Neutropenia : Causes, Symptoms, Diagnosis & Treatment

Last Updated: 24/08/2022

Neutropenia is a pathological condition characterized by a decrease in the level of neutrophils below 1500 in 1 µl of peripheral blood. The causes can be various bacterial and viral infections, autoimmune disorders, medications. The level of neutrophils is examined in a general blood test. To correct this pathology, the underlying disease is treated. In severe neutropenia, drugs are used that stimulate the formation of bone marrow leukocytes.

Classification

By origin, the following neutropenias are distinguished:

  • Hereditary - genetically determined pathologies characterized by a defect in the formation of granulocytes in bone marrow cells.
  • Acquired - develop secondarily against the background of various diseases (infectious, autoimmune, etc.).

The following main pathogenetic mechanisms for the development of neutropenia are distinguished:

  • Increased destruction of neutrophils. The destruction of neutrophilic granulocytes may be due to the action of autoantibodies, bacterial toxins, haptens, etc.
  • Violation of hematopoiesis. The occurrence of neutropenia is due to damage to hematopoietic cells by radiation, myelotoxic drugs or ineffective leukopoiesis due to impaired mitosis, maturation of neutrophils.
  • Redistribution (pseudoneutropenia). Change in the ratio between the parietal (marginal) and circulating pool, i.e. when there is a shift in the predominant number of granulocytes to the wall of blood vessels. Observed in shock conditions, splenomegaly.

Agranulocytosis is considered a separate type of neutropenia - a decrease in the number of neutrophilic granulocytes less than 500 / μl while reducing the total number of leukocytes below 1000 / μl. Most often, agranulocytosis occurs in oncohematological diseases, as well as due to long-term use of myelotoxic drugs.

Causes of neutropenia

infections

They are especially common in generalized bacterial infections (sepsis, meningococcemia, typhus) or severe viral infections (influenza, infectious mononucleosis, viral hepatitis). The mechanism for reducing the level of neutrophils can be different - the destructive effect of bacterial toxins on granulocytes, the suppression of their formation in the bone marrow, their intense loss with exudation, etc.

For bacterial infections, especially coccal etiology, "secondary wasting neutropenia" after prolonged neutrophilia is typical. The rate and extent of the fall in the number of neutrophils corresponds to the severity of the infectious process. The level of neutrophils gradually returns to normal after elimination of the pathogen. Neutropenia in some cases is a marker of poor outcome.

Taking medicines

One of the most common causes of neutropenia is medication. There are 2 main mechanisms for the development of this pathology - toxic and immune (hapten). With neutropenia of toxic origin, the drug has a depressing effect on bone marrow stem cells. In the immune mechanism, the drug binds to peripheral blood granulocytes, resulting in the formation of an autoantigen, to which autoantibodies begin to be produced.

The fundamental difference is that in the case of the toxic variant, neutropenia is dose-dependent, i.e. long-term use of drugs in high doses is necessary, and with the hapten mechanism, neutropenia occurs as an idiosyncratic reaction (it can develop even with the first dose of the drug).

Drugs that can cause hapten neutropenia:

  • Non-steroidal anti-inflammatory drugs : analgin, pyrazolone, amidopyrine.
  • Antiarrhythmic drugs : quinidine.
  • Hypoglycemic drugs : sulfonylurea derivatives (chlorpropamide).
  • Antibiotics of the penicillin group, cephalosporins.
  • Anti-tuberculosis drugs : isoniazid.
  • Thyrostatic agents : propylthiouracil, mercazolil.
  • Synthetic antimalarials : hydroxychloroquine.

Drugs that cause toxic neutropenia:

  • Antitumor agents (cytostatics): alkylating agents (chlorambucil), antimetabolites (methotrexate).
  • Antiviral drugs: synthetic nucleoside analogs (ganciclovir), reverse transcriptase inhibitors (zidovudine).
  • Sulfonamides: sulfapyrazone.
  • Antibiotics: chloramphenicol.
  • Psychotropic drugs: neuroleptics (phenothiazine).

Autoimmune diseases

Neutropenia in autoimmune diseases is most often caused by the production of autoantibodies that destroy white blood cells. There is also a rarer mechanism for the development of neutropenia in these diseases. Normally, special proteins (CD55, CD59) are located on the surface of immune cells, which protect them from cytolysis. When an autoimmune pathology occurs, the amount of these proteins decreases, which leads to increased destruction of leukocytes, mainly neutrophils and lymphocytes.

Therefore, very often in autoimmune pathologies, a decrease in the number of neutrophils occurs in conjunction with lymphopenia. Neutropenia develops slowly over several months, its level correlates with disease activity, and may persist for some time after treatment and remission.

  • Joint diseases . Rheumatoid arthritis, Felty's syndrome.
  • Diffuse diseases of the connective tissue ( collagenoses ). SLE, Sjögren's keratoconjunctivitis sicca.
  • Systemic vasculitis. Polyarteritis nodosa, giant cell arteritis (Horton's disease), Takayasu's nonspecific aortoarteritis.
  • Inflammatory bowel disease (IBD). Nonspecific ulcerative colitis (NUC), Crohn's disease.

Hereditary forms of neutropenia

This group of diseases includes neutropenias caused by mutations in genes that encode the formation of proteins that regulate the processes of bone marrow maturation or granulocyte differentiation, for example, neutrophil elastase or colony-stimulating growth factor.

These diseases are quite rare. Some of them have a benign course (cyclic neutropenia, primary immune neutropenia, Henslen's syndrome). In addition to a slight decrease in the number of neutrophils, no other clinical and laboratory abnormalities are observed.

