Basic Clinician Training TEG ®

Module 2

Technology Review of the Hemostatic Process Hemostasis Monitoring with the TEG Analyzer How the TEG Analyzer Monitors Hemostasis Parameters Tracings Blood Sample Types and Preparation Test Your Knowledge

Hemostatic Process Endothelium damaged Platelet plug formed (white clot) Thrombin generated on platelet surface Platelet-fibrin plug formed (red clot) Area of Injury Collagen Change in Platelet Shape Endothelial Cells ADP AA Platelet XII XI XIIa XIa IX VIIa / TF VII X + Ca 2+ V V Pr ombin (II) Thr XIII XIIIa tPA Plasminogen Fibrin Strands Plasmin Degradation Products Clot lysis

Routine Coagulation Tests: PT, aPTT, Platelet Counts • • Based on cascade model of coagulation    Measure protein interaction in plasma (thromboplastin) Exclude cellular contributions (platelets, monocytes, etc.) Determine adequacy of coagulation factor levels Use static endpoints  Ignore altered thrombin generation   Ignore cellular elements Ignore overall clot structure

Hemostasis Monitoring: TEG Hemostasis System • • • Whole blood test Measures hemostasis   Clot initiation through clot lysis Net effect of components TEG system     Laboratory based Point of care Remote, can be networked Flexible to institution needs

The TEG Analyzer: Description • • • Reflects balance of the hemostatic system Measures the

contributions

and

interactions

of hemostatic components during the clotting process 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 conditions of maximum thrombin generation

TEG Technology

The TEG Analyzer How It Works

TEG Technology: How It Works • • Cup oscillates Pin is attached to a torsion wire • • • Clot binds pin to cup Degree of pin movement is a function of clot kinetics • Magnitude of pin motion is a function of the mechanical properties of the clot System generates a hemostasis profile  From initial formation to lysis

Utility of TEG Analysis • • Demonstrates all phases of hemostasis    Initial fibrin formation Fibrin-platelet plug construction Clot lysis Identifies imbalances in the hemostatic system  Risk of bleeding  Risk of thrombotic event

What TEG Analysis Captures

Time

Basic Clinician Training TEG Parameters

Identification Definition

Thrombin Formation (Clotting Time) The R Parameter: Identified Initial fibrin formation • • Reaction time Fibrin creates a connection between cup and pin Pin is stationary Intrinsic, extrinsic, common pathways Pin is engaged Cup oscillates, pin remains stationary  Pin starts to oscillate with cup Time

Thrombin Formation The R Parameter: Defined Initial fibrin formation • • Time until formation of critical mass of thrombin Expression of enzymatic reaction function (i.e. the ability to generate thrombin and fibrin) Pin is stationary Intrinsic, extrinsic, common pathways Pin is engaged Cup oscillates, pin remains stationary  Pin starts to oscillate with cup

Pin is stationary Thrombin Formation Abnormalities The R Parameter: Elongated R Initial fibrin formation • • • Possible causes of imbalance:  Slow enzymatic reaction Possible etiologies:  Factor deficiency/ dysfunction  Residual heparin Common treatments:  FFP  Protamine Pin is engaged

Thrombin Formation Abnormalities The R Parameter: Short R Initial fibrin formation • Possible causes of imbalance:  Over-stimulated enzymatic reaction  Fast fibrin formation • Possible etiologies:  Enzymatic hypercoagulability • Common treatments:  Anticoagulant Pin is stationary Pin is engaged

Fibrinogen The α (Angle) Parameter: Identified Fibrin increases • Rate of increase in pin oscillation amplitude as fibrin is generated and cross-links are formed Baseline Pin is engaged

Fibrinogen The α (Angle) Parameter: Defined Fibrin increases Baseline • Kinetics of clot formation  Rate of thrombin generation  Conversion of Fibrinogen  fibrin  Interactions among fibrinogen, fibrin, and platelets  Cellular contributions Pin is engaged

Fibrinogen Abnormalities The α (Angle) Parameter: Low a Fibrin increases Pin is engaged Baseline • • • Possible causes of imbalance:  Slow rate of fibrin formation Possible etiologies:  Low fibrinogen levels or function  Insufficient rate/amount of thrombin generation  Platelet deficiency/dysfunction Common treatments:  FFP  Cryoprecipitate

