What Are the Causes of Neutropenia?

Neutropenia is a group of syndromes that occur as the absolute value of granulocytes in the surrounding blood decreases. The absolute value of neutrophils varies with age. It is 8 × 10 / L in term newborns, 6 × 10 / L in preterm infants, and 2.5 × 10 / L in the lower limit of 1 to 2 months after birth, to 1 The normal lower limit of age is 1.5 × 109 / L, and this value is regarded as the normal lower limit until adulthood. Adults and children whose absolute value is less than 1.5 × 10 / L. When the absolute value of infants from 2 weeks to 1 year old is less than 1 × 10 / L, neutropenia can be diagnosed.

Basic Information

English name

neutropenia

Visiting department

Internal medicine

Common causes

Reduced granulocyte production or stagnation of maturity, ineffective proliferation, increased destruction, multiple factors causing or pseudoreduction

Common symptoms

Dizziness, fatigue, low fever, sore throat, poor appetite, physical weakness, chills, high fever, sweating, general discomfort

Causes of neutropenia

There are many reasons for neutropenia. There are different classification methods, which can be divided into congenital or acquired, and can also be divided into five categories according to the reduction of granulocyte production, invalid proliferation, excessive destruction, compound causes, and reduction of pseudo granulocytes:

(1) Reduced granulocyte production or stagnation of maturity

1. The drug acts directly on the bone marrow

Common are methotrexate, 6-mercaptopurine, and alkylating agents such as cyclophosphamide. Granulocyte reduction caused by chloramphenicol is most common among antibiotics.

2. The role of radioactive substances

Radiation therapy of the spine, pelvis and sternum can affect bone marrow hematopoiesis and reduce granulocytes.

3. Hereditary granulocytopenia

Also known as infantile lethal granulocytopenia, it is a rare granulocytopenia and is an autosomal recessive inheritance.

4. Reticular hypoplasia with congenital leukopenia

This disease is extremely rare. Sick children develop disease immediately after birth. The thymus, systemic lymph nodes, tonsils, and intestinal collective lymph nodes are not developed or stunted. The peripheral blood lymphocytes are extremely reduced, cellular immunity is low, and plasma gamma globulin is reduced. It is caused by a defect in the development of hematopoietic stem cells. Granulocyte proliferation is low, primordial granulocytes are lacking in the bone marrow, and monocytes are also absent. The red blood cell system and megakaryocyte system are normal. Often died of severe bacterial or viral infections during infancy.

5. Neutropenia with immunoglobulin abnormalities

About half of the children have a family history and are genetically linked. The prognosis is poor, more than death within a few years of life.

6. Familial benign chronic neutropenia

It is autosomal dominant or recessive, and is more common in African and Jewish families. The prognosis is good.

7. Familial Severe Granulocytopenia

The disease may be inherited as an autosomal recessive or dominant.

8. Periodic granulocytopenia

This child is autosomal dominant, more than infants or childhood disease. Seizures are periodic, with intervals of 15 to 35 days, mostly 19 to 21 days. With the increase of age, the seizures gradually decrease, and some can return to normal after 5 to 10 years. About 35% to 50% of children have improved after splenectomy.

(Two) ineffective proliferation of granulocytes

Granulocyte ineffective hyperplasia is active hyperplasia of granulocytes in the bone marrow, but a large amount of damage is not reached before maturity, such as megaloblastic anemia caused by folic acid or vitamin B12 deficiency, and at the same time, granulocyte life is shortened.

(3) Increased granulocyte destruction

Immune neutropenia

(1) Moderate or severe agranulocytopenia occurs after birth in neonates with immunogenic granulocytopenia ,

For weeks. The mechanism is that the mother and fetal granulocyte type are incompatible. In the last 3 months of pregnancy or during labor, granulocytes with specific antigens enter the mother's blood circulation and stimulate the mother to produce IgG antibodies against fetal granulocytes. This antibody enters the fetal blood circulation and causes Aggregation and destruction of fetal neutrophils.

(2) Drug immunoreactive granulocytopenia as a hapten, a type II allergic reaction-a cytolytic response-caused in children with specific constitution. Aminopyrine is a representative of this reaction. Similar drugs include butazone, sulfa drugs, mercury preparations, and clopramazine.

