Basic Clinician Training Module 5 Hypercoagulable states

Introduction A prothrombotic or hypercoagulable state can be the result of: Hyperactive platelet function and/or Hyperactive coagulation cascade function Proper assessment of the factor(s) contributing to a hypercoagulable state is necessary to determine proper pharmacological intervention to prevent the development of a thrombotic event.

Importance of assessing the hypercoagulable state Percentage of Patients with a Thrombotic Complication By Quartiles of MA Value MA range % with Thrombotic complication McGrath DJ et al. Anesth Analg 96: SCA1-141, 2003

Insert graph from Sinai study

Assessing hypercoagulability with the TEG TEG analysis can demonstrate hypercoagulable as well as hypocoagulable states TEG analysis can differentiate between platelet hypercoagulability and enzymatic hypercoagulability.

Hypercoagulable states Platelet vs. enzymatic Hyperactive platelet function is characterized by rapid clot development and abnormally high clot strength. Hyper enzymatic pathway activity is characterized by rapid fibrin formation with subsequent clot formation.

Platelet hypercoagulability Characterized by rapid clot development with higher than normal clot strength due to hyperactive platelet function. Probable causes: Diminished endogenous platelet inhibitory mechanisms High platelet numbers Abnormal generation of platelet activators Inflammatory mediators

Platelet hypercoagulability Common conditions Antithrombin III deficiency Thrombomodulin-Protein C dysfunction or APC resistance Diminished nitric oxide synthesis/release Dysplasminogenemia High plasminogen activator inhibitor Hyperhomocysteinemia Malignancy DIC

Platelet hypercoagulability As shown by TEG Patient status: high risk for thrombotic event Probable cause: Rapid clot formation and strong clot development Common treatment: Platelet inhibitor

Platelet hypercoagulability Treatment considerations Step 1: Identify and quantify prothrombotic state Step 2: Determine therapeutic response of anti-platelet therapies WHY?: Patient resistance to aspirin and clopidogrel has been documented in the literature HOW?: TEG analysis combined with PlateletMapping assay (Module 6). Assesses platelet inhibition against total platelet function Provides personalized treatment regimen

Platelet hypercoagulability Common therapy algorithm

Enzymatic hypercoagulability Characterized by rapid fibrin generation with subsequent clot formation Probable cause(s): Loss of antithrombotic protective mechanisms APC resistance (Factor V Leiden) ATIII deficiency Dysfibrinogenemia

Enzymatic hypercoagulability As shown by TEG analysis Patient status: high risk for thrombotic event Probable cause: Rapid thrombin generation and subsequent clot formation Common treatment: Anticoagulation

Enzymatic hypercoagulability Special considerations Treatment ultimately depends on clinical situation Goal is to prevent clot formation Common inpatient treatment: heparin, LMWH, APC (activate protein C) Common outpatient treatment: LMWH or Coumadin to maintain INR > 2.0 If clots have already formed - may require fibrinolytic agent before anticoagulation

Platelet & enzymatic hypercoagulability Common conditions Heart assist device Lupus anticoagulant Cancer Orthopedic surgery Pregnancy Trauma Burns Sepsis

Platelet & enzymatic hypercoagulability As shown by 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

Interpretation Exercises Prothrombotic states

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, if any for this patient? Answer Next

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, if any for this patient? Answer Next

Exercise 3: Off-pump CABG patient Kaolin with heparinase Green: Pre-op Black: Before protamine The above are tracings 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, if any for this patient? Answer Next

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, if any for this patient? Answer Next

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, if any, for this patient? Answer Next

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 was a tracing from a pre-bypass cardiac surgical patient, what type of antifibrinolytic treatment would you consider? Answer Next

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, if any for this patient? Consider an anti-platelet agent. Back Next

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, if any for this patient? Consider treatment with both an anticoagulant and anti-platelet agent. Back Next

Exercise 3: Off-pump CABG patient Kaolin with heparinase Green: Pre-op Black: Before protamine The above are tracings 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, if any 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. Back Next

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, if any for this patient? Consider treatment with an anticoagulant. Back Next

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, if any, for this patient? Consider an anticoagulant plus an anti-platelet agent. Back Next

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 was a tracing from a pre-bypass cardiac surgical patient, what type of antifibrinolytic treatment would you consider? Since the patient is hypercoagulable, treatment with an antifibrinolytic agent may be contra- indicated at this phase in the surgery. Repeat a TEG during CPB to determine if fibrinolysis has developed and treat accordingly. Back Next

End of Module 5