Leukopenia and agranulocytosis in the elderly
Introduction
Introduction to leukopenia and agranulocytosis in the elderly Peripheral white blood cells below 4 × 109 / L called leukopenia (leukopenia), the absolute value of granulocytes continued to be less than 2 × 109 / L, called neutropenia, such as extreme lack, less than 1 × 109 / L Agranulocytosis, often accompanied by a serious infection. The etiology and pathogenesis of leukopenia and agranulocytosis are the same in most cases, with only varying degrees of reduction. basic knowledge Sickness ratio: 0.0001% Susceptible people: the elderly Mode of infection: non-infectious Complications: pneumonia sepsis
Cause
The cause of leukopenia and agranulocytosis in the elderly
(1) Causes of the disease
1. Granulocyte proliferation or maturation
Aplastic anemia, infection with X-rays, gamma rays, chemicals such as benzene and xylene, and drugs are one of the most common causes of bone marrow granulocyte-producing disorders, including anti-tumor drugs and antipyretic analgesics. Sedatives, chloramphenicol, sulfonamides, antithyroid drugs, antihistamines, hypoglycemic agents, cardiovascular drugs and diuretics.
Giant megaloblastic anemia, myelodysplastic syndrome, and the use of antimetabolites (methotrexate, 6-anthraquinone, etc.) and antithyroid drugs (hydimidazole, thiouracil, etc.) can cause granulocyte maturation disorders and ineffectiveness Generated (over-apoptosis).
2. Granulocyte destruction or excessive consumption
Connective tissue disease, autoimmune diseases and the use of aminopyrine, methyldopa, sulfathiazole and other drugs, granulocyte antibodies in the blood, causing immune neutropenia, hypersplenism and other diseases make granulocytes in a single nucleus - The phagocytic system is retained and destroyed too much. The granulocytes in the blood enter the tissue due to severe infection, and the consumption is accelerated. The damage of granulocytes is increased when the protozoa, rickettsia and virus are infected.
3. Abnormal granulocyte distribution
Anaphylactic shock, allogeneic protein reaction, viremia, etc., cause excessive transfer of granulocytes to the marginal pool, and the number of granulocytes in the circulating pool is reduced, but the total number of white blood cells is unchanged, which is called pseudogranulocyte reduction.
(two) pathogenesis
The neutrophil cell line is produced by the differentiation and maturation of pluripotent hematopoietic stem cells-myeloid hematopoietic stem cells-granulocyte-derived progenitor cells in the bone marrow. The cell dynamics can be roughly divided into three stages: the bone marrow stage, the blood stage and the tissue stage, in the bone marrow. When the progenitor cells proliferate, they are called the stem cell stage, and then the granulocytes to the mesenchymal cells. During this period, the cells can divide into the dividing and proliferating cells; they no longer divide before the release from the late granulocytes to the neutral lobular nucleus. Still in the bone marrow, the mature reserve pool, the number of neutrophils in this period is 5.59 × 109 / kg, about 8 times in the blood, in order to supplement the blood, ready to release to the blood, about half of which adhere The microvessel wall is called the edge pool; the other half flows along with the blood circulation to the circumference of the circulation pool, the total number of neutrophils is 0.7×109/kg, and the neutrophil stays in the blood for a short time, 6 After 12 hours, it was transferred to extravascular tissues (lung, oral, gastrointestinal, liver, spleen and inflammatory areas) and no longer returned, and died within 1 to 2 days.
The etiology and pathogenesis of neutropenia can be divided into three categories according to the above cell dynamics: barriers to production, destruction or excessive consumption, and abnormal distribution:
1. Neutrophil production defects
Cytotoxic drugs (anticancer drugs), benzene and radiation can directly affect dry/progenitor cells and early cells in mitosis, or inhibit their proliferation in a dose-dependent manner. Significant reduction in granulocytes is in the bone marrow maturation reserve. After the granulocyte depletion in the pool occurs, 1 to 2 weeks after administration, occasionally granulocyte-reducing drugs (Table 3) cause neutropenia only in some sensitive patients, and its pathogenesis is complex, which can be roughly classified into two types. One is that some patients have been exposed to this drug, and sudden neutropenia or deficiency (such as aminopyrine) occurs several hours after re-exposure, regardless of dose, possibly through immune-mediated mechanisms: drugs or their metabolism The product is a hapten, which binds to a protein to form an antigen, which causes the body to produce a corresponding antibody. The antigen-encapsulated leukocyte may directly dissolve or agglutinate the cells in the blood or rapidly destroy the spleen and other parts; the other is contact. A few weeks after the drug, granulocytopenia (such as phenothiazine, thiouracil, sulfonamide, etc.) occurs slowly, depending on the dose and time of administration, possibly due to inhibition of granulocytes in the bone marrow. Sulfonamides and thiouracils can also rapidly undergo neutropenia through immune-mediated mechanisms, in addition to factors that reduce granulocyte production, such as autoantibodies and/or T cells, some infections, bone marrow Infiltration and certain congenital hereditary neutropenia, vitamin B12 or folate deficiency cause granulocyte maturation disorders.
