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
• 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
• The formation of blood clot (Thrombus) in uninjured vessel.
• Thrombotic occlusion of a vessel after a relatively minor injury.
3. Components of hemostasis
Hemostasis is a complex process and actually comprises a number of distinct, but
closely linked biochemical systems. The blood platelets are responsible for
primary hemostasis and for providing the framework for subsequent coagulation
and wound healing. Fibrinolysis is required for the removal of fibrin that is no
longer needed and for the eventual remodeling of the injured area. All these
systems are closely linked to inflammation, especially through contact activation
4. Three phases of hemostasis
• Primary hemostasis
▫ formation of a platelet ‘plug’
• Secondary hemostasis
▫ consolidation of the platelet plug by fibrin
9. Fig. 1. Wound healing is a
encompassing a number of
angiogenesis and matrix
formation of a blood clot
and provides a provisional
matrix for cell migration.
Cytokines play an
important role in the
evolution of granulation
tissue through recruitment
leukocytes and stimulation
of fibroblasts and
epithelial cells. [Note:
figure is adapted from
10. Normal Hemostasis: 1
General Sequence of Events are:
Endothelial injury : it is also exposed highly thrmbogenic
subendothelial extracellular matrix (ECM) which allow platelets to adhere
ie. a shape change
Release of secretory
Within a minute secretory
product recruits several
platelets to form hemostatic
Vasoconstriction : After a initial injury there is a brief period of
arteriolar vasoconstriction due to
Reflex neurogenic mechanism
Local secretion of the factors such as
11. three main mechanisms underline the
The congregation and clumping of blood platelets at the site of vascular
injury, thus effectively plugging the site of blood leakage.
Localized constriction of the blood vessel, which minimizes further blood
flow through the area.
Induction of the blood coagulation cascade. This culminates in the
conversion of a soluble serum protein, fibrinogen, into insoluble fibrin.
Fibrin monomers then aggregate at the site of damage, thus forming a clot
(thrombus), which seals it off. These mechanisms are effective in dealing
with small vessel injuries, e.g. in capillaries and arterioles, although they
are ineffective when the damage relates to large veins/arteries.
12. Normal Hemostasis:2
General Sequence of Events are:
Polymerized fibrin & platelet aggregates form a permanent plug to
prevent any further hemorrhage
Tissue Factors: a membrane bound procougulant factors is
synthesized by the endothelium, also released at the site of injury.
It act in conjugation with secreted
platelet factor actor to activate the
coagulation cascades in activation
In turn thrombin cleave fibrinogen
into insoluble fibrine, creating a
Thrombin also induced further
platelet requirement & granules
aspect of anti-
It may activated by infectious
agents, hemodynamic factors
plasma mediators & CK
14. Antithrambic Properties
• An intact endothelium prevent platelets from meeting from highly thrmbogenic
• Nonactivated platelet do not adhere endothelium an intrinsic property of endothelium.
• If platelets are activated they are inhibited from adhering to surrounding uninjured
endothelium by prostacyclin (PGI2) & Nitric oxide
• Both mediators are potent vasodilators & Inhibitors of platelet aggregation.
• Syntasis of PGI2 is stimulated by a no of factors eg CK, thrombin, thrombomoduline
16. Figure 51–8. Diagrammatic representation of platelet activation. The external environment,
the plasma membrane, and the inside of a platelet are depicted from top to bottom.
Thrombin and collagen are the two most important platelet activators. ADP is considered
a weak agonist; it causes aggregation but not granule release. (GP, glycoprotein; R1–R5,
various receptors; AC, adenylyl cyclase; PLA2, phospholipase A2; PL, phospholipids; PLCβ,
phospholipase Cβ; PIP2, phosphatidylinositol 4,5-bisphosphate; cAMP, cyclic AMP; PKC,
protein kinase C; TxA2, thromboxane A2; IP3, inositol 1,4,5-trisphosphate; DAG, 1,2-diacylglycerol.
The G proteins that are involved are not shown.)