Thrombocytosis

Classification

The upper limit of normal platelet count varies from 350,000 to 400,000 per microliter depending on the reference intervals of the specific laboratory performing the analysis. According to the degree of increase, the following types of thrombocytosis are distinguished:

Soft
: from 350-400 to 700 thousand.
Moderate
: from 700 to 900 thousand.
Heavy
: from 900 to 1000 thousand.
Extreme
: over 1,000,000.

The cause of extreme and severe thrombocytosis is oncohematological pathologies. According to the origin of thrombocytosis there are:

Primary
(tumor, clonal). They account for approximately 10-15% of all cases of thrombocytosis. The cause is tumor diseases of the blood system.
Secondary
(reactive). The most common variety (about 85%). The cause is infectious, systemic inflammatory processes, and anemia.
False
(pseudothrombocytosis). The reason is an error in the hematology analyzer, which mistakes tumor cell fragments during treatment with chemotherapy drugs, small red blood cells, or red blood cells that have undergone hemolysis as platelets. Pseudothrombocytosis is also observed with cryoglobulinemia.
Hereditary
(family). This is a rare genetic disease, the cause of which lies in a mutation of the genes encoding the synthesis of thrombopoietin and its receptors (THPO, MPL).

Causes of thrombocytosis

Physiological conditions

An elevated platelet level does not always indicate pathology. There is physiological (short-term, transient) thrombocytosis, caused by various circumstances, for example, stress, intense physical activity. The reason is the mobilization of blood platelets, or rather their transition from the marginal position to the central blood flow in the vessels of the spleen and lungs.

In addition, minor physiological thrombocytosis is observed in children from the neonatal period to 11 years. There is also a so-called hemoconcentration thrombocytosis, which is caused by dehydration. This phenomenon is due to a decrease in the volume of the liquid part of the blood (plasma) and a relative increase in formed elements (platelets, erythrocytes, leukocytes). In this situation, it is necessary to focus on the hematocrit - with dehydration it is increased.

Infections

This is the most common cause of thrombocytosis (about 40%). An increase in the level of blood platelets develops when:

Bacterial infections
. In adults, thrombocytosis occurs mainly with local (pneumonia, pyelonephritis, meningitis, endocarditis) and systemic (sepsis, tuberculosis) bacterial infections.
Viral and fungal infections
. Thrombocytosis occurs less frequently during infection with viruses (hepatitis B, C) and pathogenic fungi (aspergillosis).
Helminthiasis.
In children, parasitic infestations (toxocariasis, ascariasis) are recognized as a common cause of an increase in the number of blood platelets.

There are two pathogenetic mechanisms for the development of thrombocytosis in response to an infectious disease. First, during the fight against pathogens, leukocytes produce a large number of inflammatory mediators, including interleukin-6, which stimulates bone marrow megacaricytopoiesis (the formation of platelet precursors). Secondly, platelets themselves are part of the anti-infective immunity - they are able to produce bactericidal substances, capture, neutralize, and even phagocytose certain types of bacteria, viruses, and foreign particles.

Platelets facilitate the migration of leukocytes to the site of infectious inflammation by interacting with endothelial cells of the vascular wall. Thrombocytosis during infections occurs abruptly, correlates with the severity of the disease, and quickly resolves after the pathogen is eliminated from the body and the inflammatory process subsides. Thrombocytosis is usually mild or moderate; in septic conditions it can reach a severe degree; in children it is somewhat more pronounced than in adults.

Autoimmune diseases

Another common cause of thrombocytosis is considered to be chronic rheumatological pathologies that occur with autoimmune inflammation. The mechanism for increasing the content of blood platelets is the overproduction of substances such as interleukin-6, colony-stimulating factors, which activate bone marrow platelet formation. The degree of thrombocytosis corresponds to the activity of inflammation (minimal during remission, maximum during relapse).

In diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE), inflammatory bowel diseases (Crohn's disease, ulcerative colitis), a mild or moderate degree is observed. In systemic vasculitis with necrotizing destruction of vessel walls, severe thrombocytosis occurs, since in vasculitis, in addition to other inflammatory mediators, tumor necrosis factor is synthesized in large quantities, which also has a stimulating effect on platelet formation. High platelet counts are especially common in children.

Anemia

Iron deficiency anemia is often the cause of thrombocytosis, especially in children. The exact mechanisms of this phenomenon have not yet been clarified, but an inverse relationship has been clearly established between reduced levels of iron metabolism (ferritin, iron-binding capacity of serum) and an increased level of blood platelets. Iron is thought to have an inhibitory effect on the maturation of megakaryocytes (precursor cells).

In addition, some pluripotent stem cells in the bone marrow are unable to transform into red blood cells under conditions of iron deficiency. As a result, a kind of “bypass” occurs and a larger percentage of stem cells begin to mature along the megakaryocyte pathway. Thrombocytosis in iron deficiency anemia is mild, sometimes moderate. Platelets quickly return to normal after correction of iron deficiency and an increase in hemoglobin.

However, as anemia worsens, platelet levels drop to a state of thrombocytopenia. The cause of iron deficiency can be a lack of iron in food, increased iron consumption (growth period in children, pregnancy, lactation) or chronic blood loss (long menstruation, bleeding from the gastrointestinal tract due to gastric ulcer).

Malignant blood diseases

The cause of approximately 15% of all thrombocytosis is hemoblastosis - chronic myeloid leukemia, Ph-negative myeloproliferative pathologies (essential thrombocythemia, polycythemia vera, and primary myelofibrosis). The increase in the number of blood platelets in these diseases is due to clonal (tumor) transformation of the megakaryocyte lineage of the bone marrow due to various mutations, which leads to hyperproduction of platelets.

These diseases are more common in adults and older people, in children - only in exceptional cases. Initially, thrombocytosis is moderate, as it progresses it increases, reaching a severe or extreme degree, which is why microcirculation disorders, arterial and venous thrombosis of various localizations often occur. The concentration of blood platelets normalizes very slowly, only after courses of specific myelosuppressive treatment.

Splenectomy

The spleen, being an organ that deposits blood, retains a large number of formed elements, including platelets. The spleen is also directly involved in thrombocytopoiesis, secreting the hormones thrombocytopenin and splenin, which suppress bone marrow maturation of megakaryocytes. Therefore, thrombocytosis after splenectomy is caused by two mechanisms: the release of platelets, normally located in the splenic depot, into the circulating blood, and the phenomenon of “disinhibition of the bone marrow,” i.e. increased platelet production.

An increase in the number of blood platelets does not occur immediately, but approximately a week after splenectomy, reaches a maximum by the 13-14th day (up to 700-800 thousand), often becoming the cause of venous thrombosis of the portal vein, and then slowly returns to normal over several weeks or months .

Injuries and surgeries

Massive tissue damage (wound during abdominal surgery, fracture, extensive burns) causes activation of the blood coagulation system, namely the vascular-platelet unit, which is the first stage of hemostasis. It involves vasospasm, as well as adhesion and aggregation of platelets at the site of damage to the vascular wall. The consumption of platelets stimulates their active release from the depot and a compensatory increase in their bone marrow production. The extent of damage correlates with the degree of thrombocytosis. This type of thrombocytosis usually does not require treatment.

Oncological diseases

The cause of thrombocytosis in solid (non-hematopoietic) tumors is the ability of cancer cells to produce interleukin-6, which stimulates thrombocytopoiesis. This feature was found in small cell lung cancer, colon adenocarcinoma, and malignant mesothelioma. In addition, tumor disintegration often causes bleeding, leading to iron deficiency anemia. The degree of thrombocytosis is usually moderate, in children it can be severe, and regresses after long-term treatment with chemotherapy.

Rare causes

Functional asplenia
: sickle cell anemia, chronic alcoholism, celiac disease.
Use of medications
: vincristine, adrenaline.
Rebound phenomenon
: development of thrombocytosis 1-2 weeks after treatment of thrombocytopenia or discontinuation of medications that cause thrombocytopenia (methotrexate, vitamin B12, prednisolone).

