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HEMOSTASISPrimary hemostasis
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 Platlets Plasma proteins
Coagulation proteins – involved in clot formation Fibrinolysis – involved in clot dissolution Serine protease inhibitors
Other minor players include Kinin system Complement system
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
Plasma Proteins Platlets
HEMOSTASIS
Hemostasis can be divided into two stagesPrimary 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 Released from megakaryocytes in the BM Megakaryocyte proliferation is stimulated by thrombopoietin
(TPO) Humoral factor 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 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
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 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
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 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
FORMATION OF PRIMARY HEMOSTATIC PLUG
PLATELETS AND SECONDARY HEMOSTASIS
Primary platelet plug is 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