Fibrinogen Abnormalities The α (Angle) Parameter: High a Fibrin increases Baseline • • • Possible causes of imbalance:  Fast rate of fibrin formation Possible etiologies:  Platelet hypercoagulability  Fast rate of thrombin generation Common treatments:  None Pin is engaged

Platelet Function The MA Parameter: Defined Maximum amplitude (MA) of pin oscillation Amplitude of pin oscillation • • • Maximum amplitude Clot strength = 80% platelets + 20% fibrinogen Platelet function influences thrombin generation and fibrin formation  relationship between R, α , and MA

Platelet Function Abnormalities The MA Parameter: Low MA Maximum amplitude (MA) of pin oscillation Amplitude of pin oscillation • • • Possible causes:  Insufficient platelet fibrin clot formation Possible etiologies:    Poor platelet function Low platelet count Low fibrinogen levels or function Common treatments:  Platelet transfusion

Platelet Function Abnormalities The MA Parameter: High MA Maximum amplitude (MA) of pin oscillation Amplitude of pin oscillation • • • Possible causes:  Excessive platelet activity Possible etiologies:  Platelet hypercoagulability Common treatments:  Antiplatelet agents  Note: Should be monitored for efficacy and/or resistance (See Module 6: Platelet Mapping)

Coagulation Index The CI Parameter: Defined • • Global index of hemostatic status Linear combination of kinetic parameters of clot development and strength (R, K, angle, MA)  CI > +3.0: hypercoagulable  CI < -3.0: hypocoagulable

Fibrinolysis: LY30 and EPL LY30 and EPL Parameters: Identified

MA

30 min • • LY30 is the percent decrease in amplitude of pin oscillation 30 minutes after MA is reached Estimated percent lysis (EPL) is the estimated rate of change in amplitude after MA is reached

Fibrinolysis: LY30 and EPL LY30 and EPL Parameters: Defined

MA

• Reduction in amplitude of pin oscillation is a function of clot strength, which depends on extent of fibrinolysis 30 min

Fibrinolytic Abnormalities LY30 Parameter: Primary Fibrinolysis • • • Possible causes:  Excessive rate of fibrinolysis Possible etiologies:  High levels of tPA Common treatments:  Antifibrinolytic agent

Fibrinolytic Abnormalities LY30 Parameter: Secondary Fibrinolysis • • Possible causes:  Rapid rate of clot formation/break down Possible etiologies:  Microvascular hypercoagulability (i.e. DIC) DIC = disseminated intravascular coagulation

Fibrinolytic Abnormalities LY30 Parameter: Secondary Fibrinolysis • • • Possible causes:  Rapid rate of clot formation/break down Possible etiologies:  Microvascular hypercoagulability (i.e. DIC) Common treatments:  Anticoagulant DIC = disseminated intravascular coagulation

Clot Strength: The G Parameter • • Representation of clot strength and overall platelet function  G = shear elastic modulus strength (dyn/cm 2 )  G = (5000*MA)/(100-MA) Relationship between clot strength and platelet function  MA = linear relationship between clot strength and platelet function  G = exponential relationship between clot strength and platelet function • More sensitive to changes in platelet function

MA vs. G (Kaolin Activated Sample) 30.0

25.0

Normal MA range (Kaolin activated) Hyperactive platelet function

20.0

15.0

10.0

5.0

Normal platelet function Hypoactive platelet function

0.0

5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 MA (mm)

TEG Parameter Summary: Definitions

Clotting Time Clot Kinetics R K

The latency period from the time that the blood was placed in the TEG® analyzer until initial fibrin formation. Represents enzymatic reaction. A measure of the speed to reach 20 mm amplitude. Represents clot kinetics.

Alpha

A measure of the rapidity of fibrin build-up and cross-linking (clot strengthening). Represents fibrinogen level.

Clot Strength MA

A direct function of the maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa. Represents maximum platelet function.

Coagulation Index Clot Stability G

A transformation of MA into dyn/cm 2 .

CI

A linear combination of R, K, alpha, MA.

LY30

A measure of the rate of amplitude reduction 30 min.after MA.

Estimates % lysis based on amplitude reduction after MA.

