Haemostasis

Q1: Define haemostasis

 Haemo= blood ( bleeding)
 Stasis= stop

 Arrest of bleeding
Definition:

 Physiological
processes to stop the
bleeding from the
injured vessel,forming
a hemostatic clot, then
dissolve blood clot
after vessel wall repair
Normal blood flow
-Vessel wall injury (Linning endothelium
injury)------ bleeding
- Platelets (thrombocytes) and coagulation
factors prevent bleeding, by forming a blood
clot
Q2:No blood clot is formed in the normal vessel:
WHY

 1-Healthy
endothelium linning
the blood vessel is
smooth, negatively collagen

charged so this will

repel platelets and
endothelium
prevent their
adhesion Cross section in arterial wall

Smooth
collagen muscle
 2- Healthy endothelium
secrete prostacyclin
and nitric oxide that
prevent platelet
aggregation
 The trigger for

haemostasis is the
endothelim injury
 Exposed collagen
Q3: Haemostasis steps
 1- vasoconstriction:
to narrow vessel lumen
 2- Platelet plug

formation
Seal the vessel opening
 3- Blood clotting

Form fibrin meshwork,

transform the plug
into clot
Q4: Mechanism of vasoconstriction after injury

 Myogenic spasm:
 Direct damage to blood
vessel
 Nervous reflex
 Traumatic pain stimulate
sympathetic nerves
 Humoral factors
 Serotonin
 Thromboxane A2
 from plalelets
 Q5:Importance of vasoconstriction
 1- Narrow vessel
wall , decrease blood
escape from the
vessel
 2- Increase the
contact between
vessel wall and the
platelets or the
coagulation factors
PLATELET PLUG
FORMATION
Q6:Steps of Platelet plug formation
 1- Platelet adhesion
 2- platelet aggregation
 3- platelet activation
 4- clot retraction
Platelet plug formation: 1- adhesion

 Platelets don’t
normally adhere to the
vessel wall
 Following endothelial
injury, subendothelial
collagen is exposed
 Von willebrand factor
is expressed on the Von willebrand
collagen factor
Platelet plug formation:1- adhesion

 Platelet adhere to the

collagen through
binding to the von
willebrand factor Von willebrand
receptor on the
platelet

Von willebrand
factor
Q: What is von willebrand factor

 protein secreted by Von willebrand

injured endothelial receptor on the
platelet
cells
 Function
 Bridge between vessel Von willebrand
factor
wall and platelet first
layer
Platelet plug formation: 2- aggregation

 Following adhesion
-platelet shape change:
Swell and become sticky
with irregular in shape
with numerous irradiating
pseudopods.
Platelet plug formation: 3- activation

 Platelets secrete:
 ADP
 Thromboxane A2
 Serotonin
Q7:What are the important chemicals released from
platelet granules

1-ADP
 Causes platelet surface
to become sticky,
ADP
increase pseudopodia,
more adhesion more
ADP release
ADP receptor
More on platelet

aggregation
Positive feedback
Q7:What are the important chemicals released from
platelet granules

2-
Serotonin
Serotonin
Q7:What are the important chemicals released from
platelet granules

3-Thromboxane A2

 Platelet aggregation, Thromboxane

vasoconstriction A2
FINALLY: Clot retraction
 pull wound edges together
 Decrease clot size
 Squeeze serum out
Summary to platelet plug events
BLOOD COAGULATION
Fibrin meshwork
Q9: Define blood coagulation
 Transformation of blood into
solid gel termed blood clot
through series of reactions
 Plasma protein (Fibrin) strands
are interlaced on the surface of
platelet plug, then covalent
cross linkage form between
them to strengthen the clot
 Fibrin clot will seal vessel until
new cell growth and vessel
repair
What is fibrin (coagulation factor
I)
 plasma protein fibrinogen
 (clotting factor) Activated Through
coagulation
(clotting)
pathway
Fibrin
Vessel clot
Injury
Plasma proteins
(Coagulation factors )

Coagulation factors are generally indicated by Roman

numerals
 Coagulation factors
I Fibrinogen VIII Antihemophilic Factor

II Prothrombin Von Willebrand Factor

III Tissue Factor IX Christmas Factor

IV Ionized Ca+2 X Stuart-Prower Factor

V Labile Factor XI Plasma Thromboplastin

Antecedent

XII Hageman Factor

VII Stable Factor XIII Fibrin-stabilizing Factor

Coagulation (clotting) pathway (cascade)

