Platelets

  Platelets.

PKGhatak,MD

 

Platelets

Little Disc but Feisty one.

The Christian name of the platelet is Thrombocyte. Platelets are tiny blood cells, about 1/5 th of an RBC. If one looks at a stained blood film, platelets may be mistaken as artifacts - tiny deposits of dark purple pigment. One can also examine platelets with a special instrument as they are floating in the bloodstream. Here, platelets appear as tiny lenses. The center appears clear because the nucleus is absent. All mammals' platelets have this characteristic and all other non-mammals, from birds down, have a nucleus in platelet cells.

Platelets are produced in bone marrow from Megakaryocytes. One megakaryocyte divides itself into individual platelets and sends them out on tiny limbs and the newly formed platelets break away. One megakaryocyte makes 1000 to 3000 platelets. A hormone, called Thrombopoietin made in the kidney and liver, is required for the normal production of platelets. As platelets are developing, they receive packets of powerful chemicals neatly packed in small granules like soldiers get their weapons and gift packages. Platelets travel to the spleen and are stationed there for a while like soldiers waiting for orders to go to the battlefields. In circulation, platelets survive about 9 days. When a platelet riches ripe old age, it is scoped up by the headhunters called macrophages of the spleen. Macrophages swallow and digest the platelet. 

Demystify medical terms.

Macro=large, phages=eaters, Mega=big. Penia= few, thin. Thrombo=clot,

Cytes=cells, Cythosis=too many cells, Pathy=lacking in function,

Structure under powerful magnification.

The outer membrane is, like all cell walls, made of two layers of fatty materials. On this surface, there are special areas called receptors by which platelets bind to certain specific proteins. The next layer contains filamentous structures that act as scaffolding providing stability and shape. Next to it is a zone of granules containing preformed cytokines, complements, serotonin and many blood clotting factors. Granules come in various sizes and shapes. They are given names of Greek alphabets, alpha, delta, and lambda. Each granule contains a set of chemicals which is different from the others. The remaining area, in the center, is loaded with microtubules going from the center to the surface of platelets.

A day in the life of Platelets.

A young platelet is happily floating around in the bloodstream, then suddenly he is pushed into a narrow tunnel(capillary) the wall of which is neatly lined with closely fitted glazed tiles (endothelial cells). As the platelet was looking around, he noticed a portion of the wall with missing tiles, and blood was oozing out. Suddenly he sees his favorite face of collagen fiber with lips colored with von Willebrand factor. He feels compelled to give a kiss on her lips (receptor protein). But lo! Now, he can't break away from her. His lips (receptors) are stuck on her lips. He notices his body shape is changing – swelling up, arms are coming out like the arms of an octopus and reaching out to other nearby platelets. As more and more platelets congregate and all the platelets are trying to kiss collagen lips, they form a heap and the mass completely covers up the missing tiles (break in endothelial surface). A mass of platelets forms a white soft clot that stops blood from flowing out. From their bodies, granular packs burst open and the chemicals spill all over. Now, an army of bridge-building-brigade assembles at the site in response to the released chemical (cytokines). Platelets release more chemicals containing construction materials (clotting factors fibrinogen, V, VIII, etc.). And the scaffolding takes the shape of a net. The net begins to trap RBCs and WBCs as they are traveling downstream with the blood. This generates a red firm clot, and it would not wash away with the moving blood. As time passes the platelets release a clot stabilizing factor and that turns the red clot to shrink in size into a hard clot, and this seals the break of the vessel permanently.

It is a story of sacrificing one's body for the common good. That is the purpose and objective of platelets.

 

Injury or disruption of the endothelium of arteries.

In coronary artery disease and following angioplasty, the endothelium is disrupted and collagen fibers are exposed. To prevent platelets from starting clot formation, antiplatelet agents like Aspirin and Clopidogrel are prescribed. After stent placement in cerebral arteries antiplatelet therapy is also used.

Thrombocytopenia.

The usual number is around 250,000/microliter, and the range is 100,000 to 4000,000/microliter. When the number falls to 50,000 spontaneous bleeding under the skin, gum, nose, and gastrointestinal tract may happen. Bleeding inside the brain, kidney and other vital organs poses a very serious problem

Some common conditions lead to Thrombocytopenia.

Cancer chemotherapy is perhaps the most important cause.  Radiation therapy to vertebrae for control of pain due to metastasis often produces marked thrombocytopenia. These therapies dry up the bone marrow.

