Clinical Utility of Thromboelastography (TEG)

Lowell Chambers, MD

Secondary Hemostasis (Coagulation Cascade)

XII XIIa

XI XIa

IX IXa + VIIIa VIIa + TF

X Xa + Va

Prothrombin (II) Thrombin (IIa)

Fibrinogen (I) Fibrin (Ia)

INTRINSIC PATH EXTRENSIC PATH(PTT) (PT)

CLASSIC COAGULATION CASCADE

Ca++

Secondary Hemostasis (Coagulation Cascade)

PHYSIOLOGIC PATHWAY

VII TF+

IX IXa VIIIa*+

X Xa + Va

II ThrombinXI XIa

Fibrinogen Fibrin

PlateletThrombin

V

VIII

Ca++

Cross-Linked*Fibrin

XIII (transglutaminase)

XIIIa

Cell-Based Hemostasis

Challenges in Coagulation Evaluation

• Evaluation of Platelet Function

• Monitoring of New generation anticoagulants

• Determination of Hyperfibrinolytic States

Coagulopathy of Trauma

ACIDOSIS

HYPOTHERMIA

HYPOTENSION

HIGH ISS

Impaired Clotting Factor FunctionImpaired Platelet Function

CNS InjuriesIncreased TF Release DIC

Long Bone Fxs

Fat Embolism

Increased IVF & PRBCs

Dilution of Clotting Factors & Platelets

COAGULOPATHY

Hess J,… Hoyt D, … Bouillon B. J Trauma 2008; 65:748-54

Prot. C Activation Hyper-fibrinolysis

Coagulopathy of Trauma

• ¼ Significant Trauma patients

• 4x increased mortality

• Multifactorial

• Currently addressed with:

Hess J,… Hoyt D, … Bouillon B. J Trauma 2008; 65:748-54

- Whole Blood - 1:1:1 Massive Transfusion Protocols

Coagulopathy of Trauma

• ¼ Significant Trauma patients

• 4x increased mortality

• Multifactorial

• Currently addressed with:

Hess J,… Hoyt D, … Bouillon B. J Trauma 2008; 65:748-54

- Whole Blood - 1:1:1 Protocols

Improved Outcomes

Consequences of Overtransfusion

• Waste

• ALI / MSOF

• Thrombosis

Hyperfibrinolysis in Trauma

• See in 2-34% of Trauma Pts

• Increased risk with increased ISS, need for transfusion, etc…

• Associated with increased mortality

Napolitano L,… Moore EE. J Trauma Acute Care Surg 2013; 74:1575-86

Fibrinolyis in Trauma

Kashuk J, Moore EE, et al. Ann Surg 2010; 252:434-44

Hyperfibrinolysis in Trauma

Napolitano L,… Moore EE. J Trauma Acute Care Surg 2013; 74:1575-86

• Randomized, multicenter trial (Europe, Asia, Africa)

• 20,127 trauma pts in 274 hospitals

• Inclusion criteria:

• TA (1gm over 10 min. then another gm over 8hr) versus Placebo

-Hemorrhagic Shock (SBP < 90, HR > 110)-High risk of substantial bleeding-Within 8 hr of injury

Tranexamic Acid in Trauma

Lancet 2010; 376:23-32

All cause mortality reduction of 1.5%.

Tranexamic Acid in TraumaLancet 2010; 376:23-32

All cause mortality reduction of 1.5% with TXA. + No harm from TXA + Low Cost (~$6.00/gm)

Potential to save 70-100,000lives annually world-wide

(NNT1 = 67)

TXA in Trauma

• Cheap

• Safe

• Effective

SO WHY NOT USE ROUTINELY IN BLEEDING TRAUMAS ?

Added to WHO “Essential Medications List” in 2011

Napolitano L,… Moore EE. J Trauma Acute Care Surg 2013; 74:1575-86

CRASH-2 Problems

Napolitano L,… Moore EE. J Trauma Acute Care Surg 2013; 74:1575-86

Deficiencies in Current Coag. Assessment of Severely Injured Trauma Pts

• No rapid, reliable assessment of hyperfibrinolysis

• Incomplete assessment of Coagulopathy of Trauma- Lack of Qualitative Platelet Evaluation

- Lack of rapid Coag. Assessment

- Inability to assess when switch from hypo to hypercoagulable occurs

Thrombelastography (TEG)

• A viscoelastic point of care hemostatic assay

• Provides a graphic presentation of clot formation & lysis

Johansson PI, et al. Scan J Trauma, Resus, & Emerg Med 2009; 17:45.