Types and causes of thrombocytosis

Thrombocytosis is of two types:

Primary thrombocytosis, in which the number of megakaryocytes in the bone marrow increases. This, in turn, leads to an increase in the number of platelets with a normal life expectancy, but impaired functions and abnormal structure. These platelets tend to be large, increasing the tendency for them to bleed and form clots that can block blood vessels. Bleeding occurs because platelet aggregation is disrupted and because most of them can be used to form blood clots. This condition can provoke serious complications: myocardial infarction, stroke, gastrointestinal bleeding. At the moment, the reasons why the division of megakaryocytes in the bone marrow is disrupted are unknown, but scientists have information that patients have a mutation in the V617F gene. Primary thrombocytosis is a myeloproliferative disorder. In such diseases, the hematopoietic function of the bone marrow is disrupted, which stimulates the formation of blood cells.
Secondary (or reactive) thrombocytosis, in which platelets function normally, but the disease itself is formed due to one of the following abnormalities:
With secondary thrombocytosis, the likelihood of bleeding and clots is usually lower than with primary thrombocytosis.
- Oncological diseases (most often ovarian, lung, stomach cancer);
Chronic or acute bleeding;
Chronic inflammation;
Taking certain medications: chemotherapy drugs and glucocorticosteroids;
Recovery from thrombocytopenia (which was caused by alcohol or vitamin B12 deficiency).

Diagnostics

Thrombocytosis is detected in a clinical blood test. Although very high platelet counts are more common in hematologic diseases, platelet levels alone cannot determine the cause of thrombocytosis. Therefore, if it is detected, you should visit a therapist. The doctor carefully asks about the patient’s complaints, how long ago the symptoms occurred, and conducts a general examination of the patient. Then, based on the data obtained, an additional examination is prescribed, including:

Blood tests
. In a general blood test, the content of other formed elements (erythrocytes, leukocytes) is determined, and the leukocyte formula is calculated. The concentration of inflammatory markers (ESR, CRP) is measured. The indicators of serum iron, TBC, ferritin are assessed. The presence of autoantibodies (RF, ACCP, antibodies to the cytoplasm of neutrophils) is checked. In case of endocarditis and sepsis, an analysis for procalcitonin and presepsin is performed.
Pathogen identification
. To identify the pathogen, microscopy, bacterial culture of urine and sputum are performed. If tuberculosis is suspected, an intradermal test with tuberculin is prescribed. Using an enzyme immunoassay, antibodies to viruses, parasites, and fungi are detected, and using the polymerase chain reaction method, their DNA and RNA are detected. To diagnose meningitis, a cerebrospinal fluid analysis is informative.
Genetic research
. In patients with myeloproliferative pathologies, mutations of Janus kinase (JAK2V617F), thrombopoietin receptors (MPL), and erythropoietin are determined using fluorescent hybridization (FISH) and PCR. Sometimes chromosomal abnormalities are detected - trisomies, deletions. In chronic myeloid leukemia, cytogenetic analysis reveals the Philadelphia chromosome (Ph).
X-ray
. On an X-ray of the lungs, in case of pneumonia, foci of darkening and infiltrates are noted, in case of tuberculosis - enlargement of the mediastinal lymph nodes, expansion of the roots of the lungs, rounded shadows (cavities) of the upper lobes of the lungs. In patients with arthritis, x-rays of the joints show a narrowing of the joint space, areas of erosion, and marginal osteoporosis.
Ultrasound
. Ultrasound of the abdominal organs in case of pyelonephritis determines compaction and expansion of the pyelocaliceal system, and in case of blood diseases - splenomegaly. In bacterial endocarditis, cardiac echocardiography reveals vegetations of the valves and sometimes effusion into the pericardial cavity.
Endoscopy
. In patients with inflammatory bowel pathologies, fibrocolonoscopy is performed, which reveals hyperemia of the mucous membrane, lack of vascular pattern, erosion, and ulcerative defects. Crohn's disease is characterized by the "cobblestone pavement" symptom - alternating deep ulcers with unchanged mucous membrane.
Histological studies
. In bone marrow aspirate for malignant hematological pathologies, hyperplasia of the megakaryocyte lineage of hematopoiesis is noted (in polycythemia vera - all three lineages), a large number of blast cells (in myeloid leukemia), proliferation of reticulin and collagen fibers (fibrosis). In case of vasculitis, a biopsy of a vessel reveals pronounced perivascular infiltration with lymphocytes and plasma cells.

