Module 5

Fibrinolysis and HyperfibrinolysisTEG Analysis

Basic Clinician Training

IntroductionTEG Analysis of Hyperfibrinolysis

Test Your Knowledge

Introduction

• Fibrinolysis Breakdown of clots, and wound healing Essential component of hemostasis Protective mechanism that limits clot formation

• Abnormal activation of the fibrinolytic pathway, resulting in bleeding Breakdown of formed fibrin clot Degradation of coagulation factors (i.e. DIC) Impairment of clot formation due to excess generation of fibrin

degradation products • Interferes with fibrin cross-linking

• Inhibits platelet function

Fibrinolysis:Physiological vs. Pathophysiological

• Physiological • Pathophysiological

• Excess plasma-free plasmin

Coagulation factor

consumption

Bleeding

Excessivefibrin(ogen)degradation

Formation of FDPs

Interference with clot formation

Fibrin-bound plasmin

Accelerated degradationof formed fibrin clot

Hyperfibrinolysis:Primary vs. Secondary

Primary • Rapid clot breakdown

Increase in circulating tPA

binding to fibrin Excess tPA -Decreased hepatic clearance

-Decreased fibrinolytic inhibitors• α2-antiplasmin

• PAI-1

Secondary• Secondary to systemic

hypercoagulability Systemic or microvascular Not localized Commonly associated with

DIC

Hyperfibrinolysis:Primary vs. Secondary

Primary • Bleeding

Rapid breakdown of clot Diminished clot formation

• Formation of FDPs Inhibition of platelet

function Interference with fibrin

cross-linking

Secondary• Bleeding

Degradation of fibrin Consumption of

coagulation factors

• Formation of FDPs Inhibition of platelet

function Interference with fibrin

cross-linking

Primary• Treat consequence of

excess circulating tPA

• Common treatment: Antifibrinolytic agent

Secondary• Treat hypercoagulability

• Common treatment: Anticoagulant

• Heparin

• LMWH

• Warfarin

Restore endogenous anticoagulation pathways

• ATIII

• APC

Hyperfibrinolysis:Primary vs. Secondary

Hyperfibrinolysis:Treatment and Monitoring

• Selection of proper treatment is critical Wrong treatment can be fatal

• TEG analysis helps

EPL > 15%or

LY30 > 7.5%YesNo

R > 10min Yes

MA < 55mm

No

YesNo

Yes

YesNo

Primary fibrinolysis

C.I.

< 1.0 > 3.0

i

Yes

Yes

No

No

Decision Tree

Fibrinolytic

Hypercoagulable

C.I. > 3.0

Low plateletfunction

Low clottingfactors

Low fibrinogenlevel

< 45º

R < 3min

Platelethypercoagulability

MA > 73mm

Enzymatichypercoagulability

Enzymatic & platelethypercoagulability

Secondary fibrinolysis

Hemorrhagic

TEG Analysis: Hyperfibrinolysis

• Hyperfibrinolysis LY30 > 7.5% EPL > 15%

• CI (coagulation index) Distinguish primary and

secondary CI = Linear combination of R,

K, alpha (α), and MA

TEG Analysis: Primary hyperfibrinolysis

Common treatment: Antifibrinolytic agent

TEG Analysis: Secondary Hyperfibrinolysis

Common treatment: Anticoagulant

DIC Characteristics

• Disseminated Intravascular Coagulation (DIC) Bacterial infections/sepsis Systemic infections Liver transplants Vascular disorders Severe trauma Solid tumors and hematological malignancies Obstetrical complications

• Placental abruptions

• Amniotic fluid emboli

Presence of toxins (snake venom, amphetamines, and other drugs)

Disseminated Intravascular Coagulation (DIC)

Ongoing systemic activation of coagulation

Intravascular depositionof fibrin

Thrombosis of smalland midsize vessels

Tissue ischemiaand organ failure

Depletion of factorsand platelets

Bleeding

Levi, M & TenCate, H. NEJM. 1999;341:1999

Secondary FibrinolysisPro-thrombotic

DIC:Diagnostic Characteristics

• Progressive disease

• No single laboratory test

• Diagnosis Clinical presentation

• Bleeding and/or disease state

Laboratory tests: • Presence of soluble fibrin monomer complexes

• Platelet count < 100,000/dL or rapidly decreasing platelet count

• Increased PT, aPTT

• Presence of FDPs

• Low levels of coagulation inhibitors (ATIII)

• TEG analysis to demonstrate progression of DIC

Progression of DIC:TEG Analysis

HypercoagulableSecondary to an underlying disorder - Inflammatory state - Down-regulation of anticoagulant mechanisms - Intravascular deposition of fibrin - Activation of fibrinolysis

Secondary fibrinolysisDegradation of fibrin and fibrinogen - Increasing FDPs - FDPs compromise clot formation and integrity - Depletion of factors

HypocoagulableConsuming factors and platelets - Bleeding

Progression of DIC:Common Treatments

HypercoagulableTreat underlying disorderRestore anticoagulation pathways

- Anticoagulant therapy - ATIII - APC

Platelet inhibition

Secondary fibrinolysisTreat underlying disorderRestore anticoagulation pathways

- Anticoagulant therapy - ATIII - APC

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

Basic Clinician Training

Exercise 1

Using the TEG decision tree, what is a likely cause(s) of bleeding in this patient?(Select all that apply)a) Residual anticoagulantb) Surgical bleedingc) Primary fibrinolysisd) Secondary fibrinolysis

What treatment(s) would you consider for this patient?

