Essential thrombocytosis
Encyclopedia
Essential thrombocythemia (ET, also known as essential thrombocytosis) is a rare chronic blood disorder characterized by the overproduction of platelets by megakaryocyte
s 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
. It is one of four myeloproliferative disorders.
in that cells of the megakaryocytic
series are more sensitive to growth factors. Platelets derived from the abnormal megakaryocytes do not function properly, which contributes to the clinical features of bleeding and thrombosis.
A mutation in the JAK2 kinase
(V617F) has been found to be associated with essential thrombocythemia in around 40-50% of cases. About 3-4% of such cases go on to develop acute leukemia. JAK2 is a member of the Janus kinase
family. This mutation may be helpful in making a diagnosis or as a target for future therapy.
. Other symptoms include epistaxis (nosebleeds) and bleeding from gums and gastrointestinal tract. One characteristic symptom is throbbing and burning of the hands and feet due to the occlusion of small arterioles by platelets (erythromelalgia
). An enlarged spleen (splenomegaly
) may be found on examination.
The following revised diagnostic criteria for essential thrombocythemia were proposed in 2005. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6.
(also known as hydroxycarbamide), interferon-α or anagrelide
. Low-dose aspirin is widely used to reduce the risk of thrombosis, but there may be an increased risk of bleeding if aspirin is initiated while the platelet count is very high.
The PT1 study compared hydroxyurea in combination with aspirin to anagrelide in combination with aspirin as initial therapy for essential thrombocytosis. Hydroxyurea was superior, with lower risk of arterial thrombosis, lower risk of severe bleeding and lower risk of transformation to myelofibrosis (although the rate of venous thrombosis was higher with hydroxycarbamide than with anagrelide).
In rare cases where patients have life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis
(a procedure that removes platelets from the blood directly).
However, well-documented medical regimes can reduce and control the number of platelets, which reduces the risk of these thrombotic or haemorrhagic events. The lifespan of a well controlled ET person is well within the expected range for a person of similar age but without ET.
and anagrelide
are contraindicated during pregnancy
and nursing
. There is current debate as to the safety of interferon
during pregnancy and nursing. Essential thrombocytosis can be linked with increased risk of spontaeous abortion or miscarriage in the first trimester of pregnancy. Throughout pregnancy, close monitoring of the mother for thrombosis and placenta is recommended to ensure blood clots are caught. Post partum, often daily injections of low dose low molecular weight heparin
(e.g. enoxaparin
) are prescribed for several weeks as this is a period where the mother is at higher risk of developing a blood clot.
Megakaryocyte
The megakaryocyte is a bone marrow cell responsible for the production of blood thrombocytes , which are necessary for normal blood clotting...
s in the 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...
in the absence of an alternative cause. In some cases this disorder may be progressive, and rarely may evolve into acute myeloid leukemia
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
or myelofibrosis
Myelofibrosis
Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
. It is one of four myeloproliferative disorders.
Epidemiology
Essential thrombocythemia is diagnosed at a rate of about 2 to 3 per 100,000 individuals annually. The disease usually affects middle aged to elderly individuals, with an average age at diagnosis of 50–60 years, although it can affect children and young adults as well.Pathophysiology
The pathologic basis for this disease is unknown. However, essential thrombocythemia resembles polycythemia veraPolycythemia 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...
in that cells of the megakaryocytic
Megakaryocyte
The megakaryocyte is a bone marrow cell responsible for the production of blood thrombocytes , which are necessary for normal blood clotting...
series are more sensitive to growth factors. Platelets derived from the abnormal megakaryocytes do not function properly, which contributes to the clinical features of bleeding and thrombosis.
A mutation in the JAK2 kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
(V617F) has been found to be associated with essential thrombocythemia in around 40-50% of cases. About 3-4% of such cases go on to develop acute leukemia. JAK2 is a member of the Janus kinase
Janus kinase
Janus kinase is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 & 2 , but were ultimately published as "Janus kinase"...
family. This mutation may be helpful in making a diagnosis or as a target for future therapy.
Clinical features
The major symptoms are bleeding and thrombosisThrombosis
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...
. Other symptoms include epistaxis (nosebleeds) and bleeding from gums and gastrointestinal tract. One characteristic symptom is throbbing and burning of the hands and feet due to the occlusion of small arterioles by platelets (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...
