Thrombocytosis
Encyclopedia
Thrombocytosis is the presence of high platelet
counts in the blood
, and can be either primary (also termed essential and caused by a myeloproliferative disease
) or reactive (also termed secondary). Although often symptomless (particularly when it is a secondary reaction), it can predispose to thrombosis
in some patients.
In a healthy individual, a normal platelet count ranges from 150,000 and 450,000 per mm³ (or microlitre) (150–450 x 109/L
). These limits, however, are determined by the 2.5th lower and upper percentile
, and a deviation does not necessary imply any form of disease. Nevertheless, counts over 750,000 (and especially over a million) are considered serious enough to warrant investigation and intervention.
, as the principal stimulants of platelet production (e.g. thrombopoietin
) are elevated in these clinical states as part of the acute phase reaction.
High platelet counts can occur in patients with polycythemia vera
(high red blood cell
counts), and is an additional risk factor for complications.
A very small segment of patients report symptoms of erythromelalgia
, a burning sensation and redness of the extremities that resolves with cooling and/or aspirin
use.
Scientific literature sometimes excludes thrombocytosis from the scope of thrombophilia
by definition, but practically, by the definition of thrombophilia as an increased predisposition to thrombosis, thrombocytosis (especially primary thrombocytosis) is a potential cause of thrombophilia. Conversely, secondary thrombocytosis very rarely causes thrombotic complications.
and erythrocyte sedimentation rate
.
If the cause for the high platelet count remains unclear, bone marrow
biopsy
is often undertaken, to differentiate whether the high platelet count is reactive or essential.
Over-medication with drugs that treat thrombocytopenia
, such as eltrombopag
or romiplostim
, may also result in thrombocytosis.
Other causes include the following
The vast majority of causes of thrombocytosis are acquired disorder
s, but in a few cases, they may be congenital
, such as thrombocytosis due to congenital asplenia.
However, in primary thrombocytosis, if platelet counts are over 750,000 or 1,000,000, and especially if there are other risk factors for thrombosis, treatment may be needed. Selective use of aspirin
at low doses is thought to be protective. Extremely high platelet counts in primary thrombocytosis can be treated with hydroxyurea
(a cytoreducing agent) or anagrelide
(Agrylin).
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
counts in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, and can be either primary (also termed essential and caused by a myeloproliferative disease
Myeloproliferative disease
The myeloproliferative diseases are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than...
) or reactive (also termed secondary). Although often symptomless (particularly when it is a secondary reaction), it can predispose to thrombosis
Thrombosis
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 and fibrin to form a blood clot to prevent blood loss...
in some patients.
In a healthy individual, a normal platelet count ranges from 150,000 and 450,000 per mm³ (or microlitre) (150–450 x 109/L
Litre
pic|200px|right|thumb|One litre is equivalent to this cubeEach side is 10 cm1 litre water = 1 kilogram water The litre is a metric system unit of volume equal to 1 cubic decimetre , to 1,000 cubic centimetres , and to 1/1,000 cubic metre...
). These limits, however, are determined by the 2.5th lower and upper percentile
Percentile
In statistics, a percentile is the value of a variable below which a certain percent of observations fall. For example, the 20th percentile is the value below which 20 percent of the observations may be found...
, and a deviation does not necessary imply any form of disease. Nevertheless, counts over 750,000 (and especially over a million) are considered serious enough to warrant investigation and intervention.
Signs and symptoms
High platelet levels do not necessarily signal any clinical problems, and are picked up on a routine full blood count. However, it is important that a full medical history be elicited to ensure that the increased platelet count is not due to a secondary process. Often, it occurs in tandem with an inflammatory diseaseInflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, as the principal stimulants of platelet production (e.g. thrombopoietin
Thrombopoietin
Thrombopoietin also known as megakaryocyte growth and development factor is a protein that in humans is encoded by the THPO gene....
) are elevated in these clinical states as part of the acute phase reaction.
High platelet counts can occur in patients with polycythemia vera
Polycythemia vera
Polycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...
(high red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
counts), and is an additional risk factor for complications.
A very small segment of patients report symptoms of erythromelalgia
Erythromelalgia
Erythromelalgia, also known as Mitchell's disease , acromelalgia, red neuralgia, or erythermalgia, is a rare neurovascular peripheral pain disorder in which blood vessels, usually in the lower extremities , are episodically blocked , then become hyperemic and inflamed...
, a burning sensation and redness of the extremities that resolves with cooling and/or aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
use.
Scientific literature sometimes excludes thrombocytosis from the scope of thrombophilia
Thrombophilia
Thrombophilia is an abnormality of blood coagulation that increases the risk of thrombosis . Such abnormalities can be identified in 50% of people who have an episode of thrombosis that was not provoked by other causes...
by definition, but practically, by the definition of thrombophilia as an increased predisposition to thrombosis, thrombocytosis (especially primary thrombocytosis) is a potential cause of thrombophilia. Conversely, secondary thrombocytosis very rarely causes thrombotic complications.
Diagnosis
Laboratory tests might include: full blood count, liver enzymes, renal functionRenal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
and erythrocyte sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
.
