Essential thrombocythemia is a tumor disease of the blood, how dangerous is it and is treatment needed? Essential thrombocythemia.

Thrombocythemia (primary, essential, idiopathic; hemorrhagic thrombocythemia, chronic megakaryocytic leukemia) is characterized by hyperplasia of the megakaryocytic lineage and an increase in the number of platelets in the peripheral blood. The disease develops at the age of 50-70 years, women predominate among patients with thrombocythemia.

Etiology

The study of glucose-6-phosphate dehydrogenase (G-6-PD) in heterozygous women with thrombocythemia, the analysis of X-chromosome DNA polymorphism and the detection of non-random chromosomal abnormalities indicate the tumor nature of the disease that can occur at different levels of hematopoiesis. But specific changes in the karyotype in thrombocythemia have not been established. In some patients, the same tumor markers were found in lymphocytes as in megakaryocytes, erythrocytes, and granulocytes. A significant increase in platelets is due to their intensive formation.

Thrombocythemia may be secondary (symptomatic, reactive). Reactive thrombocytosis develops with iron deficiency anemia; hemolysis; chronic inflammatory diseases (rheumatoid arthritis, tuberculosis, sarcoidosis, Wegener's granulomatosis, inflammatory diseases in the intestines); neoplasms (carcinoma, Hodgkin's disease, non-Hodgkin's lymphoma) and after splenectomy.

Symptoms

Clinical manifestations of the disease are nonspecific. Patients complain of general weakness, paresthesia of the hands and feet, dizziness. Some patients have a hemorrhagic syndrome (nasal and gastrointestinal bleeding, hemorrhages with minor injuries), while others have a tendency to thrombosis of small vessels (erythromelalgia, transient cerebral ischemia). But the risk of thrombosis and bleeding is weakly correlated with the number of platelets. During physical examination, a moderate enlargement of the spleen and sometimes an enlargement of the liver are found in most patients.

Diagnostics

Characteristic of thrombocythemia is a significant increase in platelets in the blood from 700 to 1000x10 9 /l and often up to 1500-3000x10 9 /l. Platelets are enlarged, platelet aggregates and fragments of megakaryocytes can be detected. However, in some patients, an increase in bleeding time and a decrease in platelet aggregation are found, reflecting a change in the functional activity of platelets. The bone marrow usually has megakaryocyte lineage hyperplasia with giant megakaryocytes and extensive platelet shedding.

Differential diagnosis of thrombocythemia is carried out:

with subleukemic myelosis, in which splenomegaly, moderate leukocytosis, neutrophilia, myeloid metaplasia, anemic and hemorrhagic syndromes, thrombocytopenia and myelofibrosis in the bone marrow are found.
with myeloproliferative diseases, in which there is an increase in the number of platelets. Unlike thrombocythemia, with true polycythemia, the total mass of red blood cells is increased, with chronic myeloid leukemia, the Philadelphia chromosome is found, with idiopathic osteomyelofibrosis, significant bone marrow fibrosis or teardrop-shaped red blood cells.

Symptomatic thrombocythemia is diagnosed when the diseases that led to its development are identified (according to clinical and laboratory studies). The functional state of platelets in symptomatic thrombocythemia is usually normal.

Treatment

If the disease is asymptomatic, treatment should not be carried out. Indications for treatment are bleeding and thrombosis with a platelet count of more than 1000x10 9 /l.

Recommended oral administration of hydroxyurea at a dose of 10-15 mg / kg / day with a mandatory weekly platelet count. The effect is observed with a decrease in the number of platelets to 600x10 9 /l and the disappearance of the clinical manifestations of the disease. For the same purpose, it is possible to use radioactive phosphorus (32 P) intravenously at a dose of 2.7 mCi per 1 m 2 of body surface. But this treatment can provoke the transformation of thrombocythemia into acute leukemia. In some patients, treatment with interferon alpha may be effective.

Anagrelide is used to reduce the number of platelets in the blood. Treatment begins with oral administration of 0.5 mg every 6 hours. In the absence of effect and good tolerability of the drug, the dose is gradually increased every week by 0.5 mg until the platelet count decreases to 600x10 9 / l or less.

Bleeding with thrombocythemia is treated with aminocaproic acid. With erythromelalgia, acetylsalicylic acid preparations are effective even without a decrease in the number of platelets. In emergency situations (heavy bleeding and thrombosis, preparation for surgery), plateletpheresis is used.

Essential thrombocythemia (ET) is a rare pathology characterized by a sharp increase in the number of platelets. Formally, it does not apply to oncological diseases of the blood, however, it has some similarities with a tumor lesion of the hematopoietic system.

What is a disease

Essential thrombocythemia (synonyms: essential thrombocytosis, primary thrombocythemia, hemorrhagic thrombocythemia, chronic megakaryocytic leukemia) is a blood pathology that consists in an increase in the number of platelets. The disease is extremely rare - 2-5 cases per 100,000 population. There is an increase in the number of platelets due to hyperplasia, i.e. an increase in the number of megakaryocytes - especially large cells of the red bone marrow, from which platelets bud, being, in fact, fragments of the cytoplasm of these mother cells, surrounded by their own membrane.

Hematologists note two types of disease - primary and secondary. Primary thrombocythemia is called essential thrombocythemia. The cause of its development is sometimes impossible to establish, while secondary thrombocythemia, as a rule, is the result of various infections, bleeding, malignant tumor lesions of the body, iron deficiency, rheumatoid arthritis, etc. In addition, it can also result from the removal of the spleen (splenectomy).

