pure red cell aplastic anemia in children
Introduction
Introduction to pure red blood cell aplastic anemia in children Pure red cell aplastic anemia (PRCA) has only developmental disorders of the red blood cell system, no change in white blood cells and platelets, young red blood cells in the bone marrow stop at the stage of directed stem cells and early red blood cells, other young red blood cells are extremely reduced, but the granulocyte system and Megakaryocytes develop normally and red blood cell life is slightly shorter than normal. Anemia is positively pigmented, and reticulocytes are reduced or absent. basic knowledge The proportion of illness: 0.001--0.002% Susceptible people: children Mode of infection: non-infectious Complications: congenital heart disease hemolytic anemia hemochromatosis thymoma
Cause
The cause of pure red blood cell aplastic anemia in children
(1) Causes of the disease
Classification
Acquired pure red aplastic anemia can be divided into two categories: congenital and acquired, according to whether the cause is clear or not, and can be divided into primary pure red aplastic anemia with unclear etiology and secondary red aplastic anemia with clear etiology.
2. Causes
It is not completely clear that a small number of patients have a family history, so consider congenital genetic abnormalities, which can be autosomal dominant or recessive, and patients may be associated with C-Kit proto-oncogene mutations and/or SI gene mutations, plasma and The erythropoietin in the urine is increased. There is no qualitative abnormality in the plasma erythropoietin, but the erythropoietin is incubated with the bone marrow cells. The former does not promote the differentiation of the young red blood cells. The addition of interleukin-3 can differentiate red blood cells, and thus it is considered that there is a qualitative abnormality of the stem cells of the red blood cell line. In recent years, it has been found that the T lymphocytes in the blood of the patient inhibit the erythroid forming unit (CFU-E) of the bone marrow and the surrounding area. Red blood burst colony forming unit (BFU-E) in blood, but this phenomenon has not been found in patients who are not sensitive to adrenocortical hormone. It has also been found that T-suppressor cells in peripheral blood and bone marrow increase, and prednisone (Prednisone) fell to normal after treatment.
Through immunoassay, a group of autoantibodies (IgG) were found in patients with this disease, which inhibited erythropoietin (anti-erythropoietin antibody), inhibited the differentiation and proliferation of erythrocytes (anti-erythrocytic antibodies) and inhibited hemoglobin synthesis (hemoglobin synthesis). Inhibitory activity such as inhibitory factor, the plasma of the patient can inhibit the formation of colonies in vitro by normal human hematopoietic stem cells, and it can also confirm the presence of such inhibitory activity in the plasma of patients, which is caused by the inhibition of erythroid hematopoietic cell differentiation and causes secondary iron metabolism abnormality due to The cause of immunoglobulin inhibitors is unknown, so it is called primary pure red aplastic anemia.
The disease is secondary to a variety of different diseases, manifested as a group of comprehensive symptoms of severe erythropoiesis suppression, more than half of which are secondary to thymoma, showing chronic type, others secondary to hemolytic anemia, viral infection ( Such as Epstein-Barr virus, influenza virus, etc.), malignant tumors, systemic lupus erythematosus, severe malnutrition and other diseases, or caused by drugs (such as chloramphenicol, phenytoin, etc.) and chemical poisoning.
(two) pathogenesis
The exact pathogenesis is still unclear, but because the thymus is an immune organ, it is related to cellular immunity. Most patients have significant effects in the treatment of corticosteroids or other immunosuppressive drugs, so it is speculated that this disease is also associated with abnormal immune function.
Congenital pure red blood cell aplastic anemia
In vitro culture, DBA patients with bone marrow erythroid progenitor cells (BFU-E) and (CFU-E) significantly reduced, causing erythroid progenitor cell proliferation and differentiation defects are internal or external, scholars around the world around this issue A variety of experimental studies have been conducted. At present, there is a consensus that DBA patients have erythroid progenitor cells with intrinsic abnormalities, which lead to their response to various hematopoietic growth factors (HGFs) that regulate erythroid progenitor cell differentiation and proliferation. Decreased, reported leukopenia and/or thrombocytopenia and leukemia in DBA patients, 28 patients with DBA anticortisol were followed up for 13 years, peripheral blood cell counts and bone marrow examinations and biopsy were performed and performed Long term culture initiating cell (LTC-IC) analysis showed that 75% of patients had severe, gross bone marrow hematopoiesis, and hematopoietic dysfunction combined with neutropenia accounted for 43% and (or The thrombocytopenia accounted for 29%. The results of the LTC-IC assay showed that the number of cloned cells in DBA patients was significantly reduced. The results suggest that the defects of severe and stubborn DBA patients are not Limited erythropoiesis, there may be three defective hematopoiesis.
