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