parameter - identified Decrease in amplitude of pin rotation 30 minutes after MA reached Time Amplitude of pin rotation MA 30 min

Fibrinolysis The LY30 parameter - defined Decrease in amplitude of pin rotation 30 minutes after MA reached MA 30 min Reduction in amplitude of pin rotation depends on extent of fibrinolysis

TEG parameter summary Definitions Latency from the time that the blood was placed in the TEG® analyzer until the initial fibrin formation. a, K Measures the rapidity (kinetics) of fibrin build-up and cross-linking, that is, the speed of clot strengthening. MA Maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa; represents platelet function G Derived from MA, represents the ultimate strength of the fibrin clot CI Coagulation Index is linear combination of the above parameters. LY30 LY30 measures the rate of amplitude reduction 30 minutes after MA. This measurement gives an indication of the stability of the clot.

TEG parameter summary Time Amplitude of pin rotation

Clot stability Clot breakdown What does TEG report? Clot strength Platelet function Clotting time Clot kinetics Clot stability Clot breakdown

“Normal” TEG tracing Time Amplitude of pin rotation 30 min

Hemorrhagic TEG tracing 30 min

Prothrombotic TEG tracing 30 min

Fibrinolytic TEG tracing 30 min

Components of the TEG tracing Example: R Actual value Normal range Parameter Units Value Normal range

TEG decision tree Qualitative

TEG decision tree Quantitative US Patent 6,787,363 Hemorrhagic Fibrinolytic Thrombotic

TEG tracing Example: hemorrhagic * * * *

TEG tracing Example: prothrombotic * * * *

TEG tracing Example: fibrinolytic * *

Summary TEG technology measures the complex balance between hemorrhagic and thrombotic systems. The decision tree is a tool to identify coagulopathies and guide therapy in a standardized way.

TEG parameters Hemostasis monitoring Review exercises TEG parameters Hemostasis monitoring Begin exercises Skip exercises

Exercise 1: TEG parameters The R value represents which of the following phases of hemostasis? Platelet adhesion Activation of coagulation pathways and initial fibrin formation Buildup of platelet-fibrin interactions Completion of platelet-fibrin buildup Clot lysis Answer Next

Exercise 2: TEG parameters Select the TEG parameters that demonstrate kinetic properties of clot formation. (select all that apply) R Angle (a) MA LY30 CI Answer Next

Exercise 3: TEG parameters The rate of clot strength buildup is demonstrated by which of the following TEG parameters? R Angle (a) MA LY30 CI Answer Next

Exercise 4: TEG parameters Which of the following TEG parameters will best demonstrate the need for coagulation factors (i.e. FFP)? R Angle (a) MA LY30 CI Answer Next

Exercise 5: TEG parameters Clot strength is dependent on which of the hemostatic components? 100% platelets 80% platelets, 20% fibrinogen 50% platelets, 50% fibrinogen 20% platelets, 80% fibrinogen 100% fibrinogen Answer Next

Exercise 6: TEG parameters Which of the following TEG parameters demonstrate a structural property of the clot? (select all that apply) R Angle (a) MA LY30 CI Answer Next

Exercise 7: TEG parameters Because the TEG is a whole blood hemostasis monitor, a low MA demonstrating low platelet function may also influence which of the following TEG parameters? R Angle (a) LY30 CI None of the above Answer Next

Exercise 8: TEG parameters Clot stability is determined by which of the following TEG parameters? R Angle (a) MA LY30 CI Answer Next

Exercise 9: TEG parameters Which of the following conditions will provide the information necessary to determine if heparin is the cause of bleeding in a patient? R value: Kaolin with heparinase R value: Kaolin vs. Kaolin with heparinase MA value: Kaolin with heparinase MA value: Kaolin vs. kaolin with heparinase Answer Next

Exercise 10: TEG parameters Which of the following parameters provides an indication of the global coagulation status of a patient? R Angle (a) MA LY30 CI Answer Next

Exercise 11: Hemostasis monitoring Which of the following statements are true regarding the PT and aPTT tests? (select all that apply) Measure coagulation factor interaction in solution Measure platelet contribution to thrombin generation Measure influence of thrombin generation on platelet function Use fibrin formation as an end point Answer Next

Exercise 12: Hemostasis monitoring The TEG analyzer can monitor all phases of hemostasis except which of the following? (select all that apply) Initial fibrin formation Fibrin-platelet plug construction Platelet adhesion Clot lysis Answer Next

Exercise1: TEG parameters The R value represents which of the following phases of hemostasis? Platelet adhesion Activation of coagulation pathways and initial fibrin formation Buildup of platelet-fibrin interactions Completion of platelet-fibrin buildup Clot lysis R Next

Exercise 2: TEG parameters Select the TEG parameters that demonstrate kinetic properties of clot formation. (select all that apply) R Angle (a) MA LY30 CI Next

Exercise 3: TEG parameters The rate of clot strength buildup is demonstrated by which of the following TEG parameters? R Angle (a) MA LY30 CI Next

Exercise 4: TEG parameters Which of the following TEG parameters will best demonstrate the need for coagulation factors (i.e. FFP)? R Angle (a) MA LY30 CI Next

Exercise 5: TEG parameters Clot strength is dependent on which of the hemostatic components? 100% platelets 80% platelets, 20% fibrinogen 50% platelets, 50% fibrinogen 20% platelets, 80% fibrinogen 100% fibrinogen Next

Exercise 6: TEG parameters Which of the following TEG parameters demonstrate a structural property of the clot? (select all that apply) R Angle (a) MA (demonstrates maximum clot strength) LY30 (demonstrates clot breakdown or the structural stability of the clot) e. CI Next

Exercise 7: TEG parameters Because the TEG is a whole blood hemostasis monitor, a low MA demonstrating low platelet function may also influence which of the following TEG parameters? R – thrombin generation occurs mainly on the surface of platelets, thus a defect in platelet function may slow the rate of thrombin and fibrin formation. Angle (a) – a defect in platelet function may slow the rate of formation of platelet-fibrin interactions, thus slowing the rate of clot buildup. LY30 CI None of the above Next

Exercise 8: TEG parameters Clot stability is determined by which of the following TEG parameters? R Angle (a) MA LY30 CI Next

Exercise 9: TEG parameters Which of the following conditions will provide the information necessary to determine if heparin is the cause of bleeding in a patient? R value: Kaolin with heparinase R value: Kaolin vs. Kaolin with heparinase MA value: Kaolin with heparinase MA value: Kaolin vs. kaolin with heparinase Next

Exercise 10: TEG parameters Which of the following parameters provides an indication of the global coagulation status of a patient? R Angle (a) MA LY30 CI (Coagulation index: a linear combination of the R, K, angle, and MA) Next

Exercise 11: Hemostasis monitoring Which of the following statements are true regarding the PT and aPTT tests? (select all that apply) Measure coagulation factor interaction in solution Measure platelet contribution to thrombin generation Measure influence of thrombin generation on platelet function Use fibrin formation as an end point Next

Exercise 12: Hemostasis monitoring The TEG analyzer can monitor all phases of hemostasis except which of the following? (select all that apply) Initial fibrin formation Fibrin-platelet plug construction Platelet adhesion (vascular mediated event that occurs in vivo, but not in vitro) Clot lysis Next

End of Module 2