Infectious causes:

Viruses, bacteria, and parasites are all known to produce low platelet counts. The dengue fever virus is notorious for producing dangerously low platelet counts. HIV, Hepatitis C virus, Lymphosarcoma, hematological malignancies and myelofibrosis are important causes.. Babesiosis due to a parasite is another example of the cause of thrombocytopenia.

Toxins:

E coli 0157.H7 toxin is a great threat to the lives of children getting infected from contaminated soil or handling live farm animals. Bacillary dysentery with shigella bacteria is also a serious problem.

Drugs:

Many drugs act directly on platelets or by decreasing the activity of the megakaryocytes.  A drug may form a  compound with platelets and the conjugate behaves like an antigen. And antibodies are produced and in turn, destroy platelets. A few well known drugs that produce low platelet counts are Quinine, Heparin, Penicillin, Sulfa drugs, Naprosyn, Hydrochlorothiazide, Procainamide, Carbamazepine,  and Rituximab.

Other important clinical conditions: 

Alcoholism, vitamin B12, and folic acid deficiency, mechanical aortic valve, post blood transfusion, Cirrhosis of the liver with hypersplenism,

More serious but not so common conditions:

ITP. (Idiopathic Thrombotic Thrombocytopenia). Here autoantibodies are again in play, but the cause remains hidden. The antibodies also attack the megakaryocytes.

TTP. (Thrombotic Thrombocytopenic Purpura). It is a highly feared illness.

In normal conditions, an enzyme, ADMTS13, is present in the blood, and keeps platelets separate, preventing them from clumping together in the blood. In an unfortunate mutation of gene/genes, less amount of this enzyme is produced and a low blood level of ADMST13 results. The condition by itself may not produce any symptoms but after an infection, even a minor one, a grave situation arises. The infecting virus or bacteria forms a complex with this ADMTS13 enzyme and after 7-10 days later autoantibodies begin to appear and the clotting starts. Tiny blood clots block all major capillaries of vital organs; medium size vessels may also be involved. Many clinical but equally serious pictures evolve. The life of patients depends on the removal of these antibodies by (plasmapheresis) and replacing plasma with normal plasma. The plasmapheresis needs to be repeated. An immunosuppressant drug is usually also required. The patient's children may inherit this deficiency.

High Platelet count (Thrombocytosis):

It is often associated with malignant conditions of the bone marrow. Megakaryocyte turns out platelets unchecked that may lead to obstruction of blood flow due to high viscosity from increased numbers of cells. The patient complains of blurred vision. And obstructed blood vessels can be directly observed by retinal examination. Chemotherapy is required to control the condition.

Drugs to prevent platelet aggregation.

Aspirin, Clopidogrel, Ticlopidine, Prasugrel and Eptifibatide are extensively used as antiplatelet agents, in preventing the clotting of stents in post angioplasty and coronary artery disease.

Aspirin: It permanently blocks enzyme COX1 on the platelet for its life span. Cox1 is necessary for generating prostaglandins G2 and H2, the precursors of clot promoting factors. Thromboxane 2.This results in the unopposed action of Thromboxane A1 which prevents platelet aggregation.

Clopidogrel, Ticlopidine and Prasugrel are considered together. They act on Platelet surface receptors P2Y2 and block these receptors to bind with ADP. This action prevents platelet aggregation.

Initially, one product claimed to be better than others, based on unfounded claims of higher potency. In practice, one product is not that great over others but the retail price is.

Eptifibatide. It binds with GPIIa / IIIb receptors on the platelet surface and prevents the receptors to bind with Fibrinogen to form fibrin which is a clot.

Antiplatelet drugs work well on the arterial side of circulation and prevent atherosclerosis but for some known reasons, the antiplatelet drugs are not effective on the veins side of the circulation in preventing blood clots.

The platelets are tiny but perform many vital functions. The primary function of platelets is to prevent bleeding by plugging the broken blood vessels. The platelets also supply various blood clotting factors. It is a source of a Neurotransmitter - Serotonin. The hormone melatonin is formed from serotonin. Because serotonin cannot cross the blood-brain barrier, serotonin is produced in the brain cells and the platelets may be another source of brain serotonin from the platelets in the cerebral circulation. Serotonin has many more important functions but is not discussed here.

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