Download - THROMBOELASTOGRAPHY FOR CARDIAC SURGEONS
THROMBOELASTOGRAPHY FOR CARDIAC SURGEONS
Andrew RonaldConsultant Cardiac Anaesthetist
Aberdeen Royal Infirmary,Aberdeen, UK
THROMBOELASTOGRAPHY
•What is Thromboelastography?
•Where does it “fit into” our usual coagulation monitoring and what (if any) new information does it give us
•Why is it useful in Cardiac Surgery?
WHAT IS THROMBOELASTOGRAPHY
Functional Description
Thromboelastography monitors the thrombodynamic
properties of blood as it is induced to clot under a low
shear environment resembling sluggish venous flow. The
patterns of change in shear-elasticity enable the
determination of the kinetics of clot formation and growth
as well as the strength and stability of the formed clot.
The strength and stability of the clot provide information
about the ability of the clot to perform the work of
haemostasis, while the kinetics determine the adequacy
of quantitative factors available to clot formation
THROMBOELASTOGRAPHYSo what does it do?
•Clot formation
•Clot kinetics
•Clot strength & stability
•Clot resolution
THROMBOELASTOGRAPHYBasic Principles
• Heated (37C) oscillating cup
• Pin suspended from torsion wire into blood
• Development of fibrin strands “couple” motion of cup to pin
• “Coupling” directly proportional to clot strength
• tension in wire detected by EM transducer
THROMBOELASTOGRAPHYBasic Principles
• Electrical signal amplified to create TEG trace
• Result displayed graphically on pen & ink printer or computer screen
• Deflection of trace increases as clot strength increases & decreases as clot strength decreases
THROMBOELASTOGRAPHYRefinements to Technique
TEG accelerants / activators / modifiers• Celite / Kaolin / TF accelerates initial coagulation
• Reopro (abciximab) blocks platelet component of coagulation
• Platelet mapping reagents modify TEG to allow analysis of Aspirin / Clopidigrol effects
Heparinase cups• Reverse residual heparin in sample• Use of paired plain / heparinase cups allows
identification of inadequate heparin reversal or sample contamination
THROMBOELASTOGRAPHY
Where does the TEG fit into coagulation monitoring and
what new information does it give us?
COAGULATION MONITORINGWhat is coagulation?
COAGULATION MONITORINGConventional tests
Tests of coagulation• Platelets
• number• function
• Clotting studies• PT• APTT• TCT
• Fibrinogen levels
Tests of fibrinolysis• Degradation
products
The TEG gives us dynamic information on all aspects of
conventional coagulation monitoring
THROMBOELASTOGRAPHYSample display
THROMBOELASTOGRAPHYThe “r” time
r time•represents period of time of latency from start of test to initial fibrin formation
•in effect is main part of TEG’s representation of standard”clotting studies”
•normal range• 15 - 23 mins (native blood)• 5 - 7 mins (kaolin-
activated)
THROMBOELASTOGRAPHYWhat affects the “r” time?
r time by• Factor deficiency • Anti-coagulation• Severe
hypofibrinogenaemia
• Severe thrombocytopenia
r time by• Hypercoagulabil
ity syndromes
THROMBOELASTOGRAPHYThe “k” time
k time•represents time taken to achieve a certain level of clot strength (where r time = time zero ) - equates to amplitude 20 mm
•normal range• 5 - 10 mins (native blood)
• 1 - 3 mins (kaolin-
activated)
THROMBOELASTOGRAPHYWhat affects the “k” time?
k time by• Factor deficiency • Thrombocytopeni
a• Thrombocytopath
y• Hypofibrinogenae
mia
k time by• Hypercoagulabil
ity state
THROMBOELASTOGRAPHYThe “” angle
angle•Measures the rapidity of fibrin build-up and cross-linking (clot strengthening)•assesses rate of clot formation
•normal range• 22 - 38 (native blood)• 53 - 67(kaolin-
activated)
THROMBOELASTOGRAPHYWhat affects the “” angle?
Angle by• Hypercoagulabl
e state
Angle by• Hypofibrinogenem
ia• Thrombocytopeni
a
THROMBOELASTOGRAPHYThe “maximum amplitude” (MA)
Maximum amplitude •MA is a direct function of the maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa and represents the ultimate strength of the fibrin clot
•Correlates to platelet function• 80% platelets• 20% fibrinogen
•normal range• 47 – 58 mm (native blood)• 59 - 68 mm (kaolin-activated)• > 12.5 mm (ReoPro-blood)
THROMBOELASTOGRAPHYWhat affects the “MA” ?