In vivo and in vitro studies, no defects or abnormalities in erythropoietin (EPO) and its receptors, stem cell factor (SCF), interleukin 3 (IL-3), and EPO levels in DBA patients were not found. Increased, high-dose EPO treatment is not effective, so erythroid progenitor cells in DBA patients are relatively insensitive to EPO, but no abnormalities in EPO receptor genes have been found. In vitro, SCF can increase the formation of erythroid progenitor colonies in DBA patients. However, no significant molecular abnormalities have been found in the study of SCF and its receptor c-kit gene. The results of these studies suggest that there may be intracellular signaling pathways or delivery molecular defects that play a role in the early erythroid differentiation. The results of increased apoptosis of erythroid progenitor cells in the absence of EPO in vitro are consistent. Recently, studies on the regulation of erythroid hematopoietic differentiation have revealed that SCL mRNA and protein levels are normal in DBA patients, but the other two proteins are normal. (E47 and HEB) are reduced, and another early-acting erythroid growth factor IL-9 is added to SCF, and IL-3 and EPO can significantly increase BFU-E in vitro in DBA patients who respond to SCF. Long, but IL-9 alone did not respond, IL-9 seems to play a role in synergy with SCF. Studies on IL-9 gene found that IL-9 and other genes are located in the major hematopoietic region of 5q31-32.2 for this region. Linkage analysis suggests that DBA defects are not controlled by known or unknown genes in the 5q hematopoietic region.
Some patients respond to cortisol treatment, suggesting that the disease may have immunological abnormalities, but it is impossible to determine the extent of immunological abnormalities that cause erythropoiesis abnormalities. Fas ligand (FasL) is present in active T cells and natural killer cells. The membrane protein on the surface, FasL binds to Fas on the surface of target cells to induce apoptosis, and soluble Fas ligand (sFasL) is present in serum. It also binds to Fas to induce apoptosis. In most patients with DBA, the serum concentration of sFasL is increased. It is suggested that the cause of cytotoxicity in DBA and the increase of serum sFasL are unknown. In some patients, lymphocyte-mediated erythroid colony formation may be inhibited, so it may be necessary for lymphocytes to produce excessive sFasL in DBA patients. Further proof in future research.
2. Children with transient erythrocytosis
Children with TEC have a history of infection 2 months before diagnosis, usually a viral infection, which causes anemia of erythroid hematopoiesis. It is mainly caused by micro-viruses, because micro-virus can inhibit patients with normal erythroid hematopoiesis. The growth of CFU-Es, but only 20% of patients can find specific antibodies, the causal relationship between the two has not been confirmed, further detection of parvovirus antigen and DNA.
Peripheral blood and bone marrow cells cultured in TEC patients, found that half of the patients had decreased erythroid progenitor cells, and patients with anemia had elevated serum EPO levels. Some TEC patients could detect IgG or inhibitory factors against normal group cells in serum. Cellular immune-mediated inhibition of progenitor cells, TEC is caused by a virus infected with CFU-E, and the patient produces antibody IgG directly against erythroid progenitor cells, which can be recovered after the production of anti-idiotypic antibodies.
Prevention
Prevention of pure red blood cell aplastic anemia in children
Congenital pure red aplastic anemia is unknown, there is a clear family genetic tendency, so we should pay attention to genetic counseling, prevent secondary acquired pure red aplastic anemia, and actively prevent severe malnutrition, viral infection, malignant tumors, etc. Disease, while avoiding chemical poisoning and caution with chloramphenicol, phenytoin and so on.
Complication
Pediatric pure red blood cell aplastic anemia complications Complications congenital heart disease hemolytic anemia hemochromatosis thymoma
Congenital malformations, congenital heart disease, urethral malformation, Turner syndrome; severe anemia can be associated with heart failure; secondary to hemolytic anemia often occur in the aplastic anemia crisis; some children may be associated with hypogammaglobulinemia Long-term anemia can cause growth and development, and severely ill children can cause hemochromatosis due to repeated blood transfusions; severe thymoma can cause airway compression or irritation.
Symptom
Pediatric pure red cell aplastic anemia symptoms common symptoms red blood cell syndrome
The onset is slow, and the obvious anemia is more than 2 to 3 months after birth. About 15% of the sick children develop symptoms within a few days after birth, but there are symptoms that start to appear at the age of 1 or even at the age of 6 years. The incidence is higher, about 1/3 of the sick children have congenital malformations such as thumb three-knuckle malformation, congenital heart disease, urethral malformation, strabismus or appearance of Turner syndrome, but the karyotype is normal or XX/ XO chimera, except for clinical abnormalities, anemia is the only symptom, no bleeding, except for heart failure, liver and spleen are not swollen.
Primary acquired pure red aplastic anemia
(1) The onset is concealed, the disease progresses slowly, and anemia is the main manifestation. The degree of anemia is different. The application of iron, folic acid and vitamin B12 is not effective.
(2) No specific signs such as liver, spleen and lymphadenopathy.
(3) Some sick children may be associated with other immune dysfunction, such as hypogammaglobulinemia.
(4) Due to long-term anemia, growth and development may be delayed, and severely ill children may cause hemochromatosis due to repeated blood transfusions.
