Hemolytic anemia in children

Introduction to hemolytic anemia in children Hemolytic anemia (haemolyticanaemias) is an anemia caused by the shortening and premature destruction of red blood cell life caused by various causes, and the destruction of red blood cells exceeds the compensatory capacity of bone marrow blood production and the red blood cell count and hemoglobin content decrease in circulation. The life span of normal red blood cells is 110 to 120 days. Under normal circumstances, about 1% of aging red blood cells are swallowed and destroyed in the spleen every day, replaced by new red blood cells, so as to maintain a constant number of red blood cells to play a normal physiological function. Normal children with large bone marrow hematopoietic potential can generally increase to 6-8 times normal. Therefore, if mild hemolysis, the number of red blood cells in the peripheral blood can be fully compensated by the increase of bone marrow hematopoietic function. At this time, although there is hemolysis in the clinic, there is no anemia; if the destruction of red blood cells exceeds the bone marrow hematopoiesis Hemolytic anemia occurs when compensatory. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: jaundice shock

Causes of hemolytic anemia in children

(1) Causes of the disease

1. Classification according to the location of hemolysis

According to the different parts of the hemolysis factor, hemolytic anemia can be divided into two categories: red blood cells and red blood cells.

(1) Red blood cell factors

(1) Defects of erythrocyte membrane: Defects in erythrocyte membrane structure may cause membrane permeability, hardness abnormality, or instability and breakage. In most cases, the defect is one or more backbone proteins, and the morphology of red blood cells is also abnormal. These hereditary membrane diseases, including hereditary spherocytosis, hereditary neutropenia, hereditary morphogenetic syndrome, hereditary malformation, hereditary apoptosus, paroxysmal nocturnal hemoglobin In urine, the erythrocyte membrane is abnormally sensitive to complement, but its membrane defect is an acquired abnormality.

(B) hemoglobin structure or production defects: abnormal hemoglobin structure, make hemoglobin insoluble or unstable, leading to red blood cell stiffness, and finally hemolysis. Found in globin-producing anemia, sickle cell anemia, hemoglobin H disease, unstable hemoglobin disease, other homozygous hemoglobin disease (CC, DI, EE), double heterozygous disorder (HbSC, sickle cell globin production barrier anemia).

(iii) Defects in erythrocyte enzymes: erythrocyte enzymes that maintain hemoglobin and the sulfhydryl group of the membrane in a reduced state or maintain a sufficient level of ATP for cation exchange may result in hemolytic anemia:

1 Lack of enzyme in erythrocyte anaerobic glycolysis: lack of pyruvate kinase, lack of phosphoglucose isomerase, lack of phosphofructokinase, lack of triose phosphate isomerase, lack of hexokinase, lack of phosphoglycerate kinase, aldehyde Lack of enzyme, lack of glycerate diphosphate mutase, and the like.

2 Lack of enzyme in erythrocyte phosphate hexose bypass: pyrimidine 5'-nucleotidase deficiency, adenosine deaminase too much, adenosine triphosphatase deficiency, adenylate kinase deficiency.

3 pentose phosphate pathway and enzyme deficiency related to glutathione metabolism: glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, glutamylcysteine synthetase deficiency, glutathione synthesis Enzyme deficiency, lack of glutathione reductase.

(2) Extracellular factors:

(1) Immune hemolytic anemia: A. Allogeneic hemolytic anemia: including neonatal hemolysis, blood group incompatibility anemia. B. Autoimmune hemolytic anemia: autoimmune hemolytic anemia caused by warm antibodies, autoimmune hemolytic anemia caused by cold antibodies, anemia associated with immune phenomena (graft rejection, immune complexes, etc.).

(2) Non-immune hemolytic anemia: including hemolytic anemia secondary to infection, microangiopathy and chemical and physical factors.

1 chemical, physical, biological factors: chemical poisons and drugs such as oxidizing drugs and chemicals, non-oxidizing drugs, benzene, benzoquinone, lead, arsenic hydroxide, sulfonamides, etc.; large area burn infection; biotoxin: uremia , hemolytic venom, poisonous scorpion poisoning, etc.

2 Traumatic and microvascular hemolytic anemia: artificial valve and other cardiac abnormalities, extracorporeal circulation, thermal injury (such as burns, burns, etc.), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, hemolytic uremic syndrome .

3 spleen hyperfunction.

4 plasma factors: A. Liver diseases: such as plasma cholesterol, fatty acid caused by fatty liver, cirrhosis, etc. caused by spur cell anemia. B. No beta lipoproteinemia. 5 Infectivity: A. Protozoa: Plasmodium, venom protozoa, kala-azar, etc. B. Bacteria: Clostridium infection (such as Clostridium), cholera, typhoid and the like. 6 hepatolenticular degeneration (Wilsons disease)

2. According to whether hemolysis is hereditary or secondary

(1) Hereditary: Same as the intraerythrocyte factor.

