blood physiology

1. Platelets and Hemostasis
Blood Physiology
Don. Siyum A. 1
Platelets and Hemostasis
By Don . Siyum a.

2. Platelets/ thrombocytes
- They are formed in the bone marrow from megakaryocytes.
- Megakaryocytes are derived from the same undifferentiated stem cells
that give rise to the erythrocytic and leukocytic cell lines.
- A single megakaryocyte typically produces about 1000 platelets.
- The hormone thrombopoietin, produced by the liver, increases the
number of megakaryocytes in the bone marrow and stimulates each
megakaryocyte to produce more platelets as needed.
- The platelet count ranges from 150,000 to 450,000 platelets/ μ L
(averaging about 250,000/ μ L).
- Platelets have a short life span, normally just 5 to 9 days.
- Aged and dead platelets are removed by fixed macrophages in the
spleen and liver.
Blood Physiology
Don. Siyum A. 2
Platelets and Hemostasis

3. Functional characteristics of platelets
- Platelets do not have nuclei and cannot reproduce.
Their granules in their cytoplasm secrets chemicals such as:-
- Thromboxane A2 -that attract more and more platelets to the injured
area.
- Serotonin- a vasoconstrictor
- Adenosine diphosphate (ADP), which attracts more platelets to the area
- Calcium- for activation of coagulation factor
- Platelet-derived growth factor (PDGF), a hormone that can cause
proliferation of vascular endothelial cells, vascular smooth muscle
fibers, and fibroblasts to help repair damaged blood vessel walls.
Blood Physiology
Don. Siyum A. 3
Platelets and Hemostasis

4. - Platelets have actin and myosin molecules, and still another contractile
protein, thrombosthenin, that can cause the platelets to contract.
- Platelets secrets also fibrin-stabilizing factor to strengthen a blood clot
Blood Physiology
Don. Siyum A. 4
Platelets and Hemostasis

5. Hemostasis
- Is the process of blood clot formation at the site of vessel injury.
- Hemostasis involves three steps that take place whenever a blood
vessel is ruptured.
1. Vasoconstriction (vascular spasm)
2. Platelet plug formation
3. Blood clot formation (coagulation)
+ Fibrin mesh development (clot retraction)
+ Clot dissolution.
- Hemostatic mechanisms can prevent hemorrhage from smaller blood
vessels, but extensive hemorrhage from larger vessels usually
requires medical intervention.
Blood Physiology
Don. Siyum A. 5
Platelets and Hemostasis

6. Steps of hemostasis
Blood Physiology
Don. Siyum A. 6
Platelets and Hemostasis

7. Blood Physiology
Don. Siyum A. 7
Platelets and Hemostasis
Step 1 Vascular spasm
• Smooth muscle contracts,
causing vasoconstriction.
Step 2 Platelet plug
formation
• Injury to lining of vessel
exposes collagen fibers;
platelets adhere.
• Platelets release chemicals
that make nearby platelets
sticky; platelet plug forms.
Step 3 Coagulation
• Fibrin forms a mesh that traps
red blood cells and platelets,
forming the clot.
Collagen
fibers
Platelets
Fibrin
Events of hemostasis.

8. 1. Vasoconstriction ( implies spasm of small blood vessels )
- Immediately after a blood vessel has been cut or ruptured, the trauma to
the vessel wall itself causes smooth muscle contraction
The contraction results from
1. Neurogenic reflex – when the vessels injured the surrounding nerve
ending also injured. These nerve ending release vasoconstrictor.
2. Myogenic constriction when smooth muscle of the wall of blood vessels
injured it will stretched first and contract strongly.
3. The injured endothelial cells also produce vasoconstrictor such as
endothelin.
The spasm can last several minutes to hours, giving ample time for the next
process; the platelet plug to take place.
Blood Physiology
Don. Siyum A. 8
Platelets and Hemostasis

9. Blood Physiology
Don. Siyum A. 9
Platelets and Hemostasis
Neurogenic reflex- The injured nerve ending release vasoconstrictor
Myogenic reflex – the injured smooth muscle of the wall of blood vessels
stretched first and contract strongly
The injured endothelial cells - produce vasoconstrictor such as endothelin
The spasm can last several minutes to hours, giving ample time for the next
process; the platelet plug to take place.

