aplastic anemia in children
Introduction
Introduction to pediatric aplastic anemia Aplasticanaemia (AA, abbreviated as aplastic anemia) is a comprehensive syndrome of bone marrow hematopoietic function due to various reasons, with a complete reduction of blood cells in the clinic and no swelling of the liver, spleen and lymph nodes. Clinical examinations such as bone marrow aspiration and bone marrow biopsy are used to confirm aplastic anemia. Those who have a good self-healing after aplastic anemia should be treated actively if they are diagnosed. basic knowledge The proportion of illness: 0.005% Susceptible people: children Mode of infection: non-infectious Complications: myocardial ischemia
Cause
Causes of childhood aplastic anemia
(1) Causes of the disease
Cause
(1) Primary: The cause is unknown, and it is more common in young adults.
(2) Secondary:
1 Drugs and chemical factors: There have been reports of aplastic anemia in dozens of drugs, but chloramphenicol is the most, and the mechanism of drug-induced aplastic anemia may be due to:
A. Toxic reaction: This is related to the size of the dose and is mostly reversible.
B. Individual acuity: It is poorly related to drug dose and often irreversible. Contact chemical factors such as benzene, paint, gasoline, pesticides, etc. are also related to aplastic anemia.
2 physical factors: a variety of ionizing radiation.
3 Infection factors: acute, chronic infections, including bacteria (typhoid fever, etc.), viruses (hepatitis, EBV, CMV, B19, etc.), parasites (malaria, etc.).
4 genetic factors: such as Fanconi anemia, pure red aplastic anemia, aplastic anemia can also be seen in twins.
5 other: paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome.
2. Classification
Pediatric aplastic anemia is divided into:
(1) Congenital (physical) or hereditary:
1 Fanconi anemia.
2 dyskeratosis congenita.
3Shwachman-Diamond syndrome is an intrinsic aplastic anemia with pancreatic dysfunction.
4 reticular dysgenesis (reticular dysgenesis).
5 no megakaryocytic thrombocytopenia (amegakaryocytic thrombocytopenia).
6 familal aplastic anemia, 7 pre-leukemia, myelodysplastic syndrome, chromosome 7 monomer.
8 non-hematologic syndromes such as Down, Dubowitz, Seckel syndrome, and the like.
(2) Acquirement:
1 idiopathic: the cause is unknown.
2 secondary: secondary to physical, chemical, biological factors, drugs, poisons, infections, hepatitis and so on.
A. Ionizing radiation.
B. Drugs and chemicals:
a. Unexpected: cytotoxic drugs, benzene, etc.
b. Specific constitution: chloramphenicol, anti-inflammatory painkillers, anti-epileptic drugs, gold preparations, etc.
C. Virus:
a. Herpes virus, Epstein-Barr virus and giant cell inclusion body virus.
b. Hepatitis virus: hepatitis B virus (HBV) and hepatitis C virus (HCV).
c. Microvirus Bl9.
d. Human immunodeficiency virus (HIV).
D. Immune diseases:
a. Eosinophilic fasitis (eosinophilic fascitis).
b. hypogammaglobulinemia.
c. Thymoma.
E. Pregnancy.
F. Paroxysmal nocturnal hemoglobinuria (PNH).
G. Pre-leukemia.
(two) pathogenesis
1. Heterogeneous hematopoietic stem cell deficiency or defect
The number of CD34 cells in the sick children was significantly reduced, and the proliferation ability of hematopoietic stem cells was decreased. More than 90% of the cultured colony forming units (CFU-C) in animal experiments and patient bone marrow stem cell cultures were lower than the normal values, and the erythroid outbreak colony forming units (BFU-E) ) and (CFU-E) are also lower than normal, and the cell cluster/colony ratio formed by CHU-C is increased, suggesting that CFU-C is impaired in self-renewal and proliferation. Further studies have found that hematopoiesis in children with aplastic anemia Stem cells are less reactive toward hematopoietic growth factors (HGFs).
2. Hematopoietic microenvironment defects
The hematopoietic microenvironment includes the microcirculation and matrix of the bone marrow. The normal bone marrow microenvironment is a necessary condition for maintaining normal hematopoiesis. Experiments have shown that when the bone marrow microcirculation is destroyed, even if the input stem cells can not grow, only the stem cells can be seen after microcirculation reconstruction. Regeneration, stromal cells can secrete many growth factors, such as stem cell factor (SCF), Flt3 (a hematopoietic stimulating factor ligand), IL-3, IL-11, etc., which can stimulate hematopoietic cell proliferation, differentiation and other functions. .