Women and men who have reached the age of 50 are at risk for this disease. In men, thrombocythemia is recorded somewhat less frequently than in women.

Reasons for development

As already noted, in some cases it is not possible to determine the cause of essential thrombocythemia, in contrast to the secondary (symptomatic) form of the disease. Specialists have established the fact that the process of increasing the number of platelets starts with the onset of pathological changes in megakaryocytes. Hematologists hypothesize that megakaryocyte hyperplasia may be caused by increased sensitivity to hormone-like proteins and peptides synthesized by the body (cytokines), or by reduced sensitivity to inhibitors - substances that inhibit cell growth.

There is also an opinion that thrombocythemia is the result of mutations that occur in hematopoietic stem cells located in the bone marrow, from which all blood elements originate. These cells, which have nothing to do with poetry, despite the name, have pluripotency, i.e. the ability to subsequently transform into cells of various tissues and organs. Hematopoietic stem cells throughout our life provide the process of renewal of blood cells to replace dead ones.

Symptoms and signs

In about 1/3 of patients, clinical manifestations are either blurred or absent altogether. In its classical form, the disease is manifested by a number of main syndromes and signs:

cerebrovascular ischemia - headaches, dizziness, cognitive impairment, nausea, dysfunction of the cerebral arteries;
hemorrhagic syndrome - hemorrhages on the skin (petychia), nosebleeds, bleeding gums, bleeding in the gastrointestinal tract and urinary system;
Raynaud's syndrome - necrotic changes in the extreme phalanges of the fingers of the upper and lower extremities due to capillary thrombosis, accompanied by pain;
erythromelalgia - a feeling of heat and throbbing pain in the arms and legs during physical exertion, a change in the color of the skin;
feeling of heaviness in both hypochondria due to enlargement of the liver and spleen;
anemia - weakness, tachycardia, shortness of breath, pallor of the skin and mucous membranes;
thrombosis of blood vessels (more often arteries, less often veins).

For pregnant women, the threat of the disease is the risk of spontaneous miscarriage, heart attack and placental abruption, placental insufficiency, leading to a lag in the development of the embryo. A child born from such a mother may also show a delay in mental, physical and intellectual development.

With a long course, the disease can go into the phase of myelofibrosis (damage to bone marrow cells, 20% of cases) and the phase of blast transformation, causing acute leukemia (2% of cases).

Diagnosis of pathology

For the diagnosis of essential thrombocythemia, it is necessary to consult a hematologist. It should be noted that the formulation of an accurate differentiated diagnosis in most cases is of considerable difficulty. The following surveys are commonly used:

examination of the patient - determination of the enlargement of the spleen and liver, the presence of hemorrhages, signs of vascular thrombosis;
a general blood test - allows you to fix deviations from the norm of blood components (fragments of megakaryocytes may be present in the blood, increased leukocytosis, a high number of platelets with a change in their shape and size, and if the hematopoiesis process is disturbed, the number of reticulocytes - young erythrocytes decreases);
- an analysis that evaluates the degree of blood clotting;
laboratory analysis of bone marrow tissue taken using trepanobiopsy and aspiration biopsy (usually from the ilium and sternum) - allows you to detect megakaryocytic hyperplasia;
molecular genetic and cytogenetic studies for the presence of gene mutations, for example, V617F JAK2, JAK2V617F and MPLW515L/K;
additional examinations of the patient (lung x-ray, gastroduodenoscopy, colonoscopy, abdominal ultrasound, etc.) - allow you to confirm or refute the presence of symptomatic (secondary) thrombocytosis caused by such causes as cancerous tumors, bleeding, infections, etc.

To make a differentiated diagnosis, hematologists must take into account a number of formal criteria adopted throughout the world:

platelet count > 600,000/mcL on two consecutive blood tests performed 1 to 2 months apart;
lack of known;
erythrocytes are normal;
lack of fibrosis in the bone marrow;
splenomegaly (enlargement of the spleen);
bone marrow hypercellularity with hyperplasia of megakaryocytes;
the presence in the bone marrow of pathological cells in the form of colonies;
normal levels of C-reactive protein and interleukin-6;
absence of iron deficiency anemia;
absence of the Philadelphia chromosome;
in women - polymorphism of the genes of the X chromosome.

Treatment options for essential thrombocythemia

Treatment of pathology involves an integrated approach.

Medical therapy

Most hematologists are of the opinion that in the absence of a pronounced clinical picture of the disease, it does not need special treatment. In this case, it is enough for the patient to be under the supervision of a specialist. You can also use drug therapy with the use of aspirin, which prevents the formation of blood clots - taking this drug significantly reduces the ability of platelets to stick to the walls of blood vessels.

In addition to aspirin, a number of other analogues are also used. Learn more about treatments with this and other drugs:

With severe symptoms, treatment with cytostatic drugs (chemotherapy) can be carried out. In many cases, this therapy reduces the number of platelets to the desired level. Moreover, it should be borne in mind that sometimes this type of treatment leads to the transformation of essential thrombocythemia into acute leukemia, and then the only treatment option is only surgical bone marrow transplantation.

In addition, the practice of using α-interferon has proven itself well for the treatment of ET. Interferon is widely used to treat pregnant women and children, since it does not adversely affect either the embryo or the child's body. But chemotherapy is usually not used in either case due to high toxicity.

