Module 2

1
Module 2
Basic Clinician Training

• TEG Technology

Review of the Hemostatic Process Hemostasis
Monitoring with the TEG Analyzer How the TEG
Analyzer Monitors Hemostasis Parameters Tracings B
lood Sample Types and Preparation Test Your
Knowledge
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Hemostatic Process
Endothelial Cells
Change in Platelet Shape
Area of Injury

• Endothelium damaged

Collagen
Platelet
AA
ADP
Platelet plug formed (white clot)
Coagulation Cascade
Thrombin generated on platelet surface
Platelet-fibrin plug formed (red clot)
tPA
Fibrin Strands
Fibrinolysis
Plasminogen
Plasmin
Degradation Products
Clot lysis
3
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

4
Hemostasis MonitoringTEG 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

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The TEG AnalyzerDescription

• 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

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TEG Technology
The TEG Analyzer How It Works
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TEG TechnologyHow 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

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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

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What TEG Analysis Captures
Amplitude of pin oscillation
Time
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TEG Parameters
Basic Clinician Training

• Identification
• Definition

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Thrombin Formation (Clotting Time)The R
Parameter Identified

• Reaction time
• Fibrin creates a connection between cup and pin

Initial fibrin formation
Intrinsic,extrinsic,commonpathways
Pin is engaged
Pin is stationary
Cup oscillates, pin remains stationary
Pin starts to oscillate with cup
?
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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)

Initial fibrin formation
Intrinsic,extrinsic,commonpathways
Pin is engaged
Pin is stationary
Cup oscillates, pin remains stationary
Pin starts to oscillate with cup
?
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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

Initial fibrin formation
Initial fibrin formation
Pin is stationary
Pin is engaged
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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

Initial fibrin formation
Pin is engaged
Pin is stationary
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FibrinogenThe a (Angle) Parameter Identified

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

Fibrin increases
Baseline
Pin is engaged
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FibrinogenThe a (Angle) Parameter Defined

• Kinetics of clot formation
• Rate of thrombin
• generation
• Conversion of Fibrinogen ? fibrin
• Interactions among fibrinogen, fibrin, and
  platelets
• Cellular contributions

Fibrin increases
Baseline
Pin is engaged
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Fibrinogen AbnormalitiesThe a (Angle) Parameter
Low a

• 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

Fibrin increases
Baseline
Pin is engaged
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Fibrinogen AbnormalitiesThe a (Angle) Parameter
High a

• Possible causes of imbalance
• Fast rate of fibrin
• formation
• Possible etiologies
• Platelet
• hypercoagulability
• Fast rate of thrombin
• generation
• Common treatments
• None

Fibrin increases
Baseline
Pin is engaged
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Platelet FunctionThe MA Parameter Defined

• Maximum amplitude
• Clot strength 80 platelets 20 fibrinogen
• Platelet function influences thrombin generation
  and fibrin formation ? relationship between R, a,
  and MA

Maximum amplitude (MA) of pin oscillation
Amplitude of pin oscillation
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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

Maximum amplitude (MA) of pin oscillation
Amplitude of pin oscillation
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Platelet Function AbnormalitiesThe MA Parameter
High MA

• 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)

Maximum amplitude (MA) of pin oscillation
Amplitude of pin oscillation
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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 gt 3.0
• hypercoagulable
• CI lt -3.0
• hypocoagulable

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Fibrinolysis LY30 and EPLLY30 and EPL
Parameters Identified

• 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

MA
30 min
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Fibrinolysis LY30 and EPLLY30 and EPL
Parameters Defined

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

MA
30 min
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Fibrinolytic AbnormalitiesLY30 Parameter
Primary Fibrinolysis

• Possible causes
• Excessive rate of fibrinolysis
• Possible etiologies
• High levels of tPA
• Common treatments
• Antifibrinolytic agent

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Fibrinolytic AbnormalitiesLY30 Parameter
Secondary Fibrinolysis

• Possible causes
• Rapid rate of clot
• formation/break-
• down
• Possible etiologies
• Microvascular
• hypercoagulability
• (i.e. DIC)

DIC disseminated intravascular coagulation
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Fibrinolytic AbnormalitiesLY30 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
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Clot StrengthThe G Parameter

• Representation of clot strength and overall
  platelet function
• G shear elastic modulus strength (dyn/cm2)
• G (5000MA)/(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

