THROMBOELASTOGRAPHY

1. G.K.Kumar THROMBOELASTOGRAPHY

2. 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? THROMBOELASTOGRAPHY

3. TEG was developed by Hartert in 1948 Thromboelastogradphy originally monitors the thrombodynamic properties of blood as it is induced to clot under a low shear environment resembling sluggish venous flow. This 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-Functional Description

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

5. THROMBOELASTOGRAPHY-Basic 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

6. 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

7. 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- Refinements to Technique

8. Where does the TEG fit into coagulation monitoring and what new information does it give us? THROMBOELASTOGRAPHY

9. What is coagulation?

10. COAGULATION MONITORING-Conventional tests Tests of coagulation • Platelets • number • function • Clotting studies • PT • APTT • TCT • Fibrinogen levels Tests of fibrinolysis • Degradation products

11. The TEG gives us dynamic information on all aspects of conventional coagulation monitoring

12. THROMBOELASTOGRAPHY - Sample display

13. 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)

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

15. 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)

16. What affects the “k” time? k time  by • Factor deficiency • Thrombocytopenia • Thrombocytopathy • Hypofibrinogenaemia k time  by • Hypercoagulability state

17. The “” 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)

18. What affects the “” angle?  Angle  by • Hypercoagulable state  Angle  by • Hypofibrinogenemia • Thrombocytopenia

19. The “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)

20. What affects the “MA” ? MA  by • Hypercoagulable state MA  by • Thrombocytopenia • Thrombocytopathy • Hypofibrinogenemia

21. Fibrinolysis 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

22. Other 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%

23. What measurements are affected by fibrinolysis? Fibrinolysis leads to: •  LY30 /  LY60 •  EPL •  A30 /  A60

24. 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 - LY30/60; EPL A30/60

25. Qualitative analysis

26. 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

27. 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 Advantages of TEG over conventional coagulation monitoring

28. Because patients bleed postoperatively It is often difficult to identify exactly why they are bleeding THROMBOELATOGRAPHYWhy might it have a role in Surgery?

29. 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?) BLEEDING IS A PROBLEM IN SURGERY?

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

31. Decreased platelet count • Heparin effect • Alien contact POSTOPERATIVE BLEEDING Intraop factors

32. Reversal of heparin • Non-functional platelet • Fibrinolysis POSTOPERATIVE BLEEDING Postop factors

33. Type of Surgery • complicated surgery • redo surgery • Cardiac surgery can be bloody! • Big pipes, big holes, big vessels POSTOPERATIVE BLEEDINGSurgical factors

34. 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

35. Stop Aspirin / Clopidigrol • Use of anti-fibrinolytics • “Cell-salvage” techniques • Surgical technique • Blood Component therapy CAN WE DO ANYTHING TO PREVENT OR MINIMISE THIS BLOOD LOSS?

36. 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 HOW DO TREAT POSTOPERATIVE BLEEDING?

37. 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 PROBLEMS ASSOCIATED WITH BLOOD & BLOOD PRODUCT USAGE

40. 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? 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

41. 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

42. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Shore-Lesserson, Manspeizer HE, DePerio 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 CLINICAL STUDIES OF TEG USE IN CARDIAC SURGERY

43. 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

44. 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

45. 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)

46. 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 & 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)

47. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery Shore-Lesserson et al, Anesth Analg 1999; 88 : 312-9 Routine transfusion group 52 patients 31/52 (60%) received blood 16/52 (31%) received FFP 15/52 (29%) received Platelets TEG-guided group 53 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

48. 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 : 575-8

49. Group 1 Microvascular 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

50. 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 Bypassvon Kier S, Royston D,Br J Anaesthesia 2001 ; 86 : 575-8