You should know that in the presence of essential thrombocythemia, vaccinations should not be given, among the contraindications to which blood diseases are noted, it is prohibited. The most common example is seasonal influenza vaccination.

thrombophoresis

With clinical manifestations of the disease that pose a danger to the life of the patient, doctors resort to thrombophoresis - a hardware procedure that allows mechanical removal of excess platelets by blood separation. This allows for some time to significantly improve the patient's condition. In addition, thrombophoresis may be used before emergency surgery to normalize platelet levels.

Diet with increased thrombosis

With ET, the diet should be balanced, able to provide the body with proteins, vitamins and trace elements. Preference should be given to products that can thin the blood. In addition, it is very important to observe the drinking regime - the amount of fluid consumed per day should be at least 2–2.5 liters.

lean meats (rabbit, chicken, turkey);
fish, especially sea, seafood, sea kale;
eggs;
dairy products;
vegetables - tomatoes, sauerkraut, beets, paprika, cucumbers, zucchini;
fruits - apples, peaches, citrus fruits;
berries - raspberries, currants (red and black), strawberries, wild berries;
walnuts, almonds, cashews;
spices - hot pepper, ginger, garlic, dill, horseradish, cinnamon;
fats - vegetable oils (sunflower, olive, linseed), fish oil.

Foods that need to be excluded from the diet, or at least limit their use:

animal fats;
sweets and confectionery;
bananas, mangoes;
strong meat broths;
canned food, marinades, smoked meats;
leafy vegetables, potatoes;
soybean oil, fish oil capsules;
fat sour cream;
alcohol.

Prohibited products - photo gallery

Traditional medicine

It should be noted right away that there is no evidence of the effectiveness of such prescriptions in the treatment of essential thrombocythemia. Moreover, such treatment can be used only after agreement with the attending physician, and not to the detriment of the traditional one.

The following prescriptions can reduce the manifestation of symptoms and improve the patient's well-being:

Infusion of blueberries, sophora, burdock roots and agrimony. Mix the ingredients in equal parts, then pour a tablespoon of raw materials with a glass of boiling water, insist, strain and add boiled water to the original volume. Take 1/3 cup three times a day 30 minutes before meals for 1-2 months.
Horse chestnut tincture. To prepare the medicine, you should take 1 tablespoon of crushed leaves, flowers and fruits of the plant, pour 300 ml of boiling water and hold for 10-15 minutes in a water bath. Then strain the drink and add boiled water to the original volume. Take twice a day for half an hour before meals for a tablespoon. The course of treatment is 10 days, after which you need to take a break for 10 days and repeat again.
A decoction of celandine, St. John's wort, blueberries, mordovnik seeds and calamus root. Mix all the ingredients in equal parts, then pour 1 tablespoon of the mixture in an enamel bowl with a glass of boiling water and boil over low heat for 5-7 minutes, then let the mixture cool, strain it and add boiled water to the original volume. Take a decoction three times a day for a tablespoon half an hour before meals.
Alcohol infusion of garlic. Grind the peeled cloves of 3 medium heads of garlic, pour them with 250 ml of alcohol or strong vodka and insist in a dark, cool place for a month. Take the infusion should be 15 drops twice a day.

Prognosis, possible complications and prevention of the disease

Among the most common complications of essential thrombocythemia:

thrombosis of coronary, cerebral and peripheral arteries;
pulmonary thromboembolism;
tissue necrosis of the lower extremities due to deep vein thrombosis;
bleeding, including internal;
swollen lymph nodes;
enlargement of the liver and spleen;
acute leukemia (very rare).

Moreover, hematologists believe that the prognosis of the disease is generally favorable, and essential thrombocythemia does not affect the life expectancy of patients. In the presence of certain pathological signs, according to the decision of the VTEC, the patient can be assigned a disability group - I, II or III (depending on the condition). After the patient's health improves, the group may be revised or removed.

As for the issue of prevention, unfortunately, there are no such measures to date.

The role of platelets in the process of blood clotting - video

Essential thrombocythemia is extremely rare, and you should know how this disease can manifest itself. This is necessary in order to timely contact a specialist, start therapy and prevent undesirable consequences and complications of this pathology.

Vatutin N.T., Doctor of Medical Sciences, Professor, Head. department
Keting E.V., Candidate of Medical Sciences, Associate Professor
Kalinkina N.V., Candidate of Medical Sciences, Associate Professor
Sklyannaya E.V., Candidate of Medical Sciences, Associate Professor
Department of Hospital Therapy, Donetsk National Medical University named after M. Gorky.

Essential thrombocythemia (ET) is a chronic myeloproliferative disease with a primary lesion of the megakaryocyte germ, increased proliferation of megakaryocytes and subsequent excessive production of platelets.

Etiology and pathogenesis of ET. ET was first described by Epstein and Gödel in 1934, but its etiology and risk factors are still not clearly defined. It is known that a pluripotent progenitor cell of the bone marrow is involved in the process. An increase in platelet production may be due to an increase in the sensitivity of megakaryocytes to cytokines and, conversely, its decrease in relation to inhibitory factors. Disruption of the bone marrow microenvironment may play a certain role. The mechanism of occurrence of thrombohemorrhagic symptoms in ET is well understood and includes both a decrease and an increase in aggregation, intracellular accumulation of certain chemicals, a decrease in the activity of ristocetin von Willebrand cofactor, an increase in the molecular weight of von Willebrand factor multimers, a deficiency of antithrombin III, proteins C and S.

