Aplastic anemia, referred to as aplastic anemia, is a group of syndromes characterized by pancytopenia, which leads to the reduction of the total volume of red bone marrow and the replacement of fat bone marrow and hematopoietic failure. According to the survey of 2/kloc-0 provinces (cities) and autonomous regions in China, the annual incidence rate is 0.74/65438+ 10,000 population, which is obviously lower than the incidence rate of leukemia. The incidence of chronic aplastic anemia is 0.60/65438+ ten thousand population, and the incidence of acute aplastic anemia is 0. 14/65438+ ten thousand population. It can occur in all age groups, but it is more common in young people; The incidence of male is slightly higher than that of female.
etiology
The incidence of aplastic anemia may be related to the following factors:
(1) Drugs are the most common pathogenic factors. There are two types of drug-induced aplastic anemia: ① dose-related, which is the toxic effect of drugs. Reaching a certain dose will cause bone marrow suppression, which is generally reversible, such as various anti-tumor drugs. Cell cycle-specific drugs, such as cytarabine and methotrexate, mainly act on mature pluripotent stem cells that are easy to divide, so when pancytopenia occurs, a certain amount of pluripotent stem cells remain in bone marrow, and aplastic anemia can be recovered after stopping taking drugs; Busulfan and nitrosourea not only act on stem cells that enter the proliferation cycle, but also on stem cells that do not enter the proliferation cycle, so it is often difficult to recover from long-term bone marrow suppression. In addition, phenytoin sodium, phenothiazine, thiouracil and chloramphenicol can also cause dose-related bone marrow suppression. ② It has little to do with dosage. Only a few patients have hematopoietic dysfunction, and allergic reactions to various drugs often lead to persistent aplastic anemia. There are many kinds of drugs, such as chloramphenicol, organic arsenic, adipic acid, trimetazidine, butazone, gold preparation, aminopyrine, piroxicam (Yantongxikang), sulfanilamide, thiamphenicol, carbimidazole (hyperthyroidism), methimazole (tabazole), chlorpromazine and so on. The most common drug-induced aplastic anemia is caused by chloramphenicol. According to the domestic investigation, the risk of aplastic anemia among those who take chloramphenicol within half a year is 33 times that of the control group, and there is a dose-response relationship. Chloramphenicol can cause the above two types of drug-induced aplastic anemia. The chemical structure of chloramphenicol contains a nitrobenzene ring, and its bone marrow toxicity is related to nitroschloramphenicol. It can inhibit the mitochondrial DNA polymerase of bone marrow cells, resulting in the reduction of DNA and protein synthesis, and also inhibit the synthesis of heme. Vacuoles and iron granular young cells can appear in the cytoplasm of young red blood cells. This inhibition is reversible, and once the drug is stopped, the hemogram will recover. Chloramphenicol can also cause allergic reactions that have little to do with dosage. Bone marrow suppression often occurs weeks or months after taking chloramphenicol, or suddenly appears during treatment. Its mechanism may be caused by directly inhibiting hematopoietic stem cells or directly damaging the chromosomes of stem cells through autoimmunity. This effect is often irreversible, even if the drug is stopped. All stem cells with genetic defects are more sensitive to chloramphenicol.
(2) The relationship between benzene and its derivatives and aplastic anemia has been confirmed by many experimental studies. After benzene enters the human body, it is easy to be fixed in fat-rich tissues. Chronic benzene poisoning, benzene is mainly fixed in bone marrow. The toxic effect of benzene on bone marrow is caused by its metabolites, which can act on hematopoietic progenitor cells, inhibit the synthesis of DNA and RNA and damage chromosomes. Since the reform and opening up, township enterprises have mushroomed. Due to the neglect of labor protection, the incidence of aplastic anemia caused by benzene poisoning has increased. Aplastic anemia caused by benzene poisoning can be divided into chronic or acute, and the latter is mostly.
(3) Ionizing radiation X-rays, γ-rays or neutrons can pass through or enter cells, directly damaging hematopoietic stem cells and bone marrow microenvironment. Long-term radiation exposure (such as radioactive source accident) can cause aplastic anemia.
