module 5 fibrinolysis and hyperfibrinolysis teg analysis basic clinician training introduction teg...
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Module 5
Fibrinolysis and HyperfibrinolysisTEG Analysis
Basic Clinician Training
IntroductionTEG Analysis of Hyperfibrinolysis
Test Your Knowledge
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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
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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
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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
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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
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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
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Hyperfibrinolysis:Treatment and Monitoring
• Selection of proper treatment is critical Wrong treatment can be fatal
• TEG analysis helps
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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
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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
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TEG Analysis: Primary hyperfibrinolysis
Common treatment: Antifibrinolytic agent
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TEG Analysis: Secondary Hyperfibrinolysis
Common treatment: Anticoagulant
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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)
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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
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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
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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
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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
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Interpretation Exercises
Fibrinolysis
Basic Clinician Training
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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
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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
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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
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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
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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
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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
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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
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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.
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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
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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.
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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.
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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.
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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.
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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.
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End of Module 5
Basic Clinician Training