 Serial activation of the coagulation factors (clotting

factors) into active enzymatic forms
 Each enzyme catalyzes the conversion of the next
clotting factor in the series to its active enzymatic form
 Finally fibrin monomers are formed
Vessel Plasma proteins
Injury (Coagulation factors )

 There are 2 (intrinsic, extrinsic) pathways , Both will

eventually join together to form the common pathway.
 Q10: Draw Coagulation pathway
Intrinsic (Contact Extrinsic (tissue
activation pathway) factor pathway)
III (tissue Injure
Exposed XII factor) d
collagen
tissue
XI VII

VII Extrinsi
Intrinsic tenase IX Ca +2 Ca+2 c tenase
I
complex complex
phospholipid
phospholipids
s

X
 The common pathway

X Ca+2
Prothrombinase
V phospholipids complex

thrombi
prothrombin n

XII
I
Q:What are the 2 coagulation pathways

Intrinsic pathway Extrinsic pathway

 Slower
 Produces large amount
of thrombin
 Everything necessary
for it is in (intrinsic to)
the blood
 Rapid
 produces thrombin in
small amounts at first
 Need components
outside the blood
vessel as tissue factor
Link between 2 pathways
Intrinsic (Contact Extrinsic (tissue
activation pathway) factor pathway)
XII III

VII
XI

VII Ca +2
IX Ca+2
I
phospholipid
phospholipids
s

X
 Q11: Role of vitamin K in haemostasis

 Fat soluble vitamin

 Absorbed in small intestine

 Requires bile salts for its

absorption
Sources of vitamin K in the
human body :
 Intestinal bacteria flora

continually synthesize
vitamin K.
 Diet.
 Q11: Role of vitamin K in haemostasis

Importance:
 necessary for the liver

formation of prothrombin,
factor ,VII, IX and X {2, 7, 9,
10}
Vitamin K deficiency:
Effect:
 subsequent deficiency of these

factors leads to bleeding

tendency
Causes:
 Obstructive jaundice

 Long antibiotic use

Q12: Role of thrombin in haemostasis

Thrombin receptor on platelet III

XII
surface
VII
XI Ca+2
VII phospholipids
IX Ca +2
I
phospholipid
s

X V
phospholipids
Ca+2
prothrombi thrombin
n

XIII
Fibrin
Fibrin polymer monomer
Q12: Role of thrombin in haemostasis

 1- conversion of fibrinogen to fibrin

 2- Activates factor 13 fibrin stabilizing factor
 3- Activate factor 5, 8 so stimulate its own
formation (positive feedback)
 4- enhance platelet activation
Q13: Role of calcium
 Calcium ions are required for acceleration of blood
clotting reaction except the first 2 steps in the
intrinsic pathway
 Calcium concentration in the blood can never get
so low to cause defect in the coagulation pathway,
because death due to tetany would preceed
Q 14:Role of platelet in coagulation

 Bond the fibrin fibers

together.
 Release of coagulation
factors as, fibrin
stabilizing factor (XIII)
 Negative charged
surface that facilitate
the assembly of
coagulation complexes
 Summary: Coagulation
 2 pathways:
 Rapid extrinsic {tissue factor III +factor VII + Ca +2+PF3 }
 Slow intrinsic{ factor12, 11, 9}, {factor 9+8 + Ca +2+PF3 }
Stimulate factor 10 X
 Common pathway: {10+ 5+ Ca+2+PF3 } stimulate
 Convert fibrinogen to thrombi
fibrin
Stimulate fibrin stabilizing
n
factor (XIII)
Stimulate factor5, 8 {+
feedback}
function Factor
Platelet adhesion Von willebrand factor
Platelet aggregation Thromboxane A2, ADP
Inhibit platelet aggregation Prostacyclin, nitric oxide
Extrinsic pathway Factor 3, 7
Intrinsic pathway Factor 12, 11, 9, 8
Common pathway Factor 10, 5, thrombin,
fibrin, 13
Convert fibrinogen to fibrin Thrombin
Stimulate fibrin stabilizing factor (XIII)
Stimulate factor5, 8 {+ feedback}
important for formation of Factor 2, 7, Vitamin K {Fat soluble
9, 10 in liver vitamin } produced by
bacterial flora, absorbed in
intestine, needs bile
ANTICLOTTING
MECHANISMS