TEGthromboelastography

•Coagulation cascade serves to stabilize the clot that has formed and further seal up the wound. The goal of the cascade is to form fibrin which will form a mesh within the platelet aggregate to stabilize the clot.

•There are major 13 factors which are involved in the coagulation cascade. All these factors are blood proteins or their derivatives. Even if one of the factor is defective, the whole clotting process is impaired leading to hemorrhage. These factors are F-I to F-XIII.

Factor Common Name Function

F-I Fibrinogen Forms clot (fibrin)

F-II Prothrombin Its active form (IIa) activates I,V,VII,VIII,XI,XIII,protein C,platelets

F-III Tissue Factor (TF) or Thromboplastin or Platelet Phosholipids

Co-factor of VII

F-IV Calcium (Ca++) Required for coagulation factors to bind to phospholipid

F-V Proaccelerin Co-factor of X with which it forms prothrombinase complex

F-VI Old name of factor Va Unassigned

F-VII Proconvertin Activates IX,X

F-VIII Anti-hemophilic Factor A Co-factor of IX with which it forms the tenase complex

F-IX Anti-hemophilic Factor B or Christmas Factor

Activates X which forms tenase complex with VIII

F-X Stuart-Prower Factor Activates II which forms prothrombinase complex with V

F-XI Anti-hemophilic Factor C or Plasma Thromboplastin Antecedent (PTA)

Activates IX

F-XII Hageman Factor Activates XI,VII & prekallikrein

F-XIII Fibrin Stabilizing Factor Crosslinks Fibrin

•There are 3 major stages in the coagulation cascade:

•Stage 1: Formation of Prothrombinase Complex (Prothrombin Activator)

•Prothrombinase is formed in two ways•Extrinsic Pathway (also known as Tissue Factor Pathway)• Intrinsic Pathway (also known as Contact Activation Pathway)

•Stage 2: Conversion of Prothrombin into Thrombin

•Stage 3: Conversion of Fibrinogen into Fibrin

Stage 2 & Stage 3 is collectively called as Final Common Pathway

STAGE 1

Extrinsic Pathway• In this pathway, the formation of

prothrombinase complex is initiated by the tissue thromboplastin

Mechanism:

• It begins with trauma to blood vessel or tissues outside the blood vessel. It releases F-VII and tissue phosholipids.F-VII comes in contact with F-III (TF or Thromboplastin) expressed on TF-bearing cells (stromal fibroblasts & leukocytes) forming an activated complex (TF-VIIa)

• TF-VIIa activates F-IX,F-X in presence of Ca++

and tissue phospholipids

• F-Xa acts on F-V and activates it

• F-Xa complexes with tissue phospholipids, F-Va, Ca++ and forms a complex called prothrombinase complex or prothrombin activator.

Intrinsic Pathway• In this pathway, the formation of prothrombinase complex

is initiated by platelets which are within the blood itself

Mechanism:

• Begins with the formation of the primary complex on collagen by HMWK, prekallikrein and F-XII Prekallikrein is converted to kallikrein and F-XII gets activated.

• Damaged platelets adhere to the wet surface of blood vessel and release platelet phospholipids i.e. F-III

• F-XIIa acts enzymatically on F-XI (Plasma Thromboplastin Antecedent) and activates it

• F-XIa acts enzymatically on F-IX and activates it in presence of Ca++

• F-IXa activates F-VIII (Anti Haemophilic Factor)

• F-IIIa,F-VIIIa and F-IXa activate F-X

• F-Xa acts enzymatically on F-V (Proaccelerin) and activates it in presence of Ca++

• F-Va,F-Xa,F-IIIa and Ca++ form a complex called prothrombin complex

STAGE 2

• In the presence of prothrombin activator or prothrombinase complex and Ca++,prothrombin is converted to thrombin

•Thrombin itself increases its own rate of formation (positive feedback mechanism)• Thrombin then activates other

components of the coagulation cascade, including F-V and F-VIII (which activates F-XI,which in turn activates F-IX)and activates and releases F-VIII from being bound to vWF

