Why the level of leukocytes in the blood is low and what to do about it

Leukopenia - what is it?
A condition called leukopenia is characterized by a decrease in the number of white blood cells in the blood. The causes of occurrence are various malfunctions in the body, i.e. pathology. But also a decrease in the number of leukocytes may be associated with a physiological problem.

Quite often, leukopenia develops in people with cancer.

The function of leukocytes is associated with ensuring the protection of the human body from harmful agents. These agents can enter the body from the outside or be formed in it.

The normal leukocyte count is 4.5x109/l - 10x109/l. If the indicator drops below 4x109/l, we can talk about a problem.

Leukocytes are different in structure; leukopenia reduces the number of certain types of them.

Classification

Low levels of white blood cells can occur in completely healthy individuals - constitutional harmless leukopenia occurs in approximately 2-5% of people. Based on their origin, pathological leukopenias are divided into:

• Hereditary (primary)
  . The low white blood cell count is caused by genetically determined disorders in the formation and maturation of cells in the red bone marrow. These include Kostman neutropenia, hereditary neutropenia of the autosomal dominant type, etc.
• Acquired (secondary)
  . More common option. Leukopenia develops as a result of the action of ionizing radiation, the adverse effect of drugs, biological agents (bacteria, viruses) or factors of immune autoaggression.

According to pathogenesis (mechanism of development), leukopenias that arise as a result of:

• Disturbances in the flow of leukocytes into the blood from the bone marrow.
  The development of leukopenia is caused by damage to hematopoietic cells or ineffective leukopoiesis due to defects in mitosis and leukocyte maturation. It is observed with long-term use of cytostatic drugs, exposure to ionizing radiation, genetic diseases, severe deficiency of vitamin B12, folic acid.
• Redistribution of leukocytes.
  There is a change in the ratio between the circulating and parietal pool of white blood cells as a result of their accumulation in the dilated capillaries of the depot organs. Occurs in states of shock.
• Reducing the residence time in the blood.
  The time of presence of leukocytes in the blood may decrease due to their destruction by antibodies (in autoimmune pathologies), toxic factors (in severe infections), and overly activated macrophages (in hypersplenism). Increased excretion of white blood cells can be observed during purulent processes - cholangitis, endometritis.

Depending on the type of cells of the leukocyte series, the following types of leukopenia are distinguished:

• Neutropenia.
  The decrease in the content of neutrophils is less than 47% of the total number of leukocytes. The most common type of leukopenia. Occurs with viral and bacterial infections, toxic effects of medications. Hereditary forms of neutropenia are also possible.
• Lymphopenia.
  Decrease in lymphocyte level below 19%. Characteristic of viral infections, collagenosis, granulomatous processes.
• Eosinopenia.
  The eosinophil content is less than 1%. It is observed with excess production of adrenal hormones (Cushing's disease/syndrome). Eosinopenia is an indicator of an unfavorable prognosis in septic processes.
• Monocytopenia.
  The indicators of monocytes in the leukocyte formula drop below 2%. Occurs in acute infections and long-term use of glucocorticoids.
• Agranulocytosis.
  A rare severe life-threatening condition characterized by complete or almost complete disappearance of neutrophils in the blood (below 0.75x10^9/l). It is observed when taking myelotoxic drugs (cytostatics, thyreostatics, some NSAIDs), or exposure to radiation.

Leukopenia is determined in a general blood test

Why might it happen to women?

Every woman who finds out about her low white blood cell count wonders what this means.
Considering that a woman is a complex organism that performs the function of childbearing, low white blood cells are caused by a whole series of causes. The first thing that low white blood cells can mean in women is constant stress at work or in the family. A woman endures emotional stress more heavily, and therefore the leukocyte level in the blood fluctuates sharply. The second is the restructuring of the body during pregnancy.

In the process of gestation, leukocytes tend to increase, since the body bears a “double load” - it protects the health of the pregnant woman and her child at the same time. If an analysis of a pregnant woman shows a small number of white cells, this is a reason to see a doctor more often.