Epidemiology of ET. The US prevalence is 3 cases per 100,000 adults, with about 6,000 new cases annually. The average age of patients at the time of diagnosis is 65-70 years, although cases of the disease have been described in young people (about 20% under 40 years old) and even children (1 case per 10,000,000 of the population). The ratio of men and women is 1.5:2. In the vast majority of cases, ET is a slowly progressive disease, in which many months and even years pass from the moment of detection of changes in the blood test to the manifestation of clinical symptoms.

ET diagnosis. Currently, there is no sufficiently sensitive and specific method for the laboratory diagnosis of ET. In the general analysis of blood, thrombocytosis of varying severity is recorded, giant platelets may occur. The level of leukocytes and erythrocytes remains within the normal range, however, moderate erythrocytosis and leukocytosis with basophilia and eosinophilia are possible. In the bone marrow, there is increased cellularity (in 90% of cases) and megakaryocytosis. Megakaryocytes in ET are dysplastic, gigantic in size, and have increased ploidy. Unlike polycythemia vera and chronic myeloid leukemia, hyperplasia of the red and granulocytic germs is usually not detected. The number of reticulin fibers in the bone marrow biopsy is increased, but collagen fibrosis is rarely noted. Platelets are functionally defective, which can be confirmed by laboratory tests for adhesive and aggregation activity. Prothrombin time and activated partial thromboplastin time are usually within limits. Bleeding time may be normal or prolonged. The life expectancy of platelets is not changed. It was previously thought that ET was not associated with any diagnostically significant genomic changes, but cytogenetic studies are required to rule out other myeloproliferative diseases. Detection of the Philadelphia chromosome and ABL-BCR translocation most often indicated in favor of chronic myeloid leukemia, which debuted with thrombocytosis, although cases of the presence of this genetic disorder in patients with a well-established diagnosis of ET and a long follow-up period were described. Currently, JAK2V617F and MPLW515L/K mutations have been identified in patients with ET. The same genetic abnormalities can be found in some cases of polycythemia vera, primary myelofibrosis, that is, they are not strictly specific.

The clinical picture of ET. Due to the violation of the qualitative characteristics of platelets in the clinical picture, not only thrombotic, but also hemorrhagic manifestations are observed with no clear correlation between the level of thrombocytosis and the frequency of thrombosis. In elderly patients, thrombotic symptoms are more often recorded due to comorbid vascular damage. Among thrombotic complications, cerebral, coronary and peripheral arterial thromboses are the most frequent, pulmonary embolism and deep vein thrombosis of the lower extremities occur somewhat less frequently. Hemorrhagic manifestations are expressed in the development of gastrointestinal, pulmonary, renal bleeding and skin hemorrhages. Splenomegaly (40-50% of cases), liver enlargement (20%), general weakness, dizziness, headache, memory and concentration disorders, dysphoric phenomena, erythromelalgia, numbness of the distal parts of the upper and lower extremities, earlobes and nose tip are not uncommon. (due to impaired microcirculation), pain in the epigastrium and along the intestine (associated mainly with a tendency to erosive and ulcerative processes in the gastrointestinal tract). Occasionally, lymphadenopathy, weight loss, sweating, itching of the skin, low-grade fever may occur. About 30% of patients are asymptomatic at the time of diagnosis. ET classification. To date, there is no classification or staging of the disease.

Differential Diagnosis primary and secondary thrombocytosis is quite difficult, so the American College of Hematology proposed the following criteria: 1) the number of platelets is more than 600,000 per μl in two consecutive blood tests performed with an interval of 1 month; 2) the absence of an identifiable cause of reactive thrombocytosis; 3) normal number of erythrocytes; 4) absence of significant fibrosis in the bone marrow (less than 1/3 of the preparation); 5) the absence of the Philadelphia chromosome; 6) splenomegaly according to physical or ultrasound examination; 7) bone marrow hypercellularity with hyperplasia of megakaryocytes; 8) the presence in the bone marrow of pathological hematopoietic progenitor cells in the form of colonies of the erythroid or megakaryocytic series with increased sensitivity to interleukin-3; 9) normal levels of C-reactive protein and interleukin-6; 10) absence of iron deficiency anemia; 11) in women - polymorphism of the genes of the X chromosome. In the presence of criteria 1-5 and more than three criteria 6-11, it is recommended to regard thrombocytosis as essential.

Therapeutic tactics in ET. Unlike secondary thrombocytosis, the diagnosis of ET involves the initiation of therapy, the intensity of which is determined by a number of factors. Young asymptomatic patients with a platelet count of less than 1,500,000 may be considered low-risk and do not require cytoreductive therapy (low doses of antiplatelet drugs are sufficient). The presence of hypertension, dyslipidemia, diabetes mellitus, smoking increases the risk of severe thrombosis even at a young age and serves as an indication for the appointment of cytostatics. The most well-studied and long-used drug of this group is hydroxyurea (hydroxyurea), which belongs to antimetabolites (inhibits deoxynucleotide synthetase). The initial dose is 500-1000 mg with further titration to keep the platelet level below 600,000 per microliter. In general, hydroxyurea is well tolerated, with side effects including myelosuppression, mucositis, and leg ulcers. The main limiting factor is its leukogenic potential. Some studies have shown an increase in the risk of developing acute myeloid leukemia with its long-term use. It is believed that interferon-alpha is devoid of this disadvantage and teratogenic effect, therefore it can be widely used in ET, especially in pregnant women. The recommended initial dose is 1 million IU three times a week with a gradual increase in dose to 3-6 million IU three times a week. The limiting point is poor portability. Some patients (17-20%) refuse treatment due to symptoms of toxicity and subjectively poor health - fever, flu-like syndrome, pain in the joints and muscles, nausea, anorexia, depression, sleep disturbances. Anagrelide, being an imidazoquinazoline derivative, selectively inhibits the maturation of megakaryocytes with minimal effect on other bone marrow progenitor cells. In 1997, anagrelide was licensed in the United States as a first-line treatment for patients with thrombocytosis associated with myeloproliferative processes. The recommended initial dose of the drug was 2 mg per day orally, with a possible further increase by 0.5 mg every 7 days until a maximum dose of 10 mg per day is reached. About 30% of patients do not tolerate even average therapeutic doses of anagrelide due to its vasodilatory and positive inotropic effects. In addition, this drug can cause fluid retention with the development of edema, cardiac arrhythmias, heart failure and worsen the course of chronic cardiovascular disease in older patients. According to many authors, anagrelide should not be administered to patients with verified cardiovascular disease; patients receiving anagrelide for a long time need a thorough examination (daily monitoring of the electrocardiogram, echocardiogram, determination of the level of troponins and natriuretic peptide at least once every 6 months). There are 11 cases of documented cardiomyopathy that developed during anagrelide therapy in patients with ET and polycythemia vera.

