Platelet ( thrombocyte ) - PowerPoint Presentation

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Platelet (

thrombocyte

)

: the smallest of the formed elements in blood, a disk-shaped, non-nucleated blood element with a fragile membrane, formed in the red bone marrow by fragmentation of

megakaryocytes

. Platelets tend to adhere to uneven or damaged surfaces, and there are an average of about 250,000 per mm

3

of blood.

The bone marrow produces from 30,000 to 50,000 platelets per mm

3

of blood daily, which means that in any ten-day period all the platelets in the body are completely replaced.

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Hemostasis

There are 3 mechanisms that work together to stop the flow of blood. They are 1-Vasoconstriction 2-Platelet plug formation 3-Clotting of blood

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1. Vasoconstriction

of a damaged blood vessel slows the flow of blood and thus helps to limit blood loss. This process is mediated by:Local controls. Vasoconstrictors such as thromboxane are released at the site of the injury. Systemic control. Epinephrine released by the adrenal glands stimulates general vasoconstriction.

2. Formation of a Platelet Plug.

When a blood vessel is damaged, the blood is exposed to collagen fibers in the basement membrane of the vessel . Platelets stick to collagen and become activated

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Activated platelets release chemicals such as ADP, and

thromboxane, that cause the aggregation of more platelets to the site of injury. Platelet aggregation results in the formation of a platelet plug which acts to stem the flow of blood from the broken vessel. It is essential that platelets become activated only at the site of a broken vessel. Otherwise activated platelets would form plugs and induce clots in inapropriate places. Healthy vessels secrete an enzyme called prostacyclin that functions to inhibit platelet activation and aggregation.

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Aspirin

inhibits platelet activation by inhibiting the action of thromboxane. By inhibiting platelet activation, aspirin limits blood clotting in general. Aspirin is used clinically as a "blood thinner" in individuals that are at risk for developing life-threatning clots. Patients with advanced atherosclerosis take one baby aspirin per day to reduce the probability of heart attack and stroke.

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3. Clotting of Blood

The blood contains about a dozen clotting factors. These factors are proteins that exist in the blood in an inactive state, but can be called into action when tissues or blood vessels are damaged. The activation of clotting factors occurs in a sequential manner. The first factor in the sequence activates the second factor, which activates the third factor and so on. This series of reactions is called the clotting cascade.

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Blood clotting is the transformation of liquid blood into a semisolid gel. Clots are made from fibers (polymers) of a protein called

fibrin. Fibrin monomers come from an inactive precursor called fibrinogen. The body of the fibrinogen molecule has caps on its ends that mask fibrin-to-fibrin binding sites. If the caps are removed then fibrin monomers polymerize to form fibrin polymers. This process requires thrombin

, the enzyme that converts fibrinogen to fibrin. This process also requires

calcium

, which acts as a kind of glue to hold the fibrin monomers to each other to form the polymeric fiber. The fibrin fibers form a loose meshwork that is stabilized by clotting

factor XIII

. The stabilized meshwork of fibrin fibers traps erythrocytes, thus forming a clot that stops the flow of blood.

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Control of the Clotting Cascade

From the diagram above we can see that thrombin is the key to the clotting mechanism. If thrombin is present then clotting will proceeds, but if thrombin is absent then clotting will not occur. How then is thrombin controlled? Thrombin is derived from an inactive precursor called prothrombin. There are two pathways that lead to the conversion of prothrombin to thrombin; (1) the intrinsic pathway and (2) the extrinsic pathway.

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Intrinsic Pathway

The intrinsic pathway, which is triggered by elements that lie within the blood inself (intrinsic to the blood), occurs in the following way. Damage to the vessel wall stimulates the activation of a cascade of clotting factors (for the sake of simplicity we will not consider the individual factors). This cascade results in the activation of factor X. Activated factor X is an enzyme that converts prothrombin

to thrombin. Thrombin converts fibrinogen to fibrin monomers, which then polymerize in fibrin fibers. Fibrin fibers form a loose meshwork that is stabilized by

crosslinks

created by factor XIII. The

stabilzed

meshwork of fibrin fibers is now a clot that traps red blood cells and platelets and thus stops the flow of blood.

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Extrinsic Pathway

The extrinsic pathway is triggered by tissue damage outside of the blood vessel. This pathway acts to clot blood that has escaped from the vessel into the tissues. Damage to tissue stimulates the activation of tissue thromboplastin, an enzyme that catalyzes the activation of factor X. At this point the intrinsic and extrinsic pathways converge and the subsequent steps are the same as those described above.

