Basic Clinician Training Module 6 Fibrinolysis and Hyperfibrinolysis TEG Analysis

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

Primary vs. Secondary Hyperfibrinolysis Treatment & 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.

Primary hyperfibrinolysis As shown by TEG analysis Common treatment: Antifibrinolytic agent

Secondary hyperfibrinolysis As shown by TEG analysis Common treatment: Anticoagulant

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

DIC Characteristics 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)

DIC Diagnostic 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

Progression of DIC TEG analysis Hypercoagulable phase Secondary to an underlying disorder - Inflammatory state - Downregulation of physiological anti- coagulant mechanisms Intravascular deposition of fibrin Activation of fibrinolysis Secondary fibrinolysis Degradation of fibrin and fibrinogen Generation of FDPs FDP’s compromise clot formation and integrity Consumption of factors and platelets Hypocoagulable Depletion of factors and platelets Bleeding

Progression of DIC Common treatments Hypercoagulable phase Treat underlying disorder Restore anticoagulation pathways Anticoagulant therapy ATIII APC Platelet inhibition Secondary fibrinolysis Hypocoagulable Replacement therapy (FFP, platelets, cryoprecipitate) - Note: may amplify inflammatory response and mediate a hyper- coagulable state, even though patient is bleeding

Interpretation exercises Fibrinolysis

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

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

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

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

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

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

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

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

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

Exercise 10 Exercise Answer Next 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

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

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

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

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

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

Exercise 6 Back Next 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

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

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

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

Exercise 10 Exercise Back Next 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

End of Module 6