Proses hemostasis

Suyasning HI
 Tujuan pembelajaran
• Peranan hemostasis
• Komponen yang terlibat dalam proses
hemostasis
- Pembuluh darah
- Trombosit
- Faktor koagulasi
- Inhibitor koagulasi
- Fibrinolisis
- Kaskade kimia hemostasis
Hematopoiesis
 HEMOSTASIS
DEPENDENT UPON:
 Vessel Wall Integrity
 Adequate Numbers of Platelets
 Proper Functioning Platelets
 Adequate Levels of Clotting Factors
 Proper Function of Fibrinolytic Pathway
 Platelets – cont.

Site of formation: Bone marrow

Steps: Stem cell

Megakaryoblast

Megakaryocyte

Platelets
 Regulation of Thrombopoiesis

• Thrombopoietin regulates the differentiation of

megakaryocytes and platelets, It is a hormone
released by the liver and kidney.
 Regulation of Thrombopoiesis cont..

• Thrombopoietin is bound to the surface of platelets

by the mpl receptor (CD 110) and destroyed,
thereby reducing megakaryocyte exposure to the
hormone.
 Regulation of Thrombopoiesis cont..
• Therefore, the rising and dropping platelet
concentrations regulate the Thrombopoietin
levels.
• Low platelets lead a higher degree of
Thrombopoietin level and therefore higher
exposure to the undifferentiated bone marrow
cells, leading to differentiation into
megakaryocytes and further maturation of these
cells.
• On the contrary, high platelet concentrations lead
to the reversal of these physiologic mechanisms
 Platelets
• Platelets are non-nucleated, small, round or oval discs.

• They are formed in the bone marrow by fragmentation of the cytoplasm of

giant cells called “Megakaryocytes”.

• Platelet count normally = 150,000-400,000/µl.

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 Function of Platelets
• Plays a role in Hemostasis = prevention of blood loss.

• Whenever a vessel is severed or ruptured, Hemostasis is

achieved by several mechanisms;
1. Vascular spasm.
2. Formation of a platelet plug.
3. Formation of a blood clot as a result of blood coagulation.
Platelet Functions

Begins with Platelet activation

 Platelet Activation

• Adhesion
• Shape change
• Aggregation
• Release
• Clot Retraction
Platelet function

Adhesion

Aggregation

Secretion
 Platelet Adhesion
• Platelets stick to exposed collagen underlying
damaged endothelial cells in vessel wall
 Platelet Release Reaction
• Platelets activated by adhesion
• Extend projections to make contact with each other
• Release Thromboxin A2, Serotonin & ADP activating other platelets
• Serotonin & Thromboxin A2 are vasoconstrictors decreasing blood
flow through the injured vessel. ADP causes stickiness
 Platelet Aggregation
• Activated platelets stick together and activate new platelets to
form a mass called a Platelet Plug
• Plug reinforced by fibrin threads formed during clotting
process
 Platelet
1. Adhesion

Endothelium

2. Shape change
Resting platelet Activated platelet
Platelet shape change and
Aggregation
 Platelet Plug Formation
1. Blood vessel injury.
2. Platelets come in contact with damaged blood vessel.
3. They become activated and adhere to the injured area.
4. This will activate even more platelets to come to the
injured area resulting in platelet plug formation.
Platelet haemostatic plug formation
 Platelet Plug formation Cont.

• The platelet plug is a loose plug that is usually

successful in blocking the blood loss if the
vascular opening is small.