2. Secondary acquired pure red aplastic anemia
(1) The disease is more common in adults, children are less common, and the clinical manifestations are pure red blood cell aplastic anemia.
(2) Clinical can be divided into two types, secondary to thymoma is often chronic, and secondary to other diseases, such as hemolytic anemia, viral infection, drug poisoning, etc., often acute transient.
(3) Clinically, except for anemia, there are primary manifestations, such as thymoma may have mediastinal mass, severe cases may cause airway compression or irritation, drug poisoning has a corresponding history of drug exposure, secondary to hemolytic Anemia is often manifested as aplastic anemia, secondary to other diseases such as viral infections, autoimmune diseases, malignant tumors, etc. have obvious primary symptoms and manifestations.
Examine
Examination of pure red blood cell aplastic anemia in children
Blood picture
Peripheral blood red blood cell count and hemoglobin value decreased, generally severe positive cells, orthochromatic anemia, individual patients may have hemoglobin as low as 100g/L at birth, reticulocytes decreased or disappeared, and generally reticulocyte hemolytic anemia There may be abnormal red blood cell morphology unique to the primary disease, and there are no abnormalities in white blood cells and platelets.
2. Bone marrow
Bone marrow puncture has a decisive diagnostic significance. Although the serum erythropoietin increases, the red blood cell system in the bone marrow is extremely low, and the granulocyte: red blood cells can be as low as 50:1 or even 200:1. Red blood cells often have mature stagnation, such as secondary. Sexually acquired pure red aplastic anemia, bone marrow nucleated cells proliferate actively, but the erythroid immature cells are reduced or absent at each stage, and the granulocyte and megakaryocyte systems are normal.
3. Biochemistry
Serum iron increased, total iron binding capacity decreased, and erythrocyte enzyme activity was normal.
4. BFU-e culture
The erythroid progenitor cells are lacking in culture and are arrested in the primitive red blood cell stage.
5. Chromosome examination
Chromosome non-specific rupture and ectopic.
6. Other
Should do B-ultrasound, to understand whether there is hepatosplenomegaly, do other imaging examination to understand whether there is congenital heart disease, urethral malformation, etc., mainly for the special examination of various primary diseases, such as thymoma can have obvious X-ray Shows mediastinal shadows.
Diagnosis
Diagnosis and diagnosis of pure red blood cell aplastic anemia in children
diagnosis
According to the age of onset, reticulocyte and bone marrow in the diagnosis of simple erythroid hyperplasia is not difficult, but it must be noted whether the use of adrenal cortex hormones, such hormones can make erythroid hyperplasia, resulting in the diagnosis of difficulty.
1. Secondary acquired pure red aplastic anemia: positive cell pigmented anemia, can exclude all kinds of childhood nutritional anemia, no white blood cells and thrombocytopenia, bone marrow is pure red aplastic anemia, secondary to various types Diagnosis of primary disease is not difficult.
2. Congenital pure red cell aplastic anemia: Diamond has proposed the diagnosis of this disease as follows.
(1) Moderate or severe anemia of unknown cause from infancy.
(2) Reticulocyte reduction.
(3) White blood cells and platelets are normal.
(4) The bone marrow young red blood cells are reduced or absent.
(5) Some are accompanied by congenital malformations.
Differential diagnosis
In addition, it needs to be identified with the following diseases:
1. Transient erythroblastopenia (transient erythroblastopenia): This disease occurs mostly in 1 to 4 years old, has a history of viral infection, mild anemia, some children have neutropenia, hemoglobin F does not increase, and more natural recovery.
2. A variety of hemolysis of the aplastic anemia crisis: short duration, more symptoms of hemolysis.
3. Acute lymphocytic leukemia : lymphocytes in the bone marrow of some patients may be differentiated from acute lymphoblastic leukemia.
4. Nutritional anemia: Congenital pure red cell aplastic anemia is differentiated from various types of nutritional anemia common in childhood, such as iron deficiency anemia (IDA) and megaloblastic anemia due to folate or vitamin B12 deficiency. Occurred in the months after birth, severe cases can also reach moderate to severe anemia, must be identified, but nutritional anemia generally have a significant incentive or malnutrition history, all red blood cell morphology test indicators (MCV , MCH , MCHC) are abnormal For example, IDA is a small cell hypochromic anemia, folic acid and vitamin B12 deficiency have large blood cell changes, and the effect is improved after supplementation with folic acid, vitamin B12 or iron.
5. Congenital pure red aplastic anemia and acquired pure red aplastic anemia identification : the characteristics of hematopoietic system lesions of natural red aplastic anemia and acquired pure red aplastic anemia are similar, the treatment methods are basically the same, but congenital pure red aplastic anemia Early onset, often within 1 month after birth , some sick children with obvious congenital malformations, and acquired pure red aplastic anemia usually start later, acquired secondary pure red aplastic anemia often has obvious primary The cause can be found.