The number of monocytes during labor is reduced. This phenomenon is called monocytopenia. If surgical intervention is performed during childbirth, eosinophils sharply decrease (eosinopenia).

Causes of leukopenia

Infections

One of the most common causes of leukopenia is viral and generalized bacterial infections. The pathogenesis of a decrease in the level of leukocytes can be different - direct damage to cells by lymphotropic viruses (HIV, Varicella-Zoster, measles), suppression of formation in the bone marrow, increased loss with exudation.

• Viral infections.
  Leukopenia develops mainly due to a decrease in the content of lymphocytes (lymphopenia). With infectious mononucleosis, influenza, and viral hepatitis, leukocytes decrease slightly and quickly return to normal after recovery. With HIV infection, the level of lymphocytes often reaches zero during the AIDS stage. Even after treatment, white blood cell counts may remain low, as HIV drugs themselves can cause leukopenia.
• Bacterial infections.
  Leukopenia occurs only in severe generalized infections (meningococcemia, rickettsial infections, peritonitis). A drop in the number of leukocytes is one of the criteria for diagnosing a septic condition and systemic inflammatory response syndrome. Neutropenia is mainly observed, its degree correlates with the severity of the disease. Regression occurs almost immediately after antibiotic therapy.

Taking medications

A wide range of drugs can lead to the development of leukopenia. There are two main mechanisms of drug-induced leukopenia: toxic damage to the bone marrow, leading to impaired hematopoiesis, and the formation of immune complexes, which results in the production of antibodies that attack the body’s own leukocytes.

Leukopenia occurs on average 15 days from the start of taking the medicine. The severity can vary from a slight decrease in the number of white blood cells to agranulocytosis. Due to the defeat of all 3 germs of hematopoiesis, a combination with anemia and thrombocytopenia (pancytopenia) is often found. In most cases, discontinuation of the drug is sufficient. If agranulocytosis develops, the use of colony-stimulating factors may be required. Medicines that most often cause leukopenia:

• Cytostatics
  : cyclophosphamide, clopambucil, methotrexate.
• Thyreostatics
  : propylthiouracil, mercazolil.
• Non-steroidal anti-inflammatory drugs
  : analgin, amidopyrine.
• Antibacterial agents
  : chloramphenicol, sulfonamides.
• Anti-inflammatory drugs
  : D-Penicillamine, sulfasalazine.
• Antipsychotic drugs (neuroleptics)
  : chlorpromazine, chlorpromazine.
• Anticonvulsants
  : carbamazepine, diazepam.

Autoimmune inflammatory diseases

Leukopenia can be caused by autoimmune diseases. In these cases, lymphocytes and neutrophils are predominantly reduced. There are two main pathogenetic mechanisms of autoimmune leukopenia - the formation of anti-leukocyte antibodies and a decrease in the expression of special proteins on the membranes of immune cells (CD55, CD59), which protect cells from cytolysis. Leukopenia is usually moderate, regresses during remission or under the influence of pathogenetic treatment. Leukopenic syndrome is characteristic of the following pathologies:

• Joint diseases
  : rheumatoid arthritis, Felty's syndrome.
• Diffuse connective tissue diseases (collagenoses)
  : systemic lupus erythematosus, Sjogren's syndrome.
• Demyelinating diseases
  : multiple sclerosis.
• Systemic vasculitis:
  granulomatosis with polyangiitis, Takayasu nonspecific aortoarteritis.
• Inflammatory bowel diseases (IBD)
  : ulcerative colitis, Crohn's disease.

Blood diseases

There are several mechanisms of leukopenia in hematological pathologies - replacement of hematopoietic tissue with malignant cells, fibrous or adipose tissue, synthesis of anti-leukocyte antibodies, deficiency of certain chemical elements for granulocytopoiesis (iron, cyanocobalamin, folic acid):