MA by• Hypercoagulabl
e state
MA by• Thrombocytopenia• Thrombocytopathy• Hypofibrinogenem
ia
THROMBOELASTOGRAPHYFibrinolysis
LY30•measures % decrease in amplitude 30 minutes post-MA
•gives measure of degree of fibrinolysis
•normal range• < 7.5% (native blood)• < 7.5% (celite-activated)
•LY60• 60 minute post-MA data
THROMBOELASTOGRAPHYOther measurements of
Fibrinolysis
A30 (A60)• amplitude at 30 (60) mins post-MA
EPL•earliest indicator of abnormal lysis
•represents “computer prediction” of 30 min lysis based on interrogation of actual rate of diminution of trace amplitude commencing 30 secs post-MA
•early EPL>LY30 (30 min EPL=LY30)•normal EPL < 15%
THROMBOELASTOGRAPHYWhat measurements are affected by
fibrinolysis?
Fibrinolysis leads to: LY30 / LY60 EPL A30 / A60
THROMBOELATOGRAPHYQuantitative analysis
• Clot formation– Clotting factors - r, k times
• Clot kinetics– Clotting factors - r, k times– Platelets - MA
• Clot strength / stability– Platelets - MA– Fibrinogen - Reopro-mod MA
• Clot resolution– Fibrinolysis - LY30/60; EPL A30/60
THROMBOELATOGRAPHYQualitative analysis
TEG v CONVENTIONAL STUDIES
Conventional tests• test various parts of coag
cascade, but in isolation• out of touch with current
thoughts on coagulation• plasma tests may not be
accurate reflection of what actually happens in patient
• difficult to assess platelet function
• static tests• take time to complete
best guess or delay treatment
TEG• global functional
assessment of coagulation / fibrinolysis
• more in touch with current coagulation concepts
• use actual cellular surfaces to monitor coagulation
• gives assessment of platelet function
• dynamic tests• rapid results rapid
monitoring of intervention
Advantages of TEG over conventional coagulation
monitoring
• It is dynamic, giving information on entire coagulation process, rather than on isolated part
• It gives information on areas which it is normally difficult to study easily – fibrinolysis and platelet function in particular
• Near-patient testing means results are rapid facilitating appropriate intervention
• It is cost effective compared to conventional tests
THROMBOELATOGRAPHYWhy might it have a role in Cardiac
Surgery?
Because patients bleed postoperatively
It is often difficult to identify exactly why they are bleeding
BLEEDING IS A PROBLEM IN IN CARDIAC SURGERY
• Why do patients bleed postoperatively?
• Can we do anything to prevent/minimize this blood loss
• How is the bleeding patient managed conventionally?
– what factors may force us to readdress this
• How can the TEG change the way we manage the bleeding patient?
• (Does use of the TEG improve patient care?)
WHY DO PATIENTS BLEED AFTER CARDIAC SURGERY?
• Preoperative & pre-CPB factors
• CPB factors
• Post-CPB factors
• Surgical Bleeding
POSTOPERATIVE BLEEDINGPreoperative / Pre-CPB factors
•Aspirin &/or Clopidigrol - anti-platelet effects
•Reopro - abciximab; anti GpIIb/IIIa agent
•Warfarin / Heparin anticoagulation
•Pre-existing clotting factor &/or platelet abnormalities
POSTOPERATIVE BLEEDINGCPB factors
•Decreased platelet count
•Heparin effect
•Alien contact
POSTOPERATIVE BLEEDINGPost-CPB factors
•Reversal of heparin
•Non-functional platelet
•Fibrinolysis
POSTOPERATIVE BLEEDINGSurgical factors
•Type of Surgery•complicated surgery• redo surgery
•Cardiac surgery can be bloody!•Big pipes, big holes, big vessels
• Blood and Surgery• Lung of pig, Pancreas of cow, Sperm of
salmon• Foreign surfaces & cellular trauma • Drug effects• Thrombin activation• Non-functional Platelets• Altered blood flow• Abnormal Coagulation & Fibrinolysis• Inflammatory response to CPB
WHY DO PATIENTS BLEED AFTER CARDIAC SURGERY?
HOW DO PATIENTS EVER CLOT AFTER CARDIAC SURGERY?
CAN WE DO ANYTHING TO PREVENT OR MINIMISE THIS
BLOOD LOSS?
