Basic Clinician Training Module 6

1. Basic Clinician TrainingModule 6 Fibrinolysis and Hyperfibrinolysis TEG Analysis

2. Introduction • Fibrinolysis is an essential component of hemostasis. • Associated with wound healing • Protective mechanism to clear thrombi from the microvasculature • Excessive activation of the fibrinolytic pathway (hyperfibrinolysis) can cause bleeding by several mechanisms, depending on the cause and magnitude: • Breakdown of formed fibrin clot • Degradation of coagulation factors (i.e. DIC) • Impair clot formation due to excess generation of fibrin degradation products • Interfere with fibrin cross-linking • Inhibit platelet function

7. Primary vs. Secondary HyperfibrinolysisTreatment & monitoring • Identification of type of hyperfibrinolysis is crucial since therapies are different • The wrong therapy can be fatal • TEG analysis is able to distinguish between primary and secondary fibrinolysis.

10. Primary hyperfibrinolysisAs shown by TEG analysis Common treatment: Antifibrinolytic agent

11. Secondary hyperfibrinolysisAs shown by TEG analysis Common treatment: Anticoagulant

12. Disseminated intravascular coagulation (DIC) Systemic and ongoing activation of coagulation Intravascular deposition of fibrin Depletion of factors and platelets Thrombosis of small and midsize vessels Bleeding Tissue ischemia and organ failure Levi, M & TenCate, H. NEJM. 1999;341:1999

13. DICCharacteristics • DIC is an acquired disorder that occurs in a variety of clinical conditions • Bacterial infections/sepsis • Systemic infections • Liver transplants • Vascular disorders • Severe trauma • Solid tumors and hematological malignancies • Obstetrical complications • Placental abruptions • Amniotic fluid emboli • Reaction to toxins (snake venom, amphetamines, drugs)

14. DICDiagnostic characteristics • No single laboratory test can establish or rule out diagnosis • Diagnosis requires a clinical presentation plus a combination of test results • Clinical presentation - bleeding and/or disease state known to be associated with DIC • Laboratory tests: • Presence of soluble fibrin monomer complexes • Platelet count < 100,000/dL or rapidly decreasing platelet count • Increased clotting times (PT, aPTT) • Presence of FDPs • Low levels of coagulation inhibitors (ATIII) • TEG analysis also demonstrates progression of DIC

15. Progression of DICTEG analysis

16. Progression of DICCommon treatments

17. Interpretation exercises Fibrinolysis

18. Exercise 1 • Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? • [Select all that apply] • Residual anticoagulant • Surgical bleeding • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Answer Next

19. Exercise 2 • Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? • [Select all that apply] • Residual anticoagulant • Surgical bleeding • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Answer Next

20. Exercise 3 • Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? • [Select all that apply] • Residual anticoagulant • Surgical bleeding • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Answer Next

21. Exercise 4 • The above patient was brought to the OR for CABGx4, on pump. Due to the initial hyper- • coagulable state (black tracing), no prophylactic antifibrinolytic was administered. The • rewarming TEG (green tracing) demonstrated the development of primary fibrinolysis. • What would be a common treatment plan for this patient? • Administer antifibrinolytic agent before termination of CPB. Repeat TEG. • Administer antifibrinolytic agent after CPB and protamine administration. • Repeat TEG. • Do not treat. Repeat TEG post-protamine. • Administer antifibrinolytic agent during CPB and platelets post-protamine. Answer Next

22. Exercise 5 • The above patient was brought to the OR for CABGx4, on pump. While opening the chest, • the surgeon commented that the patient was ‘oozy’. What is the mostly likely cause • of this condition? • Fibrinogen deficiency • Platelet deficiency/defect • Fibrinolysis • Hemodilution • Would treatment with an antifibrinolytic agent be contra-indicated? Yes or No. • If no, which antifibrinolytic agent would you use? Answer Next

23. Exercise 6 Kaolin • Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? • [Select all that apply] • Residual anticoagulant • Surgical bleeding • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Answer Next

24. Exercise 7 Kaolin • Using the TEG Decision Tree what is a likely cause of bleeding in this patient? • [Select all that apply] • Factor deficiency • Platelet deficiency/dysfunction • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Answer Next

25. Exercise 8 Kaolin • Using the TEG Decision Tree, what is your interpretation of this tracing? • (select all that apply) • Primary fibrinolysis • Secondary fibrinolysis • Fibrinolysis • Surgical bleeding • Platelet adhesion defect Answer Next

26. Exercise 9 Kaolin • Using the TEG Decision Tree, what is your interpretation of this tracing? • (select all that apply) • Primary fibrinolysis • Secondary fibrinolysis • Factor deficiency • Surgical bleeding • Platelet adhesion defect Answer Next

