Trombocitose (plaquetas sanguíneas altas)

Definição

A trombocitose é uma condição em que a contagem de plaquetas no sangue é maior que o normal. É também referido como trombocitemia. As plaquetas são um componente importante do sangue e é um fator integral no processo de coagulação do sangue. A maioria dos casos de trombocitose é transitória e a condição não produz sintomas. O diagnóstico geralmente é feito durante a triagem de outras condições médicas.

No entanto, o fato de as plaquetas desempenharem um papel tão central na coagulação do sangue significa que há um risco maior de formação de coágulos na trombocitose. Mais importante ainda, a trombocitose pode ser causada por vários distúrbios, particularmente aqueles da medula óssea, e alguns dos quais podem ser fatais se não forem tratados imediatamente.

Fisiopatologia

Formação de plaquetas

Na medula óssea, as células-tronco hematopoiéticas desenvolvem-se em células muito grandes conhecidas como megacariócitos. Essas células são cerca de 10 vezes maiores que as células vermelhas do sangue. A brotação dos megacariócitos forma fragmentos celulares conhecidos como plaquetas. Cada megacariócito pode produzir entre 5.000 e 10.000 plaquetas. Adultos saudáveis ​​médios produzem cerca de 100 bilhões de plaquetas por dia. Plaquetas extras são armazenadas no baço enquanto as plaquetas restantes circulam na corrente sanguínea.

Imagem de plaquetas de 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.

Types

There are broadly two types of thrombocytosis – primary and secondary.

Primary thrombocytosis

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

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.

Symptoms

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.
• Weakness.
• Excessive bruising.
• Bleeding in the gut and after surgery.

Causes

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
• Bleeding
• Burns
• Cancer
• Chronic inflammatory disorders
• Fractures
• Heart attack
• Infections :
  – bone
  – gastrointestinal tract
  – HIV
  – kidney
  – meninges
  – respiratory tract
  – septicemia
  – skin
  – urinary tract
• Kidney disorders including nephrotic syndrome
• Major trauma
• Newborns – preterm, low birth weight
• Pancreatitis
• Postoperatively
• Spleen removal (surgical)

Medication that may contribute to thrombocytosis includes :

• Chemotherapy
• Epinephrine
• Heparin (low-molecular weight)
• Tretinoin (acne drug)

Diagnosis

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.

Treatment

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.