Pancytopenia (PCP) is a common clinical syndrome characterized by peripheral blood with hemoglobin (Hb) < 90 g/L, white blood cells (WBC) < 4. 0 × 109/L and platelets (PLT) < 100 × 109/L for at least 2 consecutive times. The main clinical symptoms are anemia, bleeding and recurrent infections. There are many causes of pediatric hematocrit reduction, including: (1) bone marrow production disorders, which mainly include hypoplasia/invalid hematopoiesis, insufficient hematopoietic material, and malignant cell "occupancy"; (2) excessive peripheral consumption of blood cells, such as hypersplenism, autoimmune diseases caused by hematocrit reduction, etc. In this paper, we only briefly review the main diseases in order to help pediatricians in their clinical work. Aplastic anemia (AA) is caused by the failure of bone marrow hematopoiesis, and the basic hematologic manifestations are a marked decrease in peripheral blood trisomies and a decrease in bone marrow hematopoietic cells. The hereditary diseases with allogeneic cytopenia are also called bone marrow failure syndromes, mainly congenital aplastic anemia (Fanconi anemia), Schwachman-Diamond syndrome, congenital dyskeratosis congenita, anaplastic thrombocytopenic purpura ( Amegakaryocytic thrombocytopenia), etc. In the diagnosis of acquired aplastic anemia, hereditary AA should be excluded. There have been many studies on the etiology of acquired AA, and some studies have concluded that the disease should also be an autoimmune disease, or at least due to abnormal immune mechanisms, and it has also been found that excessive telomere shortening and increased telomerase activity in bone marrow cells are among the causes of hematopoietic cell failure. The clinical severity of acquired AA varies greatly, but in the majority of patients, thrombocytopenia is the most prominent of the three lineages, i.e., the megakaryocyte lineage is the first to be involved, and in some pediatric cases, neutropenia is less severe. At present, most foreign countries classify acquired AA into 3 types: heavy AA (SAA), ① neutrophils <0.5×109/L, ② platelets <20×109/L, ③ absolute number of reticulocytes <60×109/L, 2 out of 3 should be met, bone marrow manifestations: nucleated cells <25%, or nucleated cells 25%~50% but hematopoietic cells <30%; very heavy AA ( VSAA) with neutrophils <0.2×109/L, other conditions are the same as heavy AA; non-heavy AA, with complete cytopenia but not the above conditions of heavy AA. In terms of treatment, the preferred treatment for SAA with a matched sibling donor (MRD) is allogeneic bone marrow transplantation, and the cure rate of MRD transplantation for heavy AA <30 years old reported abroad is 70%-90%. If no suitable marrow donor is available, immunosuppressive therapy should be administered, with the combination of anti-thymocyte globulin/anti-lymphocyte globulin (ATG/ALG) and cyclophilin A (CSA) preferred, or monotherapy, with an efficiency rate of 60% to 76%. High-dose cyclophosphamide for the treatment of acquired AA is under investigation. The customary practice of non-heavy AA abroad is based on symptomatic management, mostly without interventional therapy, while androgen-based treatment to stimulate hematopoiesis is mostly used in China. The main diseases that should be routinely excluded from the diagnosis of acquired AA are acute hematopoietic arrest, paroxysmal sleep hemoglobinuria (PNH), and refractory anemia (RA) in myelodysplastic syndrome (MDS). Acute hematopoietic arrest, also known as hemolytic aplastic crisis (aplastic crisis), is mostly seen in various hemolytic anemias, and its occurrence is associated with microvirus B19 infection, which mostly has a self-limiting course. Although paroxysmal sleep hemoglobinuria (PNH) is rare in pediatric patients, the proportion of CD55 and CD59 positive erythrocytes should be routinely tested for the diagnosis of AA in order to exclude PNH, which is a benign clonal disease in which accelerated decay factor (DAF, CD55) on the surface of the erythrocyte membrane, membrane inhibitor of reactive hemolysis (MIRL, CD59), and membrane inhibitor of reactive hemolysis (MIRL, CD59) are glycosylated by the glycosylation process. CD59) are attached to the cell membrane via glycosylated phosphatidylinositol (GPI), and defects in GPI in PNH cause deficiency of CD55 and CD59 on the erythrocyte membrane. Flow cytometry detects the absence of CD55 and CD59 expression in some peripheral blood or bone marrow blood cells, which has both confirmatory value and can quantify these abnormal cells, and is currently the most sensitive and specific method for diagnosing PNH. 2.myelodysplastic syndrome Myelodysplastic syndrome (MDS) also belongs to the category of hematopoietic failure and is a malignant clonal disease. The cause of MDS is not well understood, as it is believed that the "ineffective