120304_introduction to hemostasis

7/29/2019 120304_Introduction to Hemostasis

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Introduction to Hemostasis

Dr.Nadjwa Zamalek Dalimoenthe, SpPK-K


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Hemostasis

Is the complex process by which thebody spontaneously stop bleeding

and maintains blood in the fluidstate within the vascularcompartment.

Normal hemostasis: rapid & localized.


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The major role of the hemostasissystem is to maintain a complete

balance of the bodys tendency

toward clotting and bleeding.


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Hemostasis can be divided into 2 stages :

Primary Hemostasis :

Platelet adhesion to exposed collagen within the

endothelium of the vessel wall.

Secondary Hemostasis :

Enzymatic activation of the coagulation proteins

to produce fibrin from fibrinogen stabilizingfragile clot formed during primary hemostasis.


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Primary Hemostasis

(platelet plug)

Secondary Hemostasis

(Hemostatic Plug)


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Platelet plugMicrocirculation

bleeding

Hemostasis plugBigger vessels

bleeding


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Hemostasis is achieved by highly integrated and

regulated interaction of major and minor systems.

Major system

Blood vessel

Platelet

Coagulation proteins Fibrinolysis system

Inhibitor proteaseserine

Minorsystem

Kinin

Complementsystem


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9

Blood vessels

artery

arteriole

capillary

Venule

Vein


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10Neurovascular Bundle (Transverse Section)

12. Lymph node : cortex

1. Sympatheticganglion nervecell bodies andnerve fibers

2. Nerves

3. Arteriole

4. Venule

5. Lymph node hilusand lympathetictissue

6. Lymphaticvessels

7. Veins

8. Nerves (o.s andt.s.)

9. Arterioles

10. Nerves

11. Lymph node :medulla

18. Lumen of large(elastic) artery

14. Capsule

15. Tunica Adventitia

16. Tunica Media

17. Internal elasticmembrane

13. Marginal sinus

19. Endothelium andsubendothelialconnective tissue

20. Adipose tissue

21. Capillaries22. Medium-sized vein(l.s) filled with blood23. Tunica media

24. Tunica adventitia25. Nerve26. Arteriole


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The role of blood vessels

Reflex

Local: serotonin, 5 hidroxy tryptamin (5HT),trhomboxan A2 (TxA2)

Collagen exposed: platelet adhesi aggregation

Coagulation

Intrinsic (XII XIIa)

Extrinsic (tissue factor/F III release)

Vaso-

constric-

tion

Triggerother

hemostasis

process


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Blood Vessel

Endothelial Cells Basement Membrane

Red Blood Cells Platelets White Cells


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Endothel cell surface thromboresistant

Synthesis and secretion of a vasodilator prostacyclin

(PGI2).

Secretion of tissue Plasminogen Activator (t-PA).

Inactivation and clearance of thrombin.

Activity of the cofactor thrombomodulin in the

thrombin dependent activation of protein C.

Degradation of proaggregating substances such asADP and vasoactive amines.


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Disk-shaped cellsproduced in the

megakaryocytes of

the bone marrow

Mature

Platelet

Megakaryocyte

Bone

Marrow

What are Platelets?


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Trombopoiesis


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Storage and Circulation

Quantity - 150,000 - 400,000/mm3Life Span - 10 days

33%

pooling

67%in the

circulation

MegakaryocyteSpleen

Roughly 2-4 m in diameter.


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Platelet Structure


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Within the matrix of the platelet are :

Microtubules. Microfilaments.

Submembranous filaments.


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Platelet participate in hemostasis by :

Providing a negatively charged phospholipid surface

for factor X and prothrombin activation.

Release of substances that mediate vasoconstriction,

platelet aggregation, coagulation (thrombingeneration), and vascular repair.

Providing surface membrane glycoprotein such as

GPIb and IIIa to attach to other platelet via

fibrinogen.


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Platelet Function

Aggregation

Coagulation

Shape

Change

Release

Fibrin

Formation

A

B

C

3 seconds

10 seconds

5 minutes

ADPRelease

Adhesion


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Platelet adhesion

The principle mechanism of platelet adhesion

involves :

Plasma

Collagen fibres

Platelet membrane glycoprotein GPIb (the

receptor for von Willebrands factor/vWF)


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The initial stage of platelet activation is as

follows :

Platelet form pseudopods organelles (-

granules, dense bodies) reorganized to the

center contraction granules spill their

contents into the open canalicular system(OCS).


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Platelet adhesion involves 3

components:

vWFGlycoprotein

Ib (GPIb)Collagen

fibers


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Platelet aggregation

Platelet activation events

Shape change SecretionCytoskeletal reassembly

Intracellular biochemical changes

Activation of 2nd messenger pathways within theplatelet


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Platelet aggregation (platelet-to-platelet interaction) is an energy

dependent process requiresATP (primarily derived from

glycolysis)


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26


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Markers of platelet activation

Beta-thromboglobulin

Platelet factor 4

Thrombospondin

PDGF


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During thrombus formation

- Thrombin

- Plasminogen

- TPA- Antiplasmin Incorporated

into the clot


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AnyQuestions?


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Coagulation

(secondary hemostasis)

Coagulation factors are designated by Roman

numerals (I to XIII)

Activation of a particular factor is designated

by a lower case a (X Xa)


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Coagulation Factors

Factor I FibrinogenFactor II ProthrombinFactor III Tissue ThromboplastinFactor IV Calcium Ions

Factor V Labile Factor, ProaccelerinFactor VII Stable Factor, ProconvertinFactor VIII Antihemophilic FactorFactor IX Christmas Factor

Factor X Stuart-Prower FactorFactor XI Plasma Thromboplastin AntecedentFactor XII Hageman FactorFactor XIII Fibrin Stabilizing Factor


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Coagulation Factors

Fibrinogen Group Factors I, V, VIII and XIII

Prothrombin Group Factors II, VII, IX and X

Contact Group Factors XI, XII

Prekallikrein (Fletcher Factor)

High Molecular Weight Kininogen (Fitzgerald

Factor)


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On the basis of physical properties,

coagulation proteins may be devided into

three groups :

Contact proteins

Prothrombin proteins Fibrinogen or thrombin-sensitive proteins.


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Blood coagulation leading to fibrin

formation can be separated into three

pathways :

Extrinsic pathway

Intrinsic pathway

Common pathway


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Coagulation Process


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Fib i l i


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Fibrinolysis Physiologic process of removing unwanted fibrin

deposits.


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Kinin System

Important in:

inflammation.

Vascular permeability.

Chemotaxis

Activated by both: coagulation & fibrinolytic

system


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Complement System

Composed of + 22 serum proteins.

Working together with antibodies & clotting

factors.

Important as mediators of immune & allergic

reaction.


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Hemostasis Tests

Screening assays in hemostasis

Monitoring of anticoagulant therapy

Disseminated Intravascular Coagulation

Thrombophilia

Inhibitor (Lupus Anticoagulant, Anti

Phospholipid Antibody)


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Hemostasis Screening Tests

1. Tourniquete Test (Rumple Leede)2. Bleeding Time

3. Clot Retraction

4. Platelet Count

5. Clotting Time

6. PT

7. APTT

8. TT9. Euglobulin Clot Lysis Time

10. D=Dimer

-Vascular & Platelet

-Platelet

-Coagulation factors

-Fibrinolysis

Trombelastograph


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Thank You Very Much

120304_introduction to hemostasis

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