10. 2. Platelet Plug Formation
- In the absence of vessel damage, platelets are repelled from each other
and from the endothelial lining of vessels.
- The repulsion of platelets from an intact endothelium is believed to be
due to prostacyclin, a type of prostaglandin produced within the
endothelium.
- Damage to the endothelium of vessels exposes subendothelial tissue to
the blood.
- When the endothelial lining of vessel is disrupted because of vessel
injury, platelets are able to stick to exposed collagen proteins.
- Sticking is facilitated by protein called von Willebrand's factor released
from the injured endothelium releases.
Blood Physiology
Don. Siyum A. 11
Platelets and Hemostasis

11. - von Willebrand's factor has hook to bind with the circulating
platelets.
- Sticking of platelets to von Willebrand's factor on the surface of the
exposed collagen is called platelets adherence.
- Once platelets adhere to Willebrand's factor it will be activated and
release thromboxane A2 and ADP to attracts more platelets to the
area.
- The mass of platelets aggregation that stick to injured vessels is
called platelet plug.
- A platelet plug is very effective in preventing blood loss in a small
vessel.
Blood Physiology
Don. Siyum A. 12
Platelets and Hemostasis

12. Blood Physiology
Don. Siyum A. 13
Platelets and Hemostasis
Prostacyclin (PGl2) & NO, which are produced by endothelial
cells, inhibit spread of platelet aggregation from the damaged site.
Platelet plug formation

13. Blood Physiology
Don. Siyum A. 14
Platelets and Hemostasis

14. Blood Physiology
Don. Siyum A. 16
Platelets and Hemostasis

15. 3. Blood Clot formation-
- Formation of blood clot (Coagulation)
- This is a phase where blood looses its fluidity becomes a jelly-solid mass.
- Clotting involves several substances known as clotting (coagulation)
factors.
These factors are released from
a. The injured vascular walls,
b. Platelets cytoplasm, &
c. hepatocytes (liver cells) release several inactive clotting factor to blood
plasma
- Most clotting factors are identified by Roman numerals that indicate the
order of their discovery (not necessarily the order of their participation in
the clotting process).
Blood Physiology
Don. Siyum A. 17
Platelets and Hemostasis

16. Blood Physiology
Don. Siyum A. 18
Platelets and Hemostasis

17. Blood-clotting cascade
- The blood-clotting cascade consists of two pathways,
1. The extrinsic pathway and
2. The intrinsic pathway.
- These two pathways ultimately converge to form a final pathway that
leads to blood clotting.
- The purpose is to ultimately stabilize the platelet plug with a fibrin
mesh.
Blood Physiology
Don. Siyum A. 19
Platelets and Hemostasis

18. Extrinsic pathway(Quick-acting)
- When the blood vessel ruptures, the traumatized (injured) tissues
release a substance called tissue thromboplastin (III).
- Thromboplastin (III) binds to the active form of protein factor VII,
and together activate factor X to its active form Xa
- The activated factor Xa in the presence of Ca2+ and factor V forms
the prothrombin activator.
- The prothrombine activator causes the conversion of prothrombine
into thrombine.
- Thrombine together with Ca2+ acts on the fibrinogen to form fibrin
monomers and this monomers are not stable to form a clot.
- Fibrin stabilizing factors (XIII) form a lot of covalent bond between
fibrin monomers to form a fibrin mesh.
- Fibrin mesh attract platelets and glycoprotein and forms stable blood
clots.
Blood Physiology
Don. Siyum A. 20
Platelets and Hemostasis

19. Blood Physiology
Don. Siyum A. 21
Platelets and Hemostasis
Extrinsic
pathway (Factor III or Thromboplastin)
Proconvertin
Stuart factor
proaccelerin
Factor II

20. Blood Physiology
Don. Siyum A. 22
Platelets and Hemostasis
Factors XIII
- Fibrin mesh attract platelets and forms stable blood clots.
Fibrin monomers are not stable to form a clot.
- Fibrin stabilizing factors (XIII) form a lot
of covalent bond between fibrin monomers
to form a fibrin mesh.