When comparing the effectiveness of hydroxyurea and anagrelide (in combination with aspirin in each group) in 809 patients with high-risk ET and a follow-up period of 39 months, the study was terminated early due to an increase in vascular events and transformation of the disease into myelofibrosis in the anagrelide group. The frequency of other side effects, including leukemia, was similar. Thus, the combination of hydroxyurea plus aspirin is superior in both efficacy and safety to anagrelide. Currently, anagrelide is recommended as a second-line therapy for intolerance to hydroxyurea and interferon-alpha.

Great hopes are pinned on the development of molecular-targeted therapy capable of inhibiting JAK2 mutation or acting on various links of the activated JAK-STAT signaling pathway.

ET prognosis. Among all myeloproliferative diseases, ET has the most favorable prognosis, and the life expectancy of patients differs little from that in a healthy population. The transformation of ET into other nosological units of the myeloproliferative group needs to be clarified, since myelosuppressive therapy itself, used in ET and aimed at preventing thrombohemorrhagic complications, may increase the risk of developing myelofibrosis and chronic myeloid leukemia.

Literature

1. Gaidukova S. M., Vidiborets S. V. Thrombocytosis in medical practice. The art of jubilation, No. 10 (2004).
2. Vannucchi A.M., Barbui T. Thrombocytosis and thrombosis. Hematology Am Soc Hematol Educ Program, (2007).
3. Tefferi A. Essential thrombocythemia: scientific advances and current practice. Curr Opin Hematol, Vol. 13(2) (2006).
4. Sanchez S., Ewton A. Essential thrombocythemia: a review of diagnostic and pathologic features. Arch Pathol Lab Med, Vol. 130(8) (2006).
5 Brière J.B. Essential thrombocythemia. Orphanet J Rare Dis, Vol. 2(1) (2007).
6. Petrides P.E. Primary thrombocythemia: diagnosis and therapy. Med Klin (Munich), Vol. 101(8) (2006).
7. Steurer M., Gastl G., Jedrzejczak W.W., Pytlik R., Lin W., Schlogl E., Gisslinger H. Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile. . Cancer, Vol. 101(10) (2004).

There is no single treatment approach, one treatment option may include aspirin. Patients >60 years of age, as well as patients with a history of thrombosis and transient ischemic attacks, require cytotoxic therapy to reduce the risk of thrombosis. According to available data, the risk of thrombosis does not correlate with platelet levels, although anecdotal evidence suggests otherwise.

Pathophysiology of essential thrombocytosis

Essential thrombocytosis usually results from the pathology of a single pluripotent stem cell clone. However, some women who meet the criteria for the diagnosis of ET have a polyclonal lesion. The age distribution of essential thrombocytosis is bimodal: one peak occurs at the age of 50-70 years, the other - at a young age (in women).

The life expectancy of platelets usually remains normal, but it may be reduced due to their sequestration in the spleen, as well as in patients with erythromelalgia accompanied by digital ischemia.

In elderly patients with atherosclerosis, a high platelet count can cause serious bleeding or, more commonly, thrombosis. Recent studies indicate that elevated white blood cell counts are an important independent risk factor for thrombosis. Although anecdotal reports (and logically) suggest that high platelet counts may increase the risk of thrombosis, one study showed an inverse relationship between platelet count and risk of thrombosis. Bleeding is a more likely complication of severe thrombocytosis (i.e., >1.5 million platelets/mcL).

Symptoms and signs of essential thrombocytosis

Common symptoms include:

weakness;
bleeding;
gout; “ocular migraine;
paresthesia of the hands and feet.

Thrombosis may cause symptoms in the affected area (eg, neurologic abnormalities in stroke or transient ischemic attacks, leg pain, leg swelling, or both in lower limb thrombosis, chest pain and dyspnoea in pulmonary embolism). Bleeding is usually minor. Finger ischemia and splenomegaly may occur. The latter is found in<50% пациентов. Изредка может наблюдаться гепатомегалия. У беременных тромбоз может быть причиной привычных выкидышей.

