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    PLT

    PLT

    Platelets

        Platelets, also called thrombocytes, are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus: they are fragments of cytoplasm that are derived from the megakaryocytes of the bone marrow, and then enter the circulation. Circulating unactivated platelets are biconvex discoid (lens-shaped) structures,:117–18 2–3 µm in greatest diameter. Activated platelets have cell membrane projections covering their surface. Platelets are found only in mammals, whereas in other animals (e.g. birds, amphibians) thrombocytes circulate as intact mononuclear cells.

        On a stained blood smear, platelets appear as dark purple spots, about 20% the diameter of red blood cells. The smear is used to examine platelets for size, shape, qualitative number, and clumping. The ratio of platelets to red blood cells in a healthy adult ranges from 1:10 to 1:20. One major function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium. They gather at the site and unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium: adhesion. Second, they change shape, turn on receptors and secrete chemical messengers: activation. Third, they connect to each other through receptor bridges: aggregation. Formation of this platelet plug (primary hemostasis) is associated with activation of the coagulation cascade with resultant fibrin deposition and linking (secondary hemostasis). These processes may overlap: the spectrum is from a predominantly platelet plug, or "white clot" to a predominantly fibrin, or "red clot" or the more typical mixture. Some would add the subsequent retraction and platelet inhibition as fourth and fifth steps to the completion of the process and still others a sixth step wound repair. Platelets also participate in both innate and adaptive  intravascular immune responses.

        What are Platelets and Why are They Important?

        The purpose of platelets.

        Platelets are the cells that circulate within our blood and bind together when they recognize damaged blood vessels. When you get a cut, for example, the platelets bind to the site of the damaged vessel, thereby causing a blood clot. There’s an evolutionary reason why they’re there. It’s to stop us from bleeding.

        What is a healthy platelet count?

        A normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. Having more than 450,000 platelets is a condition called thrombocytosis; having less than 150,000 is known as thrombocytopenia. You get your platelet number from a routine blood test called a complete blood count (CBC).

        What it means to have too many platelets (thrombocytosis).

        The medical term for having too many platelets is thrombocytosis, and there are two types:

        Primary or essential thrombocytosis – Abnormal cells in the bone marrow cause an increase in platelets, but the reason is unknown

        Essential thrombocythemia is a myeloproliferative neoplasm in which excess platelets are produced, leading to abnormal blood clotting or bleeding.

        ·         The hands and feet may burn, turn red, and tingle, and the fingertips may feel cold.

        ·         Blood tests usually provide a diagnosis, but sometimes a bone marrow biopsy is needed.

        ·         Treatments that suppress symptoms and decrease platelet production are given.

        In myeloproliferative neoplasms. the blood-producing cells in the bone marrow (precursor cells, also called stem cells) develop and reproduce excessively.

     

        Platelets (thrombocytes) are cell-like particles in the blood that help the body form blood clots. Platelets are normally produced in the bone marrow by cells called megakaryocytes. In thrombocythemia, megakaryocytes increase in number and produce too many platelets. Thrombocythemia can be

        ·         Primary (essential): Caused by a disorder of platelet-forming cells

        ·         Secondary: Caused by a disorder that triggers increased production by normal platelet-forming cells (see secondary thrombocythemia)

        Essential thrombocythemia usually occurs in people between the ages of 50 and 70. It is more common in females.

     

        Essential thrombocythemia is considered a myeloproliferative neoplasm, in which certain blood-producing cells in the bone marrow develop and reproduce excessively. The cause of is a genetic mutation usually in the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), or calreticulin (CALR) genes. JAK2 mutation causes excess cell production. The MPL and CALR mutations increase the activity of JAK2, leading to increased blood cell production.

     

        Complications.

        Serious complications are rare but can be life-threatening.

     

        Blood clots may form in almost any blood vessel. Blood clots in large blood vessels may affect the legs (deep vein thrombosis), brain (stroke), heart (heart attack), or lungs (pulmonary embolism). Blood clots in tiny blood vessels can affect the eyes, brain, and skin.

     

        Excessive bleeding also can occur. Although an increased number of platelets might be thought to always cause excessive blood clotting, a very high number of platelets can actually cause bleeding by affecting other parts of the body's clotting system.

     

        Symptoms.

        Primary thrombocythemia may or may not cause symptoms. When symptoms occur, they are due to the blockage of blood vessels by blood clots and may include

        ·         Redness and warmth of the hands and feet, often with burning pain (erythromelalgia)

        ·         Tingling and other abnormal sensations in the fingertips, hands, and feet

        ·         Chest pain

        ·         Loss of vision or seeing spots

        ·         Headaches

        ·         Weakness

        ·         Dizziness

        ·         Bleeding, usually mild (such as nosebleeds, easy bruising, slight oozing from the gums, or bleeding in the digestive tract)

        The spleen may enlarge but this is rare at the time of diagnosis and more common in females.

