Platelets

20 / 4 /10

Hemostasis

Definition: Prevention of blood loss.

Events Involved In Hemostasis

Whenever a vessel is ruptured, hemostasis is achieved by:

1. Vascular constriction

2. Formation of a platelet plug

3. Formation of a blood clot as a result of blood coagulation. 4. Eventual growth of fibrous tissue into the blood clot to close the hole in the vessel permanently.

Vascular Constriction

 In ruptured blood vessel

1. Pain impulses from the site of trauma as well as from the surrounding nervous tissue originate and reach the spinal cord. From the spinal cord order signal arise.

 The order signals pass through the sympathatic nerves

Lead to spasm of the vessel.

2. Local muscle also contribute to the vascular vasospasm. 3. local autacoid factors from the traumatized tissues and blood platelets.

 As the vessel wall is damaged the action potential developed along the vessel wall lead to vasoconstriction.
The vasospasm lasts for almost half an hour and it is directly proportional to the intensity of trauma.

Vasoconstriction resulting from local myogenic contraction of the blood vessels is initiated by direct damage to the vascular wall. In the smaller vessels, the platelets are responsible for much of the vasoconstriction by releasing a vasoconstrictor substance, thromboxane A2.

Formation of the Platelet Plug

Platelets

 Platelets or thrombocytes are small colorless, non nucleated cells.

Shape is spherical or rod shaped and become oval or disc shaped when inactivated.

Size:

1 to 4 micrometers in diameter.

Life span: 10 - days

 Development: From the pluripotentstem cells in the bone marrow. CFU-M Colony forming megakaryocytes Megakaryoblast

Promegakaryoctye
Megakaryocytes Platelets

Normal concentration:
150,000 to 300,000 per microliter.

Structure:
Cell membrane Microtubule Cytoplasm

Cell Membrane of Platelet

 It is 6 nm thick and contain lipids (phospholipids, cholesterol and glycolipids),Carbohydrates(glycocalyx), Proteins and glycoproteins.
Out of all glycoprotein and phospholipids are functionally important.

Glycopropteins
Prevents the adherence of platelets to normal endothelium. Accelerates the adherence of platelets to collagen and damaged endothelium in ruptured blood vessels. Forms a receptor for ADP and thrombin.

Phospholipids
Accelerate clotting reactions. Form precursors for thromboxane A .

Microtubules The microtubule form a ring around the cytoplasm below the cell membrane.

 The microtubules are made up of polymerized protein called tubulin .

The tubules provide structural support for the inactivated platelets to maintain disc shape.

Platelets-2
21 /4 /10

Cytoplasm
The cytoplasm of the platelets include: Golgi apparatus Endoplasmic reticulum Mitochondria Microtubule Microvessels Microfilaments Granules

Cytoplasm also contains: Proteins Enzymes Hormones. Chemical substances

Proteins
The major proteins present are contractile proteins which are responsible for the contraction of platelets:

Actin
Myosin

Thrombosthenin

 Fibrin-stabilizing factor. Clotting factor

Platelet derived growth factor (PDGF) ............. helps repair damaged vascular walls.

Enzymes
The enzymes present are adenosine
triphosphatase and the enzymes necessary for the synthesis of prostaglandin.

Hormones
Adrenaline

Serotonin
Histamine

vascular and local tissue reactions

Chemical substances:
Calcium ions Mg- ions. Adenosine triphosphate (ATP) Adenosine diphosphate (ADP)

Function Of Platelets
Its surface has glycoprotein coat that adhere it to injured endothelial cells .preventing bleeding.

Actin, myosin & thrombosthenin that are contractile proteins. cause clot retraction.

 Secretes growth factor that promotes growth & multiplication of vascular endothelial cells, vascular smooth cells & fibroblasts. repair damaged vascular wall.
Its membrane has phospholipids that activate intrinsic system of blood clotting

 Endoplasmic Reticulum and Golgi apparatus synthesize enzymes and store Ca++ ions. Have enzyme system to synthesize prostaglandins.

Life span O f Platelets

Platelets are eliminated from the circulation mainly by the tissue macrophage system in the spleen.

Mechanism of the Platelet Plug

When platelets come in contact with a damaged vascular surface, platelets attach to the exposed collagen fibers in the vascular wall. Platelets immediately change their own characteristics.

