Transcript Hemostasis Part1

Haemostasis
part1
Haima + Stasis
Prevent blood
loss
Maintains blood flo
Prevents bleeding
Components of hemostasis
Interactive
Components: vascular
Intact endothelium: Non-thrombogenic
(-)
Components: platelets
Adhesion
Activation
Aggregation
Secretion
Procoagulant
activity
Components: coagulation
pathways
Pivotal point of coagulation
Extrinsic (TF)
Initiation
Intrinsic
Amplification
Primary haemostasis I:
● Capillaries and larger blood vessels react to injury by
an immediate local temporary vasoconstriction (a reflex nervous
mechanism) to reduce the amount of blood lost.
Secundary haemostasis:
Blood coagulation factors are necessary to stop bleeding
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definitely.
I:
fibrinogen
II: prothrombin
III: tissue thromboplastin (tissue factor, TF)
IV: Ca++
V: proaccelerin
VI: VII: proconvertin
VIII: antihemophilic factor (AHF)
IX: Christmas factor (plasma thromboplastin component)
X:
Stuart factor
XI: plasma thromboplastin antecedent (PTA)
XII: Hageman factor (contact factor)
XIII: fibrin stabilizing factor (Laki-Lorand factor)
Process- primary haemostasis
• In a normal individual, coagulation is initiated
within 20 seconds after an injury occurs to the
blood vessel damaging the endothelial cells.
• Platelets immediately form a haemostatic plug
at the site of injury. This is called primary
haemostasis.
Secondary haemostasis
• Secondary haemostasis then follows—plasma
components called coagulation factors respond (in a
complex cascade) to form fibrin strands which
strengthen the platelet plug.
• Contrary to popular belief, coagulation from a cut on
the skin is not initiated by air or drying out, but by
platelets adhering to and activated by collagen in the
blood vessel endothelium.
• The activated platelets then release the contents of
their granules, these contain a variety of substances
that stimulate further platelet activation and
enhance the haemostatic process.
Coagulation cascade
• The coagulation cascade of secondary hemostasis has two
pathways, the Contact Activation pathway (formerly known
as the Intrinsic Pathway)
• And the Tissue Factor pathway (formerly known as the
Extrinsic pathway) that lead to fibrin formation.
• It was previously thought that the coagulation cascade
consisted of two pathways of equal importance joined to a
common pathway.
• It is now known that the primary pathway for the initiation
of blood coagulation is the Tissue Factor pathway. The
pathways are a series of reactions, in which a zymogen
(inactive enzyme precursor) of a serine protease and its
glycoprotein co-factor are activated to become active
components that then catalyze the next reaction in the
cascade
Prothrombin
Xa
Va
Thrombin
Fibrinogen
Fibrin
Extrinsic Pathway
TF
Prothrombin
VIIa
Xa
Va
Thrombin
Fibrinogen
Fibrin
Intrinsic pathway
XIIa
Extrinsic Pathway
XIa
TF
Prothrombin
IXa
VIIIa
VIIa
Xa
Va
Thrombin
Fibrinogen
Fibrin
Intrinsic pathway
XIIa
Extrinsic Pathway
XIa
TF
Prothrombin
IXa
VIIIa
Fibrinogen
VIIa
Xa
Va
Thrombin
Soft clot
Fibrin
XIIIa
Hard clot
Fibrin
Coagulation made easy
The PTT Pathway
The PT Pathway
Coagulation made easy
The PTT Pathway
The PT Pathway
X
The PT and the PTT pathway meet
at factor X, because “X” marks the
spot
Coagulation made easy
The PTT Pathway
The PT Pathway
V
X
Factor V is a cofactor for factor X,
and you can remember this
because V fits into the notch of
the X
Coagulation made easy
The PTT Pathway
The PT Pathway
V
X
Prothrombin
Thrombin
Factor Xa converts prothrombin (Factor II) into thrombin, the most
important enzyme on the planet
Coagulation made easy
The PTT Pathway
The PT Pathway
Thrombin, among other
things, converts the
soluble molecule
fibrinogen into a solid
fibrin clot
V
X
Prothrombin
Thrombin
Fibrinogen
Fibrin
Coagulation made easy - the PT
The PT Pathway
PT has one less letter than PTT,
and PT values are shorter than
PTT values, because the
pathway is shorter. It means
that the PT pathway is also
shorter and this is lucky, so the
lucky PT pathway uses lucky
factor 7 to activate factor X
Prothrombin
7
V
X
Thrombin
Fibrinogen
Fibrin
Coagulation made easy - the aPTT
The PTT Pathway
XII
The PTT pathway has all those
hideous roman numerals. . .
