Coagulation Profile.Platelet function test,extrinsic and intrinsic pathway

1. Dr VIKASH
Junior Resident 1,Pathology
IMS,BHU

2. Hemostasis
Normal physiological mechanism for
keeping the blood in fluid state in vascular
system and for prevention of hemorrhage by
complex interaction of blood vessels wall ,
platelets and plasma proteins.
 Primary type- Platelets plugs(b/w blood
vessels and platelets)
 Secondary type-(Activation of coagulation
factors by a series of enzymatic activity to
form fibrin clot)

3. Hemostasis
Purpose
 Ensure that coagulation mechanisms are
 activated when there is injury
 not unnecessarily activated
Restore tissue blood flow after repair of injury
(fibrinolysis)

4. Hemostatic Process
3 main steps
 Primary hemostasis: local vasoconstriction &
platelet plug formation
Coagulation cascade
 Fibrinolysis

5. Platelets
 Cytoplasmic fragmentation of megakaryocyte in bone
marrow
 Life Span- 7 to 10 days
 Normal Platelet Count-(150 – 400) × 103 per mm3.

7. Hemostatic Process
Platelet Plug Formation
• vascular injury
• release and binding of vWF to
exposed blood vessel collagen
• glycoprotein IB on platelet
surface membrane binds to vWF

8. Platelet Activation & Aggregation
exposed endothelial surface
platelets exposed to collagen
“activated”
release contents of cytoplasmic granules
adenosine diphosphate (ADP) thromboxane (Tx A2)
accelerates platelet vasoconstriction
aggregation/activation ↑ ADP release from platelets

9.  Blood Vessels-Endothelial cells
von Willebrand factor, Tissue factor , PAF
(help in clotting)
Subendothelial collagen
Prostacyclin(inhibit platelet aggregation),Protein C,
S(Inhibit coagulation),TPA(fibrinolysis)

10. Hemostatic Process
Coagulation Cascade
 to stabilize and reinforce the weak platelet plug
 fibrinogen → fibrin
 3 main steps:
1. formation of prothrombin activator
2. conversion of prothrombin into thrombin
3. conversion of fibrinogen to fibrin

11. Coagution System

14. Coagulation Mechanism
 activation of clotting factors
 requires a phospholipid surface
 tissue factor (TF) extrinsic to the blood
 activated platelet (platelet factor 3
phospholipid) intrinsic to blood
 vitamin-K dependent factors (II, VII, IX, X)
 formation of reaction complex
 labile factors : factors V and VIII

15. Bleeding Disorders
 Defect in any of the step of coagulaton system starting
from abnormalities of blood vessels,Platelets,or
Coagulation factors
 Symptoms are Petechie,Purpura,Ecchymoses,and
mucous membrane bleeding

17. Disorder of Platelets
 Disorder in no- <1,50,000/cmm
 ITP(Idiopathic Thrombocytopenic Purpura): Acute type-
Children,Viral infection,Platelet very low,Complete remission
Possible .
 Chronic type- Adult(esp female),Platelet moderately decrease,
Remission and exacerbation over a long duration.
Bone marrow show increase Megakaryocytes.
 TTP(Thrombotic thrombocytopenic purpura)-Hyaline
microthrombi due to clumping of platelets because of large
multimer of vWF. Causes Thrombocytopenia
 HUS(Hemolytic Uremic Syndrome)-Consumption of food
contaminated with E.coli esp in children. Triad of
ARF,thrombocytopenia,and microangiopathic hemolytic
anemia

18. Disorder of Platelet Function
 Characterise by Prolong Bleedind time and normal platelet
time.
 Bernard Soulier Syndrome-(Defective adhesion)
Rare, AR,Congenital absence of GpIb/IX(glycoprotein)
cause faliure of adhesion of platelet to subendothelium via
vWF.
Causes severe bleeding manifestation
 Glanzmann’s thromboaesthenia-(Defective aggregation)
Very rare,AR,Congenital absence of GpIIb/IIIa on platelet
surface.
Lab Finding-Discrete,small platelet 0n smear,poor clot
retraction

