Aplastic anemia

Introduction to aplastic anemia Aplastic anemia (AA) is a disease in which bone marrow hematopoietic stem cells and bone marrow microenvironment are severely damaged by physical, chemical, biological or unidentified factors, resulting in reduced or depleted bone marrow hematopoietic function. a group of syndromes. According to the survey of 21 provinces (municipalities) in China, the annual incidence rate is 0.74/100,000 people, which is significantly lower than the incidence of leukemia; the incidence of chronic aplastic anemia is 0.60/100,000, and the rate of acute aplastic anemia is 0.14/100,000. All age groups can develop disease, but it is more common in young adults; the incidence rate of males is slightly higher than that of females. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific population Mode of infection: non-infectious Complications: sepsis, hemochromatosis, headache, nosebleed, menorrhagia

Causes of aplastic anemia

Drug factors (40%):

It is related to the dose, which is a toxic effect of the drug. When it reaches a certain dose, it will cause bone marrow suppression, which is generally reversible. For example, various anti-tumor drugs, cell cycle-specific drugs such as cytarabine and methotrexate are mainly used for easy action. The more mature pluripotent stem cells divide, so when the whole blood cell is reduced, the bone marrow still retains a certain amount of pluripotent stem cells, and the aplastic anemia can be restored after stopping the drug.

Environmental factors (20%):

In industrial production and daily life, people have extensive exposure to benzene (C6H6) and its derivatives. Benzene is volatile and easily inhaled. It is more common in people exposed to benzene. Among them, anemia 48%, huge erythrocytosis accounted for 47%, thrombocytopenia accounted for 33%, leukopenia accounted for 15%, in the working environment of poor footwear workers, the whole blood cell reduction accounted for 2.7%, severe benzene poisoning can cause aplastic anemia.

Viral hepatitis (10%):

In 1955, Lorenz reported the first case of viral hepatitis-related aplastic anemia (HAAA). The incidence of HAAA in patients with viral hepatitis was generally considered to be 0.05% to 0.9%, and the composition ratio in patients with aplastic anemia was 3.2% to 23.9%. 80% of HAAA is caused by hepatitis C virus, a few are caused by hepatitis B virus (HBV), and Hagler divides HAAA into two types. The occurrence of HAAA is related to the direct inhibition of hematopoietic stem cells by hepatitis virus. Virus-mediated autoimmune abnormalities or anti-stem cell antibodies, viral damage to bone marrow microenvironment, and liver detoxification function also play a role in the pathogenesis of HAAA.

Occupational factors (10%):

Radiation-induced bone marrow failure is non-random, dose-dependent, and associated with tissue-specific sensitivity. Hematopoietic tissue is more sensitive to radiation, and lethal or sublethal doses (4.5 to 10 Gy) of systemic exposure can cause fatal acute re-exposure. Barriers, and rarely cause chronic aplastic anemia, only a few of the Japanese atomic bomb survivors developed delayed aplastic anemia, and large doses of local exposure can also cause serious damage to the bone marrow microenvironment, which greatly exceeds the progenitor cells. The lethal dose, long-term exposure to small doses of external exposure, such as radiologists or patients with radon or sputum in the body can occur chronic aplastic anemia.

Pathogenesis

The pathogenesis of aplastic anemia is extremely complex and is currently considered to be related to the following aspects.

1. Hematopoietic stem cell intrinsic proliferation defect

It is the main pathogenesis of aplastic anemia, based on the following:

(1) Significant reduction of hematopoietic stem cells in the bone marrow of aplastic anemia: the ability of stem cell colony formation was significantly reduced, abnormal stem cells could inhibit the function of normal stem cells, Scope and other anti-CD34 and anti-CD33 monoclonal antibodies were used in 15 patients with different severity AA and 11 normal Human bone marrow mononuclear cells (BMMNC) were stained by two-color immunofluorescence, and the number of hematopoietic stem/progenitor cells in bone marrow of AA patients and normal persons was detected by fluorescence activated cell sorting (FACS). It was found that CD34 cells in AA patients were reduced compared with normal people. % (p<0.01), CD33 cells decreased by 47%, CD34/CD33-, CD34/CD33 and CD34-/CD33 cells decreased by 67%, 80% and 44%, respectively. FACS method was used to separate bone marrow from normal and AA patients. CD34+ cells were selected and inoculated into irradiated normal stromal cells for LTBMC, respectively. The results showed that the yield of CD34 granulosa-macrophage colonies (CFU-GM) in AA patients was (3.1±1.9) colonies/105 CD34 cells. [Normal control was (74±22) colony/105CD34 cells]; explosion-type erythroid colonies (BFU-E) were (7±8) colonies/105 CD34 cells [normal control 211±65 colonies/105CD34 cells], p-all <0.01.