Diagnosis of essential thrombocytosis

Essential thrombocytosis should be suspected in those patients in whom causes of reactive thrombocytosis have been excluded. If essential thrombocytosis is suspected, a blood test, a peripheral blood smear, and cytogenetic studies, including a Philadelphia chromosome test and a BCR-ABL mutation, should be performed. Despite the existence of classic ET morphological changes, the diagnostic value of bone marrow examination has not been established. Platelet levels may spontaneously decrease during pregnancy. The bone marrow is characterized by platelet hyperplasia with an abundance of released platelets. Iron is present in the bone marrow. Essential thrombocytosis differs from other myeloproliferative diseases with thrombocytosis in that it has normal hematocrit, normal mean red blood cell volume, normal iron values, and absence of teardrop red blood cells. In this case, there may be a pronounced increase in bone marrow fibrosis (which occurs in idiopathic myelofibrosis). The JAK2 V617F mutation occurs in approximately 50% of patients. A small proportion of patients with ET have acquired mutations in the thrombopoietin receptor (c-mpl) gene.

Prognosis of essential thrombocytosis

Life expectancy is close to normal. Although the disease is often accompanied by symptoms, its course is usually benign. Serious complications due to thrombosis of arteries and veins are rare, but can be life-threatening. Transformation to leukemia is noted<2% пациентов. Эта цифра может возрастать после применения цитотоксических препаратов, особенно алкилирующих агентов.

Treatment of essential thrombocytosis

Aspirin.
Platelet-lowering drugs (eg, hydroxyurea, anagrelide).
Sometimes - thrombocytopheresis.

Most pregnant women are prescribed aspirin.

Because the prognosis is often good, potentially toxic platelet-lowering drugs should be used at reasonable doses. Common indications for their use are:

previous episodes of thrombosis or transient ischemic attacks;
age >60 years.

Other indications are conflicting. Patients with significant bleeding and severe thrombocytosis (high-risk patients) may need to be treated to lower platelet concentrations. Do patients need drugs to lower platelet levels?<60 лет, не имеющим симптомов, неясно. К препаратам, угнетающим костный мозг, которые снижают уровень тромбоцитов, относятся анагрелид, интерферон аль-фа-2Ь и гидроксимочевина (иногда в сочетании с низкой дозой аспирина). В целом гидроксимочевина считается препаратом выбора, однако некоторые клиницисты предпочитают анагрелид. Поскольку гидроксимочевина и анагрелид проходят через гематоплацентарный барьер, они не используются во время беременности. При необходимости беременным может назначаться интерферон альфа-2Ь.

Dosages and monitoring are discussed in the treatment of polycythemia vera section. The traditional goal of treatment is to lower platelet levels.<450 000/мкл без провоцирования значительных тоскических эффектов. Эту цель, однако, необходимо пересмотреть, учитывая новые данные, которые указывают на обратную взаимосвязь между уровнем тромбоцитов и риском тромбоза.

Thrombocytopheresis is used in selected patients with severe bleeding, recurrent thrombosis, or before emergency surgery to immediately lower platelet concentrations.

thrombocytosis

Thrombocytosis can occur against the background of:

chronic inflammation, such as rheumatoid arthritis, tuberculosis, sarcoidosis, Wegener's granulomatosis;
acute infection;
bleeding;
iron deficiency;
hemolysis;
malignant neoplasms (especially Hodgkin's and non-Hodgkin's lymphomas);
splenectomy;
myeloproliferative and hematological diseases.

In addition, there are familial forms of thrombocytosis, for example, due to mutations in the thrombopoietin gene or its receptor gene.

Platelet function is usually not affected. Unlike essential thrombocytosis, secondary thrombocythemia is not accompanied by an increased risk of thrombosis or bleeding, unless patients are immobilized for a long time or have severe arterial damage. In secondary thrombocytosis, the platelet count is usually<1 000 000/мкл. Его причина может оказаться очевидной после сбора анамнеза и проведения объективного осмотра (возможно, в сочетании с подтверждающими диагноз исследованиями). Анализ крови может помочь заподозрить дефицит железа или гемолиз. Если причина остается неясной, следует рассмотреть необходимость обследования на предмет миелопроли-феративного заболевания.

Removing the cause usually results in normalization of the platelet count.

thrombocytosis is an increase in the number of platelets in the blood. With thrombocytosis, the platelet count can reach about 500,000 per cc. mm. The reasons for the development of this disease can be: too rapid production of platelets in the bone marrow itself, slowing down their decay, changing their distribution in the bloodstream, etc.

Blood thrombocytosis is a provoking factor in the formation of blood clots. In certain cases, thrombocytosis can lead to bleeding due to defects in platelets and due to impaired blood microcirculation. Therapy of thrombocytosis consists in the prevention of thrombosis and the treatment of the underlying disease, which causes an increase in platelet levels.

Thrombocytosis Causes

Finding out the type of thrombocytosis is considered extremely important, because clonal blood thrombocytosis is often accompanied by the formation of thrombotic complications and requires a thorough therapeutic examination.

In other myeloproliferative pathologies (polycythemia vera, chronic, essential thrombocythemia, etc.), thrombocytosis acts as the main complication, which affects the nature of the underlying disease and leads to complications with the formation of blood clots.

There are several types of thrombocytosis: clonal thrombocytosis, primary thrombocytosis, secondary thrombocytosis. At its core, clonal and primary thrombocytosis have a similar pattern of development.

In clonal thrombocytosis, the cause of development is the defect of hematopoietic stem cells itself. These stem cells are neoplastic in nature in chronic myeloproliferative conditions. They also have a high sensitivity to thrombopoietin and are not particularly dependent on stimulation of the exocrine system. The production of platelets in this case is an uncontrolled process, while the platelets themselves are functionally defective, as a result of which their interaction with other substances and cells that stimulate thrombosis is disrupted.

