Essential thrombocythaemia

The Essential thrombocythemia ( often abbreviated ET ) is one of the manifestations of myeloproliferative neoplasms ( MPN ), that is a group of malignant diseases of the hematopoietic system. Characteristic of the ET is the persistent thrombocytosis, ie proliferation of thrombocytes ( platelets) in your blood.

Epidemiology

The incidence is according to recent studies in the U.S. and Sweden about 2.5 people per 100,000 population per year. Due to the relatively normal life expectancy, the prevalence is much higher. Bimodal age distribution, half way between 20 and 40 or 60 and 70 years. 10-25 % of patients are under 40. The disease is more common in women, the ratio of female / male is about 2:1.

Pathogenesis

The ET is, like all myeloproliferative neoplasms and in general all tumors a genetic condition. Why the disease in an individual patient occurs can usually not clearly justified. It starts from spontaneous mutations in hematopoietic stem cells that cause these stem cells can no longer exercise their normal function ( controlled formation of various blood cells). The genetic background of ET is not yet fully understood. However, important advances in knowledge have been achieved in recent years. In 2005, a mutation in the tyrosine kinase JAK2 ( V617F JAK2 mutation ) was independently described by various research groups in ET patients. About half of all clinically diagnosed cases of ET ( to the diagnostic criteria, see below) can detect this mutation. In healthy individuals, this mutation, however, is never detected. The mutation results in the tyrosine kinase JAK2 is activated permanently and uncontrolled, with the result that the clinical picture of a blood disorder arises. JAK2 - V617F mutation, however, is not detectable in only about half of the cases of ET, but also in other MPN, particularly in polycythemia vera ( in nearly 100% of the cases) and myelofibrosis ( in about 50% or less of the cases). The detection of the JAK2 V617F mutation, is also of interest therapeutically because now an authorized JAK2 inhibitor ( Ruxolitinib ) is available as a medicament.

A small percentage ( about 1%) ET patients, instead of the JAK2 mutation is a mutation in the gene for thrombopoietin receptor MPL. This mutation leads to a permanent growth stimulation of the affected blood stem cell.

In 2013 also a new gene mutation was found by several research groups, which affects the gene CALR that encodes for the protein calreticulin. Remarkably, CALR, MPL and JAK2 mutations occurred virtually exclusively, ie never shared. About 70% of MPN - patients who had no JAK2 mutation showed a CALR for mutation.

Symptoms

Microcirculation disorders or functional disorders are the most common symptoms. Thromboembolic complications are the major cause of morbidity and mortality of the disease. An increased risk of stroke and heart attack. Bleeding events were previously considered common symptoms of ET, recent studies show that larger or life-threatening bleeding in ET occur rarely and are usually observed only at very high platelet counts. This bleeding tendency is explained by a dysfunction of platelets (so-called functional von Willebrand syndrome).

Other symptoms may be caused by the lack of blood flow to parts of the body:

  • Pain when walking (lack of leg blood flow)
  • Emptiness in the head
  • Blurred vision

And in the advanced stage added:

  • Pain in the upper abdomen by enlargement of the liver and spleen

Approx. one third of all patients with ET at the time of diagnosis without symptoms and often remain symptom- free for many years.

Clinical examination and follow

Today, the diagnosis or the diagnosis is usually made in the asymptomatic stage as part of a routine examination of the blood picture. Rare cause the typical complications of the disease such as venous and arterial thrombosis, possibly. With subsequent embolism, or bleeding in the diagnosis Venous thrombosis can be localized at typical location ( deep vein thrombosis), but also occur in atypical locations ( hepatic vein thrombosis, known as Budd -Chiari syndrome, portal vein thrombosis ). Bleeding typically occur at extremely high platelet counts in excess (> 2.000.000/μl ) and are due to a dysfunction of the platelets. Other possible complications are microcirculatory disorders that can lead to a number of non-specific symptoms such as headache, abnormal sensations in the hands and feet, blurred vision, burning pain with redness in hands and feet ( erythromelalgia ).

Diagnostics

The suspected diagnosis is based on repeated detection of platelet counts > 600.000/μl without reference to causes of reactive thrombocytosis. Reactive thrombocytosis occur, for example in iron deficiency, infection, or other tumors. Occasionally found in ET also a slight leukocytosis and anemia is often present. By means of the detection of a JAK2 mutation or, more recently, the CALR mutations, and rarely also an MPL mutation today is in many cases a molecular confirmation of the diagnosis and differentiation from reactive thrombocytosis possible. A mutation in one of three genes shown above, then there is a myeloproliferative neoplasia ( MPN ). It must then be decided yet what type of MPN exactly is (ET, polycythemia vera, myelofibrosis, or other ). To avoid possible chronic myeloid leukemia ( CML) does not have to necessarily see a blood test for the typical for CML oncogene BCR -ABL done that needs to be negative. The CML is in the initial phase often associated with thrombocytosis.

An examination of the bone marrow by bone marrow biopsy is required. The bone marrow examination can clarify various issues, such as the question of the presence of bone marrow fibrosis ( connective tissue in the bone marrow ), abnormalities in megakaryocytes ( the cells that form the platelets), dysplasia ( Ausreifungsstörungen the blood cells). From the bone marrow should also necessarily a cytogenetic investigation be made to detect the presence of any chromosomal abnormalities.

The diagnosis of ET is ensured if

  • A1 plus A2 and B1 or
  • A2 plus A3 and B1 are fulfilled.

However, there are transitional cases between ET and PV ( polycythemia vera), which can be clearly assigned until later.

Therapy

There are no reliable randomized trials at the optimal time for the initiation of therapy. In order to find an optimal treatment strategy for each patient, a risk classification is made ​​according to the guidelines of the DGHO first. This distinguishes high -, intermediate - and low - risk patients.

High - risk patients

  • Criteria Age > 60 years or
  • Thromboembolic or major bleeding complications associated with the ET or
  • Platelet count > 1.500.000/μl.
  • Treatment
  • Hydroxyurea or
  • Anagrelide or
  • α - interferon

Intermediate- risk patients

  • Criteria Fulfills No high-risk criteria and
  • Thrombophiliemarker or
  • Presence of cardiovascular ( heart and blood vessels in question ) risk factors ( arterial hypertension, diabetes mellitus, hypercholesterolemia, or smoking ).

Low - risk patients

  • Criteria Age < 60 years
  • Platelet count < 1.500.000/μl and
  • Asymptomatic or only microcirculatory disturbances.
  • Treatment
  • Weight normalization,
  • Regular exercise,
  • Avoiding dehydration ( dehydration ) and long periods of sitting,
  • Notice of early symptoms of thrombosis, in this case, immediate medical contact
International Classification of Diseases for Oncology Complete blood count Budd–Chiari syndrome Hydroxycarbamide Thrombophilia Tobacco smoking Digital Object Identifier
316678
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