HEMOSTASIS

Major Components of Blood Clotting

1. Intact endothelial cells

Inhibit blood clotting

Surface not conducive to clot formation
Display membrane proteins that inhibit
clotting
Store vWF in cytoplasm granules.
Constitutively expressed and secreted
into circulation or subendothelium. (20
% made by platelets, the rest
endothelium)
Make prostacyclin inhibits platelet
aggregation

Platelet activation also induces large

morphological changes

Membrane lipids rearrange

Phosphatidyl serine which is usually on
the inner membrane of the platelet, flips
out to outer membrane where it plays a
role in binding prothrombin.

2. (Di napicrturan)

3. Platelets

Unpigmented, enucleated cells that are

fragments of larger progenitor cells
called megakaryocytes (bone marrow)
Once bound release TxA2 and serotonin
(and more) that induce vasoconstriction
to reduce blood flow and increase
platelet aggregation.

1
Step 2: Fibrin is formed by cleaving
fibrinogen (Factor I)
Thrombin catalyzes the conversion of
fibrinogen to fibrin
Fibrinogen is 2-3% of plasma protein
Fibrinogen has 3 pairs of non-identical
subunits
o A (610 res)
o B (461 res)
o (411 res)
Coagulation has been divides into two
also 2 pairs of N-linked oligosaccharides
systems:
A and B refer to parts of and
released upon thrombin cleave A (20
aa); B (18 aa)
Mechanism of Coagulation
Initiation of coagulation process may
occur via one of two pathways
Converge into common pathway
Outcome of this process is the
conversion of circulating insoluble
coagulation factors into gelatinous fibrin
clot with entrapped blood cells, a blood
clot.
The intrinsic system in which all
substances are necessary for clotting
are present in the blood
The extrinsic system in which tissue
factors is necessary for coagulation

Clotting Pathways

1. Intrinsic
4. Clotting Factors
All components are in the blood
Soluble plasma proteins Must have a negative surface (glass
Most made in liver slide)
Most are serine proteases and circulate
as zymogens 2. Extrinsic
Cascade in which clotting factors are
At least one component from tissue;
activated by selective cleavage must
injury response
have Ca++
Need tissue factor (TF) for activation of
VIIa
TF and Factor VIIa contact only after
injury
TF - Factor VIIa complex also activates
Factor Xia

Clotting is localized by requiring a negatively

charged surfaced so initially, platelets bind
collagen, and later clot formation promoted by
platelet membranes on surface of clot.

2
Extrinsic Coagulation Pathway

It is initiated by the entry of the tissue

thromboplastin intop the circulating
blood
Tissue thromboplastin is derived from
phospholipoproteins and organelle
membranes from disrupted tissue cells
(tissue factors)
Factor VII binds to these phospholipids
in the tissue cell membranes and is
activated to factor VIIa, a potent enzyme
capable of activating factor X to Xa in
the presence of ionized calcium

Final Common Pathway

Once Factor X is activated to Factor Xa,

the extrinsic and intrinsic pathway enter
a common pathway
Factor II is activated to thrombin, which
normally circulates in the blood as an
inactive factor
Following activation of Factor Xa, it
remains platelet bound and activates
Factor Va on the platelet surface is
formed near platelet bound Factor II
molecules