agranulocytosis
Introduction
Introduction to agranulocytosis The normal white blood cell count of peripheral blood is 4-10×10^9/L, and neutrophils account for 60-75%. Neutropenia is the absolute count of peripheral blood neutrophils (total number of white blood cells × percentage of neutrophils) <10 years old children less than 1.5 × 10 ^ 9 / L, 10 ~ 14 years old children less than 1.8 × 10 ^9/L, adults below 2.0×10^9/L. When neutrophils are severely reduced (less than 0.5 × 10 ^ 9 / L), it is called granulocytosis. basic knowledge The proportion of the disease: the disease is common, the incidence rate is about 0.01%-0.02%, more common in viral infection or after using certain antibiotics Susceptible people: no special people Mode of infection: non-infectious Complications: headache, nausea and vomiting, disturbance of consciousness, coma
Cause
Causes of agranulocytosis
Normal adults produce a large number of neutrophils in the bone marrow every day, about 1011 or more. Colony stimulating factors IL-3 and GM-CSF can promote G0 hematopoietic stem cells to enter the cell proliferation cycle, and G-CSF specifically induces proliferation and differentiation of granulocyte progenitor cells in the bone marrow proliferation pool. The promyelocytes stopped proliferating and continued to differentiate into a rod-shaped nucleus and a neutral lobular nucleus. These cells can stay in the bone marrow reservoir for about 5 days before entering the surrounding blood. The cause of agranulocytosis is due to the fact that certain pathogenic factors directly damage the bone marrow, causing abnormal or quantitative hematopoietic dysfunction of CFU-GM.
Drug-induced damage (25%):
Both anti-tumor drugs and immunosuppressive agents directly kill the proliferating cell population. The drug inhibits or interferes with granulocyte nucleic acid synthesis, affects cell metabolism, and blocks cell division. The direct toxic effects of the drug cause neutropenia to be associated with drug dose. Other classes of drugs can also have direct cytotoxicity or reduce granulocyte production through immune mechanisms.
Chemical poisons and radiation (20%):
Chemical benzene and its derivatives, dinitrophenol, arsenic, antimony and the like have toxic effects on hematopoietic stem cells. X-rays, gamma rays and neutrons can directly damage hematopoietic stem cells and the bone marrow microenvironment, causing acute or chronic radiation damage and neutropenia.
Immunity factor (18%):
Autoimmune neutropenia: autoantibodies, T lymphocytes, or natural killer cells act on different stages of granulocyte differentiation, causing bone marrow damage to impede granulocyte production. Common in rheumatism and autoimmune diseases. Some drugs are haptens that enter the sensitive body and bind to granulocyte membrane proteins or bind to plasma proteins to form a whole antigen to adsorb to the surface of granulocytes. These whole antigens stimulate the body to produce the corresponding anti-granulocyte antibody IgG or IgM. Agglomeration and destruction of granulocytes are caused when the drug is repeatedly administered. This is called immunopharmaceutical granulocytosis. Some patients have allergic reactions to certain drugs (sulfonamides, antipyretic analgesics, antibiotics, etc.), in addition to causing neutropenia, often accompanied by rash, urticaria, asthma, edema and other allergic manifestations. The cause of immunogenic neutropenia is independent of the dose used.
Systemic infection (15%):
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 (10%):
Lack of folic acid and vitamin B12 affect DNA synthesis. Bone marrow is hematopoietic, but cell maturation is stagnant and destroyed in the bone marrow. Some congenital agranulocytosis and acute non-lymphocytic leukemia, myelodysplastic syndrome, paroxysmal nocturnal hemoglobinuria also have maturity disorders, while granulocytes are reduced.
Prevention
Agranulocytosis prevention
1. For drugs that may cause this disease, the indications for medication should be strictly controlled and should not be abused.
2. For those who have been exposed to radioactive materials for a long time, X-rays and certain chemical substances, attention should be paid to prevention work, and blood images should be checked regularly.
3. The room keeps the air circulation fresh, avoiding the cold and preventing colds.
Complication
Agranulocytosis complications Complications, headache, nausea and vomiting, dysfunction, coma
Serious complications of this disease include toxic encephalopathy or central nervous system infection, headache, nausea, vomiting, disturbance of consciousness, and even coma. Exfoliative dermatitis can occur in patients with drug allergy. If it does not recover within a short period of time, the mortality rate is extremely high.