Answer: page 25

Exercise 2

Using the TEG decision tree, what is a likely cause(s) of bleeding in this patient?(Select all that apply)a) Residual anticoagulantb) Surgical bleedingc) Primary fibrinolysisd) Secondary fibrinolysis

What treatment(s) would you consider for this patient?

Answer: page 26

Exercise 3

This 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) indicated development of primary fibrinolysis.What would be a common treatment plan for this patient?

a) Consider administering an antifibrinolytic agent before termination of CPB. Repeat TEG. b) Consider administering an antifibrinolytic agent after CPB and protamine administration. Repeat TEG.c) Consider no treatment. Repeat TEG post-protamine.d) Consider administering an antifibrinolytic agent during CPB and platelets post-protamine.

Answer: page 27

Exercise 4

This 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?a) Fibrinogen deficiencyb) Platelet deficiency/defectc) Fibrinolysisd) Hemodilution

Would treatment with an antifibrinolytic agent be contra-indicated? Yes or No.If no, which antifibrinolytic agent would you use?

Kaolin

Answer: page 28

Exercise 5

Using the TEG decision tree, what is a likely cause(s) of bleeding in this patient?(Select all that apply)a) Residual anticoagulantb) Surgical bleedingc) Primary fibrinolysisd) Secondary fibrinolysis

What treatment(s) would you consider for this patient?

Kaolin

Answer: page 29

Exercise 6

Kaolin

Using the TEG decision tree, what is a likely cause of bleeding in this patient?(Select all that apply)a) Factor deficiencyb) Platelet deficiency/dysfunctionc) Primary fibrinolysisd) Secondary fibrinolysis

What treatment(s) would you consider for this patient? Answer: page 30

Exercise 7

Using the TEG decision tree, what is your interpretation of this tracing?(Select all that apply)a) Primary fibrinolysisb) Secondary fibrinolysis c) Fibrinolysis d) Surgical bleedinge) Platelet adhesion defect

Answer: page 31

Answer to Exercise 1

Using the TEG decision tree, what is a likely cause(s) of bleeding in this patient?(Select all that apply)a) Residual anticoagulantb) Surgical bleedingc) Primary fibrinolysisd) Secondary fibrinolysis

What treatment(s) would you consider for this patient? Consider treating the underlying disorder, plus an antiplatelet agent and an anticoagulant to inhibit or reduce thrombin generation.

Answer to Exercise 2

Using the TEG decision tree, what is a likely cause(s) of bleeding in this patient?(Select all that apply)a) Residual anticoagulantb) Surgical bleedingc) Primary fibrinolysisd) Secondary fibrinolysis

What treatment(s) would you consider for this patient? Antifibrinolytic agent

Answer to Exercise 3

This 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) indicated development of primary fibrinolysis.What would be a common treatment plan for this patient?a) Consider administering an antifibrinolytic agent before termination of CPB. Repeat TEG. Sincefibrinolysis on pump can be transient, repeat TEG. If fibrinolysis persists, treat with antifibrinolytic agent and monitor the effect. b) Consider administering an antifibrinolytic agent after CPB and protamine administration. Repeat TEG. c) Consider no treatment. Repeat TEG post-protamine. d) Consider administering an antifibrinolytic agent during CPB and platelets post-protamine.

Answer to Exercise 4

This 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?a) Fibrinogen deficiencyb) Platelet deficiency/defectc) Fibrinolysisd) Hemodilution

Would treatment with an antifibrinolytic agent be contra-indicated? NoIf no, which antifibrinolytic agent would you use? Consider aprotinin for potential platelet-protecting effects.

Answer to Exercise 5

Kaolin

Using the TEG decision tree, what is a likely cause(s) of bleeding in this patient?

(Select all that apply)a) Residual anticoagulantb) Surgical bleedingc) Primary fibrinolysisd) Secondary fibrinolysis

What treatment(s) would you consider for this patient? Consider treating with antifibrinolytic agent first. If patient continues to bleed, repeat TEG to determine need for platelets or factors.

Answer to Exercise 6

Kaolin

Using the TEG decision tree, what is a likely cause of bleeding in this patient?(Select all that apply)a) Factor deficiencyb) Platelet deficiency/dysfunctionc) Primary fibrinolysisd) 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.

Answer to Exercise 7

Using the TEG decision tree, what is your interpretation of this tracing?(Select all that apply)a) Primary fibrinolysis (cannot rule out)b) Secondary fibrinolysis (cannot rule out)c) Fibrinolysis d) Surgical bleedinge) Platelet adhesion defect

Although fibrinolysis is present, the CI value is outside those given for 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.

End of Module 5

Basic Clinician Training