Primary thrombocytosis refers to the so-called myeloproliferative syndrome, in which the work of stem cells in the bone marrow is disrupted and there is an increase in several areas of hematopoiesis in this organ. Therefore, a large number of platelets are released into the peripheral blood.

Secondary thrombocytosis develops due to an increase in the number of platelets in a chronic disease. Currently, there are several reasons for its development.

In addition to infectious agents, there are other factors: hematological (iron deficiency in anemia, the use of chemotherapy in oncological conditions); removal of the spleen (1/3 of the total number of platelets accumulates in this organ, after the removal of which the volume of blood decreases with an artificial increase in platelets); surgery and trauma; inflammatory processes provoke an increase in platelets (the level of interleukin increases, which provokes increased production of thrombopoietin); oncological conditions; drugs (corticosteroids, sympathomimetics, antimitotics, contraceptives).

Thrombocytosis during pregnancy is in most cases a reversible condition and is explained by physiological processes during childbearing. These include: a slowdown in metabolism, an increase in blood volume, iron deficiency anemia in pregnant women, etc.

Thrombocytosis symptoms

Primary thrombocytosis is classified as a myeloproliferative disease, which is manifested by a significant increase in the number of platelets in the blood. As a result, patients develop thrombohemorrhagic syndrome. This thrombocytosis is based on the development of disseminated intravascular coagulation of blood cells and microcirculation disorders. The aggregation ability of platelets is also impaired. The incidence rate in men and women is the same. The first signs of blood thrombocytosis appear more often at the age of 50 years.

Patients complain of bleeding (uterine, nasal, intestinal, renal, etc.), ecchymosis, hemorrhages of subcutaneous localization, skin and mucous membranes, tingling in the fingers and toes. In some cases, gangrene develops. In addition to bleeding, patients with thrombocytosis may have diseases such as (cold extremities, migraine headaches, blood pressure instability, shortness of breath, etc.), vein thrombosis (splenic, portal, hepatic, uterine (up to 15 mm)) .

But the appearance of blood clots can be not only in the veins, but also in the arteries (carotid, mesenteric, pulmonary, cerebral, etc.). The content of platelets in the blood reaches from 800 to 1250. In microscopic blood tests, platelets are presented in the form of large aggregates. In some cases, platelets reach gigantic sizes, with altered vacuolization and shape, with the detection of megakaryocytes or their fragments. The content of leukocytes usually does not reach high levels (10-15), the leukocyte formula is not changed. The content of hemoglobin and erythrocytes may be increased.

With recurrent bleeding, iron deficiency anemia may develop. During the study, there is no pronounced three-line hyperplasia in the bone marrow trepanobioptate, an increase in the level of megakaryocytes (more than 5 per field of view) is detected. In some cases, myelofibrosis is observed, as well as an increase in the spleen to non-expressed indicators.

Secondary thrombocytosis develops in both pathological and physiological conditions. It is characterized by the same symptoms as for the primary.

Thrombocytosis is detected during a physical examination by a doctor, a laboratory blood test, an aspiration biopsy, and a bone marrow biopsy (trepanobiopsy).

Reactive thrombocytosis

Reactive thrombocytosis is characterized by an increase in the level of platelets due to non-specific activation of thrombopoietin (a hormone that regulates the maturation, division and entry of platelets into the blood). This process stimulates the formation of a large number of platelets without pathological changes in their functional properties.

For reactive thrombocytosis, the causes of their appearance may be acute and chronic processes. Acute processes include: blood loss, acute inflammatory or infectious diseases, excessive physical activity, platelet recovery after thrombocytopenia. Chronic processes include: iron deficiency anemia, hemolytic anemia, asplenia, oncological process, rheumatism, intestinal inflammation, lung diseases, reactions to certain drugs (Vincristine, Cytokines, etc.).

Under certain conditions, the disease occurs due to ethanol poisoning (chronic alcoholism). It is very important to correctly differentiate reactive thrombocytosis because it is often confused with clonal thrombocytosis. If with clonal thrombocytosis the causes of the disease are difficult to diagnose, then for reactive thrombocytosis this does not cause any particular difficulties, although clinically they are poorly expressed. Clonal thrombocytosis is also characterized by: peripheral or central ischemia, thrombosis of large arteries and / or veins, bleeding, splenomegaly, giant platelets and impaired function, an increase in megakaryocytes. Also, clonal thrombocytosis is characterized by the detection of giant dysplastic polyploid forms with a huge content of traces of platelets in the study of their morphology.

Reactive thrombocytosis is characterized by: a normal morphological picture, the absence of central or peripheral ischemia, the absence of bleeding and splenomegaly, an increase in megakaryocytes in the bone marrow biopsy, there is no risk of developing vein and arterial thrombosis.

Dynamic observation may allow to ascertain reactive thrombocytosis with normal platelet levels during the treatment of the disease that caused thrombocytosis. For example, with injuries and neurological pathologies, thrombocytosis is formed during the first days of the disease and, thanks to correct treatment, quickly disappears within two weeks.

Cases of reactive thrombocytosis due to the use of drugs are described, which, despite significant platelet counts (about 500), does not pose a risk for the occurrence of thrombotic complications and disappears after treatment.

Therefore, in the treatment of reactive thrombocytosis, it is necessary to identify the causative disease. To do this, it is necessary to collect an anamnesis with the identification of episodes of microcirculation disorders and thrombosis in the past; laboratory blood tests, biochemical studies for markers of inflammatory processes (C-reactive protein, seromucoid, thymol test, fibrinogen); Ultrasound - examination of internal organs.

