Pancytopenia
Introduction
Introduction Pancytopenia, also known as aplastic anemia (aplastic anemia), is a type of whole blood reduction syndrome caused by bone marrow hematopoietic failure.
Cause
Cause
(1) Causes of the disease
About 50% to 75% of cases are unidentified as idiopathic, and secondary are mainly related to drugs and other chemicals, infections and radiation. The current choice is to be described as follows:
Drug
Drugs are the most common cause of disease. There are two types of drug aplastic anemia:
1 is related to the dose, which is a toxic effect of the drug. When a certain dose is reached, it 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 more mature pluripotent stem cells that are easy to divide. Therefore, when whole blood cells are reduced, bone marrow still retains a certain amount of pluripotent stem cells. Barriers can be restored; busulfan and nitrosourea not only act on stem cells entering the proliferative cycle, but also on stem cells in non-proliferative cycles, thus often leading to long-term bone marrow suppression difficult to recover. In addition, phenytoin, phenothiazine, thiouracil, and chloramphenicol can also cause dose-related myelosuppression.
2 and the dose has little relationship, only individual patients with hematopoietic disorders, multi-drug allergic reactions, often lead to persistent aplastic anemia. There are many kinds of such drugs, such as chloramphenicol, organic arsenic, adipine, trimethyl ketone, phenylbutazone, gold preparation, aminopyrine, piroxicam (inflammatory pain), sulfonamide, Sulfocin, carbamazepine (methamper), methimazole (tabazole), chlorpropamide, and the like. Drug-induced aplastic anemia is most commonly caused by chloramphenicol. According to domestic surveys, the risk of aplastic anemia in those who took chloramphenicol within three months was 33 times that of the control group, and there was a dose-response relationship. Chloramphenicol can occur in the above two types of drug aplastic anemia. The chemical structure of chloramphenicol contains a nitrobenzene ring, and its bone marrow toxicity is related to nitroso-chloramphenicol, which inhibits bone marrow cells. The inner mitochondrial DNA polymerase leads to a decrease in DNA and protein synthesis, and also inhibits the synthesis of heme, and vacuoles and iron granules may appear in the young red cytoplasm. This inhibition is reversible and the blood image is restored once the drug is stopped. Chloramphenicol can also cause an allergic reaction with little dose, causing myelosuppression to occur many weeks or months after taking chloramphenicol, or it can occur suddenly during treatment. The mechanism may be caused by autoimmunity directly inhibiting hematopoietic stem cells or directly damaging the chromosomes of stem cells. This type of action is often irreversible, even if the drug is discontinued. Where stem cells are genetically deficient, the sensitivity to chloramphenicol is increased.
Chloramphenicol is a nitrobenzene compound having a dichloroacetyl branch. Chloramphenicol has a close correlation with the onset of aplastic anemia, and its actual risk is 190,000 to 1/30,000, which is 10 to 20 times higher than that of non-contact. Domestic multi-factor analysis data showed that the risk of aplastic anemia was 6 times or 33 times higher than that of the control group, who had a history of taking chloramphenicol within 1 year or half a year before onset. According to the US Department of Medicine's Drug Reaction Registry, 50% of people use the drug within 38 days of the disease. There are two types of clinical:
(1) Reversible myelosuppression:
Mainly due to erythroid hematopoiesis, hemoglobin, reticulocyte reduction, serum iron increase, vacuoles in immature red blood cell pulp and nucleus, and iron accumulation in mitochondria. Iron kinetic studies showed that plasma iron half-life clearance time prolonged, bone marrow radioactive iron intake decreased, liver intake increased, and red blood cell radioactivity did not appear in the circulation after 8 days, which proved that patients had hemoglobin and hemoglobin synthesis inhibited.
(2) Irreversible aplastic anemia:
In 1950, the first chloramphenicol-induced aplastic anemia was reported. The disease is insidious onset, and aplastic anemia occurs several weeks to several months after exposure to chloramphenicol and is independent of the drug dose, time of administration, and route of administration. Chloramphenicol may affect the proliferation and maturation of bone marrow hematopoietic progenitor cells, competitive inhibition of mRNA formation, impaired mitochondrial protein synthesis, especially impaired iron complexase synthesis, and inhibits CFU-GM growth. . A more precise explanation is that chloramphenicol can cause vacuolation of chromosomes and damage the genetic structure of stem cells leading to aplastic anemia. It has also been suggested that patients with chloramphenicol-related aplastic anemia or family members of bone marrow cells are extremely sensitive to the inhibitory effect of the drug.
