Leukopenia and agranulocytosis

Introduction to leukopenia and agranulocytosis Leukopenia and agranulocytosis are those in which peripheral blood leukocyte counts continue to be below 4.0X109/liter and neutrophils are below (1.5 to 1.8) X109/liter. The clinical features are dizziness, fatigue, low fever, palpitations, backache, mouth ulcers, infections, etc. Drugs, physical and chemical factors or serious infections can cause the disease, but also secondary to other diseases, such as hypersplenism, aplastic anemia. If the disease is diagnosed and treated early, the prognosis is still good, otherwise it may cause bone marrow suppression, and the prognosis is poor. basic knowledge The proportion of illness: 0.04% Susceptible people: no specific people Mode of infection: non-infectious Complications: edema, sepsis

Leukopenia and the cause of agranulocytosis

Drug-induced damage (12%):

Both anti-tumor drugs and immunosuppressive agents can directly kill proliferating cell populations, drugs inhibit or interfere with granulocyte nucleic acid synthesis, affect cell metabolism, and hinder cell division. The direct toxic effects of drugs cause neutropenia to be related to drug dose, and other multi-drugs. There may also be direct cytotoxicity or reduced granulocyte production by an immune mechanism.

Immunity factor (20%):

Autoimmune neutropenia is an autoantibody. T lymphocytes or natural killer cells act on different stages of granulocyte differentiation, causing bone marrow damage to block granulocyte production. When it is common in rheumatism and autoimmune diseases, some drugs are half. The antigen enters the sensitive body and binds to the granulocyte membrane protein or binds to the plasma protein to form a whole antigen adsorbed on the surface of the granulocyte. These whole antigens stimulate the body to produce the corresponding anti-granulocyte antibody IgG or IgM, which causes granulocyte agglutination and destruction when repeated administration. This is called immunopharmaceutical neutropenia. Some patients have allergic reactions to certain drugs (sulfonamides, antipyretic analgesics, antibiotics, etc.). In addition to causing neutropenia, they are often accompanied by rashes. Allergic manifestations such as measles, asthma, edema, etc., cause immune neutropenia to be independent of the dose.

Chemical poisons and radiation (10%):

Chemical benzene and its derivatives, dinitrophenol, arsenic, antimony, etc. have toxic effects on hematopoietic stem cells. X-rays, gamma rays and neutrons can directly damage hematopoietic stem cells and bone marrow microenvironment, causing acute or chronic radiation damage. Granulocyte reduction.

Systemic infection (10%):

Bacterial infections such as mycobacteria (especially Mycobacterium tuberculosis) and viral infections such as hepatitis virus.

Abnormal cell infiltration of bone marrow (10%):

Bone marrow metastasis, hematopoietic malignancies and myelofibrosis cause bone marrow hematopoietic failure.

Cell maturation disorder - ineffective hematopoiesis (15%):

Such as folic acid and vitamin B12 deficiency, affect DNA synthesis, bone marrow hematopoietic activity, but cell maturation is stagnant and destroyed in the bone marrow, some congenital agranulocytosis and acute non-lymphocytic leukemia, myelodysplastic syndrome, paroxysmal sleep There is also a maturity disorder in hemoglobinuria, and granulocytes are reduced.

According to granulocyte dynamics and pathophysiology, the disease can be divided into four categories:

(1) Bone marrow injury: neutropenia is reduced. Normal adults produce a large number of neutrophils in the bone marrow every day, about 1011 or more. The colony-stimulating factor IL-3, GM-CSF can promote G0 hematopoietic stem cells to enter cells. During the proliferation cycle, G-CSF specifically induces the proliferation and differentiation of granulocyte progenitor cells in the myeloproliferation cell. The promyelocytes stop proliferating and continue to differentiate into a rod-shaped nucleus and a neutral lobular nucleus. These cells are entering. Before the surrounding blood can stay in the bone marrow storage pool for about 5 days, due to some pathogenic factors directly damage the bone marrow, the number or quality of CFU-GM is abnormal or hematopoietic dysfunction, which is often the most common cause of neutropenia.

(B) abnormal distribution of circulating granulocytes: only 1/2 of the neutrophils entering the blood vessels are in the circulation pool, that is, circulating with the blood flow, and another 1/2 of the neutrophils are attached to the capillaries and capillaries. The venular endothelial cells (edge pool) do not circulate with the blood flow, so they cannot be detected at the time of white blood cell count. The granulocytes between the circulation pool and the edge pool can be converted to each other. Under the condition of injection of adrenaline or stress, granulocytes can be The edge pool is rapidly transferred into the circulation pool, which makes the granulocyte count significantly increased. For example, when the amount of granulocytes in the marginal pool is relatively increased, pseudogranulocytes can be reduced. At this time, the generation and utilization of granulocytes are normal, systemic infection and allergic reaction. Acquired pseudogranulocyte deficiency that can cause reactivity.

