Hemostasis is the process by which blood is maintained in a fluid state within blood vessels and a clot is formed at the site of injury to stop bleeding. It involves platelet adhesion and aggregation to form a platelet plug, vasoconstriction, and the blood clotting cascade. Thrombosis is the formation of a blood clot within an uninjured blood vessel. The endothelium regulates hemostasis by producing anticoagulant and profibrinolytic factors but can also express procoagulant factors like tissue factor under certain conditions. A balance of pro- and anti-coagulant factors is needed to maintain normal hemostasis.

1. Dr AlokTripathi
Department of Biotechnology

2. Hemostsis &Thrombosis: Definition
• Hemostasis is result from well regulated process that maintain blood in a
fluid clot free state in a normal vessel while inducing a rapid formation of
localized hemostatic plug at the site of vascular injury.
• haemostasis—the rapid arrest of blood loss upon vascular damage, in
order to maintain a relatively constant blood volume.
• The process by which blood is maintained in a fluid state and confined to
the circulatory system
Hemostasis
• The formation of blood clot (Thrombus) in uninjured vessel.
Or
• Thrombotic occlusion of a vessel after a relatively minor injury.
Thrombosis

3. 1. Platelets adhesion and aggregation,
formation of the platelet plug
2.Vasoconstriction
3. Blood clotting
4. Final repair by connective tissue
NB!The phases are not separated but rather
manyfold interconnected
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4. http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2
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5. Classics of blood clotting
Alexander Schmidt and Paul Morawitz
discovered the enzymatic cascade nature of
blood clotting
1st phase –
activation (of
thrombokinase
which converts
prothrombin to
thrombin)
2nd phase --
coagulation
(fibrinogen is
converted to soluble
fibrin)
3rd phase –
retraction
(production of
stable fibrin)
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6. http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2
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7. Production from
megakaryocytes,
1.5-3.0 x 1011 in 1L
blood
Reservoirs of
bioactive
substances
Serotonin (5-HT)
and thromboxan
A2 potent
vasoconstrictors
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8. Factors influencing platelets adhesion
Collageen and plasma vonWillebrand factor
(vWf) iniate adhesion.
Adhesion is blocked by negative surface charge
of platelets, certain biochemical regulators (e.g.
NO, prostacyclin etc), and endothelial barrier
between collagen and blood.
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11. Diagrammatic representation of platelet activation.
The external environment, the plasma membrane, and the inside of a platelet
are depicted from top to bottom

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Intergrine: A cell surface receptors
• Cell-cell adhesion
• Cell to matrix adhesion
• SignalTransduction
• Spreading
• Apoptosis
• Migration
• Proliferation
Role of
integrine

15. Blood clots. “red thrombus”
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17. •inflammation,
•epithelialization,
•angiogenesis
•and matrix deposition.
Fig. 1. Wound healing is a
complex process
encompassing a number of
overlapping phases, including
•the formation of a blood clot re-
establishes hemostasis and provides a
provisional matrix for cell migration.
•CK play significant role in the evolution of
granulation tissue through
• recruitment of inflammatory leukocytes
•and stimulation of fibroblasts and
epithelial cells.
During inflammation,

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2nA+2nB
n(A)2 (B)2 2 n222(2222)n
Fibrin Monomer Fibrin Clot

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The disulfide rings are region containing 3 di-sulfide bonds cyclic linking homologous segment of , and 
chains. N-linked polysaccharides are represented by filled hexagons.TheArg-Gly bonds that are cleaved by
thrombin in fibrin activation are indicated

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23. The extrinsic pathway is critical in
initiating of blood clotting.
The intrinsic pathway plays an important
role in maintenance of coagulation.
There is no bleeding disorders in case of
lack XII
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24. Serine protease
inhibitors
(antithrombin III)
The protein C
system activated
by thrombin
The regulatory
influences of intact
endothelial and
blood cells
The fibrinolytic
system
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25. Antithrombin III, tissue factor pathway
inhibitor (TFPI), alpha2-macroglobulin,
C1 inhibitor jt.
Antithrombin III inhibits mainly factor
X, and factorsVII, IX, XI, XII.
Heparin and glycosaminoglycans
increase the antithrombin III activity
1000 times.
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26. Thrombomodulin and protein C are
members of an endogenous anticoagulant
system.
Thrombin complexed with
thrombomodulin loses its procoagulatory
activity, while readily activating protein C
Proteiin C destroys factorsV andVIII
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28. Endothelium
Modulate several
aspect of anti-
cougulating
properties
Anti-platelet ,Anti-
couagulent &
fibrinolytic
Exerts pro-
couagulent functions
It may activated by infectious
agents, hemodynamic factors
plasma mediators & CK

29. There is no coagulation in case of intact endothelium
Endothelial cells can produce IL-1 orTNF tissue factor,
under influence of thrombin, which has procoagulatory
activity
The surface of endothelial cells contains heparin-like
compounds, which bind antithrombin III and block
thrombin formation
Endothelial cells can produce the plasminogen activators.
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30. Platelets contain procoagulant anticoagulant
substances
Polymorphonuclear leukocytes and monocytes
produce tissue factor, factorV and present
phospholipids, which all support blood
coagulation
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31. Hypercoagulation –
thrombi and emboli,
thrombophilia
Hypocoagulation –
bleeding disorders,
hemophilia
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32. • HemophiliaA (lack
of factorVIII)
• Hemofiilia B (lack of
factor IX)
Thrombocytopenia
Deficiency of
coagulation factors
Deficiency of
vitamiin K
Vitamiin K is
important to add
gamma-
carboxyglutamate
(gla) to factors II,
VII, IX ja X.
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33. Platelets contain both substances which
activate or inhibit blood clotting
Neutrophilic granulocytes and monocytes
produce the tissue factor, the factorV, and
phospholipids which all support blood clotting
processes.
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34. In case of intact endothelium there is no clotting
Endothelial cells can produce under influence of
thrombin, IL-1,TNF the tissue factor, which can iniate
external pathway of blood clotting
On the surface of endothelium are heparin-like
substances which bind antithrombin III ühendid, mis
seovad antitrombiin III and inhibit thrombin activity.
Endothelial cells produce plasminogen activators.
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A good overview and illustrations: http://ntri.tamuk.edu/homepage-ntri/lectures/clotting.html