• Oncohematological diseases.
  Leukopenia, up to agranulocytosis, can make the debut of acute leukemia (aleukemic form) - this onset of the disease occurs in approximately 20% of cases. Almost always, blood tests additionally reveal thrombocytopenia and anemia. Leukopenia is characteristic of lymphogranulomatosis (Hodgkin's lymphoma). White blood cell levels often remain low after treatment.
• Hemolytic anemia.
  With autoimmune hemolytic anemia, hemoglobinopathies, hereditary microspherocytosis, moderate neutropenia is possible. It is noteworthy that a drop in leukocyte levels occurs outside of a crisis. The period of hemolytic crisis, on the contrary, is accompanied by slight leukocytosis.
• Dyserythropoietic anemia.
  With aplastic anemia, as well as long-term deficiency of vitamin B12 and folic acid, pancytopenia is observed due to inhibition of the functioning of all hematopoietic germs. Leukopenia in iron deficiency anemia develops only with extreme iron deficiency and is moderate in nature.

Radiation sickness

The effect of ionizing radiation adversely affects the entire human body. First and most severely affected are organs with a high rate of cellular turnover, which include the bone marrow. Under the influence of gamma rays, which have a high penetrating ability, hematopoietic stem cells lose mitotic activity.

This inevitably leads to a drop in the level of leukocytes in the blood, as well as platelets and red blood cells. In acute radiation sickness, leukopenia occurs quickly, 48-96 days after irradiation; in chronic radiation sickness, leukopenia occurs gradually, over 1 year. The severity of leukopenia directly depends on the radiation dose received. The restoration of the number of blood cells occurs slowly or does not occur at all.

Hereditary forms of leukopenia

Primary leukopenias include genetic diseases caused by mutations in genes that regulate the maturation or differentiation of leukocytes. Some mutations lead to changes in the structure of leukocyte antigens, due to which they are subject to autoimmune destruction. In the vast majority of cases, primary neutropenia occurs.

The debut occurs from the first years of life. Some of these diseases are benign in nature (cyclic neutropenia, primary immune neutropenia, lazy leukocyte syndrome, Henslen syndrome), the decrease in the number of neutrophils is insignificant, associated infections are mild, and leukopenia regresses on its own.

Other hereditary leukopenias are often accompanied by infectious complications, which often become fatal in childhood: Kostman's disease (genetically determined agranulocytosis), primary immunodeficiencies (DiGeorge syndrome, Wiskott-Aldrich syndrome), Chediak-Hegashi syndrome. In these diseases, specific treatment is required to restore normal white blood cell values.

Other reasons

• Protein fasting.
• Blood or leukocyte transfusion.
• Endocrine disorders
  : hypothyroidism, acromegaly, hypercortisolism.
• Diseases occurring with hypersplenism
  : liver cirrhosis, malaria, visceral leishmaniasis.
• Storage diseases
  : Gaucher disease, Niemann-Pick disease.

Complications

Since this disease is not independent, it also cannot be a predictor of any complications or consequences. All consequences that occur in the patient (including death) are directly related to the disease against which leukocytosis developed. Therefore, a serious excess of any type of leukocytes in the blood is a reason to conduct an in-depth examination to find out the true cause. Such a need may arise even if a person feels absolutely healthy.

Diagnostics

Leukopenia is detected by clinical blood testing. Due to the variety of etiological factors of this deviation, if it is detected, you should consult a general practitioner for a thorough history taking, physical examination, and additional examination:

• Blood tests.
  The leukocyte formula is calculated, the concentration of inflammatory markers is determined - ESR, CRP, procalcitonin. The presence of autoantibodies (antibodies to DNA, neutrophil cytoplasm, aCCP) is studied.
• Identification of infectious pathogen.
  The enzyme immunoassay method identifies antibodies to pathogens (viruses, bacteria). To confirm HIV infection, immunoblotting is prescribed. Bacterial culture of blood, sputum, and urine is carried out.
• Biopsy.
  If leukemia is suspected, a morphological examination of the bone marrow is performed, which reveals hyperplasia of the granulocytic lineage and a large number of blast cells. To diagnose lymphomas, an aspiration biopsy of an enlarged lymph node is performed; the biopsy specimen reveals lymphocytic hypercellularity and collagen proliferation.
• Genetic research.
  To confirm hereditary forms of leukopenia, it is necessary to detect mutations using polymerase chain reaction and cytogenetic studies.