• F-VIIIa is the co-factor of F-IXa, and together they form the "tenase" complex, which activates F-X and so the cycle continues.("Tenase" is a contraction of "ten" and the suffix "-ase" used for enzymes)

STAGE 3

• Thrombin converts fibrinogen (plasma protein produced by the liver) to fibrin

• Thrombin also activates F-XIII (Fibrin Stabilizing Factor) which in presence of Ca++ stabilizes the fibrin polymer through covalent bonding of fibrin monomers

Coagulation Monitoring – Conventional TestsTests Of Coagulation

* Platelets• number• function

*Clotting studies• PT• APTT

*Fibrinogen levels

Tests of Degradation* Degradation products

•Each of these tests measures a different aspect of the clotting

process, but even in combination they do not provide a complete

picture of the status of the coagulation system

•Besides evaluation of platelet function remains insensitive and

time consuming. The platelet count provides only a

quantitative, not qualitative index of platelet status.

•At present the treatment of postoperative bleeding remains empirical because of the perceived need for immediate correction of the haemostatic defect and lack of readily available measures of all phases of clot formation and breakdown , including the strength of the clot

•FFP and platelets often given with little scientific basis.

What we need?

an effective and convenient means of monitoring whole blood

coagulation which evaluates the elastic properties of whole blood

and provides a global assessment of heamostatic function.

TEGthromboelastography

TEG•Thromboelastography monitors the thrombodynamic properties of blood as it is induced to clot under a low shear environment resembling sluggish venous flow. The patterns of change in shear-elasticity enable the determination of the kinetics of clot formation and growth as well as the strength and stability of the formed clot.

•The strength and stability of the clot provide information about the ability of the clot to perform the work of hemostasis, while the kinetics determine the adequacy of quantitative factors available to clot formation.

•First developed by Dr. Hellmut Hartet at University of Heidelberg, School of Medicine in 1948 as a method to assess global hemostatic function from a single blood sample; this was the original Thromboelastography.

THROMBOELASTOGRAPHYBasic Principles

THROMBOELASTOGRAPHYBasic Principles

• Heated (37C) oscillating cup

• Pin suspended from torsion wire into blood

• Development of fibrin strands “couple” motion of cup to pin

• “Coupling” directly proportional to clot strength

• tension in wire detected by EM transducer

THROMBOELASTOGRAPHYBasic Principles

• Electrical signal amplified to create TEG trace

• Result displayed graphically on pen & ink printer or computer screen

• Deflection of trace increases as clot strength increases & decreases as clot strength decreases

THROMBOELASTOGRAPHYThe “r” time

r time

•represents period of time of latency from start of test to initial fibrin formation

•in effect is main part of TEG’s representation of standard”clotting studies”

•normal range• 15 - 23 mins (native blood)• 5 - 7 mins (kaolin-activated)

THROMBOELASTOGRAPHYWhat affects the “r” time?

•r time by• Factor deficiency • Anti-coagulation• Severe hypofibrinogenaemia

• Severe thrombocytopenia

•r time by• Hypercoagulability syndromes

THROMBOELASTOGRAPHYThe “k” time

k time

•represents time taken to achieve a certain level of clot strength (where r time = time zero ) - equates to amplitude 20 mm

•normal range• 5 - 10 mins (native blood)• 1 - 3 mins (kaolin-activated)

THROMBOELASTOGRAPHYWhat affects the “k” time?

•k time by• Factor deficiency • Thrombocytopenia• Thrombocytopathy• Hypofibrinogenaemia

•k time by• Hypercoagulability state

THROMBOELASTOGRAPHYThe “” angle

angle

•Measures the rapidity of fibrin build-up and cross-linking (clot strengthening)

•assesses rate of clot formation

•normal range• 22 - 38 (native blood)• 53 - 67(kaolin-activated)

THROMBOELASTOGRAPHYWhat affects the “” angle?

