Blood Management Today Incorporating TEG

Blood Management Today Incorporating TEG AMSECT NABM meeting Mike Miller Manager Clinical Manager Hemostasis Training Haemonitics Rx Only 2011 Haemonetics Corporation. Haemonetics, TEG, RapidTEG and Thrombelastograph are trademarks or registered trademarks of Haemonetics Corporation in the USA, other countries, or both. PlateletMapping is a trademark of Cora Healthcare. Plavix is a registered trademark of Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. All other registered trademarks are the property of their respective owners. All rights reserved. TRN-PPT-100112-US(AA) Topics to Discuss Blood Management Today Traditional Hemostasis Case Study TEG Risk Stratification PlateletMapping Assay Case study Wrap up 2 2 2011 Haemonetics Corp

Blood Management Today A Common Goal 3 2011 Haemonetics Corp 4 2011 Haemonetics Corp

Observed variation in hospital-specific transfusion rates for primary isolated CABG surgery with cardiopulmonary bypass during 2008 (N = 798 sites) Bennett-Guerrero, et al. JAMA 2010; 304:1568-75 5 2011 Haemonetics Corp Almost 20 years ago, the study by Goodnough et al showed significant variability in transfusion practice in 540 patients who underwent cardiac surgery across 18 institutions and drew attention to this problem. 6 2011 Haemonetics Corp

TEG..is there a clinical need? ACS NSQIP 2005-2009 the American College of Surgeons National Surgical Quality Improvement Program 941,496 operations in 173 hospitals 15,186186 patients t received 1 unit of fintraoperative ti transfusion 55 variables used in propensity scoring 11,855 matched pairs Complication No Transfusion Transfusion P value Mortality % 5.2 6.1 0.005 Unless your patient is actively bleeding to death, it is simply best not to transfuse any blood products. Wound Problems 9.7 11.4 <0.001 John B. Holcomb, MD University of Texas Health Science Center % Pulmonary % 11.7 15.3 <0.001 Renal % 5.5 6.8 <0.001 Cardiac % 2.0 2.4 0.06 Sepsis % 8.2 10.6 <0.001 Postop LOS (days) 10.3 11.8 <0.001 Ferraris, VA, et al. Arch Surg 2012; 147:49-55 7 2011 Haemonetics Corp Traditional Hemostasis Current Coag Testing vs TEG 8 2011 Haemonetics Corp

What does the literature say about traditional coagulation testing? Elevated activated partial thromboplastin time does not correlate with heparin rebound following surgery Teneja et al Can J Anesth 2009;56:7 Key point No relation between aptt and anti-xa activity following CPB 9 2011 Haemonetics Corp Bruce D. Spiess The aptt and INR-PT fibrinogen concentration tests and a number of other routine coagulation tests have been shown as having no predictive value (B50%) regarding hemorrhage after CPB. 10 2011 Haemonetics Corp

Bruce D. Spiess The unstimulated TEG is one of the most sensitive tests for trace amounts of heparin. 11 2011 Haemonetics Corp Extrinsic Pathway Extrinsic Pathway Tissue/Cell Defect F VIIa Ca 2+ F VII F Xa Ca 2+ F III (Tissue Thromboplastin) F X 12

Intrinsic Pathway Surface Contact Collagen FXII activator Intrinsic Pathway F XII F XIIa F XI Ca 2+ F XIa F IX Ca 2+ FIXa F X Ca 2+ F Xa 13 Common Pathway F Xa Prothrombin II Ca 2+ Thrombin IIa Fibrin polymers Fibrin monomers Fibrinogen 14

The Coagulation Cascade Intrinsic Pathway Surface Contact Collagen FXII activator Extrinsic Pathway Tissue/Cell Defect F XII F XIIa F VIIa Ca 2+ F VII F XI Ca 2+ F XIa F VIII F IX Ca 2+ F VIIIa Platelet Factor 3 F X FIXa Ca 2+ F Xa Ca 2+ F III (Tissue Thromboplastin) F X F Va F V 15 Crosslinked Fibrin Network F XIIIa Prothrombin II F XIII Fibrin polymers Ca 2+ Fibrin monomers Thrombin IIa Fibrinogen Yellow lines indicate positive feedback loops lost in isolated tests K EPL, LY30 = Platelet function R G = Clot Strength R = Reaction time to end of thrombin burst K = fibrin cross-linkage, fibrinogen function Angle = fibrinogen function MA = platelet function in mm G = MA converted to Kdynes/cm 2 LY30 = Lysis 30 minutes after MA reached 16

Heparin Effect Heparinase cup Plain cup 5.8 2.2 59.1 0.0 56.2 6.4 *2.0* *0.4* -1.0 55.0 17 Sensitivity - Testing for Presence of Heparin: Patient post-protamine and bleeding R value for KH = K Suggests no heparin present Green = kaolin with heparinase (KH) Black = kaolin only (K) R value for KH < K Suggests presence of heparin 18 2011 Haemonetics Corp

