Sei sulla pagina 1di 45

Introduction to Hemostasis

Dr.Nadjwa Zamalek Dalimoenthe, SpPK-K

Hemostasis
Is the complex process by which the body spontaneously stop bleeding and maintains blood in the fluid state within the vascular compartment. Normal hemostasis: rapid & localized.

The major role of the hemostasis system is to maintain a complete balance of the bodys tendency toward clotting and bleeding.

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 stabilizing fragile clot formed during primary hemostasis.

Primary Hemostasis (platelet plug)

Secondary Hemostasis (Hemostatic Plug)

Microcirculation bleeding

Platelet plug

Bigger vessels bleeding

Hemostasis plug

Hemostasis is achieved by highly integrated and regulated interaction of major and minor systems.

Major system
Blood vessel Platelet Coagulation proteins Fibrinolysis system Inhibitor protease serine

Minorsystem

Kinin Complement system

Blood vessels artery

Vein

arteriole

Venule

capillary

1. Sympathetic ganglion nerve cell bodies and nerve fibers 2. Nerves 3. Arteriole 4. Venule 5. Lymph node hilus and lympathetic tissue 6. Lymphatic vessels

10. Nerves

11. Lymph node : medulla 12. Lymph node : cortex 13. Marginal sinus 14. Capsule 15. Tunica Adventitia 16. Tunica Media 17. Internal elastic membrane 18. Lumen of large (elastic) artery 19. Endothelium and subendothelial connective tissue 20. Adipose tissue 21. Capillaries 22. Medium-sized vein (l.s) filled with blood 23. Tunica media 24. Tunica adventitia 25. Nerve 26. Arteriole

7. Veins

8. Nerves (o.s and t.s.)

9. Arterioles

Neurovascular Bundle (Transverse Section)

10

The role of blood vessels


Vaso Reflex constric- Local: serotonin, 5 hidroxy tryptamin (5HT), tion trhomboxan A2 (TxA2) Collagen exposed: platelet adhesi aggregation

Trigger Coagulation other hemostasis Intrinsic (XII XIIa) process Extrinsic (tissue factor/F III release)

Blood Vessel
Endothelial Cells Basement Membrane

Red Blood Cells

Platelets

White Cells

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 as ADP and vasoactive amines.

What are Platelets?


Disk-shaped cells produced in the megakaryocytes of the bone marrow
Mature Platelet
Megakaryocyte

Bone Marrow

Trombopoiesis

Storage and Circulation


Quantity - 150,000 - 400,000/mm3 Life Span - 10 days
Roughly 2-4 m in diameter. 67% in the circulation 33% pooling

Megakaryocyte

Spleen

Platelet Structure

Within the matrix of the platelet are :


Microtubules. Microfilaments. Submembranous filaments.

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 (thrombin generation), and vascular repair. Providing surface membrane glycoprotein such as GPIb and IIIa to attach to other platelet via fibrinogen.

Platelet Function
Adhesion
Shape Change Release A

ADP Release
3 seconds B

Aggregation

10 seconds

Coagulation
Fibrin Formation

5 minutes

Platelet adhesion
The principle mechanism of platelet adhesion involves :
Plasma Collagen fibres Platelet membrane glycoprotein GPIb (the receptor for von Willebrands factor/vWF)

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).

Platelet adhesion involves 3 components:

vWF

Glycoprotein Ib (GPIb)

Collagen fibers

Activation of 2nd messenger pathways within the platelet

Intracellular biochemical changes

Platelet activation events

Shape change

Secretion

Cytoskeletal reassembly

Platelet aggregation

Platelet aggregation (platelet-toplatelet interaction) is an energy dependent process requires ATP (primarily derived from glycolysis)

26

Markers of platelet activation

Beta-thromboglobulin Platelet factor 4 Thrombospondin

PDGF

During thrombus formation

- Thrombin - Plasminogen - TPA - Antiplasmin

Incorporated into the clot

Any Questions?

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)

Coagulation Factors
Factor I Factor II Factor III Factor IV Factor V Factor VII Factor VIII Factor IX Factor X Factor XI Factor XII Factor XIII Fibrinogen Prothrombin Tissue Thromboplastin Calcium Ions Labile Factor, Proaccelerin Stable Factor, Proconvertin Antihemophilic Factor Christmas Factor Stuart-Prower Factor Plasma Thromboplastin Antecedent Hageman Factor Fibrin Stabilizing Factor

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)

On the basis of physical properties, coagulation proteins may be devided into three groups :
Contact proteins Prothrombin proteins Fibrinogen or thrombin-sensitive proteins.

Blood coagulation leading to fibrin formation can be separated into three pathways :
Extrinsic pathway Intrinsic pathway Common pathway

Coagulation Process

Fibrinolysis
Physiologic process of removing unwanted fibrin deposits.

Kinin System
Important in:
inflammation. Vascular permeability. Chemotaxis

Activated by both: coagulation & fibrinolytic system

Complement System
Composed of + 22 serum proteins. Working together with antibodies & clotting factors. Important as mediators of immune & allergic reaction.

Hemostasis Tests
Screening assays in hemostasis Monitoring of anticoagulant therapy Disseminated Intravascular Coagulation Thrombophilia Inhibitor (Lupus Anticoagulant, Anti Phospholipid Antibody)

Hemostasis Screening Tests


1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Tourniquete Test (Rumple Leede) Bleeding Time Clot Retraction Platelet Count Clotting Time PT -Vascular & Platelet -Platelet APTT -Coagulation factors -Fibrinolysis TT Euglobulin Clot Lysis Time Trombelastograph D=Dimer

Thank You Very Much