3. Immune disorders
Cellular immunity and humoral immune disorders lead to abnormal regulation of hematopoietic cell proliferation. Experimental data suggest that a large number of patients with aplastic anemia often have inhibitory T (CD3, CD8) lymphocytosis, helper T (CD3, CD4) lymphocyte reduction, CD4 /CD8 ratio inversion (normal range is different due to age and gender), II-2 is hyperactive, NK cells and interferon have increased activity of cells and factors that inhibit hematopoietic stem cell proliferation and differentiation, and humoral immune disorders can also cause re In the occurrence of dysfunction, some children with partial aplastic anemia may have anti-hematopoietic antibody in the plasma. The above pathogenesis may exist simultaneously in the same sick child, or may exist alone, or several factors may exist at different degrees at the same time. Clinical efficacy is susceptible to a variety of factors.
Prevention
Pediatric aplastic anemia prevention
The treatment of aplastic anemia is extremely difficult and the prognosis is poor. It is very important to prevent the occurrence of this disease. For secondary patients, the key is to eliminate the cause of aplastic anemia.
Chemical substance
Chemical substances, especially drugs, are the most common factors leading to aplastic anemia. Therefore, it is necessary to pay attention to rational use of drugs, avoid using chloramphenicol, antipyretic and analgesic drugs as much as possible, and strictly control the application of drugs that are harmful to the hematopoietic system. Prevent the abuse of drugs that are harmful to the hematopoietic system. At the same time, observe blood images regularly during use to avoid exposure to harmful chemicals such as benzene.
2. Strengthen protective measures
When contact with damage to hematopoietic system poisons or radioactive substances, various protective measures should be strengthened. Patients should reduce the number of radiological diagnosis and treatment as much as possible to avoid excessive radiation and regularly perform blood examination.
3. Prevention of viral infection
Vigorously carry out prevention and treatment of viral hepatitis and other viral infections. Viral infection is closely related to the onset of aplastic anemia. The most common is hepatitis virus. Aplastic anemia is secondary to non-A, non-B hepatitis, but not associated with hepatitis A. It is found that some patients with aplastic anemia have a history of cold before onset, indicating that some aplastic anemia can be secondary to the common cold. Therefore, strengthen physical exercise, pay attention to food hygiene, maintain a comfortable mood, combine work and rest, enhance the body's resistance, and prevent infection secondary. Aplastic anemia.
Complication
Pediatric aplastic anemia complications Complications, myocardial ischemia
Severe and rapid progression of the disease often accompanied by ischemia and hypoxia and cardiac dysfunction. Serious infections and visceral hemorrhage, especially intracranial hemorrhage often endanger children's lives. If repeated blood transfusions can cause hemosiderosis, leading to important organ damage. Can be complicated by heart dysfunction, lack of nutrition, growth disorders and so on.
Symptom
Symptoms of aplastic anemia in children Common symptoms Repeated infection of plaque cells reduces heart enlargement, fatigue, high fever, pale heart rate, increased heart palpitations, dizziness
Clinical features
(1) Onset: Most of the patients are chronic aplastic anemia, the onset is concealed, and the progress is slow until the symptoms are obvious. It is often difficult to confirm the exact onset time. Occasionally, light cases are found during physical examination. The acute aplastic anemia has a rapid onset and progresses rapidly, and the condition is progressively aggravated. Some secondary aplastic anemia can affect the pathogenic factors such as viral hepatitis, drugs, chemical drugs or radiation exposure.
(2) Clinical symptoms: The main clinical symptoms of aplastic anemia are anemia, hemorrhage and infection caused by the decline of peripheral blood, and the severity depends mainly on the degree of hemoglobin, platelet and granulocyte decline, and the type of aplastic anemia. Relationships are described as follows according to the types of obstacles.