Heparin/LMWH 19 Normal TEG Analysis INCLUDES: Heparin LMWH Coumadin Arixtra Pradaxa Xarelto Factor Deficiency Fibrinogen Deficiency Platelet Function Clot Strength Lysis Surgical Bleeding from Hemostasis Hypercoagulability 20 EXCLUDES: Plavix Effient Brilinta Integrilin Reopro Aggrastat Pletal Persantine NSAIDs ASA Pathologic Platelet Inhibition

Example - CABG Case Heparin Challenges 21 2011 Haemonetics Corp Pt. #1 Baseline 22 2011 Haemonetics Corp

Pt. #1 Post Protamine 1 23 2011 Haemonetics Corp Pt. #1 Post Protamine 1 Tracing Overlay Reaction Time Sensitivity 24 2011 Haemonetics Corp

Pt. #1 Post Protamine 2 nd Dose 25 2011 Haemonetics Corp Pt. #1, 2hrs Later ICU (more protamine given) 26 2011 Haemonetics Corp

Pt. #1, 8hrs Later 27 2011 Haemonetics Corp Publication Date June 2005 28 2011 Haemonetics Corp

Published Papers Altogether 170 papers were identified using the reported search strategy of which 14 represented the best evidence on the topic. 29 2011 Haemonetics Corp Conclusion We conclude that thrombelastography may be useful in predicting patients who are likely to bleed postoperatively but more importantly, it can guide transfusion therapy algorithms in the bleeding cardiac surgical patient resulting in significant decreases in blood and blood component transfusion requirements. 30 2011 Haemonetics Corp

Case Study: Reducing Allogeneic Blood Use Total $ Reduction 58% Transfused Product Cost: 30 patients before TEG monitoring vs. 30 patients after TEG monitoring (Data obtained from Harris Methodist H-E-B Hospital). 31 HCA: St. David s South Austin Medical Center Number of Patients Receiving Platelet Transfusions 200 150 167 189 100 50 98 60 Total Patients Patients who received a platelet transfusion 32 0 2008 (Pre-TEG ) 2009 (Post TEG ) 58% received plt transfusion 32% received plt transfusion 26% decrease in number of patients receiving a platelet transfusion.

Risk Stratification w/ TEG Analyzer 33 2011 Haemonetics Corp Assessing Risk of Thrombosis Using TEG System Gurbel et al. J Am Coll Cardiol 2005;46:1820-6 192 patients undergoing percutaneous coronary intervention (PCI) 100% on aspirin and clopidogrel (84%) TEG used to risk stratify for post-pci events Ischemic events were significantly associated (p < 0.001) by elevated pre and post-treatment MA (> 65) McCrath et al. Anesth Analg 2005;100:1576-83 240 general surgery population TEG performed immediately after surgery 10 patients (4.2%) had 12 postoperative thrombotic events MA > 68 was predictive of thrombotic complications (p+ 0.01) (8.4% vs. 1.4%) Sources: 1 Gurbel et al. J Am Coll Cardiol 2005; 46: 1820-1826 2 McCrath DJ et al. Anesth Analg 2005 34 2011 Haemonetics Corp

Risk Stratification Thrombotic Events McCrath D et al. Anesth Analg 2005; 100:1576 Bliden KP et al. ACC Meeting 2005 When controlling for gender, race, age and ISS, elevated ma at admission was an independent predictor of PE with an odds ration of 3.5 for ma > 65 and 5.8 for ma >72. 36 2011 Haemonetics Corp

PlateletMapping Assay Monitoring Platelet Inhibition and Baseline Platelet Function PlateletMapping Assay What is it? Measures the effect of antiplatelet agents on platelet function Measures the patient s maximum platelet function as a reference point Measures the percentage of inhibition relative to the patient s reference point Measures the percentage of inhibition related to other causes: i.e. herbal supplements 38

PlateletMapping Assay What Clinical Questions Does It Answer? Pre-Op Does the patient have the potential to bleed during or after the cardiac procedure due to platelet inhibition Should we wait 5-7 Days (or less) for surgery if the patient is on an inhibitor? Should the patient potentially be put on a higher dose of the inhibitor? Post Op When there is a Normal TEG reading and the patient is bleeding Von Willebrands: R/O with DDAVP Surgical Bleed: R/O Prolene Platelet Inhibition as determined by Platelet Mapping Assay 39 Thrombelastograph Parameters R (min) - Time to initial fibrin formation induced by thrombin MA Thrombin - Maximum clot strength induced by thrombin MA Fibrin - Maximum contribution of fibrin only to MA MA ADP or A.A - Measures ADP or arachidonic acid stimulated clot strength R 0 Minutes 40

Pre-Op/ PlateletMapping Assay 41 Why PlateletMapping Assay? Personalized Platelet Therapy Patient A: 50% platelet inhibition does not provide sufficient reduction of the risk of a thrombotic or ischemic event Patient B: 50% platelet inhibition provides antithrombotic protection without risk of bleeding Patient C: 50% platelet inhibition increases risk of bleeding 42