hematopoiesis" in the bone marrow is due to excessive apoptosis and stagnation of hematopoietic precursor cells. Only granulocytopenia combined with thrombocytopenia or first lineage hematocrit reduction is rare. MDS should be differentiated from non-severe AA (chronic AA), which is sometimes not easy to distinguish. Some of the diagnosed pediatric MDS patients can be found to meet the diagnostic criteria of adult MDS (diagnostic criteria of the FAB group), with the two types of RA and refractory anemia in transformation (RAEB) being the most common, and some children are diagnosed with juvenile granulocytic-monocytic leukemia (JMML), a type different from chronic granulocytic leukemia (CMML) in adult MDS, although MDS has a poor prognosis and no specific treatment is available. The prognosis for MDS is poor and there is no specific treatment. Depending on the staging, treatment may include symptomatic support, hematopoietic stimulation, induction of differentiation, chemotherapy, etc. Allogeneic bone marrow transplantation is the only way to cure the disease. About 1/3 of pediatric MDS turns into leukemia within 2 years. 3, hemophargocytic syndrome Hemophagocytic lymphohistiocytosis (HLH) is a reactive disease of the monocyte/macrophage system, manifested by fever, hepatosplenomegaly, hematocrit, hematocrit, abnormal liver function, and hemorrhage. HLH is classified as familial or secondary, the latter can be secondary to infections, tumors, rheumatic immune diseases, etc. The basic diagnostic criteria for HLH must meet five criteria: (i) persistent fever (≥7 days, maximum temperature ≥38.5°C), (ii) fever (≥7 days, maximum temperature ≥38.5°C), and (iii) fever. 38.5°C), ② splenomegaly, ③ holocytopenia, ④ hypertriglyceridemia and/or hypofibrinogenemia, ⑤ increased phagocytosis found in bone marrow or spleen or lymph nodes without evidence of malignant disease. Familial HLH has been found to have low killing function of T- and NK-cells, a defect in the perforin gene, and multi-organ functional impairment associated with hypercytokinemia in vivo.HLH disease progression is very rapid and mortality is high. The primary root treatment for familial HLH is allogeneic bone marrow transplantation, and the preferred treatment for HLH is chemotherapy/immunotherapy, which is also required to prepare the patient for transplantation before transplantation. About half of the patients have their disease controlled with these treatments. 4. Megaloblastic anemia Megaloblastic anemia is a type of anemia caused by a deficiency of folic acid and/or vitamin B12. The most common type of megaloblastic anemia in pediatrics is nutritional megaloblastic anemia, which is mostly due to dietary factors and is more common in infants and children. The hematologic manifestations are macrocytic anemia, with megaloblastic changes in the granulocytic and megakaryocytic lineages in addition to the involvement of the erythrocytic system, which may result in a complete blood cytopenia, but not in all cases. In the bone marrow, megaloblastic changes and excessive nuclear lobulation of all cell lines are seen. In addition to the general manifestations of anemia, neuropsychiatric symptoms such as dullness of expression, unresponsiveness to the outside world, retardation of intellectual and motor development, and even regression are also seen. The diagnosis of nutritional megaloblastic anemia can be made initially based on the diet, clinical manifestations and hematological manifestations, and the diagnosis can be confirmed by the effectiveness of folic acid or/and vitamin B12 treatment, and when available, plasma folic acid and vitamin B12 concentrations can be measured. Another group of diseases manifesting as megaloblastic anemia is caused by impaired absorption, transport or metabolism of folic acid or vitamin B12, including hereditary diseases and acquired diseases, which are rare in pediatrics. 5, the hematopoietic system malignant tumors and other tumor bone marrow infiltration Pediatric hematopoietic system malignant tumors cause the decrease of whole blood cells are mainly acute leukemia, of which 70% are acute lymphoblastic leukemia (ALL), the rest are acute myeloid leukemia (AML) and so on. The clinical manifestations are mainly anemia, bleeding, infection and infiltrative manifestations such as enlarged liver and spleen lymph nodes. Some patients with acute leukemia may have decreased WBC at the beginning of the disease, along with decreased Hb and PLT, and the clinical manifestation is whole blood cytopenia. It is important to note that peripheral blood smears often reveal leukemic cells, and bone marrow aspiration smears can confirm the diagnosis. Pediatric acute leukemia chemotherapy is far more effective than adult, and the use of combined, intense, continuous and targeted chemotherapy can cure most pediatric acute