2. Benzene: In industrial production and daily life, people have extensive exposure to benzene (C6H6) and its derivatives. Benzene is volatile and easily inhaled into the body. Hematological abnormalities are more common among people exposed to benzene. Among them: anemia accounted for 48%, giant erythrocytosis accounted for 47%, thrombocytopenia accounted for 33%, and leukopenia accounted for 15%. In shoemakers with poor working conditions, total blood cell reduction accounted for 2.7%. Severe benzene poisoning can cause aplastic anemia, and there have been many domestic reports in recent years. The above-mentioned poisoning performance can occur after several weeks to several years of exposure to benzene, indicating that the susceptibility of benzene poisoning among individuals is quite different. Experts suggest that the reasonable limit of the vapor concentration in the benzene operation should be less than 10 ppm in 8 hours. At the beginning of the 20th century, it was found that benzene and its derivatives (such as trinitrotoluene, hexachlorobenzene, etc.) have toxic effects on bone marrow, and its toxic effects are mainly caused by various decomposition products, especially P-phenylquinine can be significant. Inhibits the synthesis of RNA and DNA in differentiated progenitor cells and leads to chromosomal abnormalities.
3. Viral Hepatitis In 1955, Lorenz reported the first viral hepatitis-related aplastic anemia (HAAA). It is generally believed that the incidence of HAAA in patients with viral hepatitis is 0.05% to 0.9%, and the composition ratio in patients with aplastic anemia is 3.2% to 23.9%. 80% of HAAA is caused by hepatitis C virus, and a small number is hepatitis B virus. Caused by (HBV). Hagler divides HAAA into two types:
(1) Type A: The onset is acute, the condition is heavy, the average age is 20 years old, the average interval between hepatitis and aplastic anemia is about 10 weeks, the survival time is about 11 weeks, and HBsAg(-) is about 90%.
(2) Type B: slow onset, mild condition, mostly on the basis of chronic hepatitis, the average interval between hepatitis and aplastic anemia is 6.4 years, the survival time is 2.9 years, and HBsAg can be (+), accounting for about 10%.
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.
4. Radiation-induced bone marrow failure is non-random, dose-dependent and associated with tissue-specific sensitivity. Hematopoietic tissue is more sensitive to radiation, and systemic exposure to lethal or sublethal doses (4.5 to 10 Gy) can cause fatal acute aplastic anemia, which rarely causes chronic aplastic anemia. Only a few of the Japanese atomic bomb survivors developed late-onset aplastic anemia. High-dose localized irradiation can also cause severe damage to the bone marrow microenvironment, and this dose of radiation greatly exceeds the lethal dose of progenitor cells. Chronic aplastic anemia can occur in long-term exposure to small doses of external exposure, such as a radiologist or a patient with radium or sputum in the body. It has been reported that aplastic anemia can occur several months to several years after short-term exposure to radiation. Radiation mainly acts on macromolecules in cells, affecting the synthesis of DNA, and its biological effect is to inhibit or delay cell proliferation. Both whole body irradiation and local irradiation can damage hematopoietic stem cells and microenvironment and cause bone marrow failure. The drugs that can cause aplastic anemia are shown in Table 2.
5. Immune factors Aplastic anemia can be secondary to thymoma, systemic lupus erythematosus and rheumatoid arthritis, and antibodies against hematopoietic stem cells can be found in the serum of patients. Some of the unexplained aplastic anemia may also have immune factors.
6. Genetic factors Fanconi anemia is an autosomal recessive hereditary disease that is familial. Anemia is found in 5 to 10 years old, most cases are accompanied by congenital malformations, especially the skeletal system, such as short or absent thumb, shortened, tibia shortened, short stature, small head, small eye, strabismus, deafness, kidney Deformity and cardiovascular malformations, etc., skin pigmentation is also very common. The HBF of this disease is often increased, the incidence of chromosomal abnormalities is high, and the DNA repair mechanism is defective. Therefore, the incidence of malignant tumors, especially leukemia, is significantly increased. 10% of the children have a history of close relatives.