(2) The DNA repair ability of SAA patients was significantly reduced: it could not be corrected after treatment with anti-lymphocyte globulin (ALG).

(3) Some cases effective with immunosuppressive therapy: evolved into clonal diseases during long-term follow-up, such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, acute non-lymphocytic leukemia, Tichelli et al. Eight years after ATG/ALG treatment, the incidence of these advanced clonal diseases was as high as 57%.

(4) These patients have a certain number of complement-sensitive cells in vivo: in vitro experiments have also demonstrated that aplasticized hematopoietic stem/progenitor cells are more sensitive to complement.

(5) Application of three X-linked genes (phosphoglucose kinase gene, hypoxanthine ribose phosphotransferase gene, DXS255 detected by M27 probe): detection of aplastic anemia found that 11.1% to 77% of cases are monoclonal hematopoiesis; Josten et al. used M27 probe to measure 36 cases of female AA patients. Only one case of whole blood cells showed monoclonal type. Kamp et al combined PGK, H RT and M27H three probes detected 19 cases of AA, and 18 cases could be performed. In clonality analysis, 13 (72.2%) patients were monoclonal, and 4 of them were further studied to isolate and purify their myeloid cells and lymphocytes, both of which were of monoclonal origin, indicating that early stem cells were involved, Tsuae In addition, PGK, MBPRT and M27H probes were used to detect 20 children with AA, and 18 cases could be cloned. Two of them (11.1%) granulocytes and fibroblasts were of monoclonal origin, AA clone Hematopoiesis does not imply clonal proliferation, which may reflect the depletion of hematopoietic stem cell pools and severe bone marrow failure.

(6) Bone marrow transplantation (BMT) between the unpretreated twins was successful.

2. Abnormal immune response damage hematopoietic stem cells

The autoimmune function of patients with aplastic anemia after immunosuppressive therapy may be improved. This is the most direct evidence for abnormal immune response to damage hematopoietic stem cells. Allogeneic BMT treatment of SAA requires pretreatment with immunosuppressive agents to mobilize. T lymphocytes (mainly CD8 T cell subsets) in patients with aplastic anemia are closely related to hematopoietic failure, and are often activated in acute aplastic anemia T lymphocytes, which can inhibit the formation of colonies of autologous and allogeneic progenitor cells. Zoumbos et al. The patient's T4/T8 ratio was inverted, and the activity of T8 cells was increased. The cells inhibited hematopoiesis and release of inhibitors in vitro. Gascon determined 15 cases of aplastic anemia Tac cells, 11 of which increased, and the expression of Tac antigen increased lymphocytes. The group was in a pre-activated state. Mentzel et al analyzed 9 patients with aplastic anemia and found that the -T cell subset expressed TCSl phenotype significantly increased. Blustone et al believed that -T cells, especially TCS1-T cells, may inhibit hematopoiesis. Role, aberrant patients with serum interferon (IFN-), tumor necrosis factor (TNF-) and interleukin-2 (IL-2) and other hematopoietic negative regulators Increasingly, the expression of IFN- gene is enhanced in the bone marrow cells of patients, and antibodies inhibiting the growth of autologous hematopoietic progenitor cells can be detected in individual aplastic anemia patients.