EPL

TEG Parameter Summary

Clotting time Clot kinetics Platelet function Clot strength (G) Clot stability Clot breakdown

Basic Clinician Training TEG Results

Tracings Data Decision Tree

Components of the TEG Tracing Example: R

Actual value

Time

Normal range Parameter Units Value Normal range

“Normal” TEG Tracing 30 min

Hemorrhagic TEG Tracing 30 min

Prothrombotic TEG Tracing 30 min

Fibrinolytic TEG Tracing 30 min

TEG Decision Tree Qualitative

TEG Decision Tree Quantitative Hemorrhagic

US Patent 6,787,363

Thrombotic Fibrinolytic

TEG Tracing Example: Hemorrhagic

TEG Tracing Example: Prothrombotic

TEG Tracing Example: Fibrinolytic

Basic Clinician Training TEG Blood Sampling

TEG Blood Sampling • Blood samples   Arterial or venous Samples should be consistent

TEG Blood Sampling Native • Non-modified blood samples   Assayed 4 minutes TEG software based upon assay at 4 minutes

TEG Blood Sampling Modified • Activator    Reduces variability Reduces running time Maximizes thrombin generation • • Kaolin   Activates intrinsic pathway Used for normal TEG analysis Tissue factor  Specifically activates extrinsic pathway

TEG Blood Sampling Heparin • Heparinase   Neutralizes heparin Embedded in specialized (blue) cups and pins

TEG Blood Sampling Citrated • • • • Citrated tubes are used Recalcified before analysis Standardize time between blood draw and running test Specific platelet activators are required to demonstrate effect of antiplatelet agents

Sample Type Designations

Whole blood + kaolin Sample type Conditions Wait time before run sample Sample prep K

(kaolin activated)

KH

(kaolin + heparinase)

CK

(citrate + kaolin)

CKH

(citrate + kaolin + heparinase) No anticoagulation With heparin With citrate With citrate and heparin < 6 min (recommended 4 min) < 6 min (recommended 4 min) > 6 min < 120 min Clear cup & pin Blue cup & pin (coated with heparinase) Add calcium chloride Clear cup and pin > 6 min < 120 min Add calcium chloride Blue cup & pin

Summary • • The 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.

Basic Clinician Training TEG Parameters Hemostasis Monitoring Test your knowledge of TEG parameters and hemostasis monitoring by answering the questions on the slides that follow.

Exercise 1: TEG Parameters The R value represents which of the following phases of hemostasis?

a. Platelet adhesion b. Activation of coagulation pathways and initial fibrin formation c. Buildup of platelet-fibrin interactions d. Completion of platelet-fibrin buildup e. Clot lysis Answer: page 64

Exercise 2: TEG Parameters Select the TEG parameters that demonstrate kinetic properties of clot formation. (Select all that apply) a. R b. Angle ( a ) c. MA d. LY30 e. CI Answer: page 65

Exercise 3: TEG Parameters The rate of clot strength buildup is demonstrated by which of the following TEG parameters?

a. R b. Angle ( a ) c. MA d. LY30 e. CI Answer: page 66

Exercise 4: TEG Parameters Which of the following TEG parameters will best demonstrate the need for coagulation factors (i.e. FFP)?

a. R b. Angle ( a ) c. MA d. LY30 e. CI Answer: page 67

Exercise 5: TEG Parameters Clot strength is dependent upon which of these hemostatic components?

a. 100% platelets b. 80% platelets, 20% fibrin c. 50% platelets, 50% fibrin d. 20% platelets, 80% fibrin e. 100% fibrin Answer: page 68

Exercise 6: TEG Parameters Which of the following TEG parameters demonstrate a structural property of the clot? (Select all that apply) a. R b. Angle ( a ) c. MA d. LY30 e. CI Answer: page 69

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? ( Select all that apply ) a. R b. Angle ( a ) c. LY30 d. CI e. None of the above Answer: page 70

Exercise 8: TEG Parameters Clot stability is determined by which of the following TEG parameters?

a. R b. Angle ( a ) c. MA d. LY30 e. CI Answer: page 71

Exercise 9: TEG Parameters Which of the following reagents should be used to provide the information necessary to determine if heparin is the cause of bleeding in a patient?