(2) Acquired: Same as the extracellular factor.

(two) pathogenesis

Premature destruction of red blood cells can occur extravascularly or intravascularly. Extravascular hemolysis, that is, red blood cells are destroyed by phagocytosis by spleen and macrophages in the liver (mononuclear-macrophage system). Intravascular hemolysis is the rupture of red blood cells directly in the blood circulation, and the content of red blood cells (hemoglobin) is directly released into the plasma. The red blood cells in the blood vessels are destroyed in a large amount, the hemoglobin is released into the blood circulation, hemoglobinemia occurs, and the free Hb (normal 0.02-0.05 g/plasma) in the plasma is increased (the plasma is pink or red). Free Hb pathway: 1 binds to haptoglobin (Hp) in plasma to form Hp-Hb complex and participates in biliary pigment metabolism in mononuclear-macrophage system. If the plasma has more free hemoglobin, the plasma may be pink, but since the methemoglobin is brown and the methemoglobin is brown, the pink color is masked and not easy to see. 2 When the Hp binding capacity is exceeded, it is filtered out from the glomerulus, hemoglobinuria appears, and some can be reabsorbed by the renal tubules, which are decomposed into porphyrins in the epithelial cells, and the porphyrins enter the blood circulation to form bile pigments, and the latter two are reused. Part of the hemosiderin is present in the epithelial cells, and is excreted from the urine (with hemosiderin urine) as the epithelial cells fall off. The methemoglobin is large in the molecule and does not appear in the urine. 3 Isolation of free hemin, binding to -glycoprotein in plasma to methemoglobin or hemopexin (Hx), and then into the mononuclear-macrophage system.

Pediatric hemolytic anemia prevention

Actively carrying out prenatal and postnatal care, pre-marital screening can significantly reduce the chances of birth. Promote prenatal diagnosis technology. For both parents and one of the thalassemia gene carriers, collect fetal villi, amniocytes or cord blood at 4 months of pregnancy, and obtain genomic DNA for polymerase chain reaction (PCR) technology for high-risk fetuses. Pre-diagnosis.

Should pay attention to rest, adjust the diet, eat less spicy and hot products; adjust the emotions, do not overwork, prevent colds, pay attention to avoid cold and keep warm.

Take necessary measures to actively prevent various infectious diseases, do a good job of vaccination, and avoid hemolysis caused by drugs, chemical poisons and physical and mechanical factors.

Vitamin E can be taken in an appropriate amount to prevent hemolytic anemia caused by lack of vitamin E.

Pediatric hemolytic anemia complications Complications

Concomitant jaundice, can have varying degrees of jaundice, spleen, hepatomegaly, gallstones are more common complications, bilirubin bile can occur in newborns, obstructive jaundice can occur.

Concurrent thrombosis: The interaction between the platelet membrane and plasma complement of this disease is abnormal, resulting in hypercoagulable state and thrombosis. The thrombosis of the lower extremity vein and mesenteric vein is more common. Abdominal vein embolism can cause portal hypertension.

Concurrent ulcers: patients with sickle cell anemia have ulcers on the skin of the lower extremities and are not easy to heal.

Concurrent with various crises: aplastic anemia, hemolytic crisis, giant cell anemia crisis.

Complicated failure: acute renal failure, liver failure, heart failure, DIC, etc.

In severe cases, there may be apathy or coma, shock and heart failure.

Symptoms of hemolytic anemia in children Common symptoms Frail pale complexion skin mucous membrane pale hemoglobin urinary lips pale nausea chills dizziness circulatory failure proteinuria

Most of the clinical manifestations of various hemolytic anemia lack specificity, which is related to the urgency, degree and location of hemolysis. The performance is diverse, but it has something in common. The child's skin, lips, conjunctiva, earlobe, palm and nail bed are pale, tired, and muscle weakness. May have jaundice, asthma, rapid heart rate, loss of appetite, dizziness, cold and other symptoms.

Acute hemolysis

Generally for intravascular hemolysis, acute onset, manifested as fever, chills, high fever, pale, jaundice; in addition to nausea, vomiting, chest tightness, abdominal pain; and backache, back pain, oliguria, no Urine, soy sauce color urine (hemoglobinuria), and even kidney failure. Anemia is aggravated quickly, when it is severe, it is indifferent or coma, and even peripheral circulatory failure occurs, shock.

