Essential thrombocythemia

What is essential thrombocythemia?
Essential thrombocythemia is one of the myeloproliferative diseases. It is the myeloproliferative disease variant that is characterized by platelet counts greater than 400,000. The myeloproliferative diseases also include polycythemia vera, agnogenic myeloid metaplasia, secondary myelofibrosis, and chronic myelogenous leukemia. Each of these variants has predominant features, which permit classifications, which are named for the cell type showing the most marked involvement. There is a great deal of overlap in the features of these various syndromes and transition from one to another is common.

Is essential thrombocythemia cancer?
No, as there are no cancerous cells. But it is considered a chronic hematological malignancy. This can be confusing, and insurance companies take varying views.

How does essential thrombocythemia fit in myeloproliferative disorders?
Thrombocythemia (or thrombocytosis) is defined as the occurrence of a platelet count in excess of 400,000 per microliter in the setting of a myeloproliferative disease. When this is the predominant abnormality, the syndrome is classified as essential thrombocythemia. Abnormal megakarocyte proliferation (platelet precursors) is seen in all variants of myeloproliferative disease and elevated platelet counts common in polycythemia vera, chronic myelogenous leukemia, and the proliferative states of agnogenic myeloid metaplasia. On the other hand, ET patients can also have elevated white cell count (WBC), hematocrit (HCT) and hemoglobin (HG) counts so a careful differential diagnosis is essential.

What causes essential thrombocythemia?
No one knows why it develops. In all of the myeloproliferative disorders, the stem cell that is capable of producing red cells, certain white cells, and platelets somehow goes haywire and no longer keeps the blood elements produced by the marrow in balance. In essential thrombocythemia, the marrow produces too many platelets.

What symptoms might I experience from the essential thrombocythemia?
There are any number of symptoms that can go along with this condition. Visual disturbances when platelets are too high are experienced by many. These generally are described as "light shows" or "silent migraines". Minor symptoms can include bruising, bleeding such as bleeding gums, nose bleeds, heavy menstrual periods, pain, tingling, burning or numbness in fingers and toes, skin sensations-tingling, feeling of something crawling on your arm, headache, and fatigue. More serious symptoms can include stroke, heart attack, pulmonary embolism, thrombophlebitis (pain and swelling will be usually be present in the affected leg), hemorrhage. If myeloid metaplasia is present, the patient may have a sense of fullness in the area of the liver or spleen. There may be pain in those areas.

There are also a whole gaggle of metabolic abnormalities that go along in patients with myeloproliferative disorders. These include:

• Elevated uric acid counts are seen in about half of patients with myeloproliferative disease during the course of their disease. If untreated, this leads to uric acid stones, uric acid neuropathy, acute gout, and chronic gouty arthritis. Patients may experience joint pain as a result.
• Low cholesterol levels (hypocholestoremia), particularly in those with enlarged spleens.
• Elevated histamine levels. Symptoms of increased histamine release include puritis (itching characteristically produced by bathing or showering), heartburn, acid eructation (gas), peptic ulcer, small bowel hypermotility, flushing and angioneurotic edema (swelling of skin, mucous membranes or viscera). This occurs in 2/3rds of myeloproliferative disorder patients and correlates with presence of elevated basophil count and hyperhistaminemia.
• Hypermetabolism, which commonly manifests as weakness and fatigue in the absence of anemia.

How is essential thrombocythemia diagnosed?
The diagnosis of essential thrombocythemia is primarily one of exclusion. If platelet counts are elevated with:

• no identifiable cause of secondary thrombocytosis i.e. from infection, cancer, or other disease state
• the red cell volume is normal (excludes polycythemia vera)
• iron is present in the bone marrow or reduced iron stores have been repleted by oral iron administration for one month without inducing an increase in hemoglobin
• collagen fibrosis is absent from the bone marrow biopsy (excludes myelofibrosis)
• the Philadelphia chromosome is absent from the bone marrow aspirate (excludes chronic myelogenous leukemia).

How do you differentiate between primary and secondary thrombocythemia?
By the criteria discussed above. If other disease states such as cancer, infection, etc. have been ruled out and the bone marrow findings are present, then the diagnosis is primary thrombocythemia.

What are some of the other names for this condition?
Essential thrombocytosis, thrombocytosis, primary thrombocytosis, essential thrombocythemia.

Can essential thrombocythemia be cured?
Essential thrombocythemia (ET) is a chronic condition. The only potential cure at the moment is a matched donor for bone marrow transplant. Most ET patients are not eligible for this procedure. Because of its associated risk and expense, bone marrow transplants are generally reserved for life-threatening diseases. ET patients generally do not fall in this category. But a lot can be done to reduce symptoms and risks of complications.

What is my probable life expectancy?
Essential thrombocythemia patients have an excellent chance of living out a normal lifespan if properly monitored and treated as necessary. Do keep in mind that this is a chronic hematologic malignancy and it is prudent to be monitored regularly by a hematologist, it is important to report any symptoms such as visual disturbances, unexplained pain, numbness, tingling, bruising to your physician, and for those who have had symptoms from their ET, treatment will be required. But it can be controlled, and you can live with it for a long time.