• Stop Aspirin / Clopidigrol
• Use of anti-fibrinolytics
• “Cell-salvage” techniques
• Surgical technique
• Blood Component therapy
HOW DO CARDIAC SURGEONS TREAT POSTOPERATIVE
BLEEDING?
• More Stitches / Surgicell / topical haemostatic agents
• More Protamine • Tranexamic acid • Aprotinin /Aprotinin infusion• Platelets• FFP• “Coagulation factor crash packs”• Blood• More Protamine• More Platelets & FFP +/- Cryoprecipitate• Reopening (5% nationally; 3.5% in ARI)
PROBLEMS ASSOCIATED WITH BLOOD & BLOOD PRODUCT USAGE
IN CARDIAC SURGERY
• Drain on donor pool• supply v demand
• Financial consequences• direct and indirect
• Patient consequences• “Hazards of Transfusion”
• Infective / Immunogenic / Thrombogenic problems
• “Other” problems• Patients don’t want it
Can we rationalize usage of blood & blood products in Cardiac Surgery but still ensure the right patient gets the
right component he really needs at the right time
We need to move away from the
traditional “carpet bombing” of the coagulation system in the bleeding
postoperative cardiac surgical patient with all its associated risks towards a more “targeted” clinical therapeutic
approach?
Can we use the TEG to facilitate and support this change in the management of
the bleeding patient?
We know the problems
• Bloody surgery• Anticoagulants
• Abnormal platelet function
• Damaged / ineffective platelets
• Abnormal fibrinolysis
Can the TEG help us?• Clot formation
• Clotting factors
• Clot kinetics• Clotting factors• Platelets
• Clot strength & stability
• Platelets
• Clot resolution• Fibrinolysis
CLINICAL STUDIES OF TEG USE IN CARDIAC SURGERY
• Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Shore-Lesserson, Manspeizer HE, DePerio M et alAnesth Analg 1999; 88 : 312-9
• Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypass. von Kier S, Royston DBr J Anaesthesia 2001 ; 86 : 575-8
Thromboelastography-guided transfusion algorithm reduces transfusions in complex
cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 :
312-9• Prospective blinded RCT
• Patients randomized to either routine transfusion practice or TEG-guided transfusion therapy for post-cardiac surgery bleeding
• Inclusion surgery types• single / multiple valve replacement• combined CABG + valve surgery• cardiac reoperation• thoracic aortic surgery
• Standard anaesthetic / CPB management• routine use of EACA
Thromboelastography-guided transfusion algorithm reduces transfusions in complex
cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 :
312-9
• Surgeon / Anaesthetist “blinded” to group - TEG / coag results reviewed by independent investigator who then instructed clinicians what to give
• Data collection• Coagulation studies and TEG data appropriate to
each group• Multiple time point assessment of
• Transfusion requirements• FFP requirements• platelet transfusion requirements• Mediastinal tube drainage (MTD)
Thromboelastography-guided transfusion algorithm reduces transfusions in complex
cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 :
312-9
Routine transfusion groupCoagulation tests taken after Protamine administration used to direct transfusion therapy in presence of bleeding
Transfused when Hct <25% (<21% on CPB)
Thromboelastography-guided transfusion algorithm reduces transfusions in complex
cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 :
312-9
TEG-guided groupPlatelet count + Celite & TF-activated TEG’s with heparinase modification taken at rewarm on CPB (36C) - result used to order blood products from lab
TEG samples run after Protamine administration (celite & TF activated plus paired plain / heparinase cups) used to direct actual transfusion therapy (in the presence of bleeding)
Transfused when Hct <25% (<21% on CPB)
Thromboelastography-guided transfusion algorithm reduces transfusions in complex
cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 :
312-9
Routine transfusion group52 patients
31/52 (60%) received blood
16/52 (31%) received FFP
15/52 (29%) received Platelets
TEG-guided group53 patients
22/53 (42%) received blood(p=0.06)
4/53 (8%) received FFP(p=0.002)(p<0.04 for FFP volume)
7/53 (13%) received Platelets (p<0.05)
MTD no statistical difference
Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 :
575-8
• Study design• 2 groups of 60 patients
• Group 1 - conventional v retrospective TEG-predicted therapy• Group 2 - prospective RCT - clinician-guided v TEG-guided
• Complex surgery• transplants• multiple valve / valve + revascularisation• multiple revascularisation with CPB > 100 mins
• Outcomes• FFP usage• Platelet usage• Mediastinal tube drainage (MTD)
Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 :