a. R value: Kaolin with heparinase b. R value: Kaolin vs. Kaolin with heparinase c. MA value: Kaolin with heparinase d. MA value: Kaolin vs. kaolin with heparinase Answer: page 72

Exercise 10: TEG Parameters Which of the following parameters provides an indication of the global coagulation status of a patient?

a. R b. Angle ( a ) c. MA d. LY30 e. CI Answer: page 73

Exercise 11: TEG Parameters Which of the following statements are true regarding the PT and aPTT tests? (select all that apply) a. Measure coagulation factor interaction in solution b. Measure platelet contribution to thrombin generation c. Measure the influence of thrombin generation on platelet function d. Use fibrin formation as an end point Answer: page 74

Exercise 12: TEG Parameters The TEG analyzer can monitor all phases of hemostasis except which of the following? (select all that apply) a. Initial fibrin formation b. Fibrin-platelet plug construction c. Platelet adhesion d. Clot lysis Answer: page 75

Answers to Exercise 1: TEG Parameters The R value represents which of the following phases of hemostasis?

a. Platelet adhesion

b. Activation of coagulation pathways and initial fibrin formation

c. Buildup of platelet-fibrin interactions d. Completion of platelet-fibrin buildup e. Clot lysis

Answers to Exercise 2: TEG Parameters Select the TEG parameters that demonstrate kinetic properties of clot formation. (select all that apply) a. R

b. Angle (

a

)

c. MA d. LY30 e. CI

Answers to Exercise 3: TEG Parameters The rate of clot strength buildup is demonstrated by which of the following TEG parameters?

a. R

b. Angle (

a

)

c. MA d. LY30 e. CI

Answers to Exercise 4: TEG Parameters Which of the following TEG parameters will best demonstrate the need for coagulation factors (i.e. FFP)?

a. R

b. Angle ( a ) c. MA d. LY30 e. CI

Answers to Exercise 5: TEG Parameters Clot strength is dependent upon which of these hemostatic components?

a. 100% platelets

b. 80% platelets, 20% fibrin

c. 50% platelets, 50% fibrin d. 20% platelets, 80% fibrin e. 100% fibrin

Answers to Exercise 6: TEG Parameters Which of the following TEG parameters demonstrate a structural property of the clot? (select all that apply) a. R b. Angle ( a )

c. MA (demonstrates maximum clot strength) d. LY30 (demonstrates clot breakdown or the structural stability of the clot)

e. CI

Answers to 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? (select all that apply)

a. R

– Thrombin generation occurs mainly on the surface of platelets; therefore, a defect in platelet function may slow the rate of thrombin generation and fibrin formation.

b. Angle (

a

)

– A defect in platelet function may slow the rate of formation of platelet-fibrin interactions, thereby slowing the rate of clot buildup.

c. LY30

d. CI

e. None of the above

Answers to Exercise 8: TEG Parameters Clot stability is determined by which of the following TEG parameters?

a. R b. Angle ( a ) c. MA

d. LY30

e. CI

Answers to Exercise 9: TEG Parameters Which of the following reagents should be used to provide the information necessary to determine if heparin is the cause of bleeding in a patient?

a. R value: Kaolin with heparinase

b. R value: Kaolin vs. Kaolin with heparinase

c. MA value: Kaolin with heparinase d. MA value: Kaolin vs. kaolin with heparinase

Answers to Exercise 10: TEG Parameters Which of the following parameters provides an indication of the global coagulation status of a patient?

a. R b. Angle ( a ) c. MA d. LY30

e. CI

(Coagulation Index — a linear combination of the R, K, angle, and MA)

Answers to Exercise 11: TEG Parameters Which of the following statements are true regarding the PT and aPTT tests? (select all that apply)

a. Measure coagulation factor interaction in solution

b. Measure platelet contribution to thrombin generation c. Measure the influence of thrombin generation on platelet function

d. Use fibrin formation as an end point

Answers to Exercise 12: TEG Parameters The TEG analyzer can monitor all phases of hemostasis except which of the following? (select all that apply) a. Initial fibrin formation b. Fibrin-platelet plug construction

c. Platelet adhesion

— this is a vascular mediated event that occurs

in vivo

, but not

in vitro

d. Clot lysis

Basic Clinician Training End of Module 2