1 Acute aplastic anemia (heavy aplastic anemia type I, SAA-I): Acute aplastic anemia has a rapid onset, rapid progress, dangerous condition, progressive aggravation of anemia, high frequency of blood transfusion, and often difficult to correct even if a large number of blood transfusions occur. Severe anemia, infection and hemorrhage can aggravate anemia. Because anemia is difficult to correct, clinical manifestations of pale, dizziness, palpitations, fatigue, and other manifestations of ischemia, hypoxia, and cardiac insufficiency, due to immune dysfunction and neutropenia, With severe infection, the original site of infection is more common in the oral cavity, respiratory tract, digestive tract, subcutaneous soft tissue and perianal tissue. Due to neutropenia (sepsis, subcutaneous soft tissue inflammation often occurs because of granulocyte deficiency can not form abscess, it is difficult to limit, Due to the extreme swelling of the facial cellulitis, the airway leads to suffocation and death. The pathogens are mainly Gram-negative bacilli and Staphylococcus aureus. Because of the frequent infections in the hospital, it is prone to Pseudomonas aeruginosa, Enterobacter cloacae and other resistant Infection with drug strains is also a secondary fungal infection due to repeated application of broad-spectrum antibiotics, due to a significant reduction in platelets (20 × 109 / L) The blood tends to be severe. In addition to skin purpura, a large amount of bleeding in the nasal mucosa of children requires temporary nasal filling to stop bleeding, or due to dental caries, tooth changes and damage caused by oral mucosal bleeding. In addition, it is easy to have internal bleeding, such as blood in the stool. Hematuria, especially intracranial hemorrhage, is life-threatening. It is often necessary to control a large number of platelets. Serious infections and intracranial hemorrhage are the causes of acute aplastic anemia. There have been statistics showing that if bone marrow transplantation or effective immunosuppressive therapy is not performed, With general drugs and supportive care, the average survival of SAA-I is only 3 months, and the mortality rate is 90% within half a year. Therefore, SAA-I is in fact as serious as acute leukemia.
2 Chronic aplastic anemia (CAA): Chronic aplastic anemia (CAA) refers to non-heavy aplastic anemia (NSAA), which is generally chronic aplastic anemia, with insidious onset, slow progress, and peripheral blood loss does not reach the level of severe aplastic anemia. Therefore, anemia, The degree of bleeding and infection is not as serious as that of severe aplastic anemia. However, due to the different degree of blood loss, the clinical manifestations vary greatly. Some of the mild cases may have only one or two lines of blood, and they do not have to rely on blood transfusion to maintain basic life. There is no obvious infection and bleeding tendency, while a small number of patients have a degree of decline in peripheral blood loss that does not reach the level of severe aplastic anemia, but may be significantly dependent on blood transfusion; or obvious infection and bleeding tendency, and most of the general chronic aplastic anemia is in front of Between the two, some patients with chronic aplastic anemia can be aggravated during the course of the disease, reaching the level of severe aplastic anemia and converting into chronic severe aplastic anemia.
3 Chronic severe aplastic anemia (heavy aplastic anemia-type II, SAA-II): Chronic aplastic anemia, such as worsening of the disease, as the disease progresses, the peripheral blood level drops to a certain extent to reach the standard of severe aplastic anemia, which is chronic severe aplastic anemia, although The severity of the third-line decline of chronic severe aplastic anemia is similar to that of acute aplastic anemia, but the clinical manifestations are not as good as acute aplastic anemia. For example, although the hemoglobin decline is obvious, the degree of severe anemia is often reached (the platelet life is shortened or even the infusion is invalid). Chronic severe aplastic anemia, if the condition cannot be controlled or does not improve for a long time, the final mortality rate is still high.
2. Physical examination
(1) General situation: lack of energy, fatigue, fatigue, moderate or above anemia may have low fever, if there is infection, there may be different degrees of fever, sick children due to long-term malnutrition can lead to weight loss, physical development and backward performance.
(2) skin, mucous membrane: showing varying degrees of anemia (face, lips, palpebral conjunctiva, nail bed, etc.), mucous membrane visible mucosa, severe bleeding tendency can be seen in large ecchymosis or subcutaneous hematoma, as well as gingival and nasal mucosal infiltration Blood, anemia and hemorrhage exist at the same time, but there is no jaundice, long-term dependence on blood transfusion, there may be hemochromatosis caused by hemosiderin.
(3) Hepatic spleen lymph node aplastic anemia: atrophic disease of the reticuloendothelial system, so the superficial lymph nodes are generally less affected and swollen, the tonsils are often absent in the pharynx, and there is no hepatosplenomegaly, especially no splenomegaly.
(4) Infection: When the peripheral blood granulocytes are significantly lower, the infection is difficult to trigger local inflammatory reaction, such as oral and pharyngeal infection, no local congestion; soft tissue infection without abscess formation, the boundary is unclear, so there is no obvious infection The person must consider the possibility of sepsis.
