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.
By origin, the following neutropenias are distinguished:
The following main pathogenetic mechanisms for the development of neutropenia are distinguished:
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.
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.
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:
Drugs that cause toxic neutropenia:
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.
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.
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 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.
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:
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:
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.