21. Blood Physiology
Don. Siyum A. 23
Platelets and Hemostasis
Fibrin mesh

22. Intrinsic pathways
- Caused by internal damage to the vessel wall or when there is
exposure of blood to the collagen fiber at injured blood vessel wall.
- The pathway begin when factor XII (Hageman factor) is activated by
coming into contact with exposed collagen in an injured vessel
- The activated factor XII goes to activate factor XI into factor XIa.
- This factors require cofactors like high molecule kinase(HMK)
- Factor number XI a acts on factor IX this factor requires cofactors like
Ca2+ and forms factor number IXa.
- Factor number IX in the presence of activated factor VII and Ca2+ causes
activation of factor number X into activated factor Xa.
- Then the next step is similar to extrinsic pathways.
Blood Physiology
Don. Siyum A. 24
Platelets and Hemostasis

23. Intrinsic pathway
Blood Physiology
Don. Siyum A. 25
Platelets and Hemostasis
(Accelerator globulin)
Hageman factor
Christmas factor

24. Blood Physiology
Don. Siyum A. 26
Platelets and Hemostasis
Factors XIII
- Fibrin mesh attract platelets and forms stable blood clots.
Fibrin monomers are not stable to form a clot.
- Fibrin stabilizing factors (XIII) form a lot
of covalent bond between fibrin monomers
to form a fibrin mesh.

25. Blood Physiology
Don. Siyum A. 27
Platelets and Hemostasis

26. NB.
- The extrinsic mechanism requires fewer steps to activate factor X
than the intrinsic mechanism does; it is a “shortcut” to coagulation.
- It takes 3 to 6 minutes for a clot to form by the intrinsic pathway but
only 15 seconds or so by the extrinsic pathway.
- The intrinsic pathway
- initiated when factor XII (Hagemen factor) comes in contact with
collagen fibers or foreign materials, such as when a blood sample
is put into a glass test tube.
- The pathway can be promoted by damage tissues, resulting from
internal factor such as arterial disease.
Blood Physiology
Don. Siyum A. 29
Platelets and Hemostasis

27. Clot retraction
- After a clot has formed, actin and myosin in platelets contract within
30-60 minutes.
- This pulls on the fibrin threads and draws the edges of the broken
vessel together.
- Platelets and endothelial cells secrete a mitotic stimulant named
platelet-derived growth factor (PDGF) and Vascular endothelial
growth factor (VEGF)
- Platelet-derived growth factor (PDGF) stimulates division of smooth
muscle cells and fibroblasts to rebuild blood vessel wall
- Vascular endothelial growth factor (VEGF) stimulates endothelial
cells to multiply and restore endothelial lining
Blood Physiology
Don. Siyum A. 30
Platelets and Hemostasis

28. Dissolution of Clots
- As the damaged blood vessel wall is repaired, activated factor XII
promotes the conversion of an inactive molecule(Prekallikrein) in
plasma into the active form called kallikrein.
- Kallikrein, in turn, catalyzes the conversion of inactive plasminogen
into the active molecule plasmin.
- Plasmin stimulate further plasmin production by positive feedback.
- Plasmin is an enzyme that digests fibrin into “split products,” thus
promoting dissolution of the clot.
Blood Physiology
Don. Siyum A. 31
Platelets and Hemostasis

29. Factor XII
Prekallikrein
Kallikrein
Plasminogen Plasmin
Fibrin polymer
Fibrin degradation products
The Mechanism for Dissolving Blood Clots.
Clot dissolution
Positive feedback loop

30. Prevention of Inappropriate Coagulation
1. Platelet repulsion- Platelets do not adhere to prostacycline-coating of
healthy endothelial cells.
2. Thrombin dilution
- At normal rates of blood flow the plasma thrombin is diluted so quickly that a
clot has little chance to form.
- If flow decreases, however, enough thrombin can accumulate to cause
clotting. This may causes slow blood flow and leads to circulatory shock.
3. Natural Anticoagulants
- Antithrombin produced by liver deactivate thrombin before it can act on
fibrinogen.
- Heparin secreted by mast cells and basophils
- interferes with the formation of prothrombin activator
- Deactivate thrombin before it can act on fibrinogen
Blood Physiology
Don. Siyum A. 33
Platelets and Hemostasis