The transcription level of stem cell inhibitory factor (SCI) RNA is significantly increased. Plantanias et al found that IFN- is significantly reduced in patients with aplastic anemia who are effective in immunotherapy, and can neutralize endogenous IFN- or IFN- in vitro. The patient's bone marrow CFU-GM yield was multiplied, and IFN- was released after dengue virus infection, causing lymphotoxic reaction, causing damage to stem cells and aplastic anemia. Shinjinakai et al used PCR to detect cytostatic factors in 23 aplastic anemia cells. Gene expression, found that IFN- mRNA is clearly expressed in aplastic anemia patients, and has nothing to do with blood transfusion, transforming growth factor (TGF-) is a core factor of physiological hematopoietic negative regulation, reversible inhibition of hematopoietic precursor cells Role, which is characterized by selective inhibition of proliferation and differentiation of hematopoietic precursor cells that depend on hematopoietic factors such as IL-3, GM-CSF, IL-6 and IL-9. In recent years, many interleukins have been recognized to be involved in the hematopoietic process. Some have the role of CSF cofactors, and some have colony stimulating factor activity. Nakao et al detected 17 cases of aplastic anemia, and found 10 cases of IL-1 significantly reduced, 9 of which were SAA, and some patients with aplastic anemia had significant IL-2. Increase, department Sub-patients with significantly reduced IL-3 (SCF), recently reported the use of IL-1 and IL-3 in foreign countries and anti-IL-2 receptor monoclonal antibody to treat aplastic anemia, natural killer cells (NK) can inhibit more mature hematopoiesis Progenitor cell colony growth, human NK cells also have the ability to produce IL-2/IFN-, IL-1 and CSF and other lymphokines. Yashhiro et al detected 12 cases of aplastic anemia in peripheral blood NK cells, the above results indicate The pathogenesis of the disorder has a certain relationship with the immune mechanism, but the fact that the immunosuppressant can not completely cure the aplastic anemia indicates that the aplastic anemia is not a classic autoimmune disease. The abnormal immune response is only one of the factors of aplastic anemia.

3. Hematopoietic microenvironment supports functional defects

The hematopoietic microenvironment includes stromal cells and their secreted cytokines, which support the proliferation of hematopoietic cells and promote the growth and development of various cells. There is no sufficient evidence to suggest that bone marrow stromal defects in aplastic anemia patients, but aplastic anemia bone marrow fibroblast colonies are found. The formation unit (CFU-F) and stromal cells produced a decrease in colony stimulating activity (CSA). The Institute of Hematology, Chinese Academy of Medical Sciences observed atrophy, bone marrow stromal cell atrophy, fatification, CFU-F reduction, and acute aplastic anemia. Barrier injury is more serious. Most in vitro tests show that there is no abnormality in hematopoietic growth factor (HGF) production from bone marrow stromal cells in Aplastic Anemia, erythropoietin (EPO) in blood and urine of AA patients, and colony-stimulating factor (GM) in granulocyte-macrophage cell line. -CSF), granulocyte colony-stimulating factor (G-CSF) and macrophage cell colony-stimulating factor (M-CSF) levels increased; but AA patients have decreased IL-1 production, studies have confirmed hematopoietic stem/progenitor cells in AA patients In particular, BFU-E is significantly less reactive to EPO, EPO+IL-3 and EPO+SCF than normal controls, and even lacks reactivity. Wodnar-Filipowicz et al. detected serum soluble stem cell factor (S) in 32 SAA patients. At the level of CF), serum SCF levels in SAA patients were found to be lower than those in normal controls, but the difference was not significant. The serum SCF level was higher. The prognosis was better. If AA was caused by HGF deficiency, then HGF could be cured theoretically. AA, in fact, a large number of clinical treatment results show that HGF (including SCF) can only transiently increase the peripheral blood cell level of patients, and can not change the natural course of the disease, some patients are not effective for HGF treatment, although the hematopoietic microenvironment is not caused The cause of AA, but can aggravate the condition.

4. Genetic predisposition

Aplastic anemia often has HLA-DR2 type antigen-linked tendency, HLA-DPW3 type antigen in children with aplastic anemia is significantly increased, and the proliferative ability of hematopoietic progenitor cells is often reduced in patients' families, and familial aplastic anemia is seen. Sensibility is controlled by genetics, and susceptibility to other toxicants or viruses may also be related to genetic factors. The above phenomenon indicates that a small number of aplastic anemias have a genetic predisposition to fragile bone marrow hematopoietic function.

Aplastic anemia prevention

1. Drugs with damage to the hematopoietic system should be strictly instructed to prevent abuse, and blood should be observed regularly during use.

2. Workers exposed to toxic or radioactive substances in the hematopoietic system should be strengthened with various protective measures and blood tests should be carried out regularly.

Third, vigorously carry out prevention and treatment of viral hepatitis and other viral infections.

Although there are some cases in which the cause of the aplastic anemia is unknown, many cases are caused by chemical substances, medication or exposure to radioactive materials. Therefore, preventive measures should be taken. In particular, chlorine (oxytetracycline) should be proposed, and its abuse is quite serious. Chloramphenicol in some areas investigated in China is the main cause of aplastic anemia. Medical staff and patients should be aware of their seriousness. Use with or without chloramphenicol, and replace with other antibiotics when possible. Followed by benzene, township and village enterprises have more leather shoes, and the concentration of benzene in the air exceeds the amount stipulated by the state. When farmers spray pesticides, they must do labor protection to prevent harmful substances from polluting the surrounding environment to reduce aplastic anemia. Onset.