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MA vs. G(Kaolin Activated Sample)
Normal MA range (Kaolin activated)
Hyperactive platelet function
G(dynes/cm2) x 1000
Normal platelet function
Hypoactive platelet function
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TEG Parameter SummaryDefinitions
Clotting Time R The latency period from the time that the blood was placed in the TEG analyzer until initial fibrin formation. Represents enzymatic reaction.
Clot Kinetics K A measure of the speed to reach 20 mm amplitude. Represents clot kinetics.
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.
Clot Strength 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.
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TEG Parameter Summary
Platelet function Clot strength (G)
Clotting time
Clot kinetics
Clot stability Clot breakdown
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TEG Results
Basic Clinician Training

• Tracings
• Data
• Decision Tree

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Components of the TEG TracingExample R
Actual value
Normal range
ParameterUnitsValueNormal range
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Normal TEG Tracing
30 min
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Hemorrhagic TEG Tracing
30 min
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Prothrombotic TEG Tracing
30 min
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Fibrinolytic TEG Tracing
30 min
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TEG Decision TreeQualitative
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TEG Decision TreeQuantitative
Hemorrhagic
Fibrinolytic
Thrombotic
US Patent 6,787,363
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TEG TracingExample Hemorrhagic
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TEG TracingExample Prothrombotic
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TEG TracingExample Fibrinolytic
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TEG Blood Sampling
Basic Clinician Training
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TEG Blood Sampling

• Blood samples
• Arterial or venous
• Samples should be consistent

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TEG Blood SamplingNative

• Non-modified blood samples
• Assayed 4 minutes
• TEG software based upon assay at 4 minutes

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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

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TEG Blood SamplingHeparin

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

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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

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Sample Type Designations
Whole blood kaolin
Sample type Conditions Wait time before run sample Sample prep
K (kaolin activated) No anticoagulation lt 6 min (recommended4 min) Clear cup pin
KH (kaolin heparinase) With heparin lt 6 min (recommended4 min) Blue cup pin (coated with heparinase)
CK (citrate kaolin) With citrate gt 6 min lt 120 min Add calcium chloride Clear cup and pin
CKH (citrate kaolin heparinase) With citrate and heparin gt 6 min lt 120 min Add calcium chloride Blue cup pin
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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.

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Test your knowledge of TEG parameters and
hemostasis monitoring by answering the questions
on the slides that follow.
Basic Clinician Training
TEG Parameters Hemostasis Monitoring
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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 page 64
53
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 page 65
54
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 page 66
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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 page 67
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Exercise 5 TEG Parameters

• Clot strength is dependent upon which of these
• hemostatic components?
• 100 platelets
• 80 platelets, 20 fibrin
• 50 platelets, 50 fibrin
• 20 platelets, 80 fibrin
• 100 fibrin

Answer page 68
57
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 page 69
58
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)
• R
• Angle (a)
• LY30
• CI
• None of the above

Answer page 70
59
Exercise 8 TEG Parameters

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

Answer page 71
60
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?
• 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 page 72
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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 page 73
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Exercise 11 TEG Parameters

• 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 the influence of thrombin generation on
  platelet function
• Use fibrin formation as an end point

Answer page 74
63
Exercise 12 TEG Parameters

• 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 page 75
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Answers to 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

65
Answers to 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

66
Answers to 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

67
Answers to 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

68
Answers to Exercise 5 TEG Parameters

• Clot strength is dependent upon which of these
• hemostatic components?
• 100 platelets
• 80 platelets, 20 fibrin
• 50 platelets, 50 fibrin
• 20 platelets, 80 fibrin
• 100 fibrin

69
Answers to 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)
• CI

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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)
• 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.
• Angle (a) A defect in platelet function may
  slow the rate of formation of platelet-fibrin
  interactions, thereby slowing the rate of clot
  buildup.
• LY30
• CI
• None of the above

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Answers to Exercise 8 TEG Parameters

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

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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?
• R value Kaolin with heparinase
• R value Kaolin vs. Kaolin with heparinase
• MA value Kaolin with heparinase
• MA value Kaolin vs. kaolin with heparinase

73
Answers to 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)

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Answers to Exercise 11 TEG Parameters

• 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 the influence of thrombin generation on
  platelet function
• Use fibrin formation as an end point

75
Answers to Exercise 12 TEG Parameters

• 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 this is a vascular mediated
  event that occurs in vivo, but not in vitro
• Clot lysis

76
End of Module 2
Basic Clinician Training