review of the hemostatic process hemostasis monitoring with the teg analyzer how the teg analyzer...

Review of the Hemostatic ProcessHemostasis Monitoring with the TEG AnalyzerHow the TEG Analyzer Monitors Hemostasis

ParametersTracings

Blood Sample Types and PreparationTest Your Knowledge

Module 2

TEG® Technology

Basic Clinician Training

Hemostatic Process

Endothelium damaged

Platelet plug formed (white clot)

Thrombin generated on platelet surface

Platelet-fibrin plug formed (red clot)

Clot lysis

Pr ombin (II) Thr

Ca2+

XI XIa

X

VIIa/TF VII

IX

XII XIIa

XIIIaXIII

+

V V

Platelet

Endothelial CellsChange in Platelet ShapeArea of Injury

Collagen

ADP AA

tPA

Plasminogen PlasminFibrin Strands

Degradation Products

Fibrinolysis

Coagulation C

ascade

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

• 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

Hemostasis Monitoring:TEG Hemostasis System

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 CapturesA

mp

litu

de

of

pin

osc

illa

tio

n

Time

TEG Parameters

Identification

Definition


Thrombin Formation (Clotting Time)The R Parameter: Identified

• Reaction time

• Fibrin creates a connection between cup and pin

Cup oscillates, pin remains stationary

Time

Am

plitu

de o

fpi

n os

cilla

tion

Pin starts to oscillate with

cup

Pin is stationary

Pin is engaged

Intrinsic,extrinsic,commonpathways

Initial fibrinformation

Thrombin FormationThe R Parameter: Defined

• Time until formation of critical mass of thrombin

• Expression of enzymatic reaction function (i.e. the ability to generate thrombin and fibrin)

Cup oscillates, pin remains stationary

Pin starts to oscillate with

cup

Pin is stationary

Pin is engaged

Intrinsic,extrinsic,commonpathways


Thrombin Formation AbnormalitiesThe R Parameter: Elongated R

• Possible causes of imbalance: Slow enzymatic reaction

• Possible etiologies: Factor deficiency/

dysfunction Residual heparin

• Common treatments: FFP Protamine


Pin is stationary

Pin is engaged


Thrombin Formation AbnormalitiesThe R Parameter: Short R

• Possible causes of imbalance:

Over-stimulated

enzymatic reaction Fast fibrin

formation

• Possible etiologies: Enzymatic

hypercoagulability

• Common treatments: Anticoagulant


Pin is engaged

Pin is stationary

• Rate of increase in pin oscillation amplitude as fibrin is generated and cross-links are formed

FibrinogenThe α (Angle) Parameter: Identified

Baseline

Pin is engaged

Fibrin increases

FibrinogenThe α (Angle) Parameter: Defined

• Kinetics of clot formation Rate of thrombin

generation Conversion of

Fibrinogen fibrin

Interactions among fibrinogen, fibrin, and platelets

Cellular contributions

Baseline

Pin is engaged

Fibrin increases

Fibrinogen AbnormalitiesThe α (Angle) Parameter: Low

• 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: FFPCryoprecipitate

Baseline

Pin is engaged

Fibrin increases

Fibrinogen AbnormalitiesThe α (Angle) Parameter: High

• Possible causes of imbalance: Fast rate of fibrin

formation

• Possible etiologies:Platelet

hypercoagulabilityFast rate of thrombin

generation

• Common treatments: None

Pin is engaged

Fibrin increases

Baseline

Platelet FunctionThe MA Parameter: Defined

• Maximum amplitude

• Clot strength = 80% platelets + 20% fibrinogen

• Platelet function influences thrombin generation and fibrin formation relationship between R, α, and MA

Amplitude of pin oscillation

Maximum amplitude (MA) of pin oscillation

Platelet Function AbnormalitiesThe MA Parameter: Low MA

• 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 AbnormalitiesThe MA Parameter: High MA

• Possible causes: Excessive platelet

activity

• Possible etiologies: Platelet

hypercoagulability

• Common treatments: Antiplatelet agentsNote: Should be

monitored for efficacy and/or resistance (See Module 6: Platelet Mapping)



Coagulation IndexThe 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:

hypercoagulableCI < -3.0:

hypocoagulable

• 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 EPLLY30 and EPL Parameters: Identified

MA

30 min

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

Fibrinolysis: LY30 and EPLLY30 and EPL Parameters: Defined

MA

30 min

Fibrinolytic AbnormalitiesLY30 Parameter: Primary Fibrinolysis

• Possible causes: Excessive rate of

fibrinolysis

• Possible etiologies: High levels of tPA

• Common treatments: Antifibrinolytic agent

Fibrinolytic AbnormalitiesLY30 Parameter: Secondary Fibrinolysis

DIC = disseminated intravascular coagulation

• Possible causes: Rapid rate of clot

formation/break-

down

• Possible etiologies: Microvascular

hypercoagulability

(i.e. DIC)

DIC = disseminated intravascular coagulation

Fibrinolytic AbnormalitiesLY30 Parameter: Secondary Fibrinolysis

• Possible causes: Rapid rate of clot

formation/break-

down

• Possible etiologies: Microvascular

hypercoagulability

(i.e. DIC)

• Common treatments: Anticoagulant

Clot Strength:The G Parameter

• Representation of clot strength and overall platelet function G = shear elastic modulus strength (dyn/cm2) 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

5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 850.0

5.0

10.0

15.0

20.0

25.0

30.0

G (

dyn

s/cm

2)

MA (mm)

MA vs. G(Kaolin Activated Sample)

Hyperactive platelet function

Normal platelet function

Hypoactive platelet function

G(d

ynes

/cm

2 ) x

1000

Normal MA range(Kaolin activated)

TEG Parameter Summary:Definitions

ClottingTime R The latency period from the time that the blood was placed in the TEG®

analyzer until initial fibrin formation. Represents enzymatic reaction.

