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Thrombelastograph® (TEG®) Overview
Laurel Omert MD, FACSMedical Director
Haemostasis Management
Copyright © 2009 Haemonetics Corp.
Objectives
Is there a need for TEG?How does it work?
Copyright © 2009 Haemonetics Corp.
Clinical Practice: A Constant Struggle……
BleedingThrombosis
Balance
Copyright © 2009 Haemonetics Corp.
Upsetting the Balance
• Surgery• Devices – LVADs, CPB, ECMO
• Trauma• Drugs• Stents• Flights – DVT• Smoking
Plavix is a trademark of Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership.
Copyright © 2009 Haemonetics Corp.
Bleeding
Thrombosis
How do we know where we are?
Traditional hemostasis tests
TEG
Copyright © 2009 Haemonetics Corp.
Traditional Hemostasis Monitoring
Initiation
Platelet plug formsFibrin strands form
Clot grows
Maximum clot forms
Clot degradation takes over
Clot dissolvedDamage repaired
PT/INRPTT Bleeding
TimeD-dimer
FDP
Platelet Count ΣHemostatic
status
Traditional Hemostasis Tests
Do not define the overall process, just provide pieces of the process!
Copyright © 2009 Haemonetics Corp.
“Elevated activated partial thromboplastin time does not correlate with heparin rebound following surgery”
Teneja et al Can J Anesth 2009;56:7
Key pointNo relation between aPTTand anti-Xa activity following CPB
What does the literature say about traditional coagulation testing?
Copyright © 2009 Haemonetics Corp.
Editorial Response
Can J Anesth/J Can Anesth (2009) 56:478-482
EDITORIALS
A little coagulation knowledge can be dangerous!Bruce D. Spiess, MD
Key Question“Why do we persist in using the aPTT and PT tests when our cardiac textbooks teach that these tests do not predict bleeding?”
Copyright © 2009 Haemonetics Corp.
What happens in the ICU?
Prevalence, management, and outcomes of critically ill patients with prothrombin time prolongation in the UK intensive care units
Continuing Medical Education ArticleCritical Care Medicine 2010
Timothy S. Walsh, MD; Simon J. Stanworth, MD; Robin J. Prescott, PhD; Robert J. Lee, MSc; Douglas M. Watson, MSc; Duncan Wyncoll, FRCA; Writing Committee of the Intensive Care Study of Coagulopathy (ISOC) Investigators
Key points1. 30% have abnormal INR2. Associated with greater ICU mortality3. Clinical uncertainty in how to treat
Copyright © 2009 Haemonetics Corp.
Editorial Response
Prolongation of prothrombin time in the critically ill: Is it time for decisive action?
Critical Care Medicine 2010 Vol. 38, No 10
Balraj Appadu, MD, FRCA; Peterborough, UK
Key points• Coagulation tests such as PT and aPTT poorly reflect
in vivo hemostasis• A better approach to individual bleeding risk should
be sought; newer global tests of hemostasis such as the thromboelastogram….have been effective in guiding transfusion therapy in the surgical setting.
Copyright © 2009 Haemonetics Corp.
Hemostasis Monitoring with the TEG System
• Rate of clot formation
• Strength of clot
• Stability of clotΣ Hemostatic
status
Measures entire clotting process
Measures: ∆Clot strength / time (min)
Copyright © 2009 Haemonetics Corp.
TEG Analyzer:Mechanics of Sample Measurement
Copyright © 2009 Haemonetics Corp.
TEG® 5000 AnalyzerTest Simulation
Copyright © 2009 Haemonetics Corp.
TEG Tracing and Clotting Process
Continuous monitoring of clotting processGenerates 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)
Copyright © 2009 Haemonetics Corp.
TEG Parameters: K and angle (α)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)↓ α (deg)
↓ K (min)↑ α (deg)
↑ K (min)↓ α (deg)
↓ K (min)↑ α (deg)
Clot rate
Fibrin meshFibrin platelet
Coag pathwaysplatelets
K
α
Clot rate
Fibrin meshFibrin platelet
Coag pathwaysplatelets
K
α
Dysfunction 4-8 min
α: Angle (47 - 74°)
K: Clot kinetics (0 - 4 min)
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)↓ α (deg)
↓ K (min)↑ α (deg)
↑ K (min)↓ α (deg)
↓ K (min)↑ α (deg)
↓ MA
↑ MA
↓ MA
↑ MA
Clot rate
Fibrin X-linkingFibrin platelet
Coag pathwaysplatelets
K
α
Clot rate
Fibrin X-linkingFibrin platelet
Coag pathwaysplatelets
K
α
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)
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)↓ α (deg)
↓ K (min)↑ α (deg)
↑ K (min)↓ α (deg)
↓ K (min)↑ α (deg)
↓ MA
↑ MA
↓ MA
↑ MA
Clot stability
Reduction in clot strength
Fibrinolysis
Clot stability
Reduction in clot strength
Fibrinolysis
Clot rate
Fibrin X-linkingFibrin platelet
Coag pathwaysplatelets
K
α
Clot rate
Fibrin X-linkingFibrin platelet
Coag pathwaysplatelets
K
α
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 – 8%)
Copyright © 2009 Haemonetics Corp.