(4) The relationship between viral hepatitis and aplastic anemia has been confirmed, and it is called viral hepatitis-related aplastic anemia, which is one of the most serious complications of viral hepatitis. The incidence was less than 1.0%, accounting for 3.2% of patients with aplastic anemia. The type of hepatitis causing aplastic anemia has not been determined so far, about 80% is caused by non-A and non-B hepatitis, which may be hepatitis C, and the rest is caused by hepatitis B. There are two types of aplastic anemia related to hepatitis in clinic: acute type and acute onset. The average interval between hepatitis and aplastic anemia is about 10 week, and hepatitis is in recovery, but aplastic anemia is serious, with short survival time and young onset age, and most of them are non-A and non-B hepatitis. Chronic type is a minority, most of which are mainly chronic hepatitis B, with mild illness, long interval between hepatitis and aplastic anemia and long survival period. Its pathogenesis is still unclear. Hepatitis virus can directly inhibit hematopoietic stem cells and cause chromosome aberration, which can be mediated by virus-mediated autoimmune abnormality. Virus infection can still destroy bone marrow microcirculation.
(5) Immune factor aplastic anemia can be secondary to thymoma, systemic lupus erythematosus and rheumatoid arthritis, and antibodies that inhibit hematopoietic stem cells can be found in patients' serum. Some unexplained aplastic anemia may also have immune factors.
(VI) Genetic factors Fanconi anemia is an autosomal recessive genetic disease with family characteristics. Anemia mostly occurs in 5 ~ 10 years old, and most cases are accompanied by congenital malformation, especially skeletal system, such as short or missing thumb, multiple fingers, shortened radius, short stature, microcephaly, eye fissure, strabismus, deafness, renal malformation and cardiovascular malformation, and skin pigmentation is also very common. In this disease, HBF is often increased, the incidence of chromosome abnormality is high, and the DNA repair mechanism is defective, so the incidence of malignant tumors, especially leukemia, is obviously increased. 10% of the children's parents have a history of consanguineous marriage.
(7) Paroxysmal nocturnal hemoglobinuria (PNH)PNH is closely related to aplastic anemia. 20% ~ 30% of PNH may be accompanied by aplastic anemia, and 15% of aplastic anemia may have dominant PNH, both of which are hematopoietic stem cell diseases. It was obviously changed from aplastic anemia to PNH, but the performance of aplastic anemia was not obvious. Or clearly changed from PNH to aplastic anemia, and PNH was not obvious; Or PNH with aplastic anemia, aplastic anemia with PNH red blood cells can be called aplastic anemia -PNH syndrome.
(VIII) Few cases were reported by other factors. Aplastic anemia occurs during pregnancy, relieves after delivery or induced abortion, and recurs during the second pregnancy, but most scholars think it may be a coincidence. In addition, aplastic anemia can be secondary to chronic renal failure, severe hypothyroidism or hypopituitarism of anterior pituitary.
pathogenesis
(1) A large number of experimental studies have confirmed that the lack or defect of hematopoietic stem cells is the main pathogenesis of aplastic anemia. At least half of aplastic anemia is caused by the lack of hematopoietic stem cells. In vitro culture of patients' bone marrow progenitor cells showed that the determination of CFU-GM, BFU-E, CFU-E and CFU-GEMM decreased significantly, and the colony/colony ratio formed by CFU-C increased. Successful allogeneic bone marrow transplantation and rapid recovery of hematopoietic function indicate that the pathogenesis of aplastic anemia is mainly the lack or defect of hematopoietic stem cells. If the animal stem cells are injured by busulfan first, chloramphenicol can cause further reduction of CFU-S and CFU-C and aplastic anemia, which indicates that the stem cells are probably defective first, and then aplastic anemia occurs under the action of various environmental factors.
