Post on 12-Jan-2016
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