How common/rare is essential thrombocythemia?
The published annual incidence for essential thrombocythemia ranges from 0.1-2.4/100,000. It is rare and is classified as an orphan disease.

Do patients just have elevated platelet counts?
In essential thrombocythemia (ET), in addition to elevated platelet counts, platelets generally can be abnormal in size, shape, density, and function. Spontaneous aggregation (clumping) can occur putting ET patients at higher risk for clotting events. There can also be an increased risk of bleeding. According to Dr. Gilbert, clinical manifestations are dominated by hemorrhage (bruising, nosebleeds, unexplained gastrointestinal bleeding, and postoperative hemorrhage) and microvascular occlusions erythema (redness), and burning as well as a host of neurological complaints such as headache, parathesis-numbness and tingling and transient ischemic attacks.

It also is not uncommon for all myeloproliferative disorder patients to have other elevated blood counts. For example, in addition to high platelet counts, white cell counts may also be increased.

Am I at risk if my platelets are elevated?
The answer is a definite maybe. Platelet counts alone are not predictors of complications. Elevated platelets can present a risk of thrombosis (abnormal blood clotting) or bleeding. Elevated platelets can also cause excessive bleeding during surgery and your physician is likely to want to reduce platelet counts before surgery. But this is not a monolithic, everyone acts in a predictable fashion kind of disease. You can go on the principle that risks are increased if platelet counts are elevated and then work with your doctor based on your own disease course and whether or not you are symptomatic or have independent risk factors that can complicate the course of your disease.

How is essential thrombocythemia treated?
This depends upon the patient and whether there have been symptoms or complications. The current treatment options include nothing, baby aspirin, interferon, anagrelide or hydroxyurea alone or in combination. At present Bone marrow/stem cell transplant is being evaluated in an MPD-RC clinical trial (MPD 101) as a possible cure.

Will I need a bone marrow biopsy and what are these like?
Yes. Patient experience varies. Basically, you lie down on your stomach and a special needle is used to drill into the hip bone and extract a core of bone and an aspirate of the marrow contents. Before the procedure, a local anesthetic is injected to numb the bone. But there is no way to numb the interior marrow so there will be momentary sharp pain. This procedure can be made much more comfortable by insisting that the doctor wait until the local has had a chance to take effect. Taking a mild tranquilizer about an hour before the procedure can reduce anxiety and make the procedure more comfortable. Finally, some doctors will use a combination of intravenous drugs (demerol and versed, demerol and ativan, morphine, and valium) which allows the patient to sleep through the procedure. Either way, this is an outpatient procedure usually performed in your hematologist's office.

What are the criteria for starting treatment?
This may vary from physician to physician. Generally, if the patient is not experiencing any problems from their essential thrombocythemia, baby aspirin (unless the patient tends to bleed) may be the only treatment suggested along with close monitoring. If a patient presents with a stroke, heart attack, thrombophlebitis, clearly reduction of platelet counts will be deemed necessary to get them out of danger and reduce the risk of further complications and treatment will be started immediately. If a patient shows up with enlarged spleen or liver which means that you have blood production taking place outside the bone marrow, treatment is a very good idea. When symptoms are "minor", treatment may still be appropriate both for comfort and to help slow disease progression.

What do people with essential thrombocythemia die of?
In most cases, if they are properly monitored and treated, diseases of old age. A small percentage may convert to acute leukemia. This is usually associated with prior treatment of a leukemogenic drug (a drug that, as a side effect, may initiate or progress leukemia). Some persons progress to the post-thrombocythemic myeloid metaplasia stage where blood counts fall and bleeding and infection complications become a problem.

Are there any symptoms/occurrences that signal a change or progression?
One of the reasons it is important to be monitored and to have periodic bone marrow evaluations is that changes can take place in the bone marrow that are not readily apparent by looking at blood counts or how the patient feels.

If there is a sudden change in your blood counts or a gradual shift in either direction, or you start having symptoms that weren't there a short while ago, such as bruising, headache, fatigue, swelling in your legs or abdomen, visual disturbances, headache, unexplained pain, numbness etc., find out what is going on. We also have to remember that having essential thrombocythemia does not give us a free pass on other diseases. Some will convert to polycythemia vera for example.

Does essential thrombocythemia ever affect children?
Unfortunately yes.

Do children with essential thrombocythemia react any differently than adults?
This was originally thought of as a disease of old age and symptoms were largely ignored in younger patients until the last decade or so. So there isn't much in the literature about childhood essential thrombocythemia T and most of it simply reports treatment with anagrelide.

This information was developed by the MPD-Research Consortium and is herewith used with permission.

MPD-RC. FAQ: About Essential Thrombocythemia. Available at: https://www.mpnresearchfoundation.org/images/files/essentialprimarythrombocythemia.pdf. Accessed February 10, 2014.

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