(II) Defects in Hematopoietic Microenvironment The concept of hematopoietic microenvironment includes structural components supporting hematopoiesis and hematopoietic regulatory factors in hematopoietic tissue. Hematopoietic cells proliferate and differentiate in the reticular scaffold formed by stromal cells. Stromal cell groups include fibroblasts, reticular cells and macrophages. Stromal cells can form CFU-F in vitro. Hematopoietic stem cells can only proliferate when they are surrounded by stromal cells. The bone marrow of a few aplastic anemia patients can not form CFU-F in vitro, but CFU-GM is normal, which indicates that the pathogenesis of this kind of patients is microenvironment defect. The regulating factors of hematopoiesis include many humoral factors and the interaction between cells. Some patients with aplastic anemia have abnormal humoral and cellular regulatory mechanisms of hematopoietic stem cells, including the increase of inhibitory T cells and the decrease of helper T cells, the decrease of natural killer cell activity, the increase of negative hematopoietic regulatory factors such as interferon-γ, tumor necrosis factor and interleukin -2, and the decrease of cAMP content, which may be involved in the proliferation and differentiation of hematopoietic stem cells in aplastic anemia.
(3) Immunosuppression of hematopoietic stem cells is secondary to aplastic anemia caused by systemic lupus erythematosus and rheumatoid arthritis, and there are autoantibodies against hematopoietic stem cells in serum. T lymphocytes in some patients with primary aplastic anemia can inhibit the growth of normal hematopoietic progenitor cells, and the removal of T lymphocytes can restore the normal growth of granulocytes and erythroid colonies. Although bone marrow transplantation was unsuccessful in some patients, hematopoietic function was restored due to the application of a large number of immunosuppressants. All these indicate that there are inhibitory T lymphocytes in the pathogenesis of partial aplastic anemia.
pathological change
(1) The bone marrow lesions of aplastic anemia are mainly the decrease of hematopoietic tissue, the decrease of the total volume of red bone marrow and the replacement of adipose tissue. The ratio of hematopoietic tissue to adipose tissue in normal adults is about 1∶ 1, and aplastic anemia is more than 2∶3. Hematopoietic cells (granulocytes, erythrocytes and megakaryocytes) decreased, while "non-hematopoietic cells" (lymphocytes, plasma, tissue basophils and reticular cells) increased. There are plasma exudation, hemorrhage, lymphocyte proliferation, focal fibrosis and interstitial lesions in bone marrow. Acute aplastic myelopathy develops rapidly and widely; Chronic aplastic anemia is a progressive "centripetal atrophy", which first involves the ilium, then the spinous process and sternum. Chronic aplastic anemia still has compensatory hyperplasia focus, mainly erythropoiesis with maturity disorder. Erythroid cells not only decrease in number, but also have qualitative defects. Ultrastructural observation showed that mature red blood cells were heteromorphic and petal-shaped; There are medullary changes in the cytoplasm of young red blood cells, unbalanced nuclear development and enlarged nuclear membrane pores. Alkali-resistant hemoglobin and free protoporphyrin in red blood cells increased. The activity of erythrocyte enzymes such as pyruvate kinase decreased. All of the above indicate that red blood cells are qualitatively abnormal. Iron kinetic examination showed that plasma iron increased, iron particles in young cells and tissues increased, plasma iron clearance was delayed, and iron uptake by red blood cells decreased significantly, suggesting that the erythropoiesis rate decreased. Some patients still have ineffective erythropoiesis or in situ hemolysis of bone marrow.
(2) Pathological changes of organs other than bone marrow Autopsy shows that besides skin and mucous membrane bleeding, there are also visceral bleeding, which are more common in the heart, gastrointestinal tract and lungs. The incidence of cerebral hemorrhage was 52.6%. The main causes of bleeding are thrombocytopenia and abnormal vascular wall, the latter is manifested by the morphological and functional changes of nailfold microvessels. Platelet quality is also abnormal, with small platelets accounting for 50%, irregular shape, few protrusions, transparent plasma and few particles; Platelet adhesion, aggregation and factor 3 were also significantly lower than normal. Heparin-like appeared in blood, and the content of protein C antigen and antithrombin ⅲ activity increased. Patients with aplastic anemia are prone to various infections, mainly gram-negative bacilli, including Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. In addition to skin and mucosa, the route of bacterial invasion is also an important invasion site, which is due to the decrease of gastrointestinal barrier function or bleeding and mucosal ulcer. The decline of the body's defense function is closely related to the decrease of granulocytes and monocytes and the atrophy of lymphoid tissue. The latter is marked by acute aplastic anemia, which leads to different degrees of cellular and humoral immune abnormalities. Repeated blood transfusion shows hemosiderosis and even secondary hemochromatosis. The main causes of death are intracranial hemorrhage, heart failure, pulmonary edema and various serious infections.