For the non-verbal among us…….
Copyright © 2009 Haemonetics Corp.
TEG and Clot Morphology: What do all the letters really mean?
Panel I R timeFibrin and platelet filopods
Panel II,III, IV K time and alpha angleFibrin build-up and X-linking
Panel V MARBCs packed with fibrin strands
Panels VII-X Addition of Reopro
Electron Microscopic Evaluations of Clot Morphology During ThrombelastographyKawaski et al Anesthesia Analgesia 2004;99
Copyright © 2009 Haemonetics Corp.
TEG TechnologyBlood sample types
KaolinCaCl2
Kaolin
Activator
Clear15* – 120Lab
CK
Clear< 5POC
K
Cup & PinSample timing
(minutes)Sample type
(ST)
Copyright © 2009 Haemonetics Corp.
What else can TEG do?
Heparin reversalPlatelet inhibition (PlateletMapping ®)Functional fibrinogen assayFaster: (RapidTEG ™)
Copyright © 2009 Haemonetics Corp.
TEG Technology: Heparin reversal Blood sample types
KaolinCaCl2
Kaolin
Activator
Heparinase(blue)
15* – 120Lab
CKH
Heparinase(blue)/(6 IU)
< 5POC
KH
Cup & PinSample timing
(minutes)Sample type
(ST)
Copyright © 2009 Haemonetics Corp.
Testing for presence of heparin:Patient post-protamine and bleeding
Green = kaolin with heparinase (KH)Black = kaolin only (K)R value for KH = K
Suggests no heparin present
R value for KH < KSuggests presence of heparin
Copyright © 2009 Haemonetics Corp.
What else can TEG do?
Heparin reversalPlatelet inhibition (PlateletMapping ®) Functional fibrinogen assayFaster: (RapidTEG ™)
Copyright © 2009 Haemonetics Corp.
Conversation with my aunt
Aunt: Hi Laurel, you know the doctor put me on a new drug to help my heart beat called Plavix
Aunt: Well, whatever, it’s pink and I think it upsets my stomach.
Me: It doesn’t usually do that.
Me: You really shouldn’t do that.
Aunt: You know actually, I haven’t taken it since Saturday, I forgot yesterday because I went to the bridge game
Me: That was 3 days ago!
Me: Great, it’s really to keep your blood from clotting toprotect your heart….What dose are you taking, 75 mg?
Aunt: Well, that’s okay, I just don’t take it for a day or two if that happens. Yesterday I think I skipped it….
Copyright © 2009 Haemonetics Corp.
What is Plavix doing to our patients?
Journal of the American College of Cardiology (2007) 49:657- 666
Clinical Research Interventional Cardiology
Increased Risk in Patients with High Platelet AggregationReceiving Chronic Clopidogrel Therapy UndergoingPercutaneous Coronary InterventionKevin P. Bliden and Paul A. Gurbel MD
Key Facts1. 20% PCI patients have recurrent
ischemic/thrombotic events2. Variation in platelet aggregation due to ADP
stimulation was ~60%
Copyright © 2009 Haemonetics Corp.
Plavix and the Black Box
Effectiveness of Plavix depends on activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. Patients with variants in cytochrome P-450 2C19 (CYP2C19) have:
Lower levels of the active metabolite of clopidogrel, Less inhibition of platelets3.58 times greater risk for major adverse cardiovascular events such as death, heart attack, and stroke Risk is greatest in CYP2C19 poor metabolizers.
Copyright © 2009 Haemonetics Corp.
Ideal Clot = Fibrin mesh + Platelets
Fibrin – strands formed from biochemical reactions in the bloodPlatelet – cellular element in blood
Platelets
Fibrin
Copyright © 2009 Haemonetics Corp.
Assessing specific platelet function with PlateletMapping
Thrombin-induced platelet contribution (MAT)
Clot without platelets (MAA)
1. Define overall platelet contribution to clot strength2. Define clot without platelets
Copyright © 2009 Haemonetics Corp.