 Platelets begin to swell and assume irregular forms with numerous irradiating pseudopods protruding from their surfaces

Contractile proteins in the platelets contract forcefully and cause the release of granules that contain multiple active factors

 Adenosine diphosphate (ADP) is released which causes surface of nearby circulating platelets to become sticky and it adheres to the first layer of aggregated platelets

 The aggregated platelets adhere to the von Willebrand factor that leaks into the traumatized tissue from the plasma It leads to the release of more ADP , which cause more platelets to pile up at the defected site.

 The aggregating process is reinforced by the formation of Thromboxane A2. It directly promotes platelet aggregation and further enhances it indirectly by triggering the release of even more ADP from the platelet granules. Formation of platelet plug takes place

The aggregated platelet plug not only physically seal the break in the vessel but, also perform three other important roles: Actin and myosin which were the contractile proteins in the platelets contract

 This compacts and strengthens the the plug which was initially, a loose plug.
Secondly, various chemicals released from the platelet plug include several vasoconstrictors (serotonin, epinephrine and Thromboxane A2 ) cause vascular vasospasm

 Thirdly, the platelet plug release other chemical substances that play a role in blood clotting. Platelet plugging mechanism alone is sufficient to seal tears in the capillaries and small vessels but, large holes require formation of blood clot to stop bleeding.

Limitation of Platelet Plug Normal endothelium of the vessel release Prostacyclin which prevents platelet aggregation. So, platelet plug is limited to the defected part of the vessel and does not spread to the normal vascular tissue.

Formation Of Blood Clot If there is a large defect in the vessel then blood clot + platelet plug are required to stop bleeding.

As clot on the top of platelet plug supports it and reinforces the seal over the break in the vessel.

Onset Of Formation Of Blood Clot: 15 20 sec in severe trauma. 1 2 min in minor trauma.

 Ultimate step in clot formation is the conversion of fibrinogen which is a soluble protein that is produced by the liver and is normally always present in the plasma to fibrin which is insoluble thread like molecule.
thrombin

Fibrinogen

Fibrin

 Fibrin molecules adhere to the damaged vessel surface forming a loose netlike meshwork that traps the cellular elements of blood. The clot appears red because of abundance of RBC that are trapped in it.

 The original fibrin web is weak because the fibrin threads are loosely interlaced.

Rapidly, various chemical linkages are formed between adjacent strands to strengthen and stabilize the clot mesh work.

 The cross linkage process which is catalyzed by a clotting factor known as factor XIII (Fibrin stabilizing factor).

 End Of Todays Lecture!!!

Hemostasis-1
22 /4 /10

Fibrous Organization or Dissolution of the Blood Clot

Once a blood clot has formed, it can follow one of two courses: It can become invaded by fibroblasts, which subsequently form connective tissue all through the clot.
It can dissolve.

 The usual course for a clot that forms in a small hole of a vessel wall is invasion by fibroblasts, beginning within a few hours after the clot is formed.
This event is promoted at least partially by growth factor secreted by platelets.

 Complete organization of the clot into fibrous tissue takes place within 1 to 2 weeks.
When excess blood has leaked into the tissues and tissue clots have occurred where they are not needed.

 Special substances within the clot itself usually become activated. These function as enzymes to dissolve the clot.

Mechanism of Blood Coagulation

Procoagulants:
Substances that cause or affect blood coagulation that have been found in the blood and in the tissues. promote coagulation Anticoagulants: Substances that inhibit coagulation are called Anticoagulants.

 Whether blood will coagulate depends on the balance between these two groups of substances. In the blood stream, the anticoagulants normally predominate, so that the blood does not coagulate while it is circulating in the blood vessels.

 But when a vessel is ruptured, procoagulants from the area of tissue damage become activated and override the anticoagulants, and then a clot does develop.

Three Essential Steps Involved In Clotting:

(1) In response to rupture of the vessel or damage to the blood itself, a complex cascade of chemical reactions occurs in the blood involving more than a dozen blood coagulation factors. Formation of a complex of activated substances collectively called prothrombin activator.

(2) The prothrombin activator catalyzes conversion of prothrombin into

thrombin in the presence of

sufficient amounts of ionic Ca++.

(3) The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that mesh with platelets, blood cells, and plasma to form the clot.

 The clotting cascade may be triggered by the intrinsic pathway or the extrinsic pathway:

The intrinsic pathway precipitates clotting within damaged vessels as well as clotting of blood samples in test tubes.

 All elements necessary to bring about clotting by means of the intrinsic pathway are present in the blood.

 End of todays lecture!!!