There are two categories: congenital and acquired, of which acquired accounts for the vast majority. Congenital aplastic anemia is rare, and the main type is Fanconi anemia. Acquired aplastic anemia can be divided into primary and secondary. The former has unknown causes and accounts for about 50% of acquired aplastic anemia. According to clinical manifestations, hemogram and myelogram, it can also be divided into acute and chronic types. In foreign countries, severe aplastic anemia is classified according to its severity. The latter classification standard requires two of the following three items: ① the absolute value of neutrophils < 500/mm3, ② the number of platelets < 20000/mm3, ③ reticulocytes (corrected hematocrit) <1%; The proliferation degree of bone marrow cells is lower than normal 25%, such as < 50% and hematopoietic cells < 30%. The absolute value of neutrophils < 200/mm3 is called extremely severe aplastic anemia. Acute aplastic anemia was called severe aplastic anemia type I in the 4th National Academic Conference on Aplastic Anemia 1987, and severe aplastic anemia type II in the late stage of chronic aplastic anemia.
(1) Acute aplastic anemia is characterized by acute onset and rapid progress, with bleeding and fever as the first and main manifestations. Anemia is often not obvious at the initial stage of the disease, but it gradually progresses with the development of the course. Almost all of them have bleeding tendency, and more than 60% have visceral bleeding, mainly manifested as gastrointestinal bleeding, hematuria, fundus bleeding (often accompanied by visual impairment) and intracranial bleeding. Skin mucosal bleeding is extensive and serious, which is difficult to control. Almost all of them have fever during the course of the disease, which is caused by infection. Necrotic ulcers often occur around the oropharynx and anus, leading to sepsis. Pneumonia is also common. Infection and bleeding are mutually causal, which makes the disease more and more serious. If only general treatment is used, most of them will die within one year.
(2) The onset of chronic aplastic anemia is slow, with blood separation as the first and main manifestation; Bleeding is mostly confined to the skin and mucosa, not serious; It can be complicated with infection, but it is often mainly respiratory tract, which is easy to control. If treated properly and persistently, many patients can get long-term remission or even recovery, but some patients persist for many years, or even the course of disease lasts for decades, and a few patients develop acute aplastic anemia in the later stage, which is called acute aplastic anemia.
(a) the hemogram is pancytopenia, anemia belongs to normal cell type, and it can also be mild megalobocyte. The size of red blood cells changes slightly, but there is no obvious deformity and deep staining, and generally no young red blood cells appear. Reticulocytes decreased significantly.
(2) Acute myelogram showed that the proliferation of multiple parts was reduced or severely reduced, and the number of three-line hematopoietic cells was significantly reduced, especially megakaryocytes and red blood cells; Non-hematopoietic cells increase, especially lymphocytes increase. The bone marrow images obtained by puncture in different parts of chronic type are very inconsistent, ranging from dysplasia to hyperplasia, but at least some of them must be dysplasia; If the proliferation is good, the proportion of red blood cells (carbon nuclei) tends to increase in the later stage, and their nuclei are irregularly lobulated, showing enucleation obstacles, but megakaryocytes are obviously reduced. Macroscopic observation of bone marrow smear showed that oil droplets increased, and microscopic examination of bone marrow particles showed that non-hematopoietic cells and fat cells increased, generally above 60%.
(3) Bone marrow biopsy and radionuclide bone marrow scanning Because bone marrow smear is easily influenced by peripheral blood dilution, sometimes the first or second smear examination is difficult to correctly reflect the hematopoietic situation. Bone marrow biopsy is superior to smear in estimating hyperplasia and can improve the diagnostic accuracy. Whole-body bone marrow gamma-ray photography with 99m technetium sulfide or11indium chloride can reflect the distribution of whole-body functional bone marrow, and the radioactive uptake in normal bone marrow is low or even disappears in aplastic anemia, so it can indirectly reflect the degree and location of hematopoietic tissue reduction.