19. Aspirin
 Inhibit enzyme cyclooxygenase Faliure to synthesise
Thromboxane A2 Inhibit Platelet aggregation
arachidonic acid ASPIRIN
cyclooxygenase
prostaglandin G2 NSAIDS
peroxidase
prostaglandin H2
prostacycline
thromboxane
synthetase
synthetase
prostacyclin
thromboxane A2
PG F1a
thromboxane B2

20. Inherited disorder of coagulation
 Hemophilia A(factor VIII deficiency)
 Hemophilia B(factor IX deficiency)
 von willebrand Disease(VWD)

21. Laboratory Monitoring
Prothrombin Time (PT)
 test of extrinsic pathway activity
 measures vitamin K - dependent factors activity (factors
II, VII, IX, X)
 thromboplastin + Ca+2 to plasma = clotting time
 normal values: 12-14 seconds
 International Normalized Ratio (INR)
▪ standardizes PT reporting
 normal values: 0.8 -1.2 seconds

22. Laboratory Monitoring
Prothrombin Time (PT)
monitors coumadin therapy
most sensitive to alteration in F VII levels
 prolonged: 55 % ↓ of normal F VII activity
 antithrombotic activity: reduction of factor II and
factor X activity (after several days)

23. Laboratory Monitoring
Activated Partial Prothrombin Time (aPTT)
 test for intrinsic and common pathways
 dependent on activity of all coagulation factors,
except VII and XIII
 normal values: 25 -35 seconds
monitors heparin tx & screen for hemophilia

24. Laboratory Monitoring
Activated Partial Prothrombin Time (aPTT)
 prolonged: heparin, thrombin inhibitors,
fibrin degradation products (FDP)
 citrated plasma + surface activators +
phospholipid
 prolonged only if coagulation factors reduced to <
30 % of normal

25. Laboratory Monitoring
Activated Clotting Time (ACT)
monitors heparin anticoagulation in
the OR (cardiac and vascular surgeries)
normal values: 90 - 120 seconds

26. Laboratory Monitoring
Thrombin Clotting Time (TCT)
 reflects abnormalities in fibrinogen → fibrin
 plasma + excessive amount of thrombin
 prolonged: heparin, thrombin inhibitors,
low fibrinogen, dysfibrinogenemia
 monitors hirudin, bivalirudin, LMWH tx
 INR & PT may be normal or ↑
 TCT prolonged with adequate therapeutic levels

27. Laboratory Monitoring
Thromboelastography (TEG)
 continuous profiles during all phases of
clot formation
 provides more accurate picture of in vivo coagulation process
 to evaluate:
• hypo / hypercoagulable state
• hemophilia
• dilutional coagulopathy
• rare coagulation disorders anticoagulation tx
• coagulation problems with liver transplantation

28. Thromboelastogram
(TEG)

29. Bleeding time
monitors platelet function
 not specific indicator of platelet function
 not very reliable
 very operator - dependent
 variable from each institution

30. Laboratory Monitoring
Platelet Function Analyzer (PFA) - 100
 relatively new global test of platelet adhesion and aggregation
 advantages
 noninvasive, simple, easy to perform
 very sensitive in detecting platelet defects
associated with vWD
 sensitive to dx of acquired platelet defects (ASA, NSAID,
dietary factors: excessive cocoa intake)
 monitors pro-hemostatic treatment
 DDAVP & platelet transfusions

31. LABORATORY TEST
COMPONENTS MEASURED
NORMAL
VALUES
Bleeding time platelet function
vascular integrity
3 - 10 mins
PT I, II, V, VII, IX, X 12 - 14 secs
PTT I, II, V, VIII, IX, X, XI, XII 24 - 35 secs
Thrombin time I, II 12 - 20 secs