The document provides a detailed overview of the coagulation cascade involved in clot formation, highlighting 13 major blood factors and their roles. It describes the stages of the cascade, including the extrinsic and intrinsic pathways, as well as the monitoring of coagulation through methods like thromboelastography (TEG), which measures clot dynamics and characteristics. TEG is positioned as a vital tool for assessing hemostatic function and guiding treatment decisions in various surgical contexts where bleeding risks are prevalent.

1. TEG
thromboelastography

2. • 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

3. • 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 intoThrombin
• Stage 3: Conversion of Fibrinogen into Fibrin
Stage 2 & Stage 3 is collectively called as Final Common Pathway

4. STAGE 1

5. 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 orThromboplastin) expressed onTF-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.

6. 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 (PlasmaThromboplastin
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

7. STAGE 2

8. • 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)

9. STAGE 3

10. • 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

11. Coagulation Monitoring – ConventionalTests
Tests Of Coagulation
* Platelets
• number
• function
*Clotting studies
• PT
• APTT
*Fibrinogen levels
Tests of Degradation
* Degradation products

12. •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

13. •Besides evaluation of platelet function
remains insensitive and time consuming.
The platelet count provides only a
quantitative, not qualitative index of
platelet status.

14. • 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.

15. 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.

16. TEG
thromboelastography

17. 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 originalThromboelastography.

18. THROMBOELASTOGRAPHY
Basic Principles

19. THROMBOELASTOGRAPHY
Basic 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

20. THROMBOELASTOGRAPHY
Basic 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

21. THROMBOELASTOGRAPHY
The “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)

22. THROMBOELASTOGRAPHY
What affects the “r” time?
•r time  by
• Factor deficiency
• Anti-coagulation
• Severe
hypofibrinogenaemia
• Severe
thrombocytopenia
•r time  by
• Hypercoagulability
syndromes

23. THROMBOELASTOGRAPHY
The “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)

24. THROMBOELASTOGRAPHY
What affects the “k” time?
•k time  by
• Factor deficiency
• Thrombocytopenia
• Thrombocytopathy
• Hypofibrinogenaemia
•k time  by
• Hypercoagulability
state

25. THROMBOELASTOGRAPHY
The “” 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)

26. THROMBOELASTOGRAPHY
What affects the “” angle?
• Angle  by
• Hypercoagulable
state
• Angle  by
• Hypofibrinogenemia
• Thrombocytopenia

27. THROMBOELASTOGRAPHY
The “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)

28. THROMBOELASTOGRAPHY
What affects the “MA” ?
•MA  by
• Hypercoagulable
state
•MA  by
• Thrombocytopenia
• Thrombocytopathy
• Hypofibrinogenemia

29. THROMBOELASTOGRAPHY
Fibrinolysis
•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

30. THROMBOELASTOGRAPHY
Other 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%

31. THROMBOELASTOGRAPHY
What measurements are affected by
fibrinolysis?
Fibrinolysis leads to:
•  LY30 /  LY60
•  EPL
•  A30 /  A60

32. THROMBOELATOGRAPHY
Quantitative 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

33. THROMBOELATOGRAPHY-Qualitative analysis

34. Start Minutes
Amplitude
Increased in
patients with
clotting
defects
Decreased in patients
with platelet
dysfunction or defect
fibrin formation
TEG
Reaction
time
Thromboelastography

35. 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

36. 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

37. Indications
Patient factors
• 1- Patients on aspirin and clopidrogel <7 days
• 2- Patients onWarfarin or heparin
• 3- Pre-existing platelet &/or clotting factor abnormalities

38. Indications
Vascular 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)

39. Indications
Regional 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