575-8Group 1Microvascular bleeding managed conventionally using
standard coag tests• Microvascular bleeding
• Blood loss > 400ml in first hour• Blood loss > 100ml/hr for 4 consecutive hours
• Triggers to treat• PT & / or APTT ratio >1.5 x normal• Platelet count < 50,000 /dl• Fibrinogen concentration < 0.8 mg/dl• Patients who returned to theatre (3) “replaced” by
additional pts
Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 : 575-
8
Group 1Predicted transfusion requirements using TEG algorithm • Retrospective analysis of TEG data at PW (post-warm)
sample point
Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 :
575-8
Group 1 - conventional therapy60 patients
22/60 given blood component therapy
Actual usage38 units FFP
17 units Platelets
Group 1 - TEG predicted therapy60 patients
7/60 predicted to need component therapy(p<0.05)
Predicted usage6 units FFP
2 units Platelets(p<0.05)
Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 :
575-8
Group 2• Prospective RCT arm of study
• 60 patients randomly allocated to one of two groups• Clinician-directed therapy
• products given for bleeding as judged clinically by clinical team responsible for case
• TEG algorithm-directed therapy• products given for bleeding as directed by
TEG-driven protocol
• Patients who returned to theatre for bleeding (1 in each group) were “replaced” with additional patients
Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 :
575-8
Sampling protocol • all celite-activated heparinase modified samples
• Baseline (BL)• Post-warm (PW)• Post-protamine (PP) + celite-activated plain sample
TEG treatment algorithmr>7 min but <10.5 min mild clotting factors 1 FFPr>10.5 min but <14 min mod clotting factors 2 FFP r>14min severe clotting factors 4 FFPMA<48mm mod in platelet no / function 1 platelet poolMA<40mm severe in platelet no / function 2 platelets
poolsLY30 >7.5% fibrinolysis Aprotinin
Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary
Bypassvon Kier S, Royston D, Br J Anaesthesia 2001 ; 86 :
575-8
Group 2 - Clinician-directed30 patients
10/30 received blood component therapy
16 units FFP
9 units Platelets
12 hour MTD losses [median (lower & upper quartile)]390 (240, 820)
Group 2 - TEG directed30 patients
5/30 given blood component therapy(p<0.05)
5 units FFP
1 unit Platelets(p<0.05)
12 hour MTD losses [median (lower & upper quartile)]470 (295, 820)
(NS)
There appears to be good clinical evidence that TEG can guide
therapy and decrease our blood product usage
TEG studies - caveats
• studies looked at wide range of procedures & patient management - difficult to extrapolate study findings to all units
• considerable variability in pre-study management across units
• concomitant introduction of postoperative transfusion protocols at same time as TEG may cloud TEG outcomes
• variability in TEG-guided protocols and sources of derived data- what exactly is normal in post-cardiac surgery population?
• by its very nature use of TEG facilitates early intervention, whereas use of conventional tests delays intervention. Is this enough in itself to explain apparent differences?
THROMBOELASTOGRAPHY
How do I use it?
THROMBOELASTOGRAPHY IN PRACTICE
Sampling protocol • all kaolin-activated heparinase modified
samples– Baseline (BL)– Post-warm (PW)– Post-protamine (PP) + kaolin-activated
plain sample
– further paired CITU samples for bleeding if required
Is the patient bleeding?• Check samples running / already run = PW, PP, CITU • “Eyeballing” of trends
PP r-Plain > r-Heparinase Inadequate heparin reversal Protaminer>9-10 min clotting factors FFPMA<48mm platelet no / function PlateletsLY30 >7.5% (or EPL > 15%) Hyperfibrinolysis Antifibrinolytic
Still bleeding?• repeat TEG
• still abnormal further factors as indicated• normal consider surgical bleeding
Thromboelastography in practiceResidual Heparin
Thromboelastography in practiceLong r time - clotting factor deficiency
Thromboelastography in practiceLow MA - Platelet dysfunction
Thromboelastography in practiceFibrinolysis
THROMBOELASTOGRAPHYSummary
• Thromboelastography (TEG) provides near-patient, real-time, dynamic measurements of coagulation and fibrinolysis
• It is ideally designed to provide useful information amidst the cauldron of factors which contribute to post-cardiac surgical bleeding
• Use of TEG to drive post-cardiac surgery protocols for management of bleeding has been shown to be cost-effective and will decrease the patient’s exposure to blood and blood component therapy with its concomitant well-documented risks
• Appropriate use of TEG can result in genuine cost savings in Cardiac Surgery patients
Quand on ne sait pas, on a peur
When you don’t know, you are afraid
TEG=Clotting knowledge