Hemostasis Monitoring with the TEG® System

• Rate of clot formation

• Strength of clot

• Stability of clot

Hemostaticstatus

Measures entire clotting process

Measures: ∆Clot strength / time

TEG - History• Initial description in 1948 (H Hartert)

• Important role in development of open heart surgery and liver transplantation

1950s Dr. Henry Swan & Hypothermic Open Heart Procedures

1960s Dr. Thomas Starzl & Liver Transplantation

Dr. Kurt von Koulla & Hartert TEG

Hartert H. Klin Wochenschr 1948; 26:577-83

TEG Method• 0.36 ml whole blood incubated @ 37oC in a heated, kaolin-containing cup

• Pin is suspended into cup and connected to a detector system (torsion wire)

• Cup is oscillated at an angle to the pin

• Fibrin forms between the cup and pin

• Formation of fibrin results in transmitted rotation from the cup to the pin

• Tracing is generated as a result of pin’s movement

• Pattern & duration of different aspects of tracing provides information on the clotting and lysis process

(after being collected in Citrate – if delay in running > 3 min)

Copyright © 2009 Haemonetics Corp.

TEG Tracing and Clotting Process

Continuous monitoring of clotting process

Generates parameters that relate to each phase

Time (min)

Initiation

Platelet plug formsFibrin strands form

Clot grows

Maximum clot forms

Clot degradation takes over

Clot dissolvedDamage repaired

║

║Time

Copyright © 2009 Haemonetics Corp.

Analytical SoftwareGraphical Representation

Reaction time,first significantclot formation

Achievementof certain clotfirmness

Maximum amplitude –maximum strength ofclot

Kineticsof clotdevelopment

LY30

Percent lysis30 minutesafter MA

Copyright © 2009 Haemonetics Corp.

TEG Parameters: R Reaction time(4 – 8 min)

FFPrVIIaPCC

LMWH

LMWH + ASA

FFP +Platelets

Copyright © 2009 Haemonetics Corp.

TEG Parameters: K and angle ()Rate of clot growth

R

Clot time

IIa generationFibrin formation

Coagulationpathways

R

Clot time

IIa generationFibrin formation

Coagulationpathways

Parameter

HemostaticActivity

HemostaticComponent

Hypo-coagulable

Hyper-coagulable

R (min)

R (min)

R (min)

R (min)

K (min) (deg)

K (min) (deg)

K (min) (deg)

K (min) (deg)

Clot rate

Fibrin meshFibrinplatelet

Coag pathwaysplatelets

K

Clot rate

Fibrin meshFibrinplatelet

Coag pathwaysplatelets

K

Dysfunction 4-8 min

: Angle (47 - 74°)K: Clot kinetics (0 - 4 min)

FFPCryoprecipitate

Copyright © 2009 Haemonetics Corp.

TEG Parameters: MAMaximum clot strength

R

Clot time

IIa generationFibrin formation

Coagulationpathways

R

Clot time

IIa generationFibrin formation

Coagulationpathways

Parameter

HemostaticActivity

HemostaticComponent

Hypo-coagulable

Hyper-coagulable

R (min)

R (min)

R (min)

R (min)

K (min) (deg)

K (min) (deg)

K (min) (deg)

K (min) (deg)

MA

MA

MA

MA

Clot rate

Fibrin X-linkingFibrinplatelet

Coag pathwaysplatelets

K

Clot rate

Fibrin X-linkingFibrinplatelet

Coag pathwaysplatelets

K

Maximum clot strength

Platelet – fibrin interactions

Platelets (~80%)Fibrin (~20%)

MA

Maximum clot strength

Platelet – fibrin interactions

Platelets (~80%)Fibrin (~20%)

MA

Dysfunction

Maximum amplitude(54 – 72 mm)

Platelets

ASA

Copyright © 2009 Haemonetics Corp.

