Hemostasis what means and classification

definition of hemostasis and mechanisms

1. 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

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

3. 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

4. FORMATION OF A STABLE PLUG

5. Platelets
•Platelets are cell fragments Formed in bone marrow
from megakaryocytes
•Platelet lack nuclei
•Normal count 150-400,000 /microliter
•Platelet diameter 2-4 m
•Life span 8-12 days
•Stored in spleen (30%)
•peripheral blood(70)%
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6. DEVELOPMENT OF PLATELET
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7. Active cytoplasm
Cytoplasm has Actin + myosin
Enzyme synthesis + storage of calcium
Synthesis of prostaglandins
Dense granules containing ADP, ThromboxineII, serotonin
-Liver produces hormone thrombopoietin which increases the
number of platelets
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Platelets

8. Membrane
-coat of glycoproteinsadhesion to injured area
-phospholipids activation of intrinsic pathway of coagulation
-adenylatecyclase cAMP activate other platelets
Platelets
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9. PLATELETS

10. 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

11. HEMOSTASIS
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•Hemostasis refers to the stoppage of
bleeding
•Actions that limit or prevent blood loss
include:
1. Blood vessel spasm
2. Platelet plug formation
(Adhesion and Aggregation)
3.Blood Coagulation

12. 1. BLOODVESSELSPASM
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1. Blood vessel spasm
•Triggered by pain receptors (vasoconstrictor release from
nerve ending)
•Damaged endothelium releases endothelinthat constrict
the vessels
•Smooth muscle in blood vessel contracts
•Platelet release serotonin(vasoconstrictor)

13. 2. STAGESOFPLATELETPLUGFORMATION
Platletactivation and plug
formation involves
Adhesion
Shape change
Secretion
Aggregation

14. 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

15. 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

16. CHANGE IN PLATLET SHAPE

17. SECRETION(Activation)
secretion of dense granules
Dense granules contain large amounts of ADP
ADP binds to the platelet membrane triggering the
synthesis and release of TXA
2
The release of large amounts of ADP combined
with TXA
2amplifies the initial aggregation of
platelets into a large platelet mass

18. AGGREGATION
Platlet-to-platletinteraction
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 GPIIband IIIa
Mechanism:
ADP released from platelet cytoplasm upon adherence
induces exposure of fibrinogen receptors GPIIband IIIa
Fibrinogen binds to the exposed GPIIband IIIa
Extracellular Ca++-dependent fibrinogen bridges form
between adjacent platelets, thereby promoting platelet
aggregation

20. PLATELETPLUGFORMATION
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21. FORMATION OF PRIMARY HEMOSTATIC PLUG

22. 3. BLOODCOAGULATION
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3. Blood coagulation
•A blood clot forms via series of
reactions
•Blood coagulation mechanism are
1. Intrinsic pathway
2. Extrinsic pathway

23. CLOTTINGCASCADE
Series of steps involving 12 plasma clotting
factors that lead to final conversion of fibrinogen
into a stabilized fibrin mesh
Intrinsic pathway
Involves 7 separate steps
Starts when factor XII (Hageman factor)is
activated by coming into contact with
exposed collagen in injured vessel or foreign
surface such as glass test tube
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24. Blood Coagulation
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See Intrinsic Pathway

25. CLOTTINGCASCADE
Extrinsic pathway
Requires only 4 steps
Requires contact with tissue factors
external to the blood
Tissue thromboplastin–FactotIII
released from traumatized tissue
directly activates factor X
Factor III and factor VII are required
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26. 26
COAGULATIONFACTORS
Liver and
Endothelial cell

27. 27
Blood Coagulation
See Extrinsic Pathway

28. 28
Clot Pathways
Intrinsic and Extrinsic

29. CLOTUNDER
MICROSCOPE
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30. SUMMARY
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31. what are the factors that
prevent blood clotting in
healthy
person ?
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32. FACTORSTHATPREVENTABLOOD
COAGULATION INHEALTHYPERSON
•The smooth lining of blood vessels
discourages the accumulation of platelets
and clotting factors
Endothelium releases many factors that act as anti
thrombotic and anticoagulant
Intact endothelium releases
Prostacyclin(PGI
2)-
ADP dephosphatase
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Inhibits
platelet
aggregation