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Inhibition of Excessive Clotting

It would be dangerous if blood clotting were to continue to expand beyond the boundaries of the injury. Excessive clotting is inhibited because: Clotting factors are rapidly inactivated. There are enzymes in the blood that function to inactivate clotting factors. As clotting factors are taken away from the site of injury by the blood stream, they become inactivated by these enzymes. This ensures that clotting will only occur at the site of injury and not progress steadily down the vessel.

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Fibrin fibers inhibit the activity of thrombin.

Thrombin acts to convert fibrinogen to fibrin, yet fibrin fibers have an inhibitory effect on the activity of thrombin. As the clot grows this inhibition intensifies. This constitutes a negative feedback loop, where the product of thrombin activity (fibrin) feeds back to shut off thrombin.

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Blood Clotting Disorders

HemophiliaIndividuals with this inherited disorder bleed excessively due to an inability to rapidly form blood clots. This defect could be caused by a deficiency of any of the clotting factors, however 80% of all hemophilics are deficient in factor VIII.

Vitamin K deficiency

Vitamin K is essential to the maturation of several clotting factors including factor X and

prothrombin

. In the absence of vitamin K these clotting factors are defective and thus inhibit the clotting mechanism. People with a Vitamin K deficiency experience excessive bleeding.

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Disorders of platelets:

Thrombocytopenia?Thrombocytopenia is the term for a reduced platelet (thrombocyte) count. It happens when platelets are lost from the circulation faster than they can be replaced from the bone marrow where they are made.

Thrombocytopenia can result from:

a failure of platelet production

an increased rate of removal from blood.

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Causative Factors

Other Common causes include infections (including HIV), drugs (frequently chemotherapeutic agents or alcohol, but other medications in rare cases), radiotherapy, vitamin deficiency (e.g., folate, vitamin B12), or marrow infiltration by tumor, storage diseases, or marrow failure syndromes (e.g., aplastic anemia).

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the risks of a low platelet count?

The main effect of a reduced platelet count is an increased risk of bleeding, but this rarely occurs until there are less than 80-100 thousands platelets per ml.There is not a close relationship between the number of platelets and the severity of bleeding, but there is an increasing risk of haemorrhage if platelet numbers fall or if platelet function is impaired (for example by aspirin, which reduces the 'stickiness' of the platelets).

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Thrombosis

: is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Alternatively, even when a blood vessel is not injured, blood clots may form in the body if the proper conditions present themselves. If the clotting is too severe and the clot breaks free, the traveling clot is now known as an embolus.

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Thromboembolism

: is the combination of thrombosis and its main complication, embolism. When a thrombus occupies more than 75% of surface area of the lumen of an artery, blood flow to the tissue supplied is reduced enough to cause symptoms because of decreased oxygen (hypoxia) and accumulation of metabolic products like lactic acid. More than 90% obstruction can result in anoxia, the complete deprivation of oxygen, and infarction, a mode of cell death.

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Causes

In classical terms, thrombosis is caused by abnormalities in one or more of the following:1- The composition of the blood (hypercoagulability or thrombophilia) 2-Quality of the vessel wall (endothelial cell injury)

3- Nature of the blood flow (stasis, turbulence)

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Blood clotting tests:

Before you have surgery your doctor may order blood tests to determine how quickly your blood clots. This group of tests is known as a coagulation study, individually these tests are commonly referred to as a PT (Prothrombin Time), PTT(Partial Thromboplastin Time). During some surgeries it is important that the blood not clot as quickly as normal, and medications may be given to slow the clotting time.

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. Drugs commonly used to slow clotting have a variety of names, but Heparin, Coumadin,

Lovenox and Warfarin are among the most common. In other cases, the patient may not clot quickly enough, and steps may be taken to make the blood to clot more quickly.

Prothrombin

Time Blood Test-PT

This test is done to evaluate the blood for its ability to clot. It is often done before surgery to evaluate how likely the patient is to have a bleeding or clotting problem during or after surgery.

Normal PT Values: 10-12 seconds (this can vary slightly from lab to lab)

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Partial

Thromboplastin Time Blood Test-PTT This test is performed primarily to determine if heparin (blood thinning) therapy is effective. It can also be used to detect the presence of a clotting disorder. It does not show the effects of drugs called “low molecular weight heparin” or most commonly by the brand name Lovenox.

Normal PTT Values: 30 to 45 seconds (this can value slightly from lab to lab)