(3) Granulocytopenia can occur in autoimmune diseases such as connective tissue disease, infectious mononucleosis, vascular immunoblastic lymphadenopathy, multiple blood transfusions, and chronic active hepatitis.

(4) Immunodeficiency disease with granulocytopenia

2. Reduced granulocyte life span

(1) Chronic benign neutropenia in children is a nonfamilial and good prognosis of neutropenia. The age of onset is 6 to 20 months after birth, and more men than women.

(2) Granulocytopenia due to infection Leukopenia or granulocytopenia can occur with various viral or rickettsial infections, such as viral hepatitis and infectious mononucleosis, within 24-48 hours of onset Granulocytopenia occurs, lasting approximately 3 to 5 days. Other infections, such as measles, rubella, influenza, polio, chicken pox, and typhus, are often accompanied by a decrease in granulocytes. Some bacterial or protozoal infections, such as brucellosis, typhoid fever, malaria, and black fever, can cause granulocytopenia.

(3) Secondary splenic neutropenia is mainly seen in liver cirrhosis with congestive splenomegaly, lymphoma, melanoma, malaria and Gaucher's disease, etc. Most of them have reduced whole blood cells.

(4) Granulocytes are phagocytosed in malignant proliferative diseases of the reticuloendothelial system, such as malignant histiocytosis (malignant network), malignant lymphoma, and the like.

(D) granulocytopenia caused by multiple factors

Certain drugs such as indomethacin can suppress bone marrow and increase granulocyte destruction. Malignant lymphoma with advanced bone marrow metastasis results in reduced granulocyte production, and excessive granulocyte destruction due to splenomegaly and hypersplenism.

(5) Pseudogranulocytopenia

Pseudo granulocytopenia is caused by abnormal granulocyte distribution. The fluctuation range of granulocytes in the blood around the patient is large and changes rapidly. Those without primary disease and repeated infection can be collectively referred to as benign granulocytopenia. , Congenital and pseudoneutropenia. Intermittent seizures, moderate reduction of granulocytes, and good process. When the blood flow is slowed down, granulocytes tend to attach to the walls of small blood vessels, causing granulocytes in the marginal pool to increase.

Clinical manifestations of neutropenia

The peripheral blood leukocyte count below 4.0 × 10 ⁹ / L (4000 / mm ³ ) is called leukopenia, and it is most often caused by neutropenia. The neutrophil count is less than (1.8 2.0) × 10 ⁹ / L (1800 2000 / mm ³ ), which is called granulocytopenia; less than (0.5 1.0) × 10 ⁹ / L (500 1000 / mm ³ ), called agranulocytosis, is often accompanied by severe, uncontrollable infections. Onset can be urgent and slow. The risk of infection in a patient is directly related to the time and rate of decrease in neutrophil count.

1. Moderate decrease in granulocytes

The course of disease is usually self-limiting for a short period of time, and those with slow onset often experience chronic passages and intermittent attacks. Some patients may not be infected because of the compensatory function of the body. No obvious clinical symptoms or non-specific manifestations such as dizziness, fatigue, low fever, sore throat, poor appetite, and physical decline.

2. Significantly reduced neutrophils

As low as 1.0 × 10 ⁹ / L or even completely absent, it is completely different from ordinary leukopenia. Patients may suddenly experience chills, high fever, sweating, and general discomfort. Almost all severe infections occur within 2 to 3 days. The haematological characteristics are that neutrophils are mostly above 1.0 × 10 ⁹ / L, and there is a compensatory increase in monocytes, but monocytes are slower than granulocytes in chemotaxis or phagocytosis when infection occurs. Therefore, it is difficult to protect due to severe purulent infection. Severe infections or septicemia of the lung, urinary tract, skin, oral mucosa, and skin are common. Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa are the most common. Mucosa may have necrotic ulcers.

