Thrombocytosis is a condition where the platelet count in the blood is higher than normal. It is also referred to as thrombocythemia. Platelets are an important component of blood and is an integral factor in the blood clotting process. Most cases of thrombocytosis are transient and the condition does not produce any symptoms. Diagnosis is usually made during screening for other medical conditions.
However, the fact that platelets play such a central role in blood clotting does mean that there is a higher risk of clot formation in thrombocytosis. More importantly though, thrombocytosis may be caused by various disorders particularly those of the bone marrow, and some of which can be fatal if not treated immediately.
Formation of platelets
In the bone marrow, hematopoietic stem cells develop into very large cells known as megakaryocytes. These cells are about 10 times or more large than red blood cells. Budding of the megakaryocytes forms cell fragments known as platelets. Each megakaryocyte can produce anywhere between 5,000 to 10,000 platelets. Average healthy adults produce some 100 billion platelets each day. Extra platelets are stored in the spleen while the remaining platelets circulate in the bloodstream.
Picture of platelets from Wikimedia Commons
These platelets are essentially just cell fragments. It lacks a nucleus and cannot replicate on their own. Platelets have a lifespan of about 5 to 9 days in the circulation and old platelets are removed from the bloodstream by phagocytes in the spleen and Kupffer cells in the liver. When the body needs new platelets to restore normal levels, the spleen is essentially squeezed to release its platelet stores. In this way the quantity of circulating platelets is maintained within a normal range.
Functions of platelets
When the inner lining of blood vessels (endothelium) is damaged, platelets are one of the first blood components to respond. Platelets cell fragments that are normally irregularly shaped. The platelets attach to the damaged part of the blood vessel and become activated. It changes to a more spherical shape with the formation of projections from the platelet surface leading to an almost star-shaped fragment. These changes occur within seconds of blood vessel damage and expedites the rest of the clotting process.
Although platelets are the first to respond to blood vessel injury, it cannot repair the breaks permanently. With the activation of various tissue factors and the laying down of the tougher fibrin strands along with more platelets and blood cells, a blood clot is formed. Anti-clotting drugs like aspirin are actually antiplatelet agents. These drugs inhibit the normal function of platelets to reduce the chance of clot formation. It does not completely neutralize platelet activity but diminishes it.
Abnormal platelet count
In thrombocytosis, the number of platelets produced is higher than normal and these platelets have a longer lifespan. This leads to high levels of platelets in the circulation. In most instances this high levels of platelets does not pose any significant threat to the person’s health. Naturally there is a higher risk of clot formation. However, this is not necessarily a danger in most people unless there is underlying problems such as atherosclerosis which causes narrowing of the arteries.
Apart from the potential to form clots more easily, there is a also a greater risk of bleeding. This is contradictory to what would be expected with a high platelet count. It is more likely to arise with an excessively high platelet count and an associated deficiency of another component of blood clotting known as von Willebrand factor (vWF). In most patients thrombocytosis is benign meaning that it will not lead to any complications. However, there is the potential for life threatening complications in a small percentage of cases.
There are broadly two types of thrombocytosis – primary and secondary.
Primary thrombocytosis is also known as essential thrombocytosis. It has two subtypes. One due to bone marrow disorders that results in an overproduction of many blood components, including platelets. The second subtype is due to genetic mutations that affect the regulation of megakaryocyte production.
Secondary thrombocytosis is also known as reactive thrombocytosis. It arises as a result of some underlying event, disease or the use of certain medication. It is not permanent and usually resolves once the underlying cause is removed. The underlying cause may not necessarily be a problem in the bone marrow itself but rather is a consequence of an exaggerated physiological response.
Secondary (reactive) thrombocytosis is the more common type and usually does not produce any symptoms. In most instance the symptoms that are present are due to the underlying disorder and not the thrombocytosis itself. Patient’s with primary (essential) thrombocytosis usually have a history of symptoms.
- Headache is the most common symptom.
- Dizziness and sometimes fainting.
- Episodes of blurred or double vision.
- Tingling and/or numbness of the limbs.
- Chest pain.
- Excessive bruising.
- Bleeding in the gut and after surgery.
Primary thrombocytosis is mainly due to bone marrow disorders and genetic mutations that affect the processes regulating platelet production. Reactive thrombocytosis may occur with :
- Allergic reactions
- Anemia and other blood disorders – iron-deficiency, sickle cell, thalassemia
- Chronic inflammatory disorders
- Heart attack
- Infections :
- gastrointestinal tract
- respiratory tract
- urinary tract
- Kidney disorders including nephrotic syndrome
- Major trauma
- Newborns – preterm, low birth weight
- Spleen removal (surgical)
Medication that may contribute to thrombocytosis includes :
- Heparin (low-molecular weight)
- Tretinoin (acne drug)
Thromobcytosis is usually not diagnosed based on the signs and symptoms, if present. Instead diagnostic investigations are necessary. In fat thrombocytosis is often discovered incidentally during a routine blood test. These investigations include :
- Complete blood count (CBC)
- Peripheral blood smear
- Blood clotting factors
The normal reference range is between 150 to 450 billion platelets per liter of blood. Various other tests are necessary to identify the cause of thrombocytosis if there is no clear underlying cause. Testing for different blood clotting factors can be useful in differentiating between primary and secondary thrombocytosis. Geneteic testing and a bone marrow biopsy may also be considered as part of the investigation.
Reactive thrombocytosis is usually transient and no specific treatment is needed. The underlying cause should be identified and treated for quicker resolution of thrombocytosis. Treatment is only considered for patients with excessively high levels of platelets, where complications of thrombocytosis is present or the patient is considered to be at high risk of developing complications.Medication that may be used includes :
- Aspirin to prevent the formation of blood clots.
- Anagrelide to reduce platelet count and is more frequently used for primary thrombocytosis.
- Hydroxyurea reduce blood cell count but is not specific for platelets.