     

        Older people who may already have diseases that cause blood vessel damage, such as diabetes and high blood pressure, have a higher risk of complications caused by blood clots, such as transient ischemic attacks, stroke, and heart attack.

     

        Diagnosis.

        ·         Blood tests

        ·         Genetic tests

        ·         Sometimes bone marrow biopsy

        Doctors make a diagnosis of primary thrombocythemia on the basis of the symptoms and after finding increased platelets on a blood count. Other blood tests, including genetic tests for the JAK2, CALR, or MPL mutations are done. In addition, microscopic examination of the blood may reveal abnormally large platelets, clumps of platelets, and fragments of megakaryocytes.

     

        To distinguish primary thrombocythemia from secondary thrombocythemia, which has many known causes, doctors look for signs of other conditions that could increase the platelet count. Removal of a sample of bone marrow for examination under a microscope (bone marrow biopsy) and doing genetic testing on the cells are sometimes helpful.

     

        Treatment.

        ·         Aspirin to relieve symptoms

        ·         Drugs to decrease platelet count

        Aspirin, which makes platelets less sticky and impairs clotting, may be given in small doses to help relieve mild symptoms such as redness and warmth of hands and feet, and headache, but people with significant bleeding should not take aspirin.

     

        Thrombocythemia may also require treatment with a drug that decreases platelet production. Such drugs include ruxolitinib, hydroxyurea, anagrelide, and interferon-alpha.

     

        Treatment with one of these drugs is typically started when clotting or bleeding complications develop and not just based on the platelet count.

     

        If drug treatment does not slow platelet production quickly enough, it may be combined with or replaced by plateletpheresis, a procedure reserved for emergency situations. In this procedure, blood is withdrawn, platelets are removed from it, and the platelet-depleted blood is returned to the person. However, plateletpheresis is inefficient and only a temporary solution.

     

        People with essential thrombocytosis usually have a normal life span, but some develop polycythemia vera (usually women) or myelofibrosis (usually men).

     

        Secondary thrombocytosis – The same condition as primary thrombocytosis, but may be caused by an ongoing condition or disease such as anaemia, cancer, inflammation, or infection

        When there are symptoms, they include spontaneous blood clots in the arms and legs, which if untreated can lead to heart attack and stroke. In severe cases, the patient might have to undergo a procedure called a plateletpheresis. This lowers the platelet count by removing the blood, separating out the platelets, and returning the red blood cells back to the body.

        With secondary thrombocytosis, the symptoms are usually related to the associated condition. For example, if you have an infection or anaemia, you treat those conditions and the platelet count comes down.

        Causes of secondary thrombocythemia include.

        ·         Bleeding

        ·         Removal of the spleen

        ·         Other surgical procedures

        ·         Trauma

        ·         Infections

        ·         Rheumatoid arthritis, inflammatory bowel disease, and other inflammatory disorders

        ·         Certain cancers, including chronic myeloid leukaemia

        ·         Premature destruction of red blood cells (hemolysis)

        ·         Iron deficiency

        ·         Sarcoidosis

        People with secondary thrombocythemia usually have no symptoms related to the high number of platelets (unlike people with primary thrombocythemia. Symptoms of the underlying condition usually dominate.

     

        Although an increased number of platelets might be thought to cause excessive blood clotting, this rarely happens in secondary thrombocythemia unless people also have severe arterial disease or prolonged immobility. Although some people with essential thrombocythemia have an increased risk of bleeding, this is not a concern with secondary thrombocythemia.

     

        Secondary thrombocythemia is diagnosed—and distinguished from primary thrombocythemia—when people with high platelet counts have a condition that readily accounts for the high number of platelets.

     

        To identify possible causes, doctors do blood tests, sometimes including genetic testing, and occasionally a bone marrow biopsy. Other tests such as radiologic tests may be needed to ascertain the cause of the platelet elevation.

     

        Treatment is aimed at the cause of the platelet elevation. If the treatment is successful, the platelet count will return to normal.

     

        Overview of Thrombocytopenia.

        Thrombocytopenia is a low number of platelets (thrombocytes) in the blood, which increases the risk of bleeding.

        ·         Thrombocytopenia occurs when the bone marrow makes too few platelets or when too many platelets are destroyed or accumulate within an enlarged spleen.

        ·         Bleeding in the skin and bruising occur.

