1. HEMOSTASIS
Primary hemostasis

2. 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

3. 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

4. HEMOSTASIS Defects Blood Vessels Plasma Proteins Platlets
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

5. HEMOSTASIS Primary 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

6. FORMATION OF A STABLE PLUG

7. 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

8. PRIMARY HEMOSTASIS Platelets Primary platelet plug
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

9. 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 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

10. PLATLETS

11. MATURE MAGAKARYOCYTE

12. PLATLET RELEASE

13. 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

14. 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

15. 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

16. 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

17. CHANGE IN PLATLET SHAPE

18. AGGREGATION Platlet-to-platlet interaction
Begins 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

19. 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

20. FORMATION OF PRIMARY HEMOSTATIC PLUG

21. 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