Platelet count according to Fonio

Symptoms of thrombocytosis

Typically, symptoms develop gradually. At the initial stages of the disease they may be completely absent. The main manifestations of thrombocytosis are provoked by two factors: increased bleeding or the occurrence of blood clots in the blood vessels. If thrombocythemia is secondary, then the likelihood of such disorders occurring is much lower: the number of platelets in this form of the disease is lower than in the primary one.

The main symptoms of thrombocytosis include:

pain in the feet and hands, their numbness;
headache;
irritability and weakness;
bleeding gums;
visual impairment;
blood in stool;
nosebleeds.

Correction

Conservative therapy

In most cases, to correct thrombocytosis, it is enough to eradicate the cause, i.e. treatment of the underlying disease. Short-term thrombocytosis that develops due to stress or drug administration does not require intervention. In case of persistent long-term thrombocytosis, consultation with a hematologist is necessary to identify the cause and prescribe appropriate treatment. Therapy for thrombocytosis has several areas, including:

Fighting infection
. To eliminate the infectious agent, antibacterial (amoxicillin), antifungal (fluconazole), and antiparasitic agents (mebendazole) are used. Treatment of viral hepatitis requires long-term use of peligated interferon in combination with antiviral drugs.
Treatment of iron deficiency anemia
. Correction of iron deficiency is carried out with tablet preparations (iron sulfate). For children, there are forms of syrup and drops for oral administration. The addition of ascorbic acid promotes better absorption.
Therapy of autoimmune diseases
. Treatment of autoimmune diseases is carried out using medications that suppress inflammation - glucocorticosteroids (prednisolone), immunosuppressants (cyclophosphamide).
Targeted therapy
. For myeloproliferative diseases, specific targeted treatment is prescribed to slow down the progressive growth of the malignant tumor. These drugs include Janus kinase inhibitors (ruxolitinib), tyrosine kinase inhibitors (imatinib, dasatinib).
Symptomatic treatment
. To relieve high thrombocytosis, medications are used that suppress the activity of the megakaryocyte lineage, and, consequently, the production of platelets - anagrelide, interferon-alpha, hydroxyurea. For polycythemia, regular bloodletting is successfully used as a treatment method to remove excess formed elements.
Blood thinning
. In case of high thrombocytosis, antiplatelet agents (acetylsalicylic acid) are prescribed to prevent thrombosis. In case of contraindications (peptic ulcer of the stomach, duodenum), platelet receptor blockers (clopidogrel, ticagrelor) are used. In people at high risk of thrombosis (elderly, patients with diabetes mellitus or atrial fibrillation), anticoagulants (warfarin, dabigatran) are used.

Specialized treatment

The only method that allows achieving complete recovery from a malignant hematological disease is allogeneic bone marrow transplantation. This requires HLA typing to select a compatible donor. However, due to the high risk of developing life-threatening complications, this method is used only if conservative treatment is ineffective.

Forecast

The outcome depends on both the underlying pathology and the degree of thrombocytosis. For example, acute viral infection and iron deficiency anemia are characterized by a benign course. Patients with essential thrombocythemia, with proper selection of pathogenetic and symptomatic treatment, can live more than 80 years. People with chronic myeloid leukemia, on the other hand, live about 5-10 years from diagnosis.

Since reactive thrombocytosis almost always occurs in children, their prognosis is favorable. Thrombosis is not typical for mild to moderate thrombocytosis. In extreme or severe cases, there is a very high probability of fatal thrombosis leading to myocardial infarction, pulmonary infarction, and ischemic stroke.