ClotKinetics

K 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.

G A transformation of MA into dyn/cm2.

Coagulation Index CI A linear combination of R, K, alpha, MA.

Clot Stability

LY30

EPL

A measure of the rate of amplitude reduction 30 min.after MA.Estimates % lysis based on amplitude reduction after MA.

TEG Parameter Summary

Platelet function

Clot strength (G)

Clotting time

Clot kinetics

Clot stability Clot breakdown

TEG Results

Tracings

Data

Decision Tree


Components of the TEG TracingExample: R

Actual value

ParameterUnitsValueNormal range

Time

Am

plit

ud

e o

fp

in o

scill

atio

n

Normal range

“Normal” TEG Tracing

30 min

Hemorrhagic TEG Tracing

30 min

Prothrombotic TEG Tracing

30 min

Fibrinolytic TEG Tracing

30 min

TEG Decision TreeQualitative

US Patent 6,787,363

Hemorrhagic

Thrombotic

Fibrinolytic

TEG Decision TreeQuantitative

TEG TracingExample: Hemorrhagic

TEG TracingExample: Prothrombotic

TEG TracingExample: Fibrinolytic

TEG Blood Sampling


TEG Blood Sampling

• Blood samples Arterial or venous Samples should be consistent

TEG Blood SamplingNative

• 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 SamplingHeparin

• Heparinase Neutralizes heparin Embedded in specialized (blue) cups and pins

TEG Blood SamplingCitrated

• 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

Sample type Conditions Wait time before run

sample

Sample prep

K(kaolin activated)

No anticoagulation

< 6 min(recommended

4 min)

Clear cup & pin

KH(kaolin + heparinase)

With heparin < 6 min(recommended

4 min)

Blue cup & pin (coated with heparinase)

CK(citrate + kaolin)

With citrate > 6 min

< 120 min

Add calcium chloride

Clear cup and pin

CKH(citrate + kaolin +

heparinase)

With citrate and heparin

> 6 min

< 120 min

Add calcium chloride

Blue cup & pin

Whole blood + kaolin

• 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.

Summary


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


Select the TEG parameters that demonstrate

kinetic properties of clot formation. (Select all that

apply)

a. R

b. Angle ()

c. MA

d. LY30

e. CI

Answer: page 65


The rate of clot strength buildup is demonstratedby which of the following TEG parameters?

a. R

b. Angle ()

c. MA

d. LY30

e. CI

Answer: page 66


Which of the following TEG parameters will best

demonstrate the need for coagulation factors

(i.e. FFP)?

a. R

b. Angle ()

c. MA

d. LY30

e. CI

Answer: page 67


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


Which of the following TEG parameters

demonstrate a structural property of the clot?

(Select all that apply)

a. R

b. Angle ()

c. MA

d. LY30

e. CI

Answer: page 69


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 ()

c. LY30

d. CI

e. None of the above

Answer: page 70


Clot stability is determined by which of the following

TEG parameters?

a. R

b. Angle ()

c. MA

d. LY30

e. CI

Answer: page 71


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


Which of the following parameters provides an indication

of the global coagulation status of a patient?

a. R

b. Angle ()

c. MA

d. LY30

e. CI

Answer: page 73


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


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


Select the TEG parameters that demonstrate

kinetic properties of clot formation. (select all that

apply)

a. R

b. Angle ()

c. MA

d. LY30

e. CI

The rate of clot strength buildup is demonstratedby which of the following TEG parameters?

a. R

b. Angle ()

c. MA

d. LY30

e. CI



Which of the following TEG parameters will best

demonstrate the need for coagulation factors

(i.e. FFP)?

a. R

b. Angle ()

c. MA

d. LY30

e. CI


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


Which of the following TEG parameters

demonstrate a structural property of the clot?

(select all that apply)

a. R

b. Angle ()

c. MA (demonstrates maximum clot strength)

d. LY30 (demonstrates clot breakdown or the structural stability of the clot)

e. CI

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 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



Clot stability is determined by which of the following

TEG parameters?

a. R

b. Angle ()

c. MA

d. LY30

e. CI


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


Which of the following parameters provides an indication

of the global coagulation status of a patient?

a. R

b. Angle ()

c. MA

d. LY30

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


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


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

End of Module 2


review of the hemostatic process hemostasis monitoring with the teg analyzer how the teg analyzer...

Documents

pin cup

cup pin

stationary pin

teg hemostasis system

lysis slide

clot system

fibrin cup

white clot thrombin