HAEMOSTASIS

CASE STUDY
• John, a 20 yr old male has ALL. He is receiving
chemotherapy. Two weeks after the second
treatment he noted small reddish-purple
spots on his lower legs and ankles. A CBC
revealed: Hb 9g/dL; WBC 2x109/L; Platelets
19x109/L. Consider what may be responsible
for the pancytopenia and potential
consequences of this condition.

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 Introduction to haemostasis and coagulation
mechanisms ( Extrinsic and intrinsic coagulation
mechanisms )
Introduction
• Blood circulates in a closed system
• Injury to Blood vessels results in bleeding
• Normally blood loss is minimised thru:
• Formation of clot (platelets + plasma proteins) –
Structural barrier.
• The barrier is Ltd to site so that normal blood flow is
maintained.
• Haemostatic mechanism is activated where and when
needed.
• Same elements provide surveillance mechanism that
prevents leakage of plasma and blood cells into tissues.2
 Introduction..
Haemostasis
from Greek
Blood Halt
– Process of forming the barrier to blood & limiting it to
injured site.
– Involves the interaction between vessel wall, circulating
platelets with normal function & coagulation plasma
proteins; further mechanisms are inhibitory & Fibrinolysis.
• Barrier mass is called Haemostatic plug, Blood clot or
thrombus.
• The plug is formed by the process of coagulation.

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 Stages of haemostasis
Occurs in stages:
1. Primary haemostasis
2. Secondary haemostasis
3. Fibrinolysis
1. Primary haemostasis
• Platelets interact with injured vessel & each
other.
• Clump of platelets formed : Primary Haemostatic
Plug
• Arrests bleeding temporarily because it is fragile.

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 2. Secondary haemostasis

• Generation of fibrin
• Insoluble fibrin strands are deposited to reinforce &
stabilise the PHP to allow wound healing.
• Fibrin is formed by a series of complex biochemical
reactions from soluble plasma proteins (Coagulation
proteins), as they associate with Injured vessel &
Platelet plug(PP). – Secondary haemostatic plug.
• Note that blood has now solidified at the site of injury.

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 3.Fibrinolysis

• After wound healing, additional components of

haemostatic system break down and remove the
clot.
Components of haemostasis
• Vascular (veins, arteries, capillaries)
• Platelets
• Proteins
• Fibrin-forming
• Fibrinolytic proteins
• Inhibitors
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 NOTE
• All the stages & components are controlled by
physiological and biochemical inhibitors.
• Injury can also occur to intact un-severed
blood vessels
• Blood clot occurs in the interior – Thrombosis
as in DVT

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 Role of vascular system
Composed 3 types of blood vessels
•Arteries
•Veins
•Capillaries

Structure of blood vessels is similar

- The lumen lined with continuous layer of
endothelial cells
-Luminal surface of the endothelial cells (inside the
vessels) has a thin surface of complex protein &
carbohydrate (mucopolysaccharide )- Glycocalyx
- Abluminal surface (surface to the tissue side) is
attached to basement membrane (Unique Collagen
in a matrix of adhesive proteins)

The layers above vary in thickness and composition

to constitute various blood vessels.
-Tunica intima (endothelial cells)
-Tunica media (smooth muscle)
-Tunica adventitia ( few fibroblasts)
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 Role of vascular system
• Initiate haemostasis
• When a blood vessel is injured certain chemicals are released
from activated platelets (Serotinin & Thromboxane A2) and
other damaged cells nearby (Endothelin-1) which make the
smooth muscle that surrounds the blood vessel contract. This
results in an action called vasoconstriction which causes the
opening in the blood vessel to diminish, sometimes down to
nothing.
• Conversely endothelial cells synthesize and secrete
Prostaglandin (PGI2, Prostacyclin).
• PGI causes vasodilation of the arteioles so that there is incresed
blood flow to the injured site – clotting factors as well causing
reddening of the site
• The endothelial cells of venules contract – producing gaps btn
them. Fluid from plasma leaks into tissues making them to swell
(eodema) – increased vascular permeability 9
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 Nonthrombogenic hemostatic
functions of endothelial cells
These help to prevent blood clotting from
occuring ( functions & their consequences)
» Negatively charged – Repels platelets & hemostatic proteins
» Heparin SO4 – Inhibits fibrin formation
» Thrombomodulin – ,, ,, ,,
» PGI2 – Vasodialation; inhibits platelet aggregation
» Tissue plasminogen activator (tPA) – Activates fibrinogen
system.
» Plasminogen activator inhibitor (PAI-1) – inhibits activation
of fibrinolytic system.
» Endothelin – Vasocostriction
» Nitric oxide – Vasodilation.

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 Thrombogenic hemostatic functions
of endothelial cells
These enable formation of blood clots
» Produce and process von Willebrand factor – Carrier of
factor VIII in plasma; platelet adhesion.
» Tissue thromboplastin – initiates fibrin formation

• Functions of platelets in haemostasis- To

come later presentations

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 Coagulation system

Factor XIIa,
Coagualtion Factors Factor Xia
Phospholipids Kallikrein
Ca++ t-PA

CLOTTING FIBRINOLYSIS

AT, Protein C, Protein S, PAI-1

TFPI, 1 Macroglobulin, PAI-2
 1 Antitrypisin, C 1 PAI-3
Inactivator, Heparin 2 Antiplasmin
cofator 1-Macroglobulin
TAFI
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 The haemostatic mechanism
• Reactions are described as occurring in a
cascade - waterfall-like.
• Inactive circulating coagulation factors –
Zymogens are sequentially activated.
• Each zymogen serves as a substrate and them
as an enzyme.

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Simplified diagram of the cascade

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 Coagulation Factors
FACTOR COMMON NAME
• I Fibrinogen
• II Prothrombin
• III Tissue factor
• IV Calcium
• V Proaccelerin
• VII Proconvertin (Stable factor)
• VIIIc Antihaemophilic factor
• vWf von Willebrand factor
• IX Plasma thromboplastin component(PTC)
• X Stuart Factor
• XI Plasma thromboplastin antecedent (PTA)
• XII Hageman factor
• XIII Fibrin stabilizing factor
• HMWK Fitzgerald factor (Flaujeac factor)
• Prekallikrein Fletcher factor 16
 Coagulation Pathways
In vitro initiation of coagulation occurs via two pathways
• Intrinsic pathway – requires enzymes & protein
cofactors originally present in plasma.
• Extrinsic pathway – requires enzymes & protein
cofactors originally present in plasma as well as an
activator, tissue factor, not found in blood under
normal conditions.
• Common pathway – the two pathways meet here.
Generates soluble fibrin.
Coagulation pathways are important in the diagnosis and
management of Coagulopathies (e.g. PTT for Intrinsic
pathway and PT for extrinsic pathway)
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 Intrinsic pathway
• Only plasma factors are involved.
• Major physiological activator is sub-endothelial collagen
fibres.
• WBCs in blood have tissue factor & if released may activate
extrinsic system.
• Other extra-vascular factors enter the blood stream via the
lymphatics so term Intrinsic is rather misleading.
• In vitro studies have shown this pathway to be slow
• The delay is brought about by a great number of
procoagulants involved plus sluggishness with which the clot-
promoting Platelet phospholipids become available.
• Trace the pathway..............................
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Properties and synthesis of
coagulation factors
In next lecture

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