2. Chronic hemolysis performance

Generally for extravascular hemolysis, symptoms and signs are often not obvious. Since the rate of hemolysis does not exceed the ability of bone marrow to compensate, anemia may not occur, and jaundice is not heavy. The ability of the liver to clear bilirubin is strong, and jaundice does not occur. Typical manifestations are anemia, jaundice, and splenomegaly. Symptoms are often fatigue, pale, shortness of breath, dizziness and so on. In addition to liver splenomegaly and jaundice, gallstones are more common complications, and obstructive jaundice can occur. There may also be bone pain and chronic ulcers in the lower extremities. Such hemolysis is common in hemolysis of hemoglobinopathy, hemolysis caused by abnormal erythrocyte membranes, and the like. There may be acute hemolysis and sudden onset of bone marrow failure during the course of the disease.

Normal children with large bone marrow hematopoietic potential can generally increase to 6-8 times normal. Therefore, when mild hemolysis, the number of red blood cells in the peripheral blood can be fully compensated by the increase of bone marrow hematopoietic function. At this time, although there is hemolysis in the clinic, there is no anemia. This state is called compensatory hemolysis. Sexual disease. If the destruction of red blood cells exceeds the compensatory capacity of bone marrow hematopoiesis, hemolytic anemia occurs.

Examination of hemolytic anemia in children

Blood test

(1) Blood: reduced red blood cell count, decreased hemoglobin, and increased reticulocyte (3% or more).

(2) Blood test: The morphology of red blood cells may change, or immature red blood cells and/or immature granulocytes may appear. Due to the compensatory increase in erythropoiesis, red blood cells vary in size and shape, and red blood cells carry nuclear or nuclear residues.

(3) Na252CrO4 labeled red blood cells measured the life of red blood cells, and their half life was significantly shortened.

(4) If hemolytic anemia has thrombocytopenia, bone marrow examination and DIC examination, such as coagulation test and 3P test, should be performed to exclude other diseases associated with hemolytic anemia. Bone marrow erythroid hyperplasia is active, and the ratio of granules: red is reduced or even inverted.

(5) Increased serum indirect bilirubin: However, if serum indirect bilirubin is not high, hemolytic anemia cannot be ruled out.

(6) Increased plasma free hemoglobin: or hemoglobinemia, which is more common in acute intravascular hemolysis, but can also occur in a large number of extravascular hemolysis, generally indicating a large amount of hemolysis.

(7) Reduction or disappearance of plasma-bound globin: Intravascular hemolysis is more common, indicating that the amount of hemolysis is larger, which is a more sensitive indication. Generally, after 3 to 4 days of hemolysis termination, plasma-bound globin is gradually restored. normal. Infections and malignant tumors can increase the binding of globin; while in liver disease, it can be reduced, and attention should be paid to the identification.

(8) Plasma methemoglobin (Schumm test positive): Sustained for many days after hemolysis, especially valuable for diagnosis.

2. Urine check

(1) Increased urinary bile: normal is 0 ~ 3.5mg / kg, increased in acute hemolysis, but the increase in chronic hemolysis is not obvious. As an indication of hemolysis, it is necessary to exclude liver dysfunction. The amount of fecal gallbladder is increased quantitatively.

(2) Hemoglobinuria (urinary occult blood test) positive: When a large amount of hemolysis occurs, the free hemoglobin is excessively produced, which exceeds the binding ability of the bound globin. At this time, the free hemoglobin can be filtered from the glomerulus and discharged from the urine, that is, Become hemoglobinuria. When the hemoglobinuria occurs, the benzidine test is positive. However, as an indication of hemolytic anemia, it is necessary to exclude positivity due to hematuria or myosinemia.

(3) Hemosiderin urine (Rous test) is positive: Hemosiderin is a hemoglobin reabsorbed by the renal tubules and decomposed into hemoglobin, which is further decomposed into protoporphyrin and iron. If too much iron is decomposed, The form of hemosiderin is deposited in the epithelial cells of the renal tubules, and when the cells fall off, they are excreted in the urine to become hemosiderin.

3. Determine the cause of hemolysis

Experiments on red blood cell detection:

(1) Observation of erythrocyte morphology: increased spherocytosis, found in hereditary spherocytosis and immune hemolytic anemia; target cells suggest thalassemia, hemoglobin E disease, hemoglobin C disease, etc.; helmet-shaped cells, broken cells, indicating machinery Sexual hemolytic anemia; sickle cells, indicating sickle cell anemia, often in small numbers.

(2) Red blood cell salt osmotic fragility test: The red blood cell osmotic fragility test indicates the ratio of the surface area to the volume of red blood cells, and the congenital non-immune hemolytic anemia can be initially classified. If the surface area/volume ratio of red blood cells is reduced, the brittleness is increased, suggesting an abnormal disease of erythrocyte membrane; when the surface area/volume ratio of red blood cells is increased, the brittleness is lowered, and hemoglobin disease is often indicated; and the erythrocyte fragility is normal, suggesting a erythrocyte enzyme deficiency disease.