Meds Affecting PlateletMapping Assay Platelet Inhibition GPIIb/IIIa ADP TXA 2 Reopro Plavix ASA Integrilin Persantine Aggrastat Toradol Effient Ticlid Effient Brilinta 43 Before Platelet Inhibitor (ADP) 44

After Platelet Inhibitor (ADP) Plavix, Effient, Ticlid, Brilinta, Integrilin, Aggrastat, Reopro, Persantine, Toradol, Pletal, Pathologic inhibition 45 Plavix, Effient, Ticlid, Brilinta, Integrilin, Aggrastat, Reopro, Persantine, Toradol, Pletal, Pathologic inhibition 46

Platelet Function Monitoring: Recommendations 2011 Areas of Major Revision 1. Management of dual anti-platelet therapy before operation a. POC testing for platelet ADP responsiveness is reasonable to identify Plavix non-responders who are candidates for early coronary revascularization; these might not require a 5 day wait (Level of evidence C) Timing of Surgery Circulation: Cardiovascular Interventions Platelet Function Measurement Based Strategy to Reduce Bleeding and Waiting Time In Clopidogrel-Treated Patients Undergoing Coronary Artery Bypass Graft Surgery: The TARGET- CABG Pilot Study Elizabeth Mahla, Thomas Suarez, Kevin P Bliden, Peter Rehak, Helfried Metzler, Alejandro Sequeira, Peter Cho, Jeffery Sell, John Fan, Mark Antonino, Udaya S Tantry, and Paul Gurbel Key points 1. Prospective, single center, unblinded investigation of two groups of patients who had preop PlateletMapping undergoing elective on-pump CABG: Clopidogrel treated vs Clopidogrel naïve Schedule for clopidogrel treated: 3 subsets 1. MA ADP > 50 mm = OR within 1 day 2. MA ADP 35-50 50 = OR in 3-5days 3. MA ADP < 35 = OR after 5 days 2. This strategy was associated with the same amount of bleeding as in clopidogrel naïve patients and ~50% shorter waiting time than recommended in the current guidelines (2.7days vs 5 days) Circ Cardiovasc Interv. 2012;5:261-269 48 2011 Haemonetics Corp

TARGET Study - Wait Time Impact TEG MA (ADP) > 50mm 35 50mm < 35mm Within 1 day Wait 3 5 days Wait 5 days N = 27 (31%) N = 42 (49%) N = 17 (20%) Average wait time was reduced by approximately 50% with no increase in bleeding, transfusions, or MACE (major adverse cardiac event) 49 2011 Haemonetics Corp PlateletMapping Assay TEG Analysis: MA 75.0 MA THROMBIN (complete activation) 20.7 MA ADP or MA AA (activation of non-inhibited platelets) 10.0 MA FIBRIN (no activation) % Inhibition = 83.5 % Aggregation = 16.5 % inhibition = 100 [(MA pi -MA f )/(MA t -MA f ) X 100] 50 2011 Haemonetics Corp

PlateletMapping Assay TEG Analysis: Clopidogrel Resistance 75.0 69.5 MA THROMBIN MA ADP 10.0 MA FIBRIN % Inhibition = 8.5 % Aggregation = 91.5 % inhibition = 100 [(MA pi -MA f )/(MA t -MA f ) X 100] 51 2011 Haemonetics Corp PlateletMapping Assay TEG Analysis: Plavix MA THROMBIN MA ADP MA FIBRIN 52 2011 Haemonetics Corp

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Pathologic Platelet Inhibition Not drug-induced May be due to foods or neutraceuticals May be underlying pathology May impact platelet activation or aggregation It is real, and should be considered for risk 57 Platelet Mapping Assay INCLUDES: HEMOSTASIS Hypercoagulability Lysis Surgical Bleeding from Hemostasis Factor Deficiency Fibrinogen Function Platelet 58 Function PLATELET MAPPING INTERVENTION Shows percent platelet inhibition due to: Interventional Treatment Pathologic Inhibition DRUGS: Heparin LMWH Coumadin Arixtra Pradaxa Xarelto Plavix Effient Ticlid Brilinta Reopro Integrilin Aggrastat ASA NSAIDs

Case Study Root Replacement Valve 59 59 2011 Haemonetics Corp Baseline (Secondary Fibrinolysis) 60

PlateletMapping Assay ADP Shows little inhibition AD P A KH 61 PlateletMapping Assay AA Shows full inhibition AA A KH 62

Rewarm TEG results suggest no products needed INR 3.4 (Usually 6-8 FFP given) 63 Post Protamine RT RT H Full reversal of Heparin. DDAVP given. No products given 64

Jehovah s Witness Platelet Mapping application 65 Outpatient ADP Mapping 66

Outpatient AA Mapping 67 Jehovah s Witness Decision was made to delay surgery for 5 days 2011 Haemonetics Corp. COMPANY CONFIDENTIAL

Pre-Op ADP Mapping 69 Pre-Op AA Mapping 70

71 Questions? THANK YOU AMSECT NABM!!