Basic Clinician TrainingModule 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 ComplicationBy Quartiles of MA Value

McGrath DJ et al.Anesth Analg 96:SCA1-141, 2003

0

5

10

15

20

25

30

35

16-62(n=47)

62.5-66.5(n=60)

67-71(n=56)

71.5-94.5(n=56)

MA range

% w

ith T

hrom

botic

com

plic

atio

n

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 statesPlatelet 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 hypercoagulabilityCommon 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 hypercoagulabilityAs shown by TEG

Patient status: high risk for thrombotic event

Probable cause: Rapid clot formation and strong clot developmentCommon treatment: Platelet inhibitor

Platelet hypercoagulabilityTreatment 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 hypercoagulabilityCommon 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 hypercoagulabilityAs shown by TEG analysis

Patient status: high risk for thrombotic event

Probable cause: Rapid thrombin generation and subsequent clot formationCommon treatment: Anticoagulation

• 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

Enzymatic hypercoagulabilitySpecial considerations

• Heart assist device• Lupus anticoagulant• Cancer• Orthopedic surgery• Pregnancy• Trauma• Burns• Sepsis

Platelet & enzymatic hypercoagulabilityCommon conditions

Platelet & enzymatic hypercoagulabilityAs shown by TEG analysis

Patient status: high risk for thrombotic event

Probable cause(s): • Rapid thrombin generation • Excessive platelet functionCommon 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)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. 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)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. Secondary fibrinolysis

What would be an appropriate treatment, if any for this patient?

Answer

Next

Exercise 3: Off-pump CABG patient

The above are tracings from a patient who has undergone an off-pumpCABG. What is this patient’s current hemostatic state (black tracing)?a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. Secondary fibrinolysis

What would be an appropriate treatment, if any for this patient?

Green: Pre-opBlack: Before protamine

Kaolin with heparinase

Answer

Next

Exercise 4

Answer

Next

Using the TEG Decision Tree, what is your interpretation of this tracing?(select all that apply)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. Secondary fibrinolysis

What would be an appropriate treatment, if any for this patient?

Exercise 5

Using the TEG Decision Tree, what is your interpretation of this tracing?(select all that apply)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. Secondary fibrinolysis

What would be an appropriate treatment, if any, for this patient?

Answer

Next

Exercise 6

Answer

Next

Using the TEG Decision Tree, what is your interpretation of this tracing?(select all that apply)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. Secondary fibrinolysis

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

Exercise 1

Using the TEG Decision Tree, what is your interpretation of this tracing?(select all that apply)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. 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)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. Secondary fibrinolysis

What would be an appropriate treatment, if any for this patient?Consider treatment with both an anticoagulant and anti-plateletagent.

Back

Next

Exercise 3: Off-pump CABG patient

The above are tracings from a patient who has undergone an off-pumpCABG. What is this patient’s current hemostatic state (black tracing)?a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. 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.

Green: Pre-opBlack: Before protamine

Kaolin with heparinase

Back

Next

Exercise 4

Back

Next

Using the TEG Decision Tree, what is your interpretation of this tracing?(select all that apply)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. Secondary fibrinolysis

What would be an appropriate treatment, if any for this patient?Consider treatment with an anticoagulant.

Exercise 5

Using the TEG Decision Tree, what is your interpretation of this tracing?(select all that apply)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. 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

Back

Next

Using the TEG Decision Tree, what is your interpretation of this tracing?(select all that apply)a. Platelet hypercoagulabilityb. Enzymatic hypercoagulabilityc. Platelet and enzymatic hypercoagulabilityd. Secondary fibrinolysis

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

End of Module 5