THROMBOELASTOGRAPHY FOR CARDIAC SURGEONS Andrew Ronald Consultant Cardiac

THROMBOELASTOGRAPHY FOR CARDIAC SURGEONS Andrew Ronald Consultant Cardiac Anaesthetist Aberdeen Royal Infirmary, Aberdeen, UK alronald@tiscali. co. 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

THROMBOELASTOGRAPHY So what does it do? • Clot formation • Clot kinetics • Clot strength & stability • Clot resolution

THROMBOELASTOGRAPHY Basic Principles • Heated (37 C) 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

THROMBOELASTOGRAPHY Basic 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

THROMBOELASTOGRAPHY Refinements 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 MONITORING What is coagulation?

COAGULATION MONITORING Conventional 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

THROMBOELASTOGRAPHY Sample display

THROMBOELASTOGRAPHY The “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)

THROMBOELASTOGRAPHY What affects the “r” time? r time by • Factor deficiency • Anti-coagulation • Severe hypofibrinogenaemia • Severe thrombocytopenia r time by • Hypercoagulability syndromes

THROMBOELASTOGRAPHY The “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)

THROMBOELASTOGRAPHY What affects the “k” time? k time by • Factor deficiency • Thrombocytopenia • Thrombocytopathy • Hypofibrinogenaemia k time by • Hypercoagulability state

THROMBOELASTOGRAPHY The “ ” 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)

THROMBOELASTOGRAPHY What affects the “ ” angle? Angle by • Hypercoagulable state Angle by • Hypofibrinogenemia • Thrombocytopenia

THROMBOELASTOGRAPHY The “maximum amplitude” (MA) Maximum amplitude 1. 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 2. Correlates to platelet function 1. 80% platelets 2. 20% fibrinogen 3. normal range 1. 47 – 58 mm (native blood) 2. 59 - 68 mm (kaolin-activated) 3. > 12. 5 mm (Reo. Pro-blood)

THROMBOELASTOGRAPHY What affects the “MA” ? MA by • Hypercoagulable state MA by • Thrombocytopenia • Thrombocytopathy • Hypofibrinogenemia

THROMBOELASTOGRAPHY Fibrinolysis LY 30 • measures % decrease in amplitude 30 minutes post-MA • gives measure of degree of fibrinolysis • normal range • < 7. 5% (native blood) • < 7. 5% (celite-activated) • LY 60 • 60 minute post-MA data

THROMBOELASTOGRAPHY Other measurements of Fibrinolysis A 30 (A 60) • 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>LY 30 (30 min EPL=LY 30) • normal EPL < 15%

THROMBOELASTOGRAPHY What measurements are affected by fibrinolysis? Fibrinolysis leads to: • LY 30 / LY 60 • EPL • A 30 / A 60

THROMBOELATOGRAPHY Quantitative 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 - LY 30/60; EPL A 30/60

THROMBOELATOGRAPHY Qualitative 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

THROMBOELATOGRAPHY Why 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 • Post-CPB factors • Surgical Bleeding

POSTOPERATIVE BLEEDING Preoperative / Pre-CPB factors • Aspirin &/or Clopidigrol - anti-platelet effects • Reopro - abciximab; anti Gp. IIb/IIIa agent • Warfarin / Heparin anticoagulation • Pre-existing clotting factor &/or platelet abnormalities

POSTOPERATIVE BLEEDING CPB factors • Decreased platelet count • Heparin effect • Alien contact

POSTOPERATIVE BLEEDING Post-CPB factors • Reversal of heparin • Non-functional platelet • Fibrinolysis

POSTOPERATIVE BLEEDING Surgical 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 Can the TEG help us? • Clot formation • Clotting factors • Clot kinetics • Clotting factors • Platelets • Damaged / ineffective platelets • Clot strength & stability • Platelets • Abnormal fibrinolysis • 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, De. Perio M et al Anesth Analg 1999; 88 : 312 -9 • Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypass. von Kier S, Royston D Br 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 group Coagulation 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 group Platelet count + Celite & TFactivated TEG’s with heparinase modification taken at rewarm on CPB (36 C) - 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 group TEG-guided group 52 patients 53 patients 31/52 (60%) received blood 22/53 (42%) received blood (p=0. 06) 16/52 (31%) received FFP 4/53 (8%) received FFP (p=0. 002) (p<0. 04 for FFP volume) 15/52 (29%) received Platelets 7/53 (13%) received Platelets (p<0. 05) MTD no statistical difference

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypass von 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 Bypass von Kier S, Royston D, Br J Anaesthesia 2001 ; 86 : 575 -8 Group 1 Microvascular bleeding managed conventionally using standard coag tests • Microvascular bleeding • Blood loss > 400 ml in first hour • Blood loss > 100 ml/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 Bypass von Kier S, Royston D, Br J Anaesthesia 2001 ; 86 : 575 -8 Group 1 Predicted 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 Bypass von Kier S, Royston D, Br J Anaesthesia 2001 ; 86 : 575 -8 Group 1 - conventional therapy 60 patients Group 1 - TEG predicted therapy 60 patients 22/60 given blood component therapy 7/60 predicted to need component therapy (p<0. 05) Actual usage 38 units FFP Predicted usage 6 units FFP 17 units Platelets 2 units Platelets (p<0. 05)

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypass von 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 TEGdriven 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 Bypass von 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 algorithm r>7 min but <10. 5 min r>10. 5 min but <14 min r>14 min MA<48 mm MA<40 mm LY 30 >7. 5% mild clotting factors mod clotting factors severe clotting factors mod in platelet no / function severe in platelet no / function fibrinolysis 1 FFP 2 FFP 4 FFP 1 platelet pool 2 platelets pools Aprotinin

Reduced Hemostatic Factor Transfusion using Heparinase Modified TEG during Cardiopulmonary Bypass von Kier S, Royston D, Br J Anaesthesia 2001 ; 86 : 575 -8 Group 2 - Clinician-directed 30 patients Group 2 - TEG directed 30 patients 10/30 received blood component therapy 16 units FFP 5/30 given blood component therapy (p<0. 05) 5 units FFP 9 units Platelets 1 unit Platelets (p<0. 05) 12 hour MTD losses [median (lower & upper quartile)] 390 (240, 820) 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 datawhat 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 Protamine r>9 -10 min clotting factors FFP MA<48 mm platelet no / function Platelets LY 30 >7. 5% (or EPL > 15%) Hyperfibrinolysis Antifibrinolytic Still bleeding? • repeat TEG • still abnormal further factors as indicated • normal consider surgical bleeding

Thromboelastography in practice Residual Heparin

Thromboelastography in practice Long r time - clotting factor deficiency

Thromboelastography in practice Low MA - Platelet dysfunction

Thromboelastography in practice Fibrinolysis

THROMBOELASTOGRAPHY Summary • Thromboelastography (TEG) provides near-patient, realtime, 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 costeffective and will decrease the patient’s exposure to blood and blood component therapy with its concomitant welldocumented 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