Blood Physiology Platelets and Hemostasis

Platelets and Hemostasis

Part II

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Blood Physiology Platelets and Hemostasis
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
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spleen and liver.
Blood Physiology Platelets and Hemostasis

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.
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Blood Physiology Platelets and Hemostasis

- 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

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Blood Physiology Platelets and Hemostasis

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.
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Blood Physiology Platelets and Hemostasis

Steps of hemostasis

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Blood Physiology Platelets and Hemostasis
Events of hemostasis. Step 1 Vascular spasm
• Smooth muscle contracts,
causing vasoconstriction.

Step 2 Platelet plug

formation
• Injury to lining of vessel
exposes collagen fibers;
Collagen platelets adhere.
fibers

• Platelets release chemicals

that make nearby platelets
Platelets sticky; platelet plug forms.

Step 3 Coagulation
• Fibrin forms a mesh that traps
red blood cells and platelets,
Fibrin
forming the clot.
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Blood Physiology Platelets and Hemostasis
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.
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Blood Physiology 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.
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Blood Physiology Platelets and Hemostasis

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.
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Blood Physiology Platelets and Hemostasis
- 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.
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Blood Physiology Platelets and Hemostasis

Platelet plug formation

Prostacyclin (PGl2) & NO, which are produced by endothelial cells,

inhibit spread of platelet aggregation from the damaged site.

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Blood Physiology Platelets and Hemostasis

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Blood Physiology Platelets and Hemostasis

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Blood Physiology Platelets and Hemostasis
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). Set by Binyam ,MSC. Physiology 17
Blood Physiology Platelets and Hemostasis

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Blood Physiology Platelets and Hemostasis

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.

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Blood Physiology Platelets and Hemostasis

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.
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Blood Physiology Platelets and Hemostasis

Extrinsic
pathway (Factor III or Thromboplastin)
Proconvertin

Stuart factor

proaccelerin

Factor II

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Blood Physiology Platelets and Hemostasis

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.
Factors XIII

- Fibrin mesh attract platelets and forms stable blood clots.

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Blood Physiology Platelets and Hemostasis

Fibrin mesh

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Blood Physiology Platelets and Hemostasis
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
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Blood Physiology Platelets and Hemostasis

Intrinsic pathway

Hageman factor

Christmas factor

(Accelerator globulin)

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Blood Physiology Platelets and Hemostasis

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.
Factors XIII

- Fibrin mesh attract platelets and forms stable blood clots.

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Blood Physiology Platelets and Hemostasis

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Blood Physiology Platelets and Hemostasis

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 suchSetasbyarterial disease.
Binyam ,MSC. Physiology 29
Blood Physiology Platelets and Hemostasis
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
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Blood Physiology Platelets and Hemostasis

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.

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 The Mechanism for Dissolving Blood Clots.

Prekallikrein

Factor XII

Positive feedback loop

Kallikrein

Plasminogen Plasmin

Fibrin degradation
Fibrin
products
polymer Clot dissolution
Blood Physiology Platelets and Hemostasis
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
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