Symptom
Symptoms of agranulocytosis common symptoms nausea conscious disorder high fever chills purpura exfoliative dermatitis dyspnea cough coma jaundice
Before the onset, most patients had a history of drug exposure, rapid onset, high fever, chills, headache, extreme weakness, general malaise, due to the extreme lack of granulocytes, the body's resistance decreased significantly, infection became the main complication, gums, oral mucosa, Soft palate, necrotizing ulcer in the pharyngeal isthmus, often covering grayish yellow or pale green pseudomembrane, inflammation of the skin, nasal cavity, vagina, uterus, rectum, anus, local infection often causes lymph node enlargement in the corresponding part, serious infection of the lung Cause cough, difficulty breathing, purpura, sepsis may be associated with liver damage, liver enlargement, jaundice, severe cases may be associated with toxic encephalopathy or central nervous system infection, headache, nausea, vomiting, disturbance of consciousness, even coma, drug allergy Exfoliative dermatitis can occur, and if it does not recover in a short period of time, the mortality rate is extremely high.
Examine
Examination of agranulocytosis
White blood cell and neutrophil counts are the main experimental diagnostic basis. There are toxic particles and vacuoles in the granulocyte cytoplasm, often suggesting the presence of bacterial infections. The proportion of monocytes is often compensatory. An increase in the proportion of rod-shaped nuclei (>20%) suggests that the bone marrow has sufficient granulocyte production capacity. Bone marrow images vary with the primary disease. Agranulocytosis The neutrophils at various stages of the bone marrow are extremely reduced or even completely disappeared. Granulocytes have significant toxic changes or impaired maturation. Lymphocytes, monocytes, plasma cells, and histiocytes can be increased, and young red blood cells and megakaryocytes are generally normal. When the condition is improved, the progenitor cells and the mature granulocytes in the peripheral blood appear one after another, and some may be leukemia-like blood.
After the clear presence of neutropenia, further etiological diagnosis should be performed:
1. History: Know whether there is any history of drug, chemical or radiation exposure that may cause the disease; whether there are basic diseases that cause neutropenia, such as chronic inflammation, autoimmune diseases; age of onset and family history; whether there is repeated infection History and so on.
2, bone marrow examination: to understand the proliferation and maturation of granulocytes, but also to understand whether there are basic diseases of the blood system and tumor cell metastasis.
3, the function of the bone marrow granulocyte storage pool: using pyrogens such as cholesteryl ketone, lipopolysaccharide and prednisone (or hydrocortisone), through the role of the intermediate product - "neutrophil releasing factor" Release of bone marrow granulocytes to understand the release function of granulocytes. If the white blood cell count after oral administration of prednisone 40mg for 5 hours is more than 2×109/L before administration or after intravenous injection for 3 to 4 hours with hydrocortisone 200mg, the white blood cell count is increased by 4×1095×109/ before administration. Those above L are normal.
4, edge cell granulocyte assay: Adrenalin test, subcutaneous injection of 0.2mg epinephrine 20 minutes after the white blood cell count, such as 2 × 109 / L increase or more than 1 times higher than the original level, such as no splenomegaly, suggesting Increased granulocyte count in the marginal pool, considered pseudo-neutropenia.
5, granulocyte dynamics and lifespan determination: can be measured with DF32P labeled granulocytes, is the most reliable indicator of neutrophil conversion.
Diagnosis
Diagnosis and diagnosis of neutropenia
diagnosis
According to the medical history, clinical performance and laboratory data is not difficult to make judgments.
Differential diagnosis
The disease should be distinguished from leukopenia, the latter:
(1) clinically asymptomatic, or dizziness, fatigue, low fever, loss of appetite, insomnia, dreams, chills, palpitation, etc.
(2) susceptible to viral and bacterial infections such as colds.
(3) White blood cell count (2.0 ~ 4.0) X109 / liter, the classification count can be normal, red blood cells and platelet counts are normal.
(4) Bone marrow: visible hyperplasia or mild maturation of the granulocyte system.
