Normal hemostasis and coagulation

Here's important & condensed ppt slides about hemostasis and its orchestrated steps and cogulation cascade, roles of endothelium,platelets and Coagulation protiens....!

1. 10/9/20161

2. Definition Definition 1Normal hemostasis
Tightly regulated processes Maintain blood in a fluid state in normal vessels
1Thrombosis
Pathologic counterpart Pathologic counterpart Thrombus within intact vessels
Three components:
1
. 
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3. 10/9/20163

4. Endothelium Endothelium
Key players in the regulation of
homeostasis
Have
Anti-
and
pro
thrombotic activities ;
Thrombus formation Propagation, or Dissolution occurs Dissolution occurs
exhibit
Antithrombotic activity:
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5. Mediated by;
Physical Barrier Prostacyclin
(PGI
2
)
Anti Anti
thrombotic  thrombotic 
activity activity
Prostacyclin
(PGI
2
)
Nitric oxide
(NO)
ADPase
T
inhibits platelet aggregation
10/9/20165

6. These effects are mediated by:
Endothelial membrane-associated They are cofactors Enhance plasma protein
antithrombin III
activity
Enhance plasma protein
antithrombin III
activity
modulates the activity of Thrombin Cell surface protein Directly inhibits
tissue factor,VIIa & Xa
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7. 3. Fibrinolytic properties 3. Fibrinolytic properties Endothelial cells synthesize:
Tissue-type plasminogen activator
(t-PA)
A protease that cleaves plasminogen to form
plasmin
Plasmin Plasmin
, in turn, cleaves fibrin to degrade
Plasmin Plasmin
, in turn, cleaves fibrin to degrade
thrombi
10/9/20167

8. Exposure & contact of platelets to ECM Adhesion mediated by
vWF
Endothelial release of
tissue factor
Catalytic function factors
IXa
and
Xa
i
Plasminogen activator inhibitors
(PAIs)
i
Limit fibrinolysis & favor thrombosis
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9. In summary In summary t
Intact
,
nonactivated
endothelial cells
Anti
thrombotic
t
Endothelial injury or activation
Pro
thrombotic
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10. Platelets  Platelets 
Disc
-shaped
Anucleate Anucleate
cell fragments
2-3 ꭒmin diameter 8-10 days of half-life Originate from
MEGAkaryocytes MEGAkaryocytes
Originate from
MEGAkaryocytes MEGAkaryocytes
Play a critical role in normal
hemostasis hemostasis
vascular defects
Provide a surface for activated coagulation factors
Contain
2 types 
of cytoplasmic granules
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11. i
P-selectin
i
Fibrinogen
i
Fibronectin,
i
Factors V and VIII
i
Platelet factor 4
i
PDGF
i
ADP
i
ATP
i
Calcium
i
Histamine
i
Serotonin
i
Epinephrine
10/9/201611
i
PDGF
i
TGF-β
i
Epinephrine

12. Normal Hemostasis Normal Hemostasis •general sequence of events in hemostasis 1.Transient arteriolar vasoconstriction Mediated by:
Reflex Neurogenic mechanisms Myogenic reflex contraction, and Myogenic reflex contraction, and Endothelin
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13. 2. Primary hemostasis
Endothelial injury exposes
HTSECM
,
Patelet adherence and activation Dramatic shape change Dramatic shape change Release of secretory granules Recruit additional platelets (aggregation)to form a
hemostatic plug

14. Platelet adhesion Platelet adhesion
Via interactions with
vWF
Other components of the
ECM
(e.g., fibronectin)
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15. Degranulation Importance
T
Ca+2 Ca+2Ca+2 Ca+2
is required in the coagulation cascade
TADPADPADPADP
is a potent platelet aggregator
T
Platelet
activation
negatively charged
T
Platelet
activation
negatively charged
phospholipids
on their surfaces
g
Bind calcium and serve as critical nucleation
sites
10/9/201615

16. Follows adhesion and granule release •
ADP
•
Noncleaved
fibrinogen
•
TxA
2
amplifies platelet aggregation
primary  primary 
hemostatic plug hemostatic plug
Aggregation is reversible Aggregation is reversible
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17. 3. Secondary Hemostasis
(factor III or thromboplastin) (factor III or thromboplastin)
Membrane-bound procoagulant glycoprotein
synthesized by endothelial cells
Exposed at the site of injury With factor VII , in vivo initiator of the coagulat ion With factor VII , in vivo initiator of the coagulat ion
cascade
Thrombin
generation
Cleavage of fibrinogen into insoluble fibrin Creation a fibrin meshwork Further platelet recruitment and activation
10/9/201617

18. Coagulation Cascade  Coagulation Cascade 
T
he
3
rd
arm of the hemostatic process
Amplifying
series of enzymatic conversions
Each step
proteolytically
cleaves an inactive
pro
enzyme
Thrombin Thrombin
formation is the target
Thrombin Thrombin
formation is the target
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19. 10/9/201619

21. P
Each reaction in the pathway results from
interaction of
••
Enzyme Enzyme
Activated coagulation factor
••
Substrate Substrate
proenzyme coagulation factor
•• ••
Cofactor Cofactor
Reaction accelerator
P
Assembled on a
phospholipid surface
and
P
Held together by calcium ions
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