General information

Thrombocytosis is a condition in which a person's number of platelets in the blood increases. There are more than 400,000 of them per cubic millimeter. The cause of thrombocytosis may be too active production of platelets in the red bone marrow (say, with erythremia), slowing down their breakdown (after amputation of the spleen), impaired distribution of platelets in the bloodstream (with intense physical or nervous stress) and other factors. Thrombocytosis can provoke thrombosis; in some cases, the described condition leads to bleeding due to defects in the platelets themselves (thrombocytopenic purpura) or due to poor blood microcirculation. Treatment of thrombocytosis in a child or adult consists of preventing thrombosis and treating the underlying disease that causes an increase in platelet levels.

Causes

Primary thrombocytosis is a hematological abnormality caused by disorders in the functioning of bone marrow stem cells. The result of this disorder is a significant increase in the number of platelets in the blood. The mechanism of progression of this disease is still unknown to science. A hypothesis of a clonal bone marrow disorder has been proposed. The disease is especially severe if the risk of thrombosis is increased.

The causes of secondary thrombocytosis include the following:

1. Infectious. The most common cause of the disease. Thrombocytosis is usually provoked by bacteria (very often by meningococcal infection), less often by viruses, parasites, and fungi. The disease manifests itself with clear signs. Among other symptoms, there is a violation of other blood parameters: an increase in the content of leukocytes (leukocytosis) and lymphocytes (lymphocytosis), indicating the presence of inflammation, as well as eosinophilia (an increase in the number of eosinophils), characteristic of parasitic pathogens. Simple biological tests, such as C-reactive protein, are also used for diagnostic purposes.

Among the infectious causes are the following types:

bacterial infections (pneumonia, meningitis);
viral (hepatitis, encephalitis, viral lesions of the gastrointestinal tract);
parasitic;
fungal (thrush, aspergillosis).

2. Hematological, most often – iron deficiency. Exactly how the disease develops with iron deficiency is not yet known. However, in medical practice, when symptoms of thrombocytosis are detected, a ferritin test is certainly used.

All the reasons for which there is an increase in the production of platelets in the bone marrow also cause an increase in the number of these cells due to the phenomenon of involvement. This process is typical for anemia, acute blood loss, and conditions caused by chemotherapy.

3. The cause of reactive thrombocytosis can be removal of the spleen. Normally, a third of all platelets produced accumulate in this organ. After removal of the spleen, the volume of blood distribution decreases, and the number of platelets in it artificially increases. The same phenomenon is characteristic of asplenia, in which the spleen is absent from birth. Reactive thrombocytosis in children can be observed with functional asplenia (a disease in which the spleen gradually atrophies). With asplenia, the total number of platelets is normal, but they do not find a place in the spleen and enter the general bloodstream.

4. Injuries and surgical interventions. In addition to post-traumatic stress and the consequences of surgery, thrombocytosis is caused by significant damage to human tissue due to pancreatitis, enterocolitis or tissue necrosis.

5. Inflammation can trigger an increase in the number of platelets. As a rule, this is caused by an increase in the content of pro-inflammatory interleukin. This component enhances the formation of the hormone thrombopoietin, which regulates the mechanisms of maturation, division and release of platelets into the bloodstream.

Inflammatory causes include:

juvenile rheumatoid arthritis;
spondyloarthritis;
sarcoidosis;
chronic inflammatory liver diseases;
Kawasaki syndrome;
Schonlein disease;
collagenosis

6. Malignant tumors can provoke an increase in the number of platelets in the blood. The most dangerous in this regard are considered to be both types of lymphomas, hepatoblastoma and neuroblastoma. A comprehensive examination, including a chest x-ray and ultrasound of the abdominal organs, helps diagnose a specific disease.

7. Some medications can cause platelet levels to increase. Among them are the following:

corticosteroids, including those used for inhalation;
sympathomimetics;
antimitotics.