Leukopenia : Causes, Symptoms, Diagnosis & Treatment

Last Updated: 18/08/2022

Leukopenia is a decrease in the level of leukocytes in peripheral blood below 4000 in 1 µl. The cause of this condition can be infectious, inflammatory autoimmune diseases, genetic defects of the immune system, etc. Clinically, leukopenia is manifested by an increased susceptibility of the body to various infections, but it can be completely asymptomatic. The level of leukocytes is measured when taking venous or capillary blood in the morning on an empty stomach. To correct this laboratory deviation, the underlying disease is treated.


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

  • Hereditary (primary) . The low content of leukocytes is due to genetically determined disorders in the formation and maturation of cells in the red bone marrow. These include Kostman's neutropenia, autosomal dominant hereditary neutropenia, 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 the pathogenesis (development mechanism), leukopenias are distinguished due to:

  • Violations of the flow of leukocytes into the blood from the bone marrow. The development of leukopenia is due to damage to hematopoietic cells or ineffective leukopoiesis due to defects in mitosis, maturation of leukocytes. It is observed with prolonged use of cytostatic drugs, the action of 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 depot organs. Occurs in shock.
  • Reducing the time spent in the blood. The time of presence of leukocytes in the blood may decrease due to their destruction by antibodies (with autoimmune pathologies), toxic factors (with severe infections), excessively activated macrophages (with hypersplenism). Increased excretion of white blood cells can be observed during purulent processes - cholangitis, endometritis.

Depending on the type of leukocyte cells, 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. It occurs with viral, bacterial infections, the toxic effect of medicines. Hereditary forms of neutropenia are also possible.
  • Lymphopenia. Reducing the level of lymphocytes below 19%. It is typical for viral infections, collagenoses, granulomatous processes.
  • Eosinopenia. The content of eosinophils is less than 1%. It is observed with excessive production of hormones of the adrenal cortex (Itsenko-Cushing's disease / syndrome). Eosinopenia is an indicator of poor prognosis in septic processes.
  • Monocytopenia. The indicators of monocytes in the leukocyte formula fall below 2%. It occurs with acute infections, long-term use of glucocorticoids.
  • Agranulocytosis. A rare severe life-threatening condition characterized by the 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), the action of radiation.

Leukopenia is determined in the general blood test


Causes of leukopenia


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 their loss with exudation.

  • Viral infections. Leukopenia develops mainly due to a decrease in the content of lymphocytes (lymphopenia). With infectious mononucleosis, influenza, viral hepatitis, leukocytes decrease slightly and quickly return to normal after recovery. With HIV infection, the level of lymphocytes often reaches zero at the stage of AIDS. 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, rickettsiosis, peritonitis). The fall in the number of leukocytes is one of the criteria for diagnosing a septic condition and systemic inflammatory response syndrome. There is mainly neutropenia, 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. Two main mechanisms of drug-induced leukopenia are known: toxic damage to the bone marrow, leading to impaired hematopoiesis, and the formation of immune complexes, resulting in the production of antibodies that attack the host's own leukocytes.

Leukopenia occurs on average 15 days after the start of the medication. The severity can be very different - from a slight decrease in the number of white blood cells to agranulocytosis. In connection with 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. With the development of agranulocytosis, the use of colony-stimulating factors may be required. Medications that most often cause leukopenia:

  • Cytostatics : cyclophosphamide, chlopambucil, 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

The cause of leukopenia may be autoimmune diseases. In these cases, lymphocytes and neutrophils are predominantly reduced. There are two main pathogenetic mechanisms of autoimmune leukopenia - the formation of antileukocyte antibodies and a decrease in the expression on the membranes of immune cells of special proteins (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, Sjögren's syndrome.
  • Demyelinating diseases: multiple sclerosis.
  • Systemic vasculitis: granulomatosis with polyangiitis, Takayasu's nonspecific aortoarteritis.
  • Inflammatory bowel disease (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 antileukocyte antibodies, deficiency of certain chemical elements for granulocytopoiesis (iron, cyanocobalamin, folic acid):

  • Oncohematological diseases. Leukopenia, up to agranulocytosis, can debut acute leukemia (aleukemic form) - this onset of the disease occurs in about 20% of cases. Almost always, thrombocytopenia and anemia are additionally detected in the blood test. Leukopenia is characteristic of lymphogranulomatosis (Hodgkin's lymphoma). The level of leukocytes often remains at a low level after treatment.
  • hemolytic anemia. With autoimmune hemolytic anemia, hemoglobinopathies, hereditary microspherocytosis, moderate neutropenia is possible. It is noteworthy that the fall in the level of leukocytes occurs outside the crisis. The period of hemolytic crisis, on the contrary, is accompanied by a slight leukocytosis.
  • Dyserythropoietic anemia. With aplastic anemia, as well as a long-term deficiency of vitamin B12 and folic acid, pancytopenia is observed due to the inhibition of the functioning of all hematopoietic sprouts. Leukopenia with iron deficiency anemia develops only with an extremely pronounced iron deficiency and is of a moderate nature.

Radiation sickness

The action of ionizing radiation adversely affects the entire human body. Organs with a high rate of cell renewal, which include the bone marrow, are the first and most affected. Under the influence of gamma rays, which have a high penetrating power, hematopoietic stem cells lose their mitotic activity.

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

Hereditary forms of leukopenia

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

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

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

Other reasons

  • Protein starvation.
  • Transfusion of blood or leukocyte mass.
  • Endocrine disorders : hypothyroidism, acromegaly, hypercortisolism.
  • Diseases occurring with hypersplenism : cirrhosis of the liver, malaria, visceral leishmaniasis.
  • Storage diseases : Gaucher disease, Niemann-Pick disease.


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

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

Examination of a blood smear under a microscope



Constitutional leukopenia does not require any intervention. If the cause of the development of this deviation was a drug, its urgent cancellation 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 the success of therapy is the treatment of the underlying pathology:

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


Some forms of primary leukopenia are characterized by a high mortality rate (50-90%) among children from infectious complications. With secondary leukopenia, the prognosis is more dependent on the underlying disease. Therefore, at any level of a decrease in leukocytes in the blood, a thorough examination is indicated, aimed at finding out the cause and timely initiation of treatment.

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