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
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
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
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
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