7. Paroxysmal nocturnal hemoglobinuria (PNH) PNH and aplastic anemia are closely related, 20% to 30% FNH may be associated with aplastic anemia, 15% aplastic anemia may be dominant PNH, both are hematopoietic stem cell diseases . Clearly changed from aplastic anemia to PNH, and the performance of aplastic anemia is not obvious; or clearly changed from PNH to aplastic anemia, and PNH performance is not obvious; or PNH with aplastic anemia and aplastic anemia with PNH red blood cells can be called again Barrier-PNH syndrome.
8. Other factors rare cases report that aplastic anemia occurs during pregnancy, remission after childbirth or abortion, and recurrence during the second pregnancy, but most scholars believe that it may be coincidental. In addition, aplastic anemia can be secondary to chronic renal failure, severe thyroid or anterior (glandular) pituitary hypofunction.
(two) pathogenesis
The pathogenesis of aplastic anemia is extremely complex and is currently considered to be related to the following aspects.
1. The intrinsic proliferation defect of hematopoietic stem cells is the main pathogenesis of aplastic anemia, based on the following:
(1) Hematopoietic stem cells in the bone marrow of aplastic anemia are significantly reduced: the ability of stem cell colony formation is significantly reduced, and abnormal stem cells can inhibit normal stem cell function. Scope et al. used anti-CD34 and anti-CD33 monoclonal antibodies to perform two-color immunofluorescence staining on 15 patients with different severity AA and 11 normal human bone marrow mononuclear cells (BMMNC), and detected AA by fluorescence activated cell sorting (FACS). The number of hematopoietic stem/progenitor cells in the bone marrow of patients and normal subjects was found to be 68% lower than that of normal people in AA patients.
(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 believe that the incidence of these advanced clonal diseases is as high as 57% 8 years after SAA treatment with ATG/ALG.
(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 with 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 female AA patients, and only one of them had a whole blood cell type as a monoclonal type. Kamp et al. used a combination of PGK, HRT and M27H probes to detect 19 cases of AA, and 18 cases of clonality analysis, of which 13 cases (72.2%) were monoclonal. Four 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 et al also used PGK, MBPRT and M27H probes to detect 20 children with AA, and 18 patients with clonality analysis. Two of them (11.1%) granulocytes and fibroblasts were of monoclonal origin. AA clonal hematopoiesis does not imply clonal proliferation, may reflect the depletion of hematopoietic stem cell pool, 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, which 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 engraft. A large number of in vitro experiments have shown that 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. demonstrated that the T4/T8 ratio was reversed in patients with aplastic anemia, and the activity of T8 cells was increased. This cell has the effect of inhibiting hematopoiesis and releasing inhibitory factors in vitro. Gascon determined 15 cases of aplastic anemia Tac cells, 11 of which were elevated, and increased Tac antigen expression suggested that the lymphocyte subsets were "pre-activated". Mentzel et al analyzed 9 patients with aplastic anemia and found that the -T cell subset expressed TCSl phenotype significantly increased. Blustone et al believe that the increase of -T cells, especially TCS1-T cells, may inhibit hematopoiesis. The levels of hematopoietic negative regulators such as serum interferon (IFN-), tumor necrosis factor (TNF-) and interleukin-2 (IL-2) were increased in patients with aplastic anemia. 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, and the transcription level of stem cell inhibitory factor (SCI) RNA is significantly increased. Plantanias et al found that in patients with aplastic anemia who were effective in immunotherapy, IFN- was significantly reduced in vivo, and in vitro antibody neutralizing endogenous IFN- or IFN- could double the recovery of bone marrow CFU-GM. The release of IFN- after dengue virus infection causes a lymphotoxic reaction, which causes damage to stem cells and aplastic anemia.