Relying on the results obtained with the diagnostic data, they form the tactics of treatment. With mild thrombocytosis (up to 600), with no risk of thrombosis, the patient is prescribed therapy for the underlying disease with constant monitoring of platelet count.

Essential thrombocytosis

Essential thrombocytosis is characterized by a pronounced increase in platelets, the function and morphology of which are often altered, which seems to be the cause of such manifestations as thrombosis and bleeding.

Essential thrombocytosis occurs in the elderly and older people. The clinical manifestations of the disease are very non-specific, sometimes essential thrombocytosis is detected by chance in those individuals who do not complain. However, the first clinical symptoms of the disease are spontaneous bleeding of varying severity, which often occurs in the gastrointestinal tract and often recurs over several years. There may also be hemorrhages under the skin, thrombosis that affects small vessels may be accompanied by the appearance of gangrene or peripheral ulcers, areas of erythromelalgia and chills. Some patients experience the occurrence of splenomegaly - sometimes very severe and combined with hepatomegaly. There may be infarcts of the spleen.

Laboratory diagnostics indicates an increase in platelets up to 3000, and the platelets themselves are due to morphological and functional disorders. These disorders explain the paradoxical combination of bleeding and thrombosis. The hemoglobin values and the morphological picture of platelets are within the normal range, provided that shortly before the diagnosis there was no bleeding. The number of leukocytes is also within the normal range. The duration of bleeding can be pronounced, but the time of blood clotting does not exceed the limits of normal values. A bone marrow biopsy reveals a pronounced change in the size and number of megakaryocytes, in addition to hyperplasia of erythroid and myeloid germs.

Essential thrombocytosis tends to be chronic with a gradual increase in platelets in those patients who do not receive treatment. Death is due to bleeding or thromboembolism. Treatment is to achieve normal platelet counts. As a rule, Melphalan is used for this at a dose of 375-450 MBq. To reduce the risk of bleeding, therapy should also be started in asymptomatic patients. With thrombotic pathologies, the appointment of Aspirin or acetylsalicylic acid may help.

thrombocytosis in a child

It is known that platelets are a constituent element of the blood or cells produced by the bone marrow and serve for blood clotting. The existence of individual platelets lasts up to 8 days, after which they enter the spleen, where they are destroyed. Depending on age, the number of platelets that are formed in the bone marrow can have significant differences. In newborns, their number is approximately 100-400, in children under one year old - 150-360, in children older than a year - 200-300.

The cause of the development of primary thrombocytosis in children may be either leukemia. The causes of secondary thrombocytosis, which are not associated with the hematopoietic function, are: pneumonia (pneumonia), osteomyelitis (inflammatory process of the bone marrow, followed by bone destruction), anemia (low hemoglobin in the blood).

In addition, thrombocytosis in children may indicate the presence of a bacterial or viral infection. It can be viral or tick-borne encephalitis or chickenpox virus. Any infectious disease can increase the number of platelets.

Thrombocytosis in a child can be caused by a fracture of tubular bones. This condition is noted in such patients who have undergone surgery to remove the spleen. The spleen is not the last part in the metabolism of red blood cells, and its removal can be carried out only in those diseases that interfere with normal blood clotting. These diseases include, which occurs mainly in males, and still remains incurable. In hemophilia, there is insufficient production of platelets.

Treatment of thrombocytosis in children should be carried out by treating the disease that caused the increase in platelet levels, because high-quality diagnostics plays a major role here.

thrombocytosis treatment

If clonal thrombocytosis is present, treatment should be with antiplatelet agents. These include: Acetylsalicylic acid 500 mg 3 times a day for 7 days; Clobidogrel or Ticlopidin, where the dosage is taken into account with the age and body weight of the patient. It should be borne in mind that the short-term administration of Aspirin can determine the ulcerogenic effect in it, which occurs when the drug is prescribed in minimal doses. It is necessary to exclude the presence of erosive and ulcerative lesions of the gastrointestinal tract before prescribing Aspirin (acetylsalicylic acid), because its administration can provoke bleeding.

If thrombosis or ischemia occurs due to the development of thrombocytosis, then it is necessary to carry out pronounced antiplatelet therapy using directed anticoagulants (Heparin, Bivalirudin, Livarudin, Argotoban) and daily laboratory testing of platelet levels. In severe thrombocytosis, they resort to cytostatic therapy and thrombocytopheresis (removal of platelets from the blood by separation). For successful treatment of thrombocytosis, it is necessary to conduct a comprehensive examination of the patient to identify concomitant and causative diseases.

During pregnancy, thrombocytosis is corrected with Dipyridamole 1 tab. 2 times a day, which, in addition to the antithrombotic effect, has an immunomodulatory effect and improves uteroplacental blood flow. But it is worth remembering that thrombocytosis during pregnancy is a physiological phenomenon and rarely requires correction.

In addition to drug therapy for thrombocytosis, it is important to follow a diet that is determined by a competent balanced diet and follow the principles of a healthy lifestyle. An important condition for this is the cessation of smoking and the use of ethanol (alcohol).

It is necessary to eat foods rich in iodine (kelp, nuts, seafood), calcium (dairy products), iron (red meat and offal), B vitamins (green vegetables). It will not be superfluous to use freshly squeezed juices with a high content of vitamin C (lemon, orange, pomegranate, lingonberry, etc.). Such juices should be diluted with water in a ratio of 1:1.

From traditional medicine for the treatment of thrombocytosis, the use of tincture of garlic, cocoa, ginger and hirudotherapy (treatment with leeches) is recommended.