Aplastic anemia complications Complications, sepsis, hemochromatism, headache, nosebleed, menorrhagia

1. Bleeding : Hemorrhage caused by thrombocytopenia is often the main cause of patient visits, as well as complications, manifested as skin spots and ecchymosis, bleeding gums and nosebleeds. Menorrhagia and irregular vaginal bleeding can occur in young women. Severe visceral hemorrhage such as urinary tract, digestive tract, respiratory tract and central nervous system bleeding are rare, and in the late stage of the disease, the patient has severe nosebleeds, unclear vision, headache, nausea and vomiting, often a threatening manifestation of fatal intracranial hemorrhage, clinical Pay full attention.

2. Anemia: Anemia caused by red blood cell reduction is often gradual, patients with fatigue, palpitations, shortness of breath, dizziness, tinnitus and other symptoms after the activity, the patient's hemoglobin concentration decreased slowly, mostly reduced by about 10g / L per week, a small number of patients It has strong adaptability to anemia, mild symptoms and severe anemia combined with anemia.

3. Infection : infection caused by leukopenia is the most common complication of aplastic anemia. Lighter patients may have persistent fever, weight loss, loss of appetite, and severe systemic infection. In this case, inflammation may not be limited due to low blood cells. Lack of local inflammation, severe cases can occur sepsis, infection and more bleeding, leading to death.

Complications of aplastic anemia, in addition to infection, visceral hemorrhage, chronic cases, due to long-term anemia, can occur in advanced stages of anemia, such as excessive blood transfusion, up to 10,000 ml, hemorrhagic disease can occur.

Symptoms of aplastic anemia common symptoms skin sclerotherapy hemoglobinuria fatigue high fever dizziness bone marrow hematopoietic cell aplasia anemia hematopoietic dysfunction palpitations erythrocytosis

The clinical manifestations of aplastic anemia are anemia, bleeding and infection. Chinese scholars divide aplastic anemia into acute and chronic.

1, acute type

The onset is acute, the condition is heavy, and progress is rapid.

(1) Anemia: Most of them are progressively aggravated, and the symptoms such as paleness, fatigue, dizziness, palpitations and shortness of breath are obvious.

(2) Infection: Most patients have fever, body temperature is above 38 degrees, and individual patients are in an uncontrollable high temperature from onset to death. Respiratory tract infections are most common, and others have digestive tracts, genitourinary tracts, and skin infections. Infected strains are mainly Gram-negative bacilli, Staphylococcus aureus and fungi, often with sepsis.

(3) Bleeding: There are different degrees of skin and mucous membranes and internal organs bleeding. Skin bleeding manifests as bleeding spots or large ecchymoses, small blood vesicles in the oral mucosa; may have nasal discharge, blood stasis, and bleeding of the eye-bound membrane. All organs can have bleeding, but only bleeding from organs that open outside can be clinically known. Clinically, hematemesis, blood in the stool, and blood in the urine can be seen. Women have vaginal bleeding, followed by fundus hemorrhage and intracranial hemorrhage, which often endangers the patient's life. The number of bleeding sites is reduced, and the latent surface is turned into internal organs. Often, there will be more serious bleeding.

2, chronic type

The onset and progress are slower and the condition is lighter than the acute type.

(1) Anemia: Chronic process, common pale, fatigue, dizziness, palpitations, shortness of breath after activities, etc. The symptoms of transfusion improved, but the duration of maintenance was not long.

(2) Infection: High fever is rarer than acute type, and infection is relatively easy to control.

(3) bleeding: bleeding tendency is light, mainly skin bleeding, visceral bleeding is rare. Patients with advanced cerebral hemorrhage who have died of long-term treatment. At this point, the patient may experience severe headache and vomiting.