27. Exercise 10 Exercise Kaolin • Using the TEG Decision Tree, what is your interpretation of this tracing? • (select all that apply) • Primary fibrinolysis • Secondary fibrinolysis • Normal • Factor deficiency • Platelet deficiency/dysfunction • If this patient were bleeding, what treatment(s) would you consider using? Answer Next

28. Exercise 1 • Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? • [Select all that apply] • Residual anticoagulant • Surgical bleeding • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Consider treating the • underlying disorder plus an anticoagulant to inhibit or reduce thrombin • generation. Back Next

29. Exercise 2 • Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? • [Select all that apply] • Residual anticoagulant • Surgical bleeding • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Antifibrinolytic agent Back Next

30. Exercise 3 • Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? • [Select all that apply] • Residual anticoagulant • Surgical bleeding • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Explore surgical area(s) for • possible sites of bleeding and repair as needed. Back Next

31. Exercise 4 • The above patient was brought to the OR for CABGx4, on pump. Due to the initial hyper- • coagulable state (black tracing), no prophylactic antifibrinolytic was administered. The • rewarming TEG (green tracing) demonstrated the development of primary fibrinolysis. • What would be a common treatment plan for this patient? • Administer antifibrinolytic agent before termination of CPB. Repeat TEG. • Administer antifibrinolytic agent after CPB and protamine administration. • Repeat TEG. • Do not treat. Repeat TEG post-protamine. • Administer antifibrinolytic agent during CPB and platelets post-protamine. Back Next

32. Exercise 5 • The above patient was brought to the OR for CABGx4, on pump. While opening the chest, • the surgeon commented that the patient was ‘oozy’. What is the mostly likely cause • of this condition? • Fibrinogen deficiency • Platelet deficiency/defect • Fibrinolysis • Hemodilution • Would treatment with an antifibrinolytic agent be contra-indicated? Yes or No. • If no, which antifibrinolytic agent would you use? Consider aprotinin for potential • platelet protecting effects. Back Next

33. Exercise 6 Kaolin • Using the TEG Decision Tree what is a likely cause(s) of bleeding in this patient? • [Select all that apply] • Residual anticoagulant • Surgical bleeding • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Consider treating first with • antifibrinolytic agent. If patient continues to bleed, repeat TEG to determine • need for platelets or factors. Back Next

34. Exercise 7 Kaolin • Using the TEG Decision Tree what is a likely cause of bleeding in this patient? • [Select all that apply] • Factor deficiency • Platelet deficiency/dysfunction • Primary fibrinolysis • Secondary fibrinolysis • What treatment(s) would you consider for this patient? Consider treating with • platelet transfusion. If patient continues to bleed, repeat the TEG to determine • possible contribution of fibrinolysis. Back Next

35. Exercise 8 Kaolin • Using the TEG Decision Tree, what is your interpretation of this tracing? • (select all that apply) • Primary fibrinolysis (cannot rule out) • Secondary fibrinolysis (cannot rule out) • Fibrinolysis • Surgical bleeding • Platelet adhesion defect • Although fibrinolysis is present, the CI value is outside the values indicated for • the designation as primary or secondary. Knowledge of patient history, drug • history, other laboratory tests, and bleeding status would be required to make a • definitive diagnosis. A clinical presentation of DIC would suggest secondary • fibrinolysis, and treatment with an anticoagulant. If patient continues to bleed, • repeat the TEG and consider treatment with an antifibrinolytic agent. Back Next

36. Exercise 9 Kaolin • Using the TEG Decision Tree, what is your interpretation of this tracing from a patient who is • bleeding? (select all that apply) • Primary fibrinolysis • Secondary fibrinolysis (cannot rule out) • Factor deficiency (Present, but not primary cause of bleeding. Consider treatment with • antifibrinolytic agent first. Monitor patient bleeding status. If patient still bleeding, repeat • the TEG to determine extent of factor deficiency in the absence of fibrinolysis. • Surgical bleeding • Platelet adhesion defect Back Next

37. Exercise 10 Exercise Kaolin • Using the TEG Decision Tree, what is your interpretation of this tracing? • (select all that apply) • Primary fibrinolysis (cannot rule out) • Secondary fibrinolysis (cannot rule out) • Normal • Factor deficiency • Platelet deficiency/dysfunction • If this patient were bleeding, what treatment(s) would you consider using? • Although some fibrinolysis is present, it is still within normal range. Consider • checking for surgical bleeding or treatment with DDAVP. Also, check patient • history of platelet inhibitors or possible presence of DIC. Treat accordingly. Back Next

38. End of Module 6