(4) Other tests of hematopoietic progenitor cell culture not only help to diagnose, but also help to detect whether there are inhibitory lymphocytes or whether there are inhibitory factors in serum. The activity of alkaline phosphatase in mature neutrophils increased and the activity of serum lysozyme decreased. The amount of alkaline-resistant hemoglobin increased. Chromosome examination shows that aplastic anemia is normal except Fanconi anemia, and myelodysplastic syndrome must be ruled out if there is karyotype abnormality.
diagnose
1987 the diagnostic criteria of aplastic anemia revised by the fourth national academic conference on aplastic anemia are as follows: ① the whole blood cell is reduced and the absolute value of reticulocyte is reduced. ② There is generally no splenomegaly. (3) Bone marrow examination shows that at least part of hyperplasia is reduced or severely reduced (if hyperplasia is active, megakaryocytes should be significantly reduced, and non-hematopoietic cells in bone marrow granules are increased). Do a bone marrow biopsy if possible). ④ Other diseases causing pancytopenia can be excluded, such as paroxysmal nocturnal hemoglobinuria, refractory anemia in myelodysplastic syndrome, acute hematopoietic dysfunction, myelofibrosis, acute leukemia and malignant histiocytosis. ⑤ General anti-anemia drugs are ineffective.
differential diagnosis
Aplastic anemia must be differentiated from the following diseases:
(1) Paroxysmal nocturnal hemoglobinuria, especially hemoglobinuria, is easily misdiagnosed as aplastic anemia. Hemorrhage and infection of this disease are rare, reticulocytes increase, bone marrow erythrocytes proliferate, urine hemosiderin, sugar water test and Ham test are positive, and alkaline phosphatase activity of mature neutrophils is lower than normal, which is helpful for differentiation.
(2) Myelodysplastic Syndrome (MDS)Fab collaboration group divides MDS into five types, among which refractory anemia is easily confused with atypical aplastic anemia. Although MDS suffers from pancytopenia, all three kinds of bone marrow cells are proliferating and megakaryocytes are increasing. Pathological hematopoiesis can be seen in all three lines, and abnormal karyotypes account for 20% ~ 60%. Abnormal distribution of hematopoietic precursor cells can be seen in bone marrow tissue sections.
(3) Hypoproliferative acute leukemia is more common in the elderly, and the course of disease is slow or rapid. Generally, the liver, spleen and lymph nodes are not swollen, and the whole blood cells around them are reduced, and a small number of primitive cells are not seen or occasionally seen. Focal hyperplasia of bone marrow decreased, but the percentage of primitive cells reached the diagnostic standard of leukemia.
(4) Aplastic anemia, hemolytic anemia, aplastic crisis and acute hematopoiesis stagnation can be characterized by pancytopenia, acute onset and clear inducement, which can be relieved by itself after removal, and macrophages can appear in the bone marrow of the latter. Chronic acquired pure red aplastic anemia should be differentiated from chronic aplastic anemia if there is slight decrease in white blood cells and platelets.
Including etiological treatment, supportive treatment and various measures to promote the recovery of bone marrow hematopoietic function. The chronic type is mainly androgen, supplemented by other comprehensive treatments. After long-term unremitting efforts, satisfactory curative effect can be achieved. In many cases, hemoglobin returns to normal, but platelets are at a low level for a long time, and there is no bleeding in clinic, so light work can be resumed. The prognosis of acute type is poor, and the above treatment is often ineffective. Once diagnosed, bone marrow transplantation or anti-lymphocyte globulin should be used as soon as possible.
(a) Supportive therapy should remove all substances that may cause bone marrow damage and ban all drugs that inhibit bone marrow. Actively do a good job in personal hygiene and nursing. Patients with agranulocytosis should be protected from infection. Blood transfusion should master the indications and prepare for bone marrow transplantation. Blood transfusion before transplantation will directly affect its success rate, especially the blood of family members. Generally, it is better to input concentrated red blood cells. Patients with severe bleeding should be infused with concentrated platelets, and the infusion of platelets with unit area yield or HLA can improve the curative effect. Deferamine and iron excretion should be used to treat repeated blood transfusion.
