HEMOSTASIS
Primary hemostasis
HEMOSTASIS
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Hemostasis
The process by which the body stops bleeding upon
injury and maintains blood in the fluid state in the
vascular compartment
 Process is rapid and localized
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HEMOSTASIS
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The primary players in hemostasis include
Blood vessels
 Platlets
 Plasma proteins
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Coagulation proteins – involved in clot formation
 Fibrinolysis – involved in clot dissolution
 Serine protease inhibitors
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Other minor players include
Kinin system
 Complement system
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HEMOSTASIS
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Defects
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In blood vessels, platlets or serum proteins can be
corrected by utilization of the other 2 players
In 2 of the 3 players results in pathologic bleeding
Blood Vessels
Platlets
Plasma Proteins
HEMOSTASIS
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Hemostasis can be divided into two stages
 Primary hemostasis
Response to vascular injury
 Formation of the “platelet plug” adhering to the endothelial wall
 Limits bleeding immediately
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Secondary Hemostasis
Results in formation of a stable clot
 Involves the enzymatic activation of coagulation proteins that
function to produce fibrin as a reinforcement of the platelet plug
 Gradually the stable plug will be dissolved by fibrinolysis
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FORMATION OF A STABLE PLUG
VASCULAR SYSTEM
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Smooth and continuous endothelial lining is designed to
facilitate blood flow
Intact endothelial cells inhibit platelet adherence and blood
coagulation
Injury to endothelial cells promotes localized clot formation
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Vasoconstriction
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Narrows the lumen of the vessel to minimize the loss of blood
Brings the hemostatic components of the blood (platelets and plasma
proteins) into closer proximity to the vessel wall
Enhances contact activation of platlets
 Von Willebrand factor
 Collagen fibers
 Platlet membrane glycoprotein Ib
Activated platlets enhance activation of coagulation proteins
PRIMARY HEMOSTASIS

Platelets
Interact with injured vessel wall
 Interact with each other
 Produce the primary hemostatic plug
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Primary platelet plug
Fragile
 Can easily be dislodged from the vessel wall
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PLATELETS
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Platelets
Small, anucleated cytoplasmic fragments
 Released from megakaryocytes in the BM
 Megakaryocyte proliferation is stimulated by thrombopoietin
(TPO)
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Normal platlet count is 150-400 x 109/L
Survive 9-12 days
Nonviable or aged platelets removed by spleen & liver
2/3 of platelets circulate in the peripheral blood
1/3 are sequestered in the spleen
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Humoral factor
Produced primarily by liver, kidney, spleen, BM
Produced at a relatively constant rate
These 2 pools are in equilibrium and constantly exchanging
Spontaneous hemorrhaging occurs when platlet count gets below
10 x 109/L
PLATLETS
MATURE MAGAKARYOCYTE
PLATLET RELEASE
PLATLET FUNCTION

Platlets function to
Provide negatively charged surface for factor X and
prothrombin activation
 Release substances that mediate vasoconstriction,
platlet aggregation, coagulation, and vascular repair
 Provide surface membrane proteins to attach to other
platlets, bind collagen, and subendothelium
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PLATELETS
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Are the primary defense against bleeding
Circulate in resting state
Have minimal interaction with other blood components or the
vessel wall
 Morphology of resting platelet is smooth, discoid
 When stimulated by endothelial damage, platlets become
activated and they
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Become round and ‘sticky’
Build a hemostatic plug
Provide reaction surface for proteins that make fibrin
Aid in wound healing
Platlet activation and plug formation involves
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Adhesion
Shape change
Secretion
Aggregation
ADHESION
Damage to endothelium exposes blood to the
subepithelial tissue matrix with adhesive
molecules
 Platlet receptor GPIb binds to subendothelium
collagen fibers through von Willebrand’s factor
(vWF)
 Platlet adherence stops the initial bleeding
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SHAPE CHANGE
Following vessel injury and platlet exposure to
external stimuli, platlets change shape from
circulating discs to spheres with pseudopods
 Shape change is mediated by an increase in
cytosolic calcium
 Exposure of platlet membrane phospholipids
promotes the assembly of vitamin-K dependent
factors on the platlet membrane surface
 Activated platlets adhere to exposed collagen
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CHANGE IN PLATLET SHAPE
AGGREGATION
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Platlet-to-platlet interaction
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Begins 10-20 seconds after vascular injury and platlet adhesion
Requires dense granule release from the adhering platlets
Requires Ca++ and ATP
Requires fibrinogen and fibrinogen receptors GPIIb and IIIa
Mechanism:
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ADP released from platlet cytoplasm upon adherence induces exposure
of fibrinogen receptors GPIIb and IIIa
Fibrinogen binds to the exposed GPIIb and IIIa
Extracellular Ca++-dependent fibrinogen bridges form between
adjacent platlets, thereby promoting platlet aggregation
This is primary or reversible aggregation
Secondary aggregation begins with the release of dense granules
Secondary aggregation is considered irreversible
SECRETION
Secondary aggregation begins with platlet
secretion of dense granules
 Dense granules contain large amounts of ADP
 ADP binds to the platlet membrane triggering
the synthesis and release of TXA2
 The release of large amounts of ADP combined
with TXA2 amplifies the initial aggregation of
platlets into a large platlet mass
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FORMATION OF PRIMARY HEMOSTATIC
PLUG
PLATELETS AND
SECONDARY HEMOSTASIS
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Primary platelet plug is
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Unstable and easily dislodged
Secondary hemostasis
Fibrin formation stabilizes the platelet plug
 Proteins interact to form fibrin assemble on negatively
charged membrane phospholipids of activated platelets
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