(3) Determination of erythrocyte enzyme activity: It has a definite diagnostic significance for erythrocyte enzyme deficiency. Since erythrocyte enzyme deficiency is less common, erythrocyte enzyme activity measurement is generally considered after excluding other common hemolytic causes.

(4) Acid hemolysis test: The patient's red blood cells were mixed with normal normal serum supplemented with 1/6 N hydrochloric acid. After incubation for 1-2 hours in a 37 ° C incubator, hemolysis was observed, which was positive, and positive results indicated paroxysmal nocturnal hemoglobinuria. The saccharification hemolysis test was also used as a screening test for the diagnosis of paroxysmal nocturnal hemoglobinuria.

(5) The sucrose hemolysis test and the hot hemolysis test were positive in PNH. If there are a large number of red blood cell fragments in peripheral blood, it may be considered as red blood cell debris syndrome, including microangiopathic hemolytic anemia, hemolytic uremic syndrome, paroxysmal marching hemoglobinuria, thrombotic thrombocytopenic purpura, artificial heart valve device. , DIC, etc.

(6) Autolysis test: Hemolysis can be corrected by ATP without being corrected by glucose, suggesting a lack of pyruvate kinase.

Experiment on hemoglobin

(1) Hemoglobin electrophoresis: It has a definite diagnostic significance for hemoglobin disease.

(2) Anti-human globulin test (Coombs test): This test is a basic test for identifying immunological hemolytic anemia and non-immune hemolytic anemia. Coombs test is positive, suggesting immunological hemolytic anemia; Coombs test is negative, generally It suggests that its hemolytic anemia is non-immune.

(3) methemoglobin reduction test: the normal methemoglobin reduction rate is >75%, and the reduction rate is decreased when G-6PD is lacking. In addition, the positive results of the fluorescence spot test, the ascorbate-cyanide test and/or the denatured globin vesicle formation test also indicated a lack of G6PD. G6PD lacks a definitive assay that requires enzyme quantification. The erythrocyte hemolysate is incubated with G6PD and NADP, and the reduction rate of NADP to NADPH is determined by spectrophotometer at 340 nm.

(4) Isopropanol test and/or heat denaturation test: A positive result indicates unstable hemoglobin.

4. Imaging examination

1. B ultrasound: visible liver, splenomegaly, gallstones (chronic hemolytic anemia).

2. X-ray inspection:

(1) Chest X-ray examination to understand the heart and lungs.

(2) Bone X-ray changes bone X-ray examination of cortical bone thinning, widening of the bone marrow cavity, the skull showed a brush-like change.

Diagnosis and diagnosis of hemolytic anemia in children

diagnosis

Ask the medical history for a positive family history, or history of infection, medication, blood transfusion, and past seizures. There are clinical manifestations of anemia, jaundice and splenomegaly. The possibility of the presence of hemolytic anemia should be considered. Laboratory examination of peripheral blood red blood cells and hemoglobin decreased to varying degrees, reticulocytes increased, may have red blood cell morphology abnormalities. Serum indirect bilirubin and LDH are elevated. Red blood cell life is shortened. Urine hemoglobin was positive and urinary bile increased. Bone marrow like young red blood cells proliferate, the ratio of redness is reduced or inverted. Congenital hemolytic anemia erythrocyte fragility test, blood test abnormalities. Acquired hemolytic anemia was positive for the Coombs test.

Differential diagnosis

Identification of various types of hemolytic anemia:

According to the positive or negative of direct and indirect tests of anti-human globulin (Coombs) to distinguish immunity (Coombs test positive, blood type is not hemolysis) and non-immunity (Coombs test negative); non-immune hemolytic anemia can be based on red blood cell morphology, Brittleness test, glucose incubation fragility test, methemoglobin reduction test, acid hemolysis test (Ham's), D55/CD59 flow cytometry analysis, Hein's body, hemoglobin electrophoresis, etc. Caused by hemolytic anemia.

1. Autoimmune hemolytic anemia: warm antibody type AIHA is mostly chronic onset, easy to repeat, some patients have a history of acute attacks, chills, fever, jaundice, back pain, etc. during hemorrhage, hemoglobinuria is common in paroxysmal Cold cold hemoglobinuria, rarely seen in cold agglutinin disease, often repeated, and difficult to control later. Sometimes the destruction of red blood cells can be compensated by the formation of bone marrow erythropoiesis, and there is no clinical anemia, that is, only autoimmune hemolysis (AIH).

2. Thalassemia: is a group of hereditary hemolytic anemia. A common feature is that one or more of the globin peptide chains in hemoglobin are reduced or not synthesized due to defects