2. Neutrophils destroy or consume too much blood or tissue
It can be divided into two kinds of immune and non-immune factors. The former, such as neutrophils, is encapsulated by antibodies or antigen-antibody complexes and is destroyed in tissues such as blood or spleen. It is found in systemic lupus erythematosus and rheumatoid arthritis. Immune disease, certain non-cytotoxic drugs, certain infections (such as chronic hepatitis) and allogeneic neonatal neutropenia; the latter such as sepsis causes neutrophils to be consumed in the blood or inflammation site, spleen Hyperfunction makes neutrophils destroy too much in the spleen.
3. Abnormal neutrophil distribution
The transfer of granulocytes to the marginal pool leads to an increase in granulocytes attached to the pool, and the granulocytes in the circulating pool are relatively reduced, but the total number of granulocytes is not reduced, so it is called pseudoneutrophy, which is found in congenital or constitutional leave. Atrophic neutropenia, in addition to acquired bacteria such as severe bacterial infection, malnutrition, malaria, etc., often accompanied by decreased neutrophil production or increased damage, so the total number of granulocytes can also be reduced.
It should be noted that the above pathogenesis is comprehensive in some causes, and some of them have not yet clarified its mechanism.
When the co-infection occurs, there are chills, chills, high fever, severe oral cavity, necrotizing ulcers of the tongue and throat, and inflammation or abscesses in the lungs, urinary tract, hepatobiliary and facial or perianal skin, often accompanied by oral and pharyngeal ulcers. In the submandibular and cervical lymph nodes, due to the lack of granulocytes, there are few granulocytes entering the inflammation site. When the lungs are infected, there is often no purulent sputum. X-ray examination can be free of inflammatory infiltration shadows; abscesses may be absent or Very little pus formation, severe sepsis, liver often swollen or liver and spleen at the same time, and even jaundice.
Prevention
Elderly leukopenia and prevention of agranulocytosis
For workers exposed to radiation and chemical poisons such as benzene, a strict protection system must be established and blood images should be checked regularly. For patients treated with cytotoxic drugs, blood samples should be examined 1 to 3 times, and the number of granulocytes should be reduced or stopped in time. Drugs; for non-cytotoxic drugs that occasionally cause neutropenia, you must master the indications for medication, especially when taking drugs that are more likely to cause neutropenia (such as aminopyrine, methimazole, etc.), patients should check blood for weekly Those who have had a history of drug allergy or who have had granulocytopenia after treatment should avoid taking similar drugs.
Complication
Elderly leukopenia and neutropenia complications Complications pneumonia
Common co-infections are associated with stomatitis, otitis media, bronchitis, pneumonia, sepsis, etc.
Symptom
Symptoms of leukopenia and agranulocytosis in the elderly Common symptoms Loss of appetite, weakness, hypothermia, bacterial infection, fatigue, complete blood cell reduction, high fever, dizziness, leukopenia
1. Symptomatic clinical manifestations
(1) Leukopenia: Primary leukopenia has only systemic symptoms such as fatigue, hypothermia, and may be associated with mononucleosis and no serious infection. The clinical manifestations of secondary leukopenia are determined by the primary disease. Can also be associated with stomatitis, otitis media, bronchitis, pneumonia and other secondary infections, peripheral white blood cells mostly in the range of (2 ~ 4) × 109 / L, lymphocytes relatively increased, granulocyte cytoplasm can have toxic particles and The vacuolar degeneration, the hemoglobin and platelet counts are generally normal, the bone marrow is normal in the early stage, or there is a low granulocyte regeneration or a maturation disorder.
(2) neutropenia: rapid onset, due to a large number of granulocyte destruction in a short period of time, patients can suddenly chills, sweating and high fever and other systemic symptoms, and the performance of general leukopenia is completely different, self-sufficiency, discomfort The absolute value of neutrophils is often lower than 0.5×109/L, and severe infection occurs almost within 2 to 4 days. The cause of this disease is the same as leukopenia, but the most common cause is drug reaction, which may have a related medical history. The examination revealed that the mucous membranes of the mouth, throat, rectum, anus, vagina or uterus may have necrotizing ulcers, and sometimes progress to sepsis rapidly, may have local lymph nodes and swelling, a few patients have liver, splenomegaly, poor prognosis The rate is as high as 50% to 90%. If the symptoms are relieved, the body temperature drops, and the rise of peripheral blood leukocytes is a manifestation of improvement and recovery.