• Then, during the process of blood coagulation,

the stronger fibrin threads are formed that will
strengthen the platelet plug.
 Platelet Plug
Aggregation of platelets at the site
of injury to stop bleeding
• Exposed collagen attracts platelets
• Activated platelets release of
platelet ADP & TXA2   the
stickiness of platelets   Platelets
aggregation  plugging of the cut
vessel

• Intact endothelium secret prostacyclin 

inhibit aggregation
 Activated Platelets
Secrete:
1. 5HT(serotonin)  vasoconstriction
2. Platelet phospholipid (PF3)  clot
formation
3. Thromboxane A2 (TXA2) is a
prostaglandin formed from arachidonic
acid
Function:
– vasoconstriction
– Platelet aggregation
(TXA2 inhibited by aspirin)
Clotting
Factors
 EXTRINSIC
MECHNANISM
FOR INITIATING
CLOTTING
 INTRINSIC
MECHNANISM
FOR INITIATING
CLOTTING
ROLE OF THROMBIN IN HEMOSTASIS
ACTION OF THROMBIN ON FIBRONOGEN TO FORM
FIBRIN
The Intrinsic Pathway
Blood trauma
or contact
with collagen The Extrinsic Pathway
Tissue trauma
F XII F XIIa
HMW Kininogen
Prekallikrein
Tissue factor (TF)
FXI FXIa
Ca++ FVIIa FVII
F IX F IXa
Ca++
FVIII
PLTs
Ca++

FX F Xa
Blood
FV
PLTs, Ca++ clot
Prothrombin Thrombin
FINAL COMMON Fibrin
Fibrinogen
PATHWAY
 Bleeding Disorders

• Excessive bleeding can result from;

– Platelet defects: deficiency in number (thrombocytopenia)
or defect in function.
– Deficiency in coagulation factors (e.g. hemophilia).
– Vitamin K deficiency.
 Bleeding Disorders Cont…

• Hemophilia:
– ↑ bleeding tendency.
– X-linked disease.
– Affects males.
– 85% due to FVIII deficiency (hemophilia A), and 15% due to FIX
deficiency (hemophilia B).

• Vitamin K deficiency & liver disease:

– Almost all coagulation factors are synthesized in the liver.
– Prothrombin, FVII, FIX, & FX require vitamin K for their synthesis.
The Intrinsic Pathway
Blood trauma
or contact
with collagen The Extrinsic Pathway
Tissue trauma
F XII F XIIa
HMW Kininogen
Prekallikrein
Tissue factor (TF)
FXI FXIa
Ca++ FVIIa FVII
F IX F IXa
Ca++
FVIII
PLTs
Ca++

Hemophilia FX F Xa
Blood
FV clot
PLTs, Ca++

Prothrombin Thrombin

Fibrinogen Fibrin
 Anticoagulants

• Heparin
– Liver, lungs, mast cells, basophils
– Direct antithrombin
– Prevent the conversion of Prothrombin to Thrombin
– Injection only
– 6-8 hours

• Warfarin
– Almost all coagulation factors are synthesized in the liver.
– Suppresses the synthesis of Prothrombin, FVII, FIX, & FX vitamin
K dependent factors
– Orally
– 48 hours
 HEMOSTASIS
1. VASCULAR PHASE
2. PLATELET PHASE
3. COAGULATION PHASE
4. FIBRINOLYTIC PHASE
 PLATELET PHASE
PLATELETS ADHERE TO THE DAMAGED
SURFACE AND FORM A TEMPORARY PLUG.
Coagulation Phase
Notes:
Extrinsic Pathway-

Intrinsic Pathway-

Common Pathway-
COAGULATION PHASE
THROUGH TWO SEPARATE PATHWAYS
THE CONVERSION OF FIBRINOGEN
TO FIBRIN IS COMPLETE.
 FIBRINOLYTIC PHASE
ANTICLOTTING MECHANISMS ARE ACTIVATED
TO ALLOW CLOT DISINTEGRATION AND REPAIR
OF THE DAMAGED VESSEL.
 LABORATORY EVALUATION
• PLATELET COUNT
• BLEEDING TIME (BT)
• PROTHROMBIN TIME (PT)
• PARTIAL THROMBOPLASTIN TIME (PTT)
• THROMBIN TIME (TT)
 PLATELET COUNT
 NORMAL 100,000 - 400,000 CELLS/MM3

< 100,000 Thrombocytopenia

50,000 - 100,000 Mild Thrombocytopenia

< 50,000 Sev Thrombocytopenia

 Control of Coagulation
• Requirements

• Clot Retraction

• Fibrinolysis
Thank you for listening