). An enlarged spleen (splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
) may be found on examination.
Diagnostic criteria
The diagnosis of essential thrombocythemia requires the presence of a persistent thrombocytosis of greater than 600 x103/L in the absence of an alternative cause.The following revised diagnostic criteria for essential thrombocythemia were proposed in 2005. The diagnosis requires the presence of both A criteria together with B3 to B6, or of criterion A1 together with B1 to B6.
- A1. Platelet count > 600 x 109/L for at least 2 months
- A2. Acquired V617F JAK2 mutation present
- B1. No cause for a reactive thrombocytosis
- normal inflammatory indices
- B2. No evidence of iron deficiency
- stainable iron in the bone marrow or normal red cell mean corpuscular volume
- B3. No evidence of 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...
- hematocrit < midpoint of normal range or normal red cell mass in presence of normal iron stores
- B4. No evidence of chronic myeloid leukemia
- But the Philadelphia chromosomePhiladelphia chromosomePhiladelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t...
may be present in up to 10% of cases. Patients with the Philadelphia chromosome have a potential for the development of acute leukemia, especially acute lymphocytic leukemia.
- But the Philadelphia chromosome
- B5. No evidence of myelofibrosisMyelofibrosisMyelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, osteomyelofibrosis and primary myelofibrosis is a disorder of the bone marrow...
- no collagen fibrosis and ≤ grade 2 reticulin fibrosis (using 0–4 scale)
- B6. No evidence of a myelodysplastic syndrome
- no significant dysplasia
- no cytogenetic abnormalities suggestive of myelodysplasia
Treatment
Not all patients will require treatment at presentation. In those who are at increased risk of thrombosis or bleeding (older age, prior history of bleeding or thrombosis, or very high platelet count), reduction of the platelet count to the normal range can be achieved using hydroxyureaHydroxyurea
Hydroxycarbamide or hydroxyurea is an antineoplastic drug, first synthesized in 1869, used in myeloproliferative disorders, specifically polycythemia vera and essential thrombocythemia...
(also known as hydroxycarbamide), interferon-α 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:...
. Low-dose aspirin is widely used to reduce the risk of thrombosis, but there may be an increased risk of bleeding if aspirin is initiated while the platelet count is very high.
The PT1 study compared hydroxyurea in combination with aspirin to anagrelide in combination with aspirin as initial therapy for essential thrombocytosis. Hydroxyurea was superior, with lower risk of arterial thrombosis, lower risk of severe bleeding and lower risk of transformation to myelofibrosis (although the rate of venous thrombosis was higher with hydroxycarbamide than with anagrelide).
In rare cases where patients have life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis
Apheresis
Apheresis is a medical technology in which the blood of a donor or patient is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation...
(a procedure that removes platelets from the blood directly).
Prognosis
Essential thrombocytosis is sometimes described as a slowly progressive disorder with long asymptomatic periods punctuated by thrombotic or hemorrhagic events.However, well-documented medical regimes can reduce and control the number of platelets, which reduces the risk of these thrombotic or haemorrhagic events. The lifespan of a well controlled ET person is well within the expected range for a person of similar age but without ET.
Special care related to pregnancy
HydroxyureaHydroxyurea
Hydroxycarbamide or hydroxyurea is an antineoplastic drug, first synthesized in 1869, used in myeloproliferative disorders, specifically polycythemia vera and essential thrombocythemia...
and 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:...
are contraindicated during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
and nursing
Nursing
Nursing is a healthcare profession focused on the care of individuals, families, and communities so they may attain, maintain, or recover optimal health and quality of life from conception to death....
. There is current debate as to the safety of interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
during pregnancy and nursing. Essential thrombocytosis can be linked with increased risk of spontaeous abortion or miscarriage in the first trimester of pregnancy. Throughout pregnancy, close monitoring of the mother for thrombosis and placenta is recommended to ensure blood clots are caught. Post partum, often daily injections of low dose low molecular weight heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
(e.g. enoxaparin
Enoxaparin
Enoxaparin is a low molecular weight heparin marketed under the trade names Lovenox and Clexane, among others. It is an anticoagulant used to prevent and treat deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection...
) are prescribed for several weeks as this is a period where the mother is at higher risk of developing a blood clot.