Hypercoagulable States

1. Basic Clinician Training Hypercoagulable States Module 4 Introduction Hypercoagulable States Test Your Knowledge

2. Introduction • Prothrombotic or hypercoagulable state • Hyperactive platelet function • Hyperactive coagulation cascade function • Prevention of development of a thrombotic event • Proper assessment of the factors contributing to a hypercoagulable state, which is necessary to determine proper pharmacological intervention

3. Assessing Risk of Thrombosis:Cardiac Patients (Post PCI) Gurbel et al. “Platelet Reactivity in Patients and Recurrent Events Post-Stenting” J Am Coll Cardiol 2005; 46: 1820-1826

4. Assessing Risk of Thrombosis:General Surgical Patients McGrath DJ et al. Anesth Analg 2005

5. Assessing Risk of Thrombosis Cardiac patients (Post PCI) General surgical patients McGrath DJ et al. Anesth Analg 2005 Gurbel et al. “Platelet Reactivity in Patients and Recurrent Events Post-Stenting” J Am Coll Cardiol 2005; 46: 1820-1826

6. Assessing Hypercoagulability with the TEG Analyzer TEG analysis • Demonstrates hypercoagulable and hypocoagulable states • Platelets • Coagulation pathways • Enzymatic pathways • Aids in identifying • Type and magnitude of imbalance • Specific hemostatic interpretation

7. Decision Tree EPL > 15% No or Yes LY30 > 7.5% C.I. C.I. > 3.0 No Yes Hemorrhagic < 1.0 > 3.0 R > 10min R < 3min No Primary fibrinolysis Yes Secondary fibrinolysis No Yes Fibrinolytic Low clotting factors Platelet hypercoagulability MA > 73mm MA < 55mm No Yes Yes No Low platelet function Enzymatic hypercoagulability Enzymatic & platelet hypercoagulability a < 45º Yes Hypercoagulable Low fibrinogen level

8. Hypercoagulable States:Platelet vs. Enzymatic • Hyperactive platelet function • Characterized by rapid clot development and abnormally high clot strength • Enzymatic pathway hypercoagulability • Characterized by rapid fibrin formation, with subsequent clot formation

9. Platelet Hypercoagulability • Rapid clot development, with higher than normal clot strength • Hyperactive platelet function • Probable causes • Diminished endogenous platelet inhibitory mechanisms • High platelet numbers • Abnormal generation of platelet activators • Inflammatory mediators

10. Platelet Hypercoagulability Common conditions • Sepsis • Disseminated Intravascular Coagulation (DIC) • Malignancy • Thrombomodulin-Protein C dysfunction • Activated protein C (APC) resistance • Antithrombin III deficiency • Diminished nitric oxide synthesis/release • Dysplasminogenemia • High plasminogen activator inhibitor • Hyperhomocysteinemia

11. Platelet HypercoagulabilityTEG Tracing Patient status:High risk for thrombotic event Probable cause: Rapid clot formation and strong clot development Common treatment: Platelet inhibitor

12. Platelet HypercoagulabilityTreatment Considerations Best Treatment • Step 1: Identify and quantify prothrombotic state • Step 2: Determine therapeutic response to antiplatelet therapy • WHY?: Resistance to aspirin and clopidogrel • HOW?: TEG analysis with PlateletMapping assay • Assess platelet inhibition against maximum platelet function • Provide personalized treatment regimen

13. Enzymatic Hypercoagulability • Rapid thrombin generation, leading to clot formation • Probable causes: • Loss of antithrombotic protective mechanisms • APC resistance (Factor V Leiden) • ATIII deficiency • Dysfibrinogenemia • Hyperactive platelets

14. Enzymatic HypercoagulabilityTEG Analysis Patient status:High risk for thrombotic event Probable cause: Rapid thrombin generation and subsequent clot formation Common treatment: Anticoagulation

15. Enzymatic HypercoagulabilitySpecial Considerations Treatmentdepends on clinical situation • Goal is to prevent clot formation • Common inpatient treatment: heparin, LMWH, APC (activated protein C) • Common outpatient treatment: LMWH or warfarin to maintain INR > 2.0, slightly higher R (10-14 minutes) • Patient may require fibrinolytic agent before anticoagulation if clots have already formed.

16. Platelet and Enzymatic Hypercoagulability Common conditions • Sepsis • Trauma • Pregnancy • Cancer • Orthopedic surgery • Burns • Lupus anticoagulant • Heart assist device

17. Platelet & Enzymatic Hypercoagulability TEG Analysis Patient status:High risk for thrombotic event • Probable cause(s): • Rapid thrombin generation • Excessive platelet function • Common treatment(s): • Anticoagulation and/or • Platelet inhibitor

18. Basic Clinician Training Interpretation Exercises Prothrombotic States

19. Exercise 1 • Using the TEG decision tree, what is your interpretation of this tracing? • (Select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? Answer: page 25

20. Exercise 2 • Using the TEG decision tree, what is your interpretation of this tracing? • (Select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? Answer: page 26

21. Exercise 3 Kaolin with heparinase Green: Pre-op Black: Before protamine • These tracings are from a patient who has undergone an off-pump • CABG. What is this patient’s current hemostatic state (black tracing)? • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? Answer: page 27

22. Exercise 4 • Using the TEG decision tree, what is your interpretation of this tracing? • (Select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? Answer: page 28

23. Exercise 5 • Using the TEG decision tree, what is your interpretation of this tracing? • (Select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? Answer: page 29

24. Exercise 6 • Using the TEG decision tree, what is your interpretation of this tracing? • (select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • If this tracing were from a pre-bypass cardiac surgical patient, • what type of antifibrinolytic treatment would you consider? Answer: page 30

25. Answer to Exercise 1 • Using the TEG decision tree, what is your interpretation of this tracing? • (select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? • Consider an anti-platelet agent.

26. Answer to Exercise 2 • Using the TEG decision tree, what is your interpretation of this tracing? • (select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? • Consider treatment with both an anticoagulant and an anti-platelet • agent.

27. Answer to Exercise 3 Kaolin with heparinase Green: Pre-op Black: Before protamine • These tracings are from a patient who has undergone an off-pump • CABG. What is this patient’s current hemostatic state (black tracing)? • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? • Although the R value is within normal range, the pre-op value was • lower than normal. Consider half the normal protamine dose, plus • an anti-platelet agent.

28. Answer to Exercise 4 • Using the TEG decision tree, what is your interpretation of this tracing? • (select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? • Consider treatment with an anticoagulant.

29. Answer to Exercise 5 • Using the TEG decision tree, what is your interpretation of this tracing? • (select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • What would be an appropriate treatment for this patient? • Consider treatment with both an anticoagulant and an anti-platelet agent.

30. Answer to Exercise 6 • Using the TEG decision tree, what is your interpretation of this tracing? • (select all that apply) • Platelet hypercoagulability • Enzymatic hypercoagulability • Platelet and enzymatic hypercoagulability • Secondary fibrinolysis • If this tracing were from a pre-bypass cardiac surgical patient, • what type of antifibrinolytic treatment would you consider? • None.Since the patient is hypercoagulable, treatment with an antifibrinolytic • agent may be contra-indicated. Repeat a TEG analysis during CPB to • determine if fibrinolysis has developed, and treat accordingly.

31. Basic Clinician Training End of Module 4