        ·         Doctors use blood tests to make the diagnosis and determine the cause.

        ·         Sometimes treatment (such as platelet transfusion, prednisone and drugs to increase platelet production, or removal of the spleen) is needed.

        Platelets are cells that circulate in the bloodstream and help blood clot. The blood usually contains about 140,000 to 440,000 platelets per microliter (140 × 109 to 440 × 109 per litre). When the platelet count falls below about 50,000 platelets per microliter of blood (50 × 109 per litre), bleeding can occur even after relatively minor injury. The most serious risk of bleeding, however, generally does not occur until the platelet count falls below 10,000 to 20,000 platelets per microliter of blood (10 × 109 to 20 × 109 per litre). At these very low levels, bleeding may occur without any recognized injury.

        Causes.

        Many disorders can cause thrombocytopenia.

        Thrombocytopenia can occur when the bone marrow does not produce enough platelets, as happens in leukemia or other bone marrow disorders.

        Infection with hepatitis C virus, the human immunodeficiency virus (HIV, the virus that causes acquired immunodeficiency syndrome [AIDS]), Epstein-Barr virus (the usual cause of mononucleosis), and many other viruses may result in thrombocytopenia.

     

        Platelets can become entrapped in an enlarged spleen, as happens in cirrhosis of the liver, myelofibrosis, and Gaucher disease, reducing the number of platelets in the bloodstream.

     

        Massive red blood cell transfusions can dilute the concentration of platelets in the blood.

     

        Finally, the body may use or destroy too many platelets, as occurs in many disorders, three of the most notable being immune thrombocytopenia, thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome.

         

        Some drugs such as heparin, certain antibiotics, ethanol, anticancer drugs, and quinine can also cause thrombocytopenia. Drug-induced cytopenia may be the result of

        ·         Decreased platelet production by the bone marrow (caused by bone marrow toxicity)

        ·         Increased platelet destruction (immune-mediated thrombocytopenia)

     

        Symptoms.

        Bleeding in the skin may be the first sign of a low platelet count. Many tiny red dots (petechiae) often appear in the skin on the lower legs, and minor injuries may cause bruises (ecchymoses or purpura). The gums may bleed, and blood may appear in the stool or urine. Menstrual periods may be unusually heavy. Bleeding may be hard to stop.

     

        Bleeding worsens as the number of platelets decreases. People who have very few platelets may lose large amounts of blood into their digestive tract or may develop life-threatening bleeding in their brain even though they have not been injured.

     

        The rate at which symptoms develop can vary depending on the cause and severity of thrombocytopenia.

     

        Diagnosis.

        ·         Blood tests to measure platelet count and clotting

        ·         Other tests for disorders that may cause a low platelet count

        Doctors suspect thrombocytopenia in people who have abnormal bruising and bleeding. They often check the number of platelets routinely in people who have disorders that might cause thrombocytopenia. Sometimes they discover thrombocytopenia when blood tests are done for other reasons in people who have no bruising or bleeding.

     

        Determining the cause of thrombocytopenia is critical to treating the condition. Certain symptoms may help determine the cause. For example, people usually have a fever when thrombocytopenia results from an infection. In contrast, they usually do not have a fever when the cause is immune thrombocytopenia, thrombotic thrombocytopenic purpura, or hemolytic-uremic syndrome.

     

        An enlarged spleen, which a doctor may be able to feel during a physical examination, suggests that the spleen is trapping platelets and that thrombocytopenia results from a disorder that is causing the spleen to enlarge.

     

        The platelet count may be measured with an automated counter to determine the severity of thrombocytopenia, and a sample of blood may be examined under a microscope to provide clues to its cause. A sample of bone marrow removed and examined under a microscope (bone marrow biopsy and aspiration) may occasionally be needed to provide information about platelet production.

     

        Treatment.

        ·         Avoidance of injury and drugs that affect platelets

        ·         Sometimes platelet transfusion

        Treating the cause can often treat the thrombocytopenia. Thrombocytopenia caused by a drug usually is corrected by stopping the drug. Thrombocytopenia caused by autoimmune destruction of platelets (as in immune thrombocytopenia) is treated with prednisone to lessen platelet destruction, drugs to increase the production of platelets in the bone marrow, and sometimes removal of the spleen (splenectomy).

     

        People with a low platelet count and abnormal bleeding usually should not take drugs that impair platelet function (such as aspirin or nonsteroidal anti-inflammatory drugs).

     

        People who have a very low platelet count are often treated in a hospital. When bleeding is severe, platelets may be transfused, although sometimes the transfused platelets also are destroyed by the underlying disorder.


    Published on 2 June 2019