Other pathologies, such as Kostman's disease, primary immunodeficiencies, Chediak-Hegasi syndrome, have a very severe course, often leading to death from secondary infections in early childhood. The level of neutrophils is extremely low, often up to agranulocytosis.

Radiation sickness

Ionizing radiation has a pronounced inhibitory effect on organs that have a high frequency of cell renewal. The bone marrow is one of these organs. By acting on the key phases of mitosis, radiation suppresses the maturation of blood cells from stem cells. This leads to pancytopenia, i.e. a decrease in the number of leukocytes, erythrocytes, platelets.

The level of neutrophils begins to decrease one of the first, and the rate and intensity of the development of neutropenia is determined by the dose of radiation - in acute radiation sickness this happens in a few days, in chronic radiation sickness - in a few months.

Neutropenia, like pancytopenia, persists until hematopoietic stem cell transplantation is performed.

Blood diseases

Blood diseases are also often accompanied by neutropenia. The pathogenesis of its occurrence can be different - replacement of hematopoietic tissue with fibrosis, fatty infiltration or atypical malignant cells, the formation of antibodies to blood cells, etc.

  • Oncohematological diseases (leukemia). In about 20% of cases of acute leukemia, neutropenia (aleukemic form) is observed in the early stages of the disease.
  • hemolytic anemia. In some patients with autoimmune hemolytic anemia, Minkowski-Choffard anemia, hemoglobinopathies, neutropenia is noted in the blood during the interictal period, which is replaced by neutrophilia in the crisis stage.
  • Dyserythropoietic anemia. In hereditary and acquired aplastic anemia, neutropenia is observed against the background of pancytopenia. A distinctive feature of aplastic anemia is the combination of neutropenia with relative lymphocytosis.

Diagnostics

If neutropenia is detected in blood tests, it is necessary to consult a general practitioner to find out the cause. At the appointment, the doctor clarifies which medications the patient is taking, whether he is registered for a chronic disease. Important information can be given by the patient's life history, for example, if a person suffers from frequent recurrent infections of the respiratory tract, skin, and genitourinary system from early childhood, the doctor may suspect a hereditary form of neutropenia. Additional studies are scheduled, including:

  • General blood analysis. In a number of diseases, in addition to neutropenia, there is a decrease in the concentration of hemoglobin, the number of erythrocytes, and platelets. Infections and autoimmune disorders are accompanied by an increase in ESR. In malignant blood diseases, the presence of immature forms of granulocytes - metamyelocytes, myelocytes, blast cells - is noted.
  • General urine analysis. Many autoimmune rheumatological pathologies lead to damage to the glomerular apparatus of the kidneys (nephropathy), which is manifested by proteinuria, leukocyturia, and hematuria.
  • Immunological research. In people with hemolytic anemia and drug-induced hapten neutropenia, the Coombs test is positive. In viral hepatitis, serum markers are detected - HBsAg, anti-HCV.
  • Immunophenotyping. The study of peripheral blood by flow cytometry allows you to accurately determine the type of leukemia - myeloid, monoblast, megakaryoblast.
  • Genetic research. By detecting mutations in the LYST HAX1, GFI1 genes, it is possible to accurately diagnose hereditary (primary) forms of neutropenia.
  • Histological studies. In case of suspected acute leukemia, a morphological examination of the bone marrow obtained by sternal puncture or trepanobiopsy is performed. There is a decrease in the sprouts of normal hematopoiesis, a large number of atypical blast cells.

Correction

Depending on the degree of neutropenia, concomitant diseases and the severity of the patient's condition, treatment can be carried out both on an outpatient basis and in a hospital. In the case of agranulocytosis, the patient must be hospitalized. First of all, you need to cancel the drug that caused neutropenia, and replace it with a drug similar in pharmacological group, but not having such a side effect. Conservative therapy also includes:

  • Antibiotics. In patients with generalized bacterial infections, at least 2 antibacterial drugs with a wide spectrum of action (penicillins, cephalosporins) are used; antibiotics from the tetracycline group are effective in rickettsiosis.
  • Antiviral. Severe influenza is an indication for the appointment of neuraminidase inhibitors. For the treatment of viral hepatitis B and C, nucleoside analogues, interferons, DNA polymerase inhibitors are used.
  • Anti-inflammatory drugs. In order to suppress autoimmune inflammation, drugs of adrenal cortex hormones (glucocorticosteroids), synthetic antimalarial drugs, derivatives of 5-aminosalicylic acid are used.
  • colony stimulating factors. With severe neutropenia, and especially agranulocytosis, the introduction of myeloid growth factors is indicated, which activate the processes of hematopoiesis in stem cells.
  • Chemotherapy. For each type of leukemia, a special treatment protocol is provided, including various combinations of chemotherapy drugs and glucocorticoids.
  • Bone marrow transplant . In case of ineffectiveness of the use of drugs, the only method of treatment is stem cell transplantation from an individually selected donor using the HLA system.

Forecast

Neutrophils are the main cells of the immune defense against various microorganisms (bacteria, fungi), so neutropenia significantly increases the risk of infection with infectious diseases and aggravates their course several times. Agranulocytosis is a life-threatening condition requiring immediate specific therapy.

Latest Articles

  1. Noise in ears (September 30)
  2. Stamping gait (September 30)
  3. Wobbly gait (September 30)
  4. Shuffling gait (September 30)
  5. Sneezing (September 30)
  6. Cylindruria (September 30)
  7. Lameness (September 30)
  8. Chorea (September 30)
  9. Cold sweat (September 29)
  10. Chyluria (September 29)