TEG Parameters: LY30Clot Breakdown

R

Clot time

IIa generationFibrin formation

Coagulationpathways

R

Clot time

IIa generationFibrin formation

Coagulationpathways

Parameter

HemostaticActivity

HemostaticComponent

Hypo-coagulable

Hyper-coagulable

R (min)

R (min)

R (min)

R (min)

K (min) (deg)

K (min) (deg)

K (min) (deg)

K (min) (deg)

MA

MA

MA

MA

Clot stability

Reduction in clot strength

Fibrinolysis

Clot stability

Reduction in clot strength

Fibrinolysis

Clot rate

Fibrin X-linkingFibrinplatelet

Coag pathwaysplatelets

K

Clot rate

Fibrin X-linkingFibrinplatelet

Coag pathwaysplatelets

K

Maximum clot strength

Platelet – fibrin(ogen) interactions

Platelets (~80%)Fibrin(ogen (~20%)

MA

Maximum clot strength

Platelet – fibrin(ogen) interactions

Platelets (~80%)Fibrin(ogen (~20%)

MA

30 min LY30

EPL

30 min LY30

EPL

LY30 > 7.5%EPL > 15%

N/A

LY30 > 7.5%EPL > 15%

N/A

Dysfunction

Lysis at 30 minutes(0 – 7.5%)

TXAACA

Copyright © 2009 Haemonetics Corp.

TEG: Basic Patterns

Copyright © 2009 Haemonetics Corp.

Hemostasis Monitoring with the TEG® System

• Rate of clot formation

• Strength of clot

• Stability of clot

Hemostaticstatus

Measures entire clotting process

Measures: ∆Clot strength / time

Clinical Experience with standard TEG

• Majority of experience is with Cardiac & Liver Surgery

• > 20 clinical studies with > 4500 pts in last 25 years

• Varying quality (3 rand. clin. trials)

• Uniform findings of superiority of TEG over routine coagulation tests.

Johansson PI, et al. Scan J Trauma Resus Emerg Med. 2009; 17:45

Standard TEG in Massive Tranfusion

• European Prospective Trial

• n=832 massively bleeding pts (21% trauma)

• TEG-guided patients:

Johansson PI, et al. Vax Sang 2009; 96:111-8

- 20% VS 32% mortality- > FFP- > Plts

TEG in Trauma

Johansson PI, et al. Scan J Trauma Resus Emerg Med. 2009; 17:45

TEG in Trauma• Differentiates different etiologies of the Coagulopathy

of Trauma

• Quicker & more accurate than coags.

• Permits ID of Hyperfibrinolysis

• Differentiates hyper VS hypocoagulability

• Gives info. on coag status with newer anticoag. agents

Johansson PI, et al. Scan J Trauma Resus Emerg Med. 2009; 17:45

RapidTEG

• Tissue Factor added to Kaolin in cup

• Cuts processing time by ~ 50%:- r-TEG 19.2 min to completion- TEG 29.9 min “- Coags 34.1 min “

Jeger V, et al. J Trauma 2009; 66:1253-7Holcomb JB, et al. Ann Surg 2012; 256:476-86

Software available facilitating viewing of TEG on monitor in ICU/OR real-time so initial information available within minutes.

r-TEG Tracing Comparison

Standard TEG

RapidTEG

Differences: R range: 0-1 min & use ACT

U Colorado Experience

More “Goal Directed” Therapy “LEAN” Goals met c blood products needed

Kashuk JL, Moore EE, et al. Transfusion 2012; 52:23-33

U Colorado Case Study• 38 yo F auto VS ped. patient

• HD unstable from intra-abd bleeding

• Emergent Trauma Lap.Initial r-TEG in OR

- PRBCs for hemorrhagic shock- FFP for prolonged ACT - Platelets for depressed MA- 5 gm EACA for elevated LY30

U Colorado Case Study• Intra-abd. Bleeding controlled but still “oozey”

2nd r-TEG in OR

- Improved coagulopathy (improved ACT)- Improved platelet function (improved MA)- Persistent Fibrinolysis (Sign. Increased LY30 still)

Additional EACA administered

U Colorado Case Study

• Pt continued to stabilize

• “Oozing” resolved

3rd r-TEG in OR

Ann Surg 2012; 256:476

r-TEG U Texas Experience

…

Holcomb JB, et al. Ann Surg 2012; 256:476

U Texas Approach• Unstable Pt: 1:1:1 Transfusion

• Once surgical hemostasis achieved:

Holcomb JB, et al. Ann Surg 2012; 256:476

Baylor Approach

• ~ 10 year experience with TEG-directed resusc.