If the cause for the high platelet count remains unclear, bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
is often undertaken, to differentiate whether the high platelet count is reactive or essential.
Causes
Increase platelet counts can be due to a number of disease processes:- Essential (primary)
- Essential thrombocytosisEssential thrombocytosisEssential thrombocythemia is a rare chronic blood disorder characterized by the overproduction of platelets by megakaryocytes in the bone marrow in the absence of an alternative cause. In some cases this disorder may be progressive, and rarely may evolve into acute myeloid leukemia or myelofibrosis...
(a form of myeloproliferative diseaseMyeloproliferative diseaseThe myeloproliferative diseases are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than...
) - Other myeloproliferativeMyeloproliferative diseaseThe myeloproliferative diseases are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than...
disorders such as chronic myelogenous leukemiaChronic myelogenous leukemiaChronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood...
, polycythemia veraPolycythemia veraPolycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...
, myelofibrosis
- Essential thrombocytosis
- Reactive (secondary)
- Inflammation
- Surgery (which leads to an inflammatory state)
- Hyposplenism (decreased breakdown due to decreased function of the spleenSpleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
) - SplenectomySplenectomyA splenectomy is a surgical procedure that partially or completely removes the spleen.-Indications:The spleen, similar in structure to a large lymph node, acts as a blood filter. Current knowledge of its purpose includes the removal of old red blood cells and platelets, and the detection and fight...
- AspleniaAspleniaAsplenia refers to the absence of normal spleen function and is associated with some serious infection risks. Hyposplenism is used to describe reduced splenic functioning, but not as severely affected as with asplenism.-Congenital:...
(absence of normal spleen function) or hyposplenism - Hemorrhage and/or iron deficiencyIron deficiency (medicine)Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...
Over-medication with drugs that treat thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, such as eltrombopag
Eltrombopag
Eltrombopag is a medication that has been developed for conditions that lead to thrombocytopenia . It is a small molecule agonist of the c-mpl receptor, which is the physiological target of the hormone thrombopoietin...
or romiplostim
Romiplostim
Romiplostim is a fusion protein analog of thrombopoietin, a hormone that regulates platelet production. The drug was developed by Amgen and is marketed under the trade name Nplate through a restricted usage program called NEXUS...
, may also result in thrombocytosis.
Other causes include the following
- Kawasaki diseaseKawasaki diseaseKawasaki disease , also known as Kawasaki syndrome, lymph node syndrome and mucocutaneous lymph node syndrome, is an autoimmune disease in which the medium-sized blood vessels throughout the body become inflamed. It is largely seen in children under five years of age...
- Soft tissue sarcomaSoft tissue sarcomaA soft-tissue sarcoma is a form of sarcoma that develops in connective tissue, though the term is sometimes applied to elements of the soft tissue that are not currently considered connective tissue.-Risk factors:...
- OsteosarcomaOsteosarcomaOsteosarcoma is an aggressive cancerous neoplasm arising from primitive transformed cells of mesenchymal origin that exhibit osteoblastic differentiation and produce malignant osteoid...
- DermatitisDermatitis-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
(rarely) - Inflammatory bowel diseaseInflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
- Rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
- NephritisNephritisNephritis is inflammation of the nephrons in the kidneys. The word "nephritis" was imported from Latin, which took it from Greek: νεφρίτιδα. The word comes from the Greek νεφρός - nephro- meaning "of the kidney" and -itis meaning "inflammation"....
- Nephrotic syndromeNephrotic syndromeNephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
- bacterial diseases,including PneumoniaPneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
, SepsisSepsisSepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, meningitisMeningitisMeningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
, Urinary tract infectionUrinary tract infectionA urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...
s, and septic arthritis.
The vast majority of causes of thrombocytosis are acquired disorder
Acquired disorder
An acquired disorder is a medical condition which develops post-fetally; in contrast with a congenital disorder, which is present at birth. A congenital disorder may be antecedent to an acquired disorder ....
s, but in a few cases, they may be congenital
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
, such as thrombocytosis due to congenital asplenia.
Treatment
Often, no treatment is required or necessary for reactive thrombocytosis. In cases of reactive thrombocytosis of more than 1,000x109/L, it may be considered to administer daily low dose aspirin (such as 65 mg) to minimize the risk of stroke or thrombosis.However, in primary thrombocytosis, if platelet counts are over 750,000 or 1,000,000, and especially if there are other risk factors for thrombosis, treatment may be needed. Selective use of aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
at low doses is thought to be protective. Extremely high platelet counts in primary thrombocytosis can be treated with hydroxyurea
Hydroxyurea
Hydroxycarbamide or hydroxyurea is an antineoplastic drug, first synthesized in 1869, used in myeloproliferative disorders, specifically polycythemia vera and essential thrombocythemia...
(a cytoreducing agent) or anagrelide
Anagrelide
Anagrelide is a drug used for the treatment of essential thrombocytosis , or overproduction of blood platelets. It also has been used in the treatment of chronic myeloid leukemia. -Mechanism:...
(Agrylin).