33. FACTORSTHATPREVENTABLOOD
COAGULATION INHEALTHYPERSON
Plasmin –plasma protein produced by
liver, is present in blood in an inactive
form plasminogen
tPA –Tissue plasminogenactivator from
tissue converts plasminogen to plasmin
which causes degradation of fibrin
Applied –tPA genetically engineered is
used in myocardial infarction to dissolve
thrombus in coronary artery
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34. FACTORSTHATPREVENTA
BLOODCOAGULATION IN
HEALTHYPERSON
Heparin sulphate –bind and activate
antithrombinIII.
AntithrombinIII inactivate thrombin.
-Some cells such as basophilsand mast
cells secrete heparin (an anticoagulant)
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35. FATEOFBLOODCLOTS
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•After a blood clot forms it retracts and
pulls the edges of a broken blood vessel
together while squeezing the fluid serum
from the clot
•Platelet-derived growth factor stimulates
smooth muscle cells and fibroblasts to
repair damaged blood vessel walls
•Plasmin digests the blood clots

36. IMPORTANT
•A thrombusis an abnormal blood clot inside the blood
vessel
•An embolusis a blood clot moving through the blood
vessels
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37. 37

38. CLINICALAPPLICATION
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39. ABNORMALBLOODCLOTTING
Thrombus
Abnormal intravasculaarclot attached to a vessel wall
Emboli
Freely floating clots
Factors that can cause thromboembolism
Roughened vessel surfaces associated with atherosclerosis
Imbalances in the clotting-anticlottingsystems
Slow-moving blood
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40. I. Hepatic failure
almost all clotting factors are made in the liver
II. Vitamin K deficiency
required for II (prothrombin), VII, IX, and X
III. Hemophilia
Factor VIII (hemophilia A 1/10,000),
IV. Factor IX (hemophilia B 1/100,000)
Coagulation Defects
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41. BLEEDINGDISORDER-
THROMBOCYTOPENIA
Thrombocytopenia
(decrease platelet)
There is bleeding in
small capillaries and
blood vessels, mucosa,
skin
ITP Idiopathic
thrombocytopenic
purpura -autoimmune
(common)
PURPURIC SPOTS ON
SKIN : minute
hemorrhages in
subcutaneous tissue
41Thrombocytopenic
Purpura

42. HEMOPHILIA
It is an X-linked disorder resulting from a
deficiency in factor VIII
Hemophilia Ais classic hemophilia (a disease
referring to the inability to clot blood).
Individuals with deficiencies infactor VIIIsuffer
Joint and muscle hemorrhage,
Easy bruising and
Prolonged bleeding occurs from wounds.
Treatment of hemophilia A is accomplished by
infusion of factor VIII concentrates prepared from
either human plasma or by recombinant DNA
technology.
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43. HEMOPHILIA
It’s a X
linked
recessive
disease
Females
are
carriers
Male
suffer
from
disease.
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44. HEMOPHILIAB
Hemophilia Bresults from deficiencies in factor IX.
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45. REGULATIONOFTHEAGGREGATE STATEOF
BLOOD
Normally, there is no intravascular blood clotting or
it occurs to a small extent. The fragile process of
the regulation of blood coagulation involves many
factors and systems:
• Presence of the inhibitors of pro-coagulants in
plasma.
• Many factors are in the inactive state.
• The concentration of pro-coagulants decreases
due to fibrinolysis. Therefore, a thrombus is not
formed in the blood vessels of fast blood flow but
develops in the blood vessels of low blood flow.
• Pro-coagulants are inactive in the blood.

46. REGULATIONOFTHEAGGREGATE STATEOF
BLOOD
On the whole, the mechanism of the regulation of
coagulation is neuro-humoral. In the body there are
special chemoreceptors reacting to the
concentrations of thrombin, plasmin, and other
factors of the coagulation and antico-agulation
systems in the blood.
The stimulation of the sympathetic nervous system
increases the speed of blood coagulation
(hypercoagulation).
It is pronounced in stress, pain, and is
accompanied by the collateral release of adrenalin.

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