• Use conventional TEG rather than r-TEG

Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86

Baylor Experience

• In October 2009 instituted 1:1:1 MTP

• Reviewed outcomes 21 months before & after

• Compared outcomes with TEG-directed VS reflexive 1:1:1 MTP

Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86

Baylor Experience

Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86

Baylor Experience

• No improved survival in MTP with increased FFP utilization

• Some subsets of MTP with worse outcomes

Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86

Baylor Approach

Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86

? Mt Carmel Approach

Tapia NM, … Mattox KL, Suliburk J. J Trauma Acute Care Surg 2013; 74: 378-86

> 3.0% TXA

U Texas Approach

Holcomb JB, et al. Ann Surg 2012; 256:476

TEG & PE risk assessment• Prospective Study with 2,070 consecutive Cat. 1 Trauma Alerts

(2009-11) at U Texas, Houston

• All had r-TEG

• 53 (2.5%) PEs at median of 6 days (range 2-31 days)

•

Cotton B, … Holcomb J. J Trauma Acute Care Surg 2012; 72:1470-7

Sens. 82%Spec. 53%

TEG & PE risk assessment

Cotton B, … Holcomb J. J Trauma Acute Care Surg 2012; 72:1470-7

Sens. 49%Spec. 87%

• Prospective Blinded Cohort Study

• 240 pts undergoing major non-cardiac surgery

• Routinely drew ran TEG 2 hr postop & followed

• 12 thrombotic complications in 10 pts(6 MI, 2 DVT, 2 PE, 2 CVA)

TEG & Postop Thrombosis

TEG & Postop Thrombosis

TEG & Postop Thrombosis

New Anticoagulant Monitoring

Holcomb JB, et al. Ann Surg 2012; 256:476

TEG & LMWH

• LMWH not typically monitored

• Anti-Xa levels used when needed:

• TEG Delta R (with & without heparinase) appears to be a better index of LMWH dose adequacy

- Limited availability- Inconsistent data

White H, et al. Blood Coag & Fibrinolysis 2012; 23:304-10Van PY, … Schreiber M. J Trauma 2009; 66:1509-17

TEG & LMWH

Van PY, … Schreiber M. J Trauma 2009; 66:1509-17

R < 0.4 associated with DVT & calls for LMWH dose

Anti-platelet issues

• Surgical issue: risk of bleeding VS risk of ischemic events

• Medical / Cardiac Issue: variance of response

• Current “Gold Standard” in platelet monitoring is Light Transmission Platelet Aggregometry (LTA) :

- Requires specialized labs- Poorly standardized between labs- Not routinely used clinically

Agarwal S, et al. Anesthesiology 2006; 105:676-83

Conventional TEG & Antiplatelets

• Not helpful

• Kaolin-induced thrombin generation overshadows any platelet effect

• Lab & clinical experiences have demonstrated normal TEG MAs in specimens with definitive platelet inhibition on LTA

Agarwal S, et al. Anesthesiology 2006; 105:676-83

Platelet Mapping

• Modified TEG c Heparin added to prevent thrombin activity.

• Then add ADP or Arachidonic Acid to determine the contribution of the ADP & TxA2 receptors.

• Correlates well with the unwieldy standard of Light Transmission Aggregometry.

Mylotte D, et al. Cardiovasc Hematolog Agents Med Chem 2011; 9:14-24Agarwal S, et al. Anesthesiology 2006; 105:676-83

Platelet Mapping

Platelet Mapping

Wohlauer MV, Moore EE, et al. J Am Coll Surg 2012; 214: 739-46Agarwal S, et al. Anesthesiology 2006; 105:676-83

Minimal Platelet Inhibition: - minimal risk of bleeding - ischemia risk

Severe Platelet Inhibition: - risk of bleeding - minimal ischemia risk

Platelet Mapping

>50% Inhibition Response30-50% Inhibition Partial Response< 30% Inhibition Lack of Response

Agarwal S, et al. Anesthesiology 2006; 105:676-83

% Inhibition = 100 - [(MAADP or AA – MAFibrin) / (MAThrombin – MAFibrin) X 100]

TEG vs LTA vs PFA

65

60

Agarwal S, et al. Anesthesiology 2006; 105:676-83

91% Correlation between LTA & TEG

TEG vs LTA vs PFA

Agarwal S, et al. Anesthesiology 2006; 105:676-83

Preop Antiplatelet Assessment

• Current Anesthesia Policy at U of Wales:

• “Allows for informed rather than empirical platelet transfusions.”

- < 30% Platelet inhibition: proceed with surgery

- > 30% Platelet Inhibition: wait or administer platelets

Kauer J, et al. British J Anaesthesia; 2009; 103:304-5

Post PCI

J Am Coll Cardiol 2005; 46:1820-6

(n 38) (n 154)

Post PCI

Gurbel PA, et al. J Am Coll Cardiol 2005; 46:1820-6

Clinical Utility of TEG

• Direct resuscitation of severely injured pts

• Guide anticoagulation therapy

• Guide anti-platelet therapy