Assessing specific platelet function with PlateletMapping
Clot without platelets (MAA)
Agonist-induced platelet contribution (MAADP)
3. Define effect of agonist on platelet contribution to clot strength
ADP (Plavix ® )AA (Aspirin)
Copyright © 2009 Haemonetics Corp.
Assessing specific platelet function with PlateletMapping: Let’s subtract
Copyright © 2009 Haemonetics Corp.
PlateletMapping in non-emergent PCI:Patients receiving ASA and Plavix
Adenosine diphosphate-induced platelet-fibrin clot strength: A new thromboelastographic indicaton of long-term post-stentingischemic events
Interventional Cardiology
Paul A. Gurbel, MD; Kevin P. Bliden, BS, Irene A. Navickas, BS; et al
Key points1. Therapeutic range for MAADP = 31- 47 2. TEG can serve to personalize
antiplatelet treatment to reduce ischemic events and bleeding
American Heart Journal 2010
Copyright © 2009 Haemonetics Corp.
Personalized Platelet Analysis
Patient A: 50% platelet inhibition does not provide sufficient reduction of the risk of a thrombotic or ischemic eventPatient B: 50% platelet inhibition provides antithrombotic protection without risk of bleedingPatient C: 50% platelet inhibition increases risk of bleeding
Copyright © 2009 Haemonetics Corp.
What else can TEG do?
Heparin reversalPlatelet inhibition (PlateletMapping®)Functional fibrinogen assayFaster: (RapidTEG ™)
Copyright © 2009 Haemonetics Corp.
Functional fibrinogen
Used for determination of fibrinogen levelPartitions clot strength into two components
Contribution of platelets (MAP)Contribution of fibrin (MAFF)
Platelets
Fibrin
MA = MAP + MAFF
Copyright © 2009 Haemonetics Corp.
Functional fibrinogen
MA = 47 (low)MAFF = 6.3 (low)
Patient may benefit from FFP, cryoprecipitate or fibrinogen concentrate (Haemocomplettan®)
Copyright © 2009 Haemonetics Corp.
What else can TEG do?
Heparin reversalPlatelet inhibition (PlateletMapping®)Functional fibrinogen assayFaster: (RapidTEG ™)
Copyright © 2009 Haemonetics Corp.
RapidTEG
Kaolin +TF15* – 120Lab
CK
Kaolin +TF< 5POC
K
ActivatorSample timing
(minutes)Sample type
Copyright © 2009 Haemonetics Corp.
A faster TEG assay; ACT in < 1 minuteActivates both extrinsic and intrinsic coagulation pathwaysCleared by FDA for ACT
RapidTEG (TEG ACT Test)
Copyright © 2009 Haemonetics Corp.
Tracing Comparison
Standard TEG
RapidTEG
Copyright © 2009 Haemonetics Corp.
Case # 1 - Resuscitation
46 year old status post MCC, arrived in the ED pulselessdue to profound hemorrhagic shock*
Copyright © 2009 Haemonetics Corp.
TEG # 1 Coagulopathic bleeding
Treatment: Amicar (and other products)
TEG (White): Primary fibrinolysis
Copyright © 2009 Haemonetics Corp.
TEG # 2 Coagulopathic bleeding slows
TEG (Green): Primary fibrinolysis improving
Copyright © 2009 Haemonetics Corp.
TEG # 3 Coagulopathic bleeding stops
TEG (Pink): Normal
Copyright © 2009 Haemonetics Corp.
Patient Profile
ISS 25
RBC 0-6 hrs 23
FFP 0-6 hrs 12
PLT 0-6 hrs 2
Cryo 0-6 hrs 4
pH in ED 7.08
Temp in ED (C ) 34.7
Copyright © 2009 Haemonetics Corp.
Case # 1 – Recovery
Pre-op
Post-op pelvic fracture stabilization
Copyright © 2009 Haemonetics Corp.
The hypercoagulable side…..
Copyright © 2009 Haemonetics Corp.
TEG is not just for bleeding……
Thrombosis
Bleeding
Balance
Copyright © 2009 Haemonetics Corp.
Why do some (2-22%) patients on “DVT prophylaxis” get VTE?
Key point1. TEG R time differentiated enoxaparin
treated patients who developed DVT from those who did not
2. Antifactor Xa levels were not significantly different when comparing patients with DVT and without DVT
Copyright © 2009 Haemonetics Corp.
But what about the $$$$????
Anesthesia Analgesia (1999; 88:312-319)
Thromboelastography-Guided Transfusion Algorithm Reduces Transfusions in Complex Cardiac SurgeryLinda Shore-Lesserson MD, Heather E. Manspeizer MD, Marietta DePerio RN, Sanjeev Francis BS, Frances Vela-Cantos RN, and M. Arisan Ergin MD
Departments of Anesthesiology and Cardiothoracic Surgery, Mount Sinai Medical Center, New York, New York
ObjectiveProspective, randomized trial to compare bleeding and transfusion requirements in cardiac surgical patients at moderate to high risk of bleeding using a TEG-guided algorithm or standard laboratory coagulation testing.
