Hypercoagulable States

Basic Clinician Training

Module 4

IntroductionHypercoagulable StatesTest Your Knowledge

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

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

Assessing Risk of Thrombosis:General Surgical Patients

McGrath DJ et al.Anesth Analg 2005

Assessing Risk of Thrombosis

McGrath DJ et al.Anesth Analg 2005

General surgical patients

Cardiac patients (Post PCI)

Gurbel et al. “Platelet Reactivity in Patients and Recurrent Events Post-Stenting”J Am Coll Cardiol 2005; 46: 1820-1826

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

Decision Tree

EPL > 15%or

LY30 > 7.5%YesNo

R > 10min Yes

MA < 55mm

No

YesNo

Yes

YesNo

Primary fibrinolysis

C.I.

< 1.0 > 3.0

Yes

Yes

No

No

Fibrinolytic

Hypercoagulable

C.I. > 3.0

Low plateletfunction

Low clottingfactors

Low fibrinogenlevel

< 45º

R < 3min

Platelethypercoagulability

MA > 73mm

Enzymatichypercoagulability

Enzymatic & platelethypercoagulability

Secondary fibrinolysis

Hemorrhagic

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

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

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

Platelet Hypercoagulability

Platelet HypercoagulabilityTEG Tracing

Patient status: High risk for thrombotic event

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

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

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

Enzymatic HypercoagulabilityTEG Analysis

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

Patient status: High risk for thrombotic event

Enzymatic HypercoagulabilitySpecial Considerations

Treatment depends 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.

Platelet and Enzymatic Hypercoagulability

Common conditions

• Sepsis

• Trauma

• Pregnancy

• Cancer

• Orthopedic surgery

• Burns

• Lupus anticoagulant

• Heart assist device

Platelet & Enzymatic Hypercoagulability TEG Analysis

Probable cause(s): • Rapid thrombin generation • Excessive platelet functionCommon treatment(s): • Anticoagulation and/or• Platelet inhibitor

Patient status: High risk for thrombotic event

Interpretation Exercises

Prothrombotic States

Basic Clinician Training

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 for this patient?

Answer: page 25

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 for this patient?

Answer: page 26

Exercise 3

These tracings are 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 for this patient?

Kaolin with heparinase

Green: Pre-opBlack: Before protamine

Answer: page 27

Exercise 4

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 for this patient?

Answer: page 28

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 for this patient?

Answer: page 29

Exercise 6

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

Answer: page 30

Answer to 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 for this patient?Consider an anti-platelet agent.

Answer to 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 for this patient?Consider treatment with both an anticoagulant and an anti-plateletagent.

Answer to Exercise 3

These tracings are 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 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

Answer to Exercise 4

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 for this patient?Consider treatment with an anticoagulant.

Answer to 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 for this patient?Consider treatment with both an anticoagulant and an anti-platelet agent.

Answer to Exercise 6

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 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.

End of Module 4

Basic Clinician Training