Examination of aplastic anemia

(1) Blood image

It is a complete blood cell reduction, anemia is a normal cell type, can also be mild red blood cells, red blood cells are slightly different in size, but no obvious deformity and multi-staining phenomenon, generally no young red blood cells appear, reticulocytes significantly reduced, a few cases early Only one or two lines of cells can be reduced, anemia is heavier, severe anemia (Hb 30 ~ 60g / L), mostly positive cell anemia, a small number of moderate, large cell anemia, red blood cell morphology No obvious abnormalities, the absolute value of reticulocytes decreased, the proportion of acute aplastic reticulocytes was less than 1%, neutrophils, eosinophils, monocytes, lymphocytes decreased in absolute value, especially neutropenia Acute aplastic anemia is less than 0.5×109/L. The platelet is not only small in number, but also has a small shape, which can cause prolonged bleeding, increased vascular fragility, and poor blood clot retraction. Acute aplastic barrier platelets are often lower than 10×109/L. .

(2) Bone marrow

The acute type is multi-site hyperplasia reduced or severely reduced, the three-line hematopoietic cells are significantly reduced, especially megakaryocytes and young red blood cells; non-hematopoietic cells, especially lymphocytosis, the bone marrow images obtained from different chronic sites are inconsistent, can be hyperplasia Poor to hyperplasia, but at least one part of the hyperplasia; such as good proliferation, the proportion of late red blood cells (carbon nuclei) often increased, the nuclear irregular lobulated, showing denucleation disorders, but megakaryocytes significantly reduced, bone marrow coating The naked eye observed an increase in oil droplets, and the bone marrow microscopic examination showed no increase in non-hematopoietic cells and fat cells, generally more than 60%.

(3) Bone marrow biopsy and radionuclide bone marrow scanning

Because the bone marrow smear is susceptible to the dilution of the surrounding blood, sometimes the secondary smear test is difficult to correctly reflect the hematopoietic condition, and the bone marrow biopsy is superior to the smear in estimating the proliferative condition, which can improve the correctness of the diagnosis and cure 99m. Or systemic bone marrow gamma photography of 111 indium chloride can reflect the distribution of systemic functional bone marrow. The radioactive uptake of normal bone marrow in the case of aplastic anemia is low or even disappears, so it can indirectly reflect the extent and location of hematopoietic tissue reduction.

(4) Other inspections

Hematopoietic progenitor cell culture not only helps in diagnosis, but also helps detect the presence or absence of inhibitory lymphocytes or serum in the presence or absence of inhibitory factors, mature neutrophil alkaline phosphatase activity, serum lysozyme activity is reduced, alkali resistance The amount of hemoglobin is increased. In addition to the chromosomal aberrations of Fanconi anemia, the general aplastic anemia is normal. If there is a karyotype abnormality, the myelodysplastic syndrome must be excluded.

1. Ultrastructure of bone marrow

The chronic aplastic anemia showed obvious pathological hematopoiesis. The immature erythrocyte membrane showed chrysanthemum-like changes, the cytoplasm had more vacuoles, the nuclear membrane was dilated, and the abnormally shaped red blood cells increased by about 90%. The above changes were rare in acute aplastic anemia.

2. Hematopoietic progenitor cell culture

Granulocytes, mononuclear progenitor cells (CFU-GM), erythroid progenitor cells (BFU-E, CFU-E) and megakaryocyte progenitor cells (CFU-Meg) are reduced, acute aplastic fibroblast progenitor cells (CFU-F) ) also reduced, half of chronic aplastic anemia is normal, half is reduced, neutrophil alkaline phosphatase (N-ALP) aplastic anemia in neutrophil formation, resulting in a significant increase in bone marrow and peripheral blood N-ALP, the condition After improvement, N-ALP can return to normal.

3. Hematopoietic growth factor (HGF)

There was no significant increase in acute aplastic anemia. Chronic aplastic anemia serum granulocyte or granulocyte-macrophage colony-stimulating factor (G/GM-CSF) increased, and urine and plasma erythropoietin levels increased significantly, reaching 500-1000 times normal. Iron metabolism, serum iron-binding protein saturation increased, plasma 59Fe clearance time prolonged, bone marrow to 59Fe intake decreased, erythroferrin intake was lower than normal, iron incorporation of circulating red blood cells decreased, patients often need Blood transfusion (200-250mg per 400ml of red blood cells), the iron intake increased, and there was no corresponding increase in iron output. The 24h urinary iron was only 1mg, causing serum iron, bone marrow cells inside and outside the iron, liver and spleen and other organs to increase iron.

4. Red blood cell free protoporphyrin (FEP)

Acute aplastic anemia is severely damaged by bone marrow. The use of free protoporphyrin in red blood cells is less, and it can be slightly increased. Chronic aplastic anemia may increase FEP significantly due to hemoglobin biochemical synthesis disorder.