leukemias. Another hematopoietic malignancy is non-Hodgkin's lymphoma (NHL), which is a malignant tumor originating in the lymph nodes and other lymphoid tissues. The main clinical manifestations are painless, progressive, non-inflammatory enlargement of the cervical lymph nodes and mediastinal masses, as well as symptoms of pressure caused by enlarged lymph nodes (cough, shortness of breath, abdominal pain, diarrhea, nausea, vomiting, etc.) and other lymphatic tissue involvement. The final diagnosis depends mainly on the pathological results of lymph node biopsy. Treatment is based on chemotherapy. Modern chemotherapy can also cure most children with NHL. Other pediatric malignancies that present early with bone marrow metastases are neuroblastoma (NB) - malignant tumors that originate from neural crest cells of the embryonic sympathetic nervous system. The age of onset is <5 years in most cases. The adrenal gland is the most frequent site of origin, presenting as a painless mass in one quarter of the rib cage, which may extend beyond the midline, irregular and hard, and can occur anywhere along the sympathetic axis in the neck, mediastinum, abdomen, and pelvis. 75% of cases have systemic metastases by the time of diagnosis, with bone and bone marrow metastases being the most common. Bone metastases cause bone pain, and extensive bone marrow metastases can cause complete blood cytopenia, and a large number of tumor cells can be seen in the bone marrow. For patients with advanced disease, especially those with extensive metastases, autologous bone marrow rescue (autologous bone marrow transplantation) can be performed after mega-dose chemotherapy. 6. Hypersplenism Clinical manifestations of hypersplenism include splenomegaly and one or more types of blood cell reduction, with corresponding increase in bone marrow hematopoiesis and decrease in whole blood cells, mostly in patients with advanced disease. There are many reasons for hypersplenism in children, but the following are the most common ones: (1) infection, most often viral hepatitis, malaria, etc.; (2) congestive splenomegaly caused by portal hypertension, often combined with hypersplenism, such as hepatic sclerosis, hepatomegaly, etc.; (3) chronic hemolytic anemia, such as hereditary spherocytosis, thalassemia, etc.; (4) autoimmune diseases; (5) lysosomal storage disease, which is mostly autosomal recessive inheritance. The cause of the disease is an impairment in the synthesis of one of the lysosomal enzymes, causing the deposition of intermediate metabolites in a variety of tissues, organs and cells; the spleen is a common organ of deposition, and the most common types are Gaucher disease (Gaucher disease) and Niemann-Pick disease (NPD), the former being due to a decrease in b The former is due to a decrease or deficiency of b-glucocerebrosidase, which prevents the breakdown of glucocerebrosides, and the latter is due to a congenital deficiency of sphingomyelin, which prevents the normal breakdown of sphingomyelin, resulting in a large number of lipid-laden foam cells in the mononuclear macrophage system (liver, spleen, etc.) and in the nervous system. The neurological manifestations are prominent in those with early onset of disease, such as developmental delay, mental retardation, and convulsions. The hepatosplenomegaly, especially after the splenomegaly is obvious, may show anemia, hemorrhage and other signs of complete cytopenia. The finding of foamy cells (e.g., Gaucher cells, Niemann-Pick cells, etc.) by bone marrow aspiration can identify such diseases, but the final type of enzyme defect should depend on enzymatic examination or genetic diagnosis. Currently, except for Gaucher disease, which can be treated with enzyme replacement therapy, the rest can only be treated symptomatically, and allogeneic bone marrow transplantation is one of the treatment options. 7. Autoimmune diseases and other diseases causing allogeneic cytopenia In the diagnosis of allogeneic cytopenia, there is a group of diseases that often need to be clinically excluded, namely autoimmune diseases, the most important of which is systemic lupus erythematosus (SLE), which is a multi-systemic disease, and the hematological system is also a commonly involved system. Statistics show that most children with SLE have hematologic involvement, mainly in the form of anemia with reticulocytosis and positive Coomb's test, leukopenia in about 50% of children, and thrombocytopenia in 15%-30%. Some children have first signs of first-line, second-line, or even whole blood cytopenia. Some severe infectious diseases (sepsis, cornual tuberculosis, typhoid, etc.), EBV, CMV, HIV and other viral infections, uremic syndrome, and certain medications have their own clinical features, and it is not difficult to distinguish them. The treatment principle is to treat the primary disease.