2. Asymptomatic
Often, the degree of leukopenia and the disease are different, and the liver is slightly reduced (1.0 to 1.95) × 109 / L). There is less chance of infection, and there are no special symptoms in the clinic. It is often found when blood tests are performed for other reasons. However, due to certain diseases, only the primary symptoms appear.
3. Atypical symptoms
When the number of white blood cells is reduced or the granulocyte is absent, and the infection has not yet occurred, the patient may experience fatigue, weakness, dizziness, and loss of appetite.
White blood cell count is the most important experimental diagnosis. White blood cell count is susceptible to many factors. Therefore, the general leukopenia often needs multiple repetitions to determine. Peripheral blood test and white blood cell classification are necessary. Granulocyte cytoplasm has toxic particles and empty. Bubbles often indicate bacterial infection; mononuclear cell ratio is often compensatory; such as increased proportion of rod-shaped granulocytes (>20%) suggesting that the bone marrow has sufficient granulocyte production capacity, indicating that bone marrow damage is recovering or granulocyte is temporarily retained. In the edge pool, transfer to the outside of the blood vessels.
Examine
Examination of leukopenia and agranulocytosis in the elderly
Laboratory examination: the number of peripheral white blood cells is below 2 × 109 / L, the absolute value of granulocytes is less than 0.5 × 109 / L, the percentage of neutrophils is often below 10% ~ 20%, sometimes even completely absent, granulocytes Significant toxic changes, lymphocytes relatively increased, sometimes mononuclear cells increased slightly, hemoglobin and platelets were generally normal, bone marrow was granulocyte proliferation and maturation was blocked, only the original granules and bone marrow of promyelocytic or granulocyte aplastic disorders The cells of megakaryocytes and young red cells are generally normal, and the plasma cells, lymphocytes and histiocytes may increase slightly. When the disease recovers, the young particles are seen in the surrounding blood, and other mature granulocytes and monocytes are also picked up one after another. Leukemia-like blood.
Imaging examination: For patients with leukopenia and neutropenia, if there is an infection, if you take X-ray positive signs of pneumonia or bronchitis on the chest X-ray, you may have a positive sign of lung abscess or pleural effusion. B ultrasound often has swelling of the spleen.
Diagnosis
Diagnosis and differentiation of leukopenia and agranulocytosis in the elderly
Diagnostic criteria
According to the absolute count of white blood cells and granulocytes, the diagnosis and judgment of the severity of this disease can be established. The second step of diagnosis is to find the cause of leukopenia. It is necessary to pay attention to whether there is a history of medicinal chemicals and radiation exposure, and whether there is chronic inflammation. Basic diseases such as autoimmune diseases, repeated infections, etc. If the patient has a history of serious infection or exposure to poison, a reduction in whole blood cells, or a combination of red blood cells/thrombocytopenia, a bone marrow examination, including bone marrow biopsy, bone marrow must be performed. The performance of elephants varies with the primary disease. Selective agranulocytosis has extremely reduced or even completely disappeared neutrophils in the bone marrow. The granulocytes have obvious toxic changes or mature obstruction, young red blood cells and megakaryocytes. The cells are generally normal, the condition is improved, and the peripheral blood can also appear in the peripheral blood during the recovery of granulocytes. The simple granulocytes are reduced without the etiology and underlying diseases, no recurrent infection, and the clinical experience is good, possibly familial/congenital Agranulocytopenia or pseudoneutropenia.
To determine the exact cause of neutropenia is often difficult, the following special tests can help understand the pathogenesis of neutropenia:
1 Detection of bone marrow granulocyte storage function: After using adrenal cortex hormone, the bone marrow granulocytes can be released to understand the amount and release function of bone marrow storage granulocytes, intravenous hydrocortisone 200mg or oral prednisone 40mg, white blood cells after 5h It is normal to count more than 2×109/L before the administration.
Detection of function of 2-cell edge pool: subcutaneous injection of adrenaline 0.2mg, white blood cell count increased by 2×109/L after injection or increased by more than 1 time before injection, suggesting that granulocytes are excessively clustered on blood vessel wall or blood. On the endothelial cells of the sinus (edge pool), if there is no spleen, it can be considered as pseudogranulocyte reduction.
3 detection of leukocyte lectin or neutrophil antibody: positive results can be measured in the serum of patients with immune neutropenia, but multiple blood transfusions or maternal women can also be positive.
4DF32P labeled neutrophil cell dynamics assay: can understand the formation of granulocytes.
Differential diagnosis
Aplastic anemia
With anemia, thrombocytopenia, generally no liver and spleen and lymphadenopathy, bone marrow examination can be identified.
2. Myelodysplastic syndrome
More common in the elderly, there are three lines of peripheral blood reduction, bone marrow pathological hematopoiesis, often chromosomal abnormalities, bone marrow examination is helpful to identify.
3. Leukemia
Especially white blood cell non-leukocytic leukemia, often accompanied by anemia, bleeding symptoms, bone marrow examination can be identified.