(2) Androgen is the first choice for the treatment of chronic aplastic anemia. There are four kinds of commonly used androgens: ① 17α- alkyl androgens, such as stanazolone, methoxyandrosterone, medroxyprogesterone, fluoroprogesterone, denafil and so on. ② Testosterone esters: such as testosterone propionate, testosterone heptanoate, testosterone cyclopropanate, testosterone undecanoate (An Xiong) and mixed testosterone esters (testosterone propionate, testosterone valerate and testosterone undecanoate) are also called "Bao Li"; ③ non-17α- alkyl androgens, such as norong phenylpropionate and norong sebacate; ④ Intermediate active metabolites: such as phenylcholone and danazol. Testosterone enters the body and forms stronger 5α- dihydrotestosterone through the action of 5α- degrading enzymes in renal tissues and macrophages, which promotes the production of erythropoietin in kidneys, and macrophages produce granulocyte macrophage colony stimulating factor. There are 5β- degrading enzymes in the medulla of liver and kidney, which degrade testosterone into 5β- dihydrotestosterone and benzoranolol, which directly stimulate hematopoietic stem cells and promote their proliferation and differentiation.
Therefore, androgen can only play its role on the basis of a certain amount of hematopoietic stem cells remaining, and acute and severe aplastic anemia is often ineffective. Chronic aplastic anemia has a certain curative effect, but the dose should be large and the duration should be long. Testosterone propionate 50 ~ 100 mg/d intramuscular injection, Kanglilong 6 ~ 12 mg/d oral injection, An Xiong 120 ~ 160 mg/d oral injection and Qiao Libao 250mG intramuscular injection twice a week for at least 6 months.
Domestic reports show that the effective rate is 34.9% ~ 8 1%, and the remission rate is 19% ~ 54%. The red system has a good curative effect. Generally, reticulocytes begin to rise one month after treatment, then hemoglobin rises, and white blood cells begin to rise two months later, but many platelets are difficult to recover. Some patients are dependent on androgen, and the recurrence rate is 25% ~ 50% after drug withdrawal. Taking medicine after recurrence is still effective. Testosterone propionate has great male side effects, such as acne, increased hair, coarse voice, female amenorrhea, accelerated bone maturation in children, early epiphyseal fusion, and some water and sodium retention. Local masses often appear after repeated intramuscular injection of C- testis, so it is advisable to inject them in multiple places in turn. The positive side effect of 17α alkyl androgen is lighter than that of testosterone, but its hepatotoxicity is obviously greater than that of testosterone. After taking the medicine, alanine aminotransferase increased in most patients, and in severe cases, intrahepatic cholestasis jaundice occurred, and a few patients even developed hepatic angiosarcoma and liver cancer, but they could dissipate by themselves after stopping taking the medicine.
(3) Bone marrow transplantation is the best method to treat aplastic anemia caused by stem cell deficiency, which can achieve the goal of radical cure. Once diagnosed as severe or extremely severe aplastic anemia, the age is less than 20 years old, and there are HLA-compatible donors, allogeneic bone marrow transplantation should be the first choice in qualified hospitals, and the long-term disease-free survival rate after transplantation can reach 60% ~ 80%, but transplantation should be carried out as soon as possible, because the newly diagnosed patients often transfuse red blood cells and platelets, which is easy to make the recipients allergic to the secondary histocompatibility antigen of blood donors, leading to an increase in the incidence of transplant rejection. For patients who have not received blood transfusion or rarely received blood transfusion after diagnosis, cyclophosphamide pretreatment can be used, and intravenous drip of 50mg/kG every day for 4 days.
Allogeneic bone marrow transplantation has been used to treat severe aplastic anemia in China, and it has been successfully reported. All successful transplants are expected to be cured. Fetal hepatocyte suspension infusion has been widely used to treat aplastic anemia in China. Some people think that it can promote or assist the recovery of hematopoietic function, and its exact curative effect and mechanism need further study.
