HEMOSTASIS

 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
HEMOSTASIS
 The primary players in hemostasis include
 Blood vessels
 Platelets
 Plasma proteins
 Coagulation proteins – involved in clot formation
 Fibrinolysis – involved in clot dissolution
HEMOSTASIS
 Defects
 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

 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

 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
FORMATION OF A STABLE PLUG
VASCULAR SYSTEM
 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
 Vasoconstriction
 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

 Primary platelet plug

 Fragile
 Can easily be dislodged from the vessel wall
PLATELETS
 Platelets
 Small, anucleated cytoplasmic fragments
proliferation is stimulated by thrombopoietin (TPO)
 Produced primarily by liver, kidney, spleen, BM
 Produced at a relatively constant rate
 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
 These 2 pools are in equilibrium and constantly exchanging
 Spontaneous hemorrhaging occurs when platelet count gets below 10 x
109/L
PLATELETS
PLATELET FUNCTION
 Platelets 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
PLATELETS
 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
 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
 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
SHAPE CHANGE
 Following vessel injury and platelet exposure to external
stimuli, platelets change shape from circulating discs to
spheres with pseudopods
 Shape change is mediated by an increase in cytosolic
calcium
 Exposure of platelet membrane phospholipids promotes
the assembly of vitamin-K dependent factors on the
platelet membrane surface
 Activated platelets adhere to exposed collagen
CHANGE IN PLATLET SHAPE
AGGREGATION
 Platlet-to-platlet interaction
 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:
 ADP released from platelet 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 platelets,
thereby promoting platelet 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 platelet secretion of
dense granules
 Dense granules contain large amounts of ADP

 ADP binds to the platelet membrane triggering the

synthesis and release of TXA2
 The release of large amounts of ADP combined with
TXA2 amplifies the initial aggregation of platelets into a
large platelet mass
FORMATION OF PRIMARY HEMOSTATIC
PLUG