3. Deficiency of granulocytes due to mediating inflammatory response

The signs and symptoms of infection are usually not obvious; such as severe pneumonia, only slight infiltration on the chest radiographs, and no purulent sputum; severe skin infections do not cause edema; pyelonephritis does not see pyuria. The infection spreads quickly and progresses to sepsis. The case fatality rate is very high. Acute disease can often find the cause, such as aminopyrine or radiation damage. After the withdrawal of the drug, the body temperature returned to normal and the peripheral blood leukocytes recovered, indicating that the condition has improved. Failure to control infections in time can result in death.

Neutropenia test

Blood image

Red blood cells, hemoglobin, and platelets were approximately normal. The total number of white blood cells and the percentage of neutrophils decreased (the total number of white blood cells of the decimal type was normal), and the ANC (the total number of white blood cells × the percentage of neutrophils) was lower than the normal level. Leukocyte classification may include monocytes, eosinophils, and mildly increased lymphocytes.

Bone marrow

Generally, the red blood cell lines and megakaryocytes did not change significantly. In vitro culture of bone marrow stem cells found that the number of granulocyte colonies was reduced and the colony / cluster ratio was <1, indicating that granulocyte proliferation was poor. Patient serum was added to the culture system and patient serum was not added. The two groups were compared to observe the number of colonies and the degree of differentiation. To know whether there are factors that inhibit the proliferation and differentiation and maturation of granulocytes in the patient's serum. The disease is pseudogranulocytopenia, and it can be seen that bone marrow granulocytic hyperplasia and cell composition are basically normal.

3. Examination of granulocyte reserve

Subcutaneous injection of 1 epinephrine 0.1ml, count and classify before injection and 5, 10, 15, 30 minutes after injection. If the granulocytes rise to normal after injection, it means that the granulocyte decrease is due to adhesion to the blood vessel wall. Granulocytes increase; or due to spleen enlargement, the spleen contracts after administration and causes granulocytes to rise.

4. Check factors that damage granulocytes

If it is suspected to be connective tissue disease or due to immunity, you should measure antinuclear antibodies, look for lupus cells, do a white blood cell agglutination test, white blood cell anti-human globulin consumption test, hemolysin and lysozyme index. But note that false positives appear.

5. Exercise test

If the neutropenia is reduced before the exercise, and increases to normal after the exercise, it means that the neutrophils attached to the blood vessel wall are increased, which is a pseudoneutrophil decrease.

6.X-ray chest examination, B-ultrasound

In the case of co-infection, X-ray chest radiography and B-ultrasound were selected according to clinical manifestations.

Diagnosis of neutropenia

It should be clear whether there is a familial or congenital factor based on the medical history and family history, especially the infection medication. The absolute value of granulocytes in childhood is less than 1.5 × 10 ⁹ / L, and the diagnosis can be made when the infant is less than 1.0 × 10 ⁹ / L. If necessary, exercise tests, adrenaline tests, and factors that damage granulocytes can be performed according to the condition.

Treatment for neutropenia

The principle of treatment is to treat the primary disease according to its etiology, prevent secondary infection, and appropriately transfusion of fresh blood.

Remove the cause

Treatment of primary disease. If the granulocytes decrease due to drugs, etc., the drug should be stopped immediately and the exposure to radiation or other chemical poisons should be stopped. Caused by hypersplenism, which is prone to repeated severe infections, can be performed for splenectomy.

2. Prevent secondary infections

Patients who do not have fever should not abuse antibiotics. Inappropriate treatment can cause drug resistance and bacterial flora disorders. When fever develops and infection is suspected, you should be hospitalized immediately. As soon as infection occurs, broad-spectrum bactericidal antibiotics should be applied as soon as possible. Such as cephalosporins, especially second and third generation cephalosporins. If the number of granulocytes is less than 0.5 × 10 / L, it should be strictly isolated. Regular ultraviolet irradiation in the ward should pay attention to the oral cavity of children. The number of granulocytes is below 0.2 × 10 / L. To prevent intestinal infections, all food and utensils should be disinfected. For patients with fever, it is necessary to actively search for infections, select appropriate antibiotics, and use bactericidal antibiotics as much as possible.

3. blood transfusion

Those with a sharp decrease in granulocytes can transfuse fresh blood or isolated white blood cells to help the body control the infection, but the effect is not certain.