(4) Immunosuppressants are suitable for severe aplastic anemia over 40 years old or without suitable donors. The most commonly used are antithymocyte globulin (ATG) and antilymphocyte globulin (ALG). Its mechanism may be mainly through relieving the inhibitory effect of inhibitory T lymphocytes on bone marrow hematopoiesis, and some people think that it also has the effect of immune stimulation, promoting the proliferation of stem cells by producing more hematopoietic regulatory factors, or directly stimulating hematopoietic stem cells themselves. The dose varies from source to source, with horse ALG10 ~15 mg/(kg d) and rabbit ATG 2.5 ~ 4.0 mg/(kg d) for ***5 days. After dilution with normal saline, skin test should be done first, and then intravenous drip should be done slowly. If there is no response, the total dose is 8. Hydrocortisone was given intravenously at the same time, with the dosage of 1/2 before ALG/ATG infusion and 1/2 after infusion. Patients should be placed in protective isolation. To prevent serum sickness, prednisone1mg/(kg d) was taken orally on the 5th day, halved on the 5th day, and stopped on the 30th day. It is not advisable to use high-dose adrenocortical hormone to avoid aseptic necrosis of femoral head. The curative effect needs 1 month, and some begin to appear after 3 months. The effective rate of severe aplastic anemia can reach 40% ~ 70%, and 50% of effective patients can survive for a long time. Adverse reactions include allergic reactions such as fever, chills and rash, as well as infection and bleeding caused by neutropenia and thrombocytopenia. Intravenous infusion can cause phlebitis, and serum sickness occurs 7 ~ 10 days after treatment. Cyclosporin A(CSA) is also a commonly used drug to treat severe aplastic anemia. Because of its convenience and safety, it is more commonly used than ALG/ATG. Its mechanism may selectively act on T lymphocyte subsets, inhibit T cell activation and proliferation, and inhibit the production of IL-2 and IFN-γ. The dose is10 ~12 mg/(kg d), and most cases need long-term maintenance treatment, and the maintenance dose is 2 ~ 5 mg/(kg d). The effective rate of severe aplastic anemia can also reach 50% ~ 60%, and it takes more than 1 ~ 2 months for the curative effect to appear. Adverse reactions include hepatorenal toxicity, hirsutism, gingival swelling and muscle tremor. To use drugs safely, it is advisable to monitor the blood drug concentration, and the safe and effective blood drug concentration ranges from 300 ng/ml to 500 ng/ml. The effect of modern immunosuppressants on severe aplastic anemia is similar to that of bone marrow transplantation, but the former can't be cured, and there are long-term complications, such as clonal diseases, including MDS, PNH and leukemia.
(5) Chinese medicine should focus on tonifying kidney, benefiting qi and promoting blood circulation. Commonly used Chinese medicines include cornu Cervi Degelatinatum, Rhizoma Curculiginis, Herba Epimedii, Radix Astragali, Radix Rehmanniae, Polygoni Multiflori Radix, Radix Angelicae Sinensis, Herba Cistanches, Radix Morindae Officinalis, Fructus Psoraleae, Semen Cuscutae, Fructus Lycii and Colla Corii Asini. Androgen is commonly used to treat chronic aplastic anemia in China, and it is combined with traditional Chinese medicine to tonify the kidney.
(6) The combination therapy of hematopoietic cytokines and aplastic anemia is anemia caused by hematopoietic stem cell diseases, and the endogenous plasma EPO levels are all above 500 U/L. Recombinant human EPO needs a large dose to be effective in the treatment of aplastic anemia, and the general dose will not achieve any effect. Recombinant human colony stimulating factor, including G-CSF, GM-CSF or IL-3, may be effective in improving neutrophils and reducing infection, but it is ineffective in improving anemia and thrombocytopenia unless used in large doses. However, hematopoietic cytokines are expensive and only used as auxiliary drugs for the treatment of severe aplastic anemia. For example, ALG/ATG is often complicated with infection due to severe agranulocytosis, leading to early death. Combined application of rHG-CSF at this time can improve early agranulocytosis and reduce mortality. Combined therapy can improve the therapeutic effect of severe aplastic anemia, including ALG/ATG combined with CSA, CSA combined with androgen and so on. In the European blood and bone marrow transplantation group, the combined treatment of ALG, CSA, methylprednisolone and rhG-CSF has improved the effective rate of severe aplastic anemia to 82%.
1. Drugs harmful to hematopoietic system should be strictly controlled to prevent abuse. Observe the blood picture regularly during use.
2. Workers exposed to toxic substances or radioactive substances that damage the hematopoietic system should strengthen various protective measures and conduct blood tests regularly.
3 vigorously carry out the prevention and treatment of viral hepatitis and other viral infections.
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