(5) Others: Anemia can cause heart rate to increase, systolic murmur in the anterior region, severe heart failure, and long-term anemia can lead to heart enlargement. Patients with visceral hemorrhage, such as intracranial hemorrhage, may have corresponding intracranial hypertension. Signs of the nervous system, often caused by incorrect long-term use of corticosteroids, the shape and appearance of drug-induced Cushing's syndrome. This disease is mainly characterized by progressive anemia, skin mucosa and/or visceral hemorrhage and repeated infection. More than no liver, spleen and lymph nodes.
Examine
Examination of aplastic anemia in children
1. Blood picture: The three lines of cells are reduced, showing positive cells, positive pigmented anemia, reticulocytes <1%; the total number of white blood cells is mostly reduced, but there are also normal ones. At this time, the relative value of lymphocytes is often increased.
2. Bone marrow: Acute type is low or severe hypoplasia, chronic type is mostly proliferative, visible focal hyperplasia, megakaryocytes are significantly reduced, non-hematopoietic cells are increased, lymphocytes plus non-hematopoietic cells in bone marrow granules are often >50 %, the degree of myeloproliferation can be divided into:
(1) hyperplasia extremely reduced type: multiple parts of bone marrow were not found or only a few hematopoietic cells, mostly reticular cells, plasma cells, tissue basophils, lymphocytes and fat cells.
(2) hypoplasia type: multiple parts or part of the bone marrow primitive or immature cells are absent, only a small number of hematopoietic cells, mainly mature type, non-hematopoietic cells.
(3) hyperplasia (normal) type: normal bone marrow hyperplasia, the number of megakaryocytes decreased, non-hematopoietic cells increased.
(4) Proliferative active type: erythroid or granulocyte is more common than normal, primitive and immature cells are also visible, megakaryocytes are rare, non-hematopoietic cells are rare, this type should exclude hemolytic anemia, and children with aplastic anemia more than two types see.
3. Determination of serum iron, magnesium and zinc: elevated blood iron, magnesium and zinc.
4. Serum EPO, free erythrocyte protoporphyrin (FEP), HbF chronic EPO, FEP and HbF increased.
5. Ts lymphocyte dysfunction: acute T, B lymphocytes are severely affected, NK cells and CD4 / CD8 ratio is significantly lower than chronic, chronic type mainly involving B lymphocytes.
6. Hematopoietic stem cell culture: CFU-E, GM-CFU decreased, chest X-ray showed heart enlargement; B-ultrasound without liver, spleen, lymph node enlargement; intracranial hemorrhage, brain CT examination should be done.
Diagnosis
Diagnosis and diagnosis of aplastic anemia in children
diagnosis
Clinical classification
(1) Acute aplastic anemia (also known as severe aplastic anemia type I, SAA-I):
1 clinical: acute onset, short course of disease (1 to 7 months), anemia is progressive, often accompanied by severe infection, skin, mucosal extensive bleeding or visceral bleeding, about 1/3 of the diseased liver may have mild swelling ( 1 to 3 cm below the ribs, but the spleen and lymph nodes are not swollen.
2 blood: in addition to the rapid decline in hemoglobin, must have 2 of the following 3 items:
A. Reticulocyte
(2) Chronic aplastic anemia:
1 Clinical: slow onset, long course of disease (more than 1 year), anemia, bleeding, infection 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. Three or two lines of cells are reduced, at least one part of the proliferative, such as focal hyperplasia, the proportion of erythrocytic common late red is increased, megakaryocytes are significantly reduced.
B. Increased number of adipocytes and non-hematopoietic cells in bone marrow granules.
4 When the chronic aplastic anemia worsens 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 (SAA-II).
2. Classification based on hematopoietic progenitor cell culture results
In addition, there are still 4 types of aplastic anemia based on the results of bone marrow hematopoietic progenitor cell culture:
(1) Hematopoietic stem cell defects (50% to 60%).
(2) Increase in T suppressor cells (21.4% to 33%).
(3) Increased inhibitory factor in the serum of patients (about 21.4%).
(4) Hematopoietic microenvironmental defects (about 7.1%).
Differential diagnosis
Aplastic anemia must be associated with leukemia, myelodysplastic syndrome, myelofibrosis, paroxysmal nocturnal hemoglobinuria (PNH), severe iron deficiency anemia, megaloblastic anemia, hypersplenism, bone marrow metastases, hematopoietic cell synthesis Identification, malignant histiocytosis, malignant lymphoma, etc. The main basis for identification is bone marrow smear, bone marrow biopsy, identification of congenital (physical) and acquired aplastic anemia.