How are we going to
remember them? Hmmmmm.
......
XI
IX
VIII
Prothrombin
V
X
Thrombin
Fibrinogen
Fibrin
Coagulation
made
easy
the
aPTT
The PTT Pathway
T
Well, just remember that the
PTT is a basic TENET of
hematology.
TENET stands for. . . . . .
E
N
E
T
Prothrombin
V
X
Thrombin
Fibrinogen
Fibrin
Coagulation made easy - the
aPTT
The PTT Pathway
Twelve
Eleven
Nine
Eight
Ten
Prothrombin
V
X
Thrombin
Fibrinogen
Fibrin
Coag Made Easy: PT and PTT both Prolonged
The PTT Pathway
The PT Pathway
V
X
Prothrombin (II)
Fibrinogen
These factors are in the
common pathway
Coag Made Easy: Only PT Prolonged
7
Deficiency of Factor VII will prolong the PT but not the PTT
Coag Made Easy: Only PTT
Prolonged
Twelve
Eleven
Nine
Eight
Ten
Deficiencies of Factors 12, 11, 9 and 8 will
prolong the PTT and not the PT.
Remember that factor 10 is in the
common pathway, and affects BOTH the
PT and the PTT
Platelet
mediated by GP-IbAdhesion
on platelet surface and vWF
C
O
L
L
A
G
E
N
fibrinoge
n
GP-Ib
von Willebrand Factor
endothelial
cells
C
O
L
L
A
G
E
N
von Willebrand Factor
• Synthesized & stored in endothelial cells and
megakaryocytes (also stored in platelets)
• Forming bridge between subendothelial collagen
and Plt
• Carrier molecule for Factor VIII Coagulant Protein
(vWF is also known as Factor VIII
Related Antigen)
• Circulates as series of multimers (in various sizes)
• Large, high molecular weight multimers required
for normal hemostasis
Platelet Activation
release of a and electron dense granules
C
O
L
L
A
G
E
N
•Release of platelet’s
cytoplasmic products
•activation of platelet factor
III (PF-3)
PF-3 serves as a binding site for
cofactor V & VIII
•production of thrombin
GP-IIb, IIIa
Platelet Aggregation
GP IIb-IIIa - fibrinogen interaction
C
O
L
L
A
G
E
N
•formation of primary plug
•activated platelets synthesize and
secrete TXA2
TXA2:
1. promotes plt aggregation
2. vasoconstriction
3. release of plt factor (ADP)
Aspirin inhibits TXA2 and
ADP
Coagulation Factors
negative charged surface
XII
XI
tissue
factor
IX
VIII
VII
X
V
II
I
XIII
Stable clot
•Intrinsic Pathway
•Extrinsic Pathway
•Common Pathway
•majorities are serine
proteases
•circulate as inactive forms
(require activation to function)
•majority produced in liver
Coagulation Factors
negative charged surface
XII
XI
tissue
factor
IX
VIII
•Intrinsic Pathway
•Extrinsic Pathway
•Common Pathway
VII
X
V
II
I
XIII
Stable clot
•majorities are serine
proteases
•circulate as inactive forms
(require activation to function)
•majority produced in liver
•many require vit K for
synthesis
•II, VII, IX, X
•protein C, S
Newer Concepts of Coagulation Reactions
2 main functions of tissue factor (TF)
1) to activate factor X to Xa
2) to activate factor IX to IXa
Control Mechanisms
1) TF pathway inhibitor
2) Protein C system
3) Antithrombin (e.g. AT III)
4) Glycoaminoglycans
APC: activated protein C
AT : antithrombin
GAG: glycoaminoglycans
T : thrombin
PC : protein C
S : protein S
TF : tissue factor
TM : thrombomodulin
Platelet PLUG