Shinjinakai et al used PCR to detect the gene expression of cytostatic factors in 23 aberrant mononuclear cells, and found that IFN- mRNA was expressed in aplastic anemia patients and was not associated with blood transfusion. Transforming growth factor (TGF-) is a core factor in the negative regulation of physiological hematopoiesis, and it has a reversible inhibitory effect on hematopoietic precursor cells, which is characterized by selective inhibition of IL-3, GM-CSF, IL-6 and Proliferation and differentiation of hematopoietic precursor cells of hematopoietic factors such as IL-9. In recent years, it has been recognized that many interleukins are involved in the process of hematopoiesis, some act as CSF cofactors, and some have colony stimulating factor activity. Nakao et al detected 17 cases of aplastic anemia, and found that 10 cases of IL-1 were significantly reduced, 9 of which were SAA. IL-2 was significantly increased in some patients with aplastic anemia, and IL-3 (SCF) was significantly reduced in some patients. Recently, reports of the treatment of aplastic anemia with IL-1 and IL-3 and monoclonal antibodies against IL-2 receptor have been reported abroad. Natural killer cells (NK) can inhibit the colony growth of more mature hematopoietic progenitor cells, and human NK cells also have the ability to produce various lymphokines such as IL-2/IFN-, IL-1 and CSF. Yashhiro et al detected 12 cases of aplastic anemia in peripheral blood NK cells decreased. The above results indicate that the pathogenesis of aplastic anemia has a certain relationship with the immune mechanism, but the fact that immunosuppressive agents can not completely cure aplastic anemia indicates that aplastic anemia is not a classic autoimmune disease, and 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 currently insufficient evidence to suggest bone marrow stromal defects in patients with aplastic anemia, but a decrease in colony-stimulating activity (CSA) produced by aplastic anemia bone marrow fibroblast colony forming units (CFU-F) and stromal cells.
The Institute of Hematology, Chinese Academy of Medical Sciences observed atrophy, fatification, and reduction of CFU-F in bone marrow stromal cells, and acute aplastic anemia was more severe than chronic aplastic anemia. Most in vitro tests have shown 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 granulocyte-macrophage colony-stimulating factor (GM-CSF). Cell line colony-stimulating factor (G-CSF) and macrophage cell colony-stimulating factor (M-CSF) levels were increased; however, IL-1 production was decreased in AA patients. Studies have confirmed that hematopoietic stem/progenitor cells of AA patients, especially BFU-E, are significantly less reactive to EPO, EPO+IL-3 and EPO+SCF than normal controls, and even lack reactivity. Wodnar-Filipowicz et al detected the level of serum soluble stem cell factor (SCF) in 32 SAA patients. The serum SCF level of SAA patients was lower than that of normal controls, but the difference was not significant. The serum SCF and high level had better prognosis. If AA is due to a lack of HGF, then theoretically HGF can cure 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 the cause of AA, it can aggravate the condition.
4. Genetic predisposition
Aplastic anemia often has an HLA-DR2 type antigen-linked tendency, and the HLA-DPW3 type antigen in children with aplastic anemia is significantly increased. The proliferative ability of hematopoietic progenitor cells is often reduced in the family members, and familial aplastic anemia is seen. Susceptibility to chloramphenicol in patients with aplastic anemia is genetically controlled, 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.
Examine
an examination
Related inspection
Blood routine biochemical examination alkaline spotted red blood cell count
The diagnostic criteria for aplastic anemia revised in the Fourth National Conference on Aplastic Indus in 1987 are as follows:
1 Whole blood cells are reduced, and the absolute value of reticulocytes is reduced.
2 generally no splenomegaly.
3 bone marrow examination showed that at least one part of the hyperplasia was reduced or severely reduced (such as hyperplasia, megakaryocytes should be significantly reduced, non-hematopoietic cells should be seen in the bone marrow granules. Those with conditions should be examined by bone marrow biopsy).
4 can exclude other diseases that cause whole blood cell reduction, such as paroxysmal nocturnal hemoglobinuria, refractory anemia in myelodysplastic syndrome, acute hematopoietic dysfunction, myelofibrosis, acute leukemia, malignant histiocytosis.
5 general anti-anemia drug treatment is invalid.
In 1964, the basis of diagnosis of aplastic anemia proposed by the Institute of Hematology, 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. Reticulocytes.