• Angle by• Hypercoagulable state

• Angle by• Hypofibrinogenemia

• Thrombocytopenia

THROMBOELASTOGRAPHYThe “maximum amplitude” (MA)

Maximum amplitude

•MA is a direct function of the maximum dynamic properties of fibrin and platelet bonding via GPIIb/IIIa and represents the ultimate strength of the fibrin clot

•Correlates to platelet function• 80% platelets• 20% fibrinogen

•normal range• 47 – 58 mm (native blood)• 59 - 68 mm (kaolin-activated)• > 12.5 mm (ReoPro-blood)

THROMBOELASTOGRAPHYWhat affects the “MA” ?

•MA by• Hypercoagulable state

•MA by• Thrombocytopenia• Thrombocytopathy• Hypofibrinogenemia

THROMBOELASTOGRAPHYFibrinolysis

•LY30

•measures % decrease in amplitude 30 minutes post-MA

•gives measure of degree of fibrinolysis

•normal range• < 7.5% (native blood)• < 7.5% (celite-activated)

•LY60• 60 minute post-MA data

THROMBOELASTOGRAPHYOther measurements of Fibrinolysis

•A30 (A60)

• amplitude at 30 (60) mins post-MA

•EPL

•earliest indicator of abnormal lysis

•represents “computer prediction” of 30 min lysis based on interrogation of actual rate of diminution of trace amplitude commencing 30 secs post-MA

•early EPL>LY30 (30 min EPL=LY30)

•normal EPL < 15%

THROMBOELASTOGRAPHYWhat measurements are affected by fibrinolysis?

Fibrinolysis leads to:• LY30 / LY60 • EPL• A30 / A60

THROMBOELATOGRAPHYQuantitative analysis

• Clot formation• Clotting factors - r, k times

• Clot kinetics• Clotting factors - r, k times• Platelets - MA

• Clot strength / stability• Platelets - MA• Fibrinogen - Reopro-mod MA

• Clot resolution• Fibrinolysis - LY30/60; EPL A30/60

THROMBOELATOGRAPHY-Qualitative analysis

Start Minutes

Amplitude

Increased in patients with

clotting defects

Decreased in patients with platelet

dysfunction or defect fibrin formation

TEG

Reaction time

Thromboelastography

TEG treatment algorithm

• r>7 min but <10.5 min mild clotting factors 1 FFP

• r>10.5 min but <14 min mod clotting factors 2 FFP

• r>14min severe clotting factors 4 FFP

• MA<48mm mod in platelet no/function 1platelet

• MA<40mm severe in platelet no/function 2platelet

Indications

Cardiac Surgery

• Cardiac surgical procedures that have a moderate to high risk of requiring a blood transfusion (1) should have the full cardiac protocol.

• 1 Combined procedures eg CABG + AVR• 2 Multiple valve replacement/repair• 3 Aortic Root surgery• 4 Thoracic Aortic surgery• 5 Re-do operations• 6 Emergency surgery – especially patients from the cardiac catheter

lab.• 7 Anticipated prolonged cardiopulmonary bypass

IndicationsPatient factors

• 1- Patients on aspirin and clopidrogel <7 days

• 2- Patients on Warfarin or heparin

• 3- Pre-existing platelet &/or clotting factor abnormalities

IndicationsVascular Surgery.

• ‘Open’ procedures on the thoracic aorta.

• ‘Open’ abdominal procedures where a significant blood loss is anticipated.

• Patient factors: 1 – 3 as above *

• Regional anaesthetic techniques (see below)

IndicationsRegional anaesthetic techniques (inc. use in Obstetrics)

• If the platelet count is between 50 –80,000 a TEG should be performed if a regional technique is considered necessary.

• If the platelet count is > 80,000 a TEG is not necessary unless there are additional factors.

• A regional technique is not advised if the platelet count is < 50,000.

•A TEG should be performed if a regional technique is considered necessary within 12 hours following prophylactic LMWH or 24 hours post therapeutic LMWH