Examination of a blood smear under a microscope

When to see a doctor

If you experience a general feeling of malaise or one of the symptoms described above for no apparent reason, you should consult a specialist. Such symptoms are characteristic of a large number of diseases and can also be a sign of leukocytosis. Therefore, you should contact a competent specialist for advice. JSC “Medicine” (clinic of Academician Roitberg) employs experienced specialists with extensive experience and high qualifications. The clinic is located in the center of Moscow: 2nd Tverskoy-Yamskaya lane, 10.

Correction

Constitutional leukopenia does not require any intervention. If the development of this deviation is caused by a drug, its immediate discontinuation is necessary. With a pronounced decrease in leukocytes or agranulocytosis, they resort to the introduction of granulocyte colony-stimulating factor (G-CSF) or infusion of donor granulocytes. The main condition for successful therapy is treatment of the underlying pathology:

• Elimination of the pathogen.
  Oseltamivir is used to treat influenza, and antiretroviral drugs (zidovudine, saquinavir) are used to combat HIV infection. For bacterial infections, antibiotics are prescribed.
• Anti-inflammatory therapy.
  To achieve remission of autoimmune diseases, glucocorticosteroids, immunosuppressants, and 5-aminosalicylic acid derivatives are used.
• Chemotherapy.
  If oncohematological pathology is confirmed, combinations of chemotherapeutic agents are prescribed - chlorambucil, vincristine, etoposide.
• Bone marrow transplantation.
  In case of ineffectiveness of chemotherapy for hematological malignancies, as well as in severe primary neutropenia, hematopoietic stem cell transplantation is performed.

Symptoms

Leukopenia, as a rule, is determined accidentally during a preventive study, since it does not have specific clinical symptoms.

The first signs of a decrease in leukocytes may appear when bacterial, viral or infectious complications are involved in the pathological process.

What this entails:

• Increased body temperature;
• The appearance of aphthae on the mucous membranes of the mouth;
• Increased gum bleeding;
• Pustular infections;
• Tachycardia;
• Headache;
• Anxiety;
• Pain in the left hypochondrium (associated with an enlarged spleen).

All symptoms of leukopenia must be carefully examined, so in this case, consultation with a doctor is mandatory.

Is it possible to increase the level of leukocytes and neutrophils?

Chemotherapy drugs are toxic substances. There are indications and contraindications for their use, because they can both help the patient and cause great harm if used thoughtlessly. The only appropriate and reasonable method to increase the level of white blood cells and neutrophils is to wait.

Yes this is true.

Firstly, because each organism has its own characteristics and is not always able to recover by the time specified by the recommendations.

The intervals between cycles are optimal, but a deviation from the timing by 1-2 weeks (sometimes more, if necessary) is acceptable if there are contraindications to chemotherapy.

Secondly, any drugs that stimulate an increase in the level of leukocytes and neutrophils are dangerous because after several such stimulations, the bone marrow reserve can be depleted, and after this, recovery will take much longer and will be associated with possible complications.

If leuko- and neutropenia is constant, and the body does not recover properly even with increasing intervals between cycles, then specialized drugs are prescribed, which should be used only under the supervision of a doctor in strictly indicated situations.

Any so-called immunomodulators, immune stimulants will not bring any benefit, there will be no effect from them, because leukocytes will still decrease during chemotherapy, as it should be, but at the same time such drugs can provoke the development of undesirable reactions.

Treatment of leukocytosis

Features and causes of appearance do not provide for symptomatic treatment of leukocytosis. Therapy is prescribed after the underlying disease has been established, the development and progression of which has provoked a jump in the level of leukocytes. Accordingly, treatment methods in each individual case will be very individual.

Antibiotics are used to treat infectious diseases. Steroid drugs can be used to eliminate inflammation. Reducing uric acid in the body with the help of special drugs helps prevent the destruction of body tissues, which can also cause leukocytosis, etc. When talking about the treatment of leukocytosis, we are talking about the disease that caused it.

At our multidisciplinary medical center, doctors prescribe safe and effective treatment using an individual approach and many years of experience.