B. Significantly reduced white blood cells, neutrophils.
C. Platelets.
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) Changes in 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, the diagnostic criteria for severe aplastic anemia (SAA) proposed by Camitta (1976) are used abroad: 70% of peripheral blood neutrophils can be diagnosed as SAA; those who do not meet the above criteria are light aplastic anemia (MAA). In recent years, many scholars have no difficulty in diagnosing typical cases of granulocytes. According to the clinical combination of anemia, hemorrhage, infection, peripheral blood, complete blood cells, bone marrow hyperplasia and other diseases that cause whole blood cell reduction, you can determine diagnosis. For a few atypical cases, it can be identified by observing pathological hematopoiesis, bone marrow biopsy, hematopoietic progenitor cell culture, hemolysis test, chromosome, oncogene, and radionuclide bone marrow scan.
Diagnosis
Differential diagnosis
1. Paroxysmal nocturnal hemoglobinuria (PNH) is more difficult to distinguish from paroxysmal nocturnal hemoglobinuria. However, the bleeding and infection of this disease are less and lighter, the absolute value of reticulocytes is greater than normal, the bone marrow is more proliferative, the young red blood cells are more proliferative, the hemosiderin urine test (Ruos) is positive, and the acidified serum hemolysis test (Ham ) and venom test (CoF) more positive, red blood cell micro-complement sensitivity test (mCLST), CD55, CD59, etc. can detect PNH red blood cells, N-ALP decreased, plasma and erythrocyte cholinesterase decreased significantly.
2. Myelodysplastic syndrome (MDS) is more difficult to distinguish from refractory anemia (RA) in MDS. However, the disease is characterized by pathological hematopoiesis. Peripheral blood often shows uneven red blood cell size. It is easy to see huge red blood cells, nucleated red blood cells, and monocytes, showing immature granulocytes and abnormal platelets. Marrow hyperplasia is more active, there are two or three lines of pathological hematopoiesis, giant juvenile and multinucleated red blood cells are more common, medium and young granules increase, nucleoplasmic development is unbalanced, and nuclear abnormalities or excessive lobulation are seen. There are many megakaryocytes, lymphoid small megakaryocytes are more common, histochemistry shows nucleated red blood cell glycogen (PAS) positive, annular iron granules increase, and small megakaryocytic enzymes are positive. Further, it can be identified based on bone marrow biopsy, leukemia progenitor cell culture (CFU-L), chromosome, oncogene, and the like.
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 to identify: 1 anemia, reticulocyte can be 0, with neutropenia, but thrombocytopenia is less obvious, bleeding is lighter; 2 bone marrow hyperplasia is more active, second or third line is reduced, but red The system is reduced to a large original red blood cell at the end of the film; 3 the condition is self-limiting, no special treatment is needed, and can be recovered in 2 to 6 weeks; 4 serum copper is significantly increased, and red blood cell copper is reduced.
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)
In particular, low-proliferative AL can be a chronic process, liver, spleen, lymph nodes, peripheral blood, complete blood cells, bone marrow hyperplasia, easy to be confused with aplastic anemia. Careful observation of blood and multiple parts of the bone marrow, you can find that the original grain, single, or primordial lymphocytes increased significantly. Bone marrow biopsy also helps to confirm the diagnosis.
6. Malignant histiocytosis (MH)
Often accompanied by non-infectious high fever, progressive failure, liver, spleen, lymph node enlargement, jaundice, hemorrhage is heavier, peripheral blood whole blood cells are significantly reduced, abnormal tissue cells can be seen. Multi-site bone marrow examination can find abnormal tissue cells, often with phagocytosis.
7. Pure red blood cell aplastic anemia
The aplastic anemia crisis and acute hematopoietic stagnation of hemolytic anemia can be a complete blood cell reduction, acute onset, clear cause, and can be relieved after removal. The latter can appear giant red blood cells in the bone marrow. Chronic acquired pure red aplastic anemia with mild reduction of white blood cells and platelets should be distinguished from chronic aplastic anemia.
8. Other
The diseases to be excluded are: pure red blood cell aplastic anemia, megaloblastic anemia, bone marrow metastasis cancer, renal anemia, hypersplenism and so on.