Copyright © 2009 Haemonetics Corp.
Shore-Lesserson Data
Key points1. Less blood tx intraop, post op and ICU (NS)2. Volume of FFP tx significantly lower with TEG3. FFP tx to significantly lower proportion of patients4. Platelets tx to significantly lower proportion of patients
Copyright © 2009 Haemonetics Corp.
Our immediate goals…
Expand the use of TEG in cardiac surgeryFind the TEG “niche” in trauma /critical care
Copyright © 2009 Haemonetics Corp.
Publications List
More than 3000 total publications.
Over 200 listed on our website.
Copyright © 2009 Haemonetics Corp.
Questions?
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?? ???? ??
? ? ?? ? ? ? ? ??
Copyright © 2009 Haemonetics Corp.
TEG in Cardiac Surgery
Causes of Bleeding after Cardiopulmonary Bypass
Common (95-99%)Defective surgical hemostasisAcquired transient platelet dysfunction
Less common (1-5%)Other platelet dysfunctionThrombocytopeniaVitamin K deficiencyDICInherited hemostatic defectsSystemic fibrinolysisHeparinProtamine excess
Modified from Woodman RC et al: Blood 76:1683, 1990
Copyright © 2009 Haemonetics Corp.
A faster TEG assayActivates both extrinsic and intrinsic coagulation pathwaysCleared by FDA for ACT
RapidTEG (TEG ACT Test)
Copyright © 2009 Haemonetics Corp.
TEG ACTCalculated parameter from RapidTeg Assay
Key points1. TEG ACT correlated with Hepcon and
Hemochron2. Less effect of hemodilution than
Hemochron3. ACT in < 1 minute
Copyright © 2009 Haemonetics Corp.
Hemochron vs. TEG® ACT
Comparison testing was done at 2 clinical sitesThe results demonstrate a strong correlation
Regression Analysis
y = 1.057x - 17.274r = 0.905
0
200
400
600
800
1000
1200
0 200 400 600 800 1000 1200
Hemochron ACT (sec)
TEG
AC
T (s
ec)
Copyright © 2009 Haemonetics Corp.
1. DVT occurs in ~60% untreated trauma patients, 1.13% of treated
2. In treated patients, incidence of pulmonary embolus is 0.45%*
3. VTE is 3rd most common cause of death in trauma patients; mortality rate is 8.9%
Three facts about DVT/PE
*2,332/519,268 ptsKnudson et al; UCSFASA 2011 data
Copyright © 2009 Haemonetics Corp.
TEG is not just for bleeding……
Thrombosis
Bleeding
Balance
Copyright © 2009 Haemonetics Corp.
TEG and ECMO and LVAD
PubMED Search over 10 years8 citations “thrombelastography and ECMO”
2 citations “thrombelastography and LVAD”
Copyright © 2009 Haemonetics Corp.
Thrombelastography and LVAD
Bleeding and thromboembolic complications are commonHigh shear rates cause platelet dyfunctionDysfunction resembles acquired von Willebrandsyndrome associated with formation of microaggregatesand bleedingCase study shows:
Hypercoagulability by ROTEM and PFA-100Hypocoagulability by routine coagsThrombus formation on cannula, so Plavix started
Steinlechner et al, Ann Thorac Surg 2009; 87(1)131Fries et al, Ann Thorac Surg 2003; 76(5)1593
Copyright © 2009 Haemonetics Corp.
BaselinePre ECMO
Copyright © 2009 Haemonetics Corp.
ECMO (1 Hour)
Copyright © 2009 Haemonetics Corp.
ECMO (2 Hour)
Copyright © 2009 Haemonetics Corp.
ECMO (4 Hour)
Copyright © 2009 Haemonetics Corp.
Plavix and the Black Box
WARNING: DIMINISHED EFFECTIVENESS IN POOR METABOLIZERSSee full prescribing information for complete boxed warning.
Effectiveness of Plavix depends on activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. (5.1)
Poor metabolizers treated with Plavix at recommended doses exhibit higher cardiovascular event rates following acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) than patients with
normal CYP2C19 function. (12.5)Tests are available to identify a patient's CYP2C19 genotype and can
be used as an aid in determining therapeutic strategy. (12.5)Consider alternative treatment or treatment strategies in patients
identified as CYP2C19 poor metabolizers. (2.3, 5.1)