(3) The demand for granulocytes in extravascular tissues is increased, and the consumption of accelerated granulocytes in the blood vessels is generally only a few hours (half of the period of stay is 6h), that is, migration to the extravascular and into the tissue, performing its defense and clearing "waste" Function, about 1 to 2 days of death, in the case of bacterial, fungal, viral or rickettsial infection, allergic reactions, etc., regulated by granulocyte-producing factors GM-CSF and G-CSF, the rate of granulocyte production increases, The granulocyte is released from the bone marrow to the peripheral blood and into the tissue, and the phagocytosis and bactericidal activity are enhanced. However, when the infection is severe, the body is not responsive to normal body fluid stimulation, and some leukocyte adhesion molecules on the neutrophils (CD11) /CD18, etc. and adhesion molecules on vascular endothelial cells (ICAM-1) are activated by inflammatory mediators, allowing leukocytes to adhere to the vessel wall and migrate through the endothelial cells to the tissue, eventually showing transient granulocytes in the blood. Reduction, autoimmune neutropenia and granulocyte consumption in spleen patients can exceed the ability to produce in the bone marrow, and granulocytopenia can occur.

(D) mixed factors: such as chronic idiopathic neutropenia, periodic neutropenia, etc., the above three types of leukopenia are often mixed in the clinic, should pay attention to analysis.

Leukopenia and prevention of agranulocytosis

Leukocytes are an important factor in the body's resistance to and elimination of the invasion of foreign bacteria, viruses, fungi and other pathogenic substances. The most important component is neutrophils. When white blood cells are reduced, it is easy to cause the invasion of pathogenic substances, and multiple infections occur. There is no special effect of white blood cell drugs, so it is necessary to strengthen physical exercise, improve physical fitness, and enhance the body's ability to resist disease. It does not need to rely too much on drug treatment. Due to the deterioration of human living environment, chemical and radiation, etc., strengthen Personal hygiene and cooperation with doctors and nurses, oral, skin, perineal care is the key, although the disease is dangerous, should be full of confidence to overcome the disease, in today's medical care level, laminar flow ward, hematopoietic growth factors, component blood transfusion and Under the early treatment of various antibiotics, patients can recover and discharge.

Leukopenia and complications of agranulocytosis Complications edema sepsis

(A) oral infection: This is the most common complication of leukopenia, early tonsil swelling, pharyngeal mucosal ulcers, followed by necrotic edema, mucosal flushing and cervical lymphadenopathy.

(B) acute perianal abscess: can quickly form ulcers, necrosis and pseudomembrane.

(C) systemic systemic infection: sepsis is the main threat of this disease, the mortality rate is as high as 30% to 40%.

Leukopenia and agranulocytosis symptoms Common symptoms Dizziness, weakness, weak appetite, fatigue, exfoliative dermatitis, low fever

1. Leukopenia: generally have dizziness, fatigue, limbs, soreness, loss of appetite, low fever, insomnia and other non-specific symptoms, a few asymptomatic, some patients have repeated oral ulcers, lung infections or urinary tract infections.

2. Agranulocytosis: frequent onset, often high fever, chills, headache, fatigue or extreme weakness, sometimes oral, nasal, skin, rectum, anus, vagina and other mucosa can appear necrotic ulcers, allergic to drugs Exfoliative dermatitis can occur at the same time. In severe cases, central nervous system symptoms can occur, and sepsis or sepsis often occurs rapidly leading to death.

Examination of leukopenia and agranulocytosis

1. Blood: red blood cells and platelet counts are normal, some malignant tumors infiltrate the bone marrow, accidental acute radiation accidents can be accompanied by anemia and thrombocytopenia, white blood cell counts are <4 × 109 / L, neutrophil counts in the absence of granulocytes <0.5×109/L, lymphocytes or monocytes are relatively increased, neutrophils often have toxic particles in the cytoplasm, and vacuoles are denatured. In severe cases, nuclear left or naive cells are seen, and atypical Lymphocytes and abnormal cells.

2. Bone marrow: It varies with the cause, and there is no obvious change in the early stage. It can also show the "mature barrier" of a number of young granulocytes and the reduction of mature granulocytes, or the granules in the extreme stage of the disease, and the recovery period gradually appears. Granulocytes at each stage.

3. Bone marrow biopsy: It has important value for bone marrow fibrosis, bone marrow metastasis, lymphoma, etc. Bone marrow examination can help differential diagnosis of MDS.

4. Bone marrow culture: CFU-GM colony culture in vitro can understand the myeloproliferative activity, bone marrow neutrophil reserve, help identify the direct toxicity of drugs or immune factors inhibit granulocyte production.

5. The adrenaline test helps to identify whether it is pseudo-neutropy.

6. Anti-neutrophil antibody assays help identify whether it is immunogranulocytopenia.

7. Antinuclear antibody (ANA), rheumatoid factor (RF) titer determination, immunoglobulin assay.

8. Determination of serum lysozyme: elevated lysozyme suggests that granulocytopenia or deficiency is caused by excessive destruction, lysozyme normal or reduced granulocyte production.

Diagnosis and differentiation of leukopenia and agranulocytosis

diagnosis

1. Leukopenia: the number of white blood cells in peripheral blood is lower than 4.0 X10^9/L for various reasons, the standard for children is 10-14 years old is lower than 4.5X10^9/L, and 5-9 years old is lower than 5.0 X10^ 9/L, less than 5 years old and less than 5.5 X 10^9/L.

2. Neutropenia and agranulocytosis: the absolute value of peripheral blood neutrophils is less than 2.0 X 10^9/L in adults, called neutropenia; less than 0.5X10^9/ L is called neutrophil deficiency.

Differential diagnosis

(1) Patients with high fever must distinguish the causal relationship between infection and agranulocytosis.

(B) granulocytosis recovery period attention and acute leukemia identification.

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