5. Erythrocyte membrane variation

Electrophoretic analysis of erythrocyte membrane protein components showed that the 4.2 protein in the aplastic anemia band was reduced, and the 5 and 4.1 proteins were significantly increased, which was related to the integrity and deformability of the erythrocyte membrane.

6. Red blood cell survival period and its damage site

51Cr-labeled red blood cells were used to detect the semi-survival time of erythrocytes in chronic aplastic anemia. The shortening was 61%, the spleen localization index was 48%, and the spleen death index was 26%. It was important for the selection of splenectomy and estimation of curative effect.

7. Immune function

The acute aplastic anemia SK-SD and OT test responses were significantly reduced, the chronic aplastic anemia was slightly reduced, the absolute value of acute aplastic anemia T cells was significantly reduced, the number of early and mature B cells was significantly reduced, and the conversion rate of lymphocytes to ConA was reduced. The PHA transformation reaction was low, and the 3H-TdR incorporation was significantly reduced, indicating that the acute aplastic anemia T and B cells were seriously affected, suggesting that the pluripotent hematopoietic stem cells were damaged, the number of chronic aplastic anemia T cells was normal, and the number of early and mature B cells was reduced. The rate of stimulation of ConA and PHA stimulation was increased, and the 3H-TdR incorporation was slightly reduced, indicating that chronic aplastic anemia is mainly caused by B cell involvement, and the damage is mainly in the myeloid progenitor stage.

Diagnostic identification of aplastic anemia

diagnosis

In 1964, the basis of the diagnosis of aplastic anemia proposed by the Institute of Hematology of the Chinese Academy of Medical Sciences, after more than 20 years of clinical practice in China, and two revisions, was determined in 1987 as the current diagnostic criteria for aplastic anemia in China. The details are as follows.

1. Complete blood cell reduction, reduced absolute value of reticulocytes.

2. Generally no splenomegaly.

3. Bone marrow examination at least one site of hyperplasia or severe reduction.

4. Can exclude other diseases that cause whole blood cell reduction, such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, acute hematopoietic dysfunction, myelofibrosis, acute leukemia, malignant histiocytosis.

5. General anti-anemia drug treatment is invalid

(1) Acute aplastic anemia (AAA), also known as severe aplastic anemia (SAAI):

1 clinical manifestations: acute onset, anemia is progressive, often accompanied by severe infection, visceral bleeding.

2 blood: in addition to the rapid decline in hemoglobin, must have 2 of the following 3 items:

A. Reticulocyte <1%, (corrected by hematocrit) The absolute value is <0.015×1012/L.

B. Leukocytes are significantly reduced, neutrophils <0.5×109/L.

C. Platelets <20 x 109 / L.

3 bone marrow elephant:

A. Multi-site hyperplasia: Three lines of hematopoietic cells are significantly reduced, non-hematopoietic cells are increased, such as hyperplasia, lymphocytes should be increased.

B. Increased non-hematopoietic cells and adipocytes in bone marrow.

(2) Chronic aplastic anemia (CAA):

1 clinical manifestations: slow onset, anemia, infection, bleeding is lighter.

2 blood: hemoglobin declines slowly, reticulocytes, white blood cells, neutrophils and platelets are often higher than acute aplastic anemia.

3 bone marrow elephant:

A. Decrease in the third or second line: at least one part of the hyperplasia is reduced. For example, in the proliferative active red line, there is often an increase in the proportion of latent red carbon in the carbon core, and the megakaryocytes are significantly reduced.

B. Increased bone marrow granule fat cells and non-hematopoietic cells.

(3) If the disease changes during the course of the disease: clinical manifestations, blood and bone marrow are the same as acute aplastic anemia, called severe aplastic anemia type II (SAAII).

At present, foreign countries follow the criteria for serious aplastic anemia (SAA) proposed by Camitta (1976): peripheral blood neutrophils <0.5×109/L, platelets<20×109/L, anemia and reticulocytes <1%, with the above 2 of 3 items, with severe reduction of bone marrow hyperplasia (<25% of normal), or hypoplasia (25% to 50% of normal), of which non-hematopoietic cells >70%, can be diagnosed as SAA; Those who meet the above criteria are light aplastic anemia (MAA). In recent years, many scholars have determined SAA with granulocyte <0.2×109/L as a very severe aplastic anemia (VSAA).

The diagnosis of typical cases is not difficult. According to the clinical combination of anemia, hemorrhage, infection performance, peripheral blood whole blood cell reduction, bone marrow hyperplasia and other diseases that cause whole blood cell reduction, the diagnosis can be confirmed. For a few atypical cases, By observing pathological hematopoiesis, bone marrow biopsy, hematopoietic progenitor cell culture, hemolysis test, chromosome, oncogene, and radionuclide bone marrow scan, etc. were identified.

Differential diagnosis

Aplastic anemia should be identified primarily with the following diseases.

1. Paroxysmal nocturnal hemoglobinuria (PNH): It is more difficult to distinguish from paroxysmal nocturnal hemoglobinuria. However, the disease has less bleeding and less infection. The absolute value of reticulocyte is greater than normal. The bone marrow hyperplasia is active, the red blood cell proliferation is more obvious, the hemosiderin urine test (Ruos) can be positive, the acidified serum hemolysis test (Ham) and the snake venom test (CoF) are more positive, the red blood cell micro complement sensitivity test (mCLST), CD55 PHO red blood cells can be detected by CD59, N-ALP is reduced, and plasma and erythrocyte cholinesterase are significantly reduced.

2. Myelodysplastic syndrome (MDS): It is difficult to distinguish from refractory anemia (RA) in MDS, but the disease is characterized by pathological hematopoiesis. Peripheral blood often shows uneven red blood cell size, easy to see huge red blood cells and Nuclear red blood cells, mononuclear cells, immature granulocytes and abnormal platelets, hyperactive bone marrow hyperplasia, two or three lines of pathological hematopoiesis, giant juvenile and multinucleated red blood cells are more common, medium and young granules increase, nucleoplasm development imbalance, There are many nuclear abnormalities or excessive lobes, many megakaryocytes, lymphoid small megakaryocytes are more common, histochemistry shows erythrocyte glycogen (PAS) positive, annular iron granules increase, small megakaryocyte enzymes are positive, further According to bone marrow biopsy, leukemia progenitor cell culture (CFU-L), chromosome, oncogene and other tests were identified.

3. Acute hematopoietic stagnation is often caused by infections and drugs. Children with malnutrition are associated with high fever, severe anemia, rapid progress, and many misdiagnosed as acute aplastic anemia. The following characteristics are helpful in identifying:

1 Anemia is heavy, reticulocytes can be 0, with neutropenia, but thrombocytopenia is not obvious, bleeding is lighter.

2 Myeloid hyperplasia is more active, and the second or third line is reduced, but with the red line reduction, huge primitive red blood cells can be seen at the end of the film.

3 The condition is self-limiting, no special treatment is needed, and it can be recovered in 2 to 6 weeks.

4 serum copper increased significantly, red blood cell copper decreased.

4. Myelofibrosis (MF): Chronic cases often have splenomegaly, peripheral blood can be seen in immature granulocytes and nucleated red blood cells, bone marrow puncture multiple dry pumping, bone marrow biopsy shows collagen fibers and (or) reticular fibers significantly hyperplasia.

5. Acute leukemia (AL): especially low-proliferative AL can be a chronic process, liver, spleen, lymphadenopathy, peripheral blood, complete blood cells, bone marrow hyperplasia, easy to be confused with aplastic anemia, should carefully observe the blood and multiple parts Bone marrow, can be found in the original grain, single, or primordial lymphocytes significantly increased, bone marrow biopsy also helps to confirm the diagnosis.

6. Malignant histiocytosis (MH): often accompanied by non-infectious hyperthermia, progressive failure, liver, spleen, lymphadenopathy, jaundice, hemorrhage is heavier, peripheral blood whole blood cells are significantly reduced, abnormal tissue cells can be seen, multiple parts Bone marrow examination can find abnormal tissue cells, often with phagocytosis.

7. Pure red blood cell aplastic anemia: Aplastic anemia crisis and acute hematopoietic stagnation, can be a complete blood cell reduction, acute onset, a clear cause, can be relieved after removal, the latter can appear in the bone marrow Pre-existing red blood cells, chronic acquired pure red aplastic anemia, if there is a slight decrease in white blood cells and platelets, attention should be paid to the identification of chronic aplastic anemia.

8. Other diseases that need to be excluded are: pure red blood cell aplastic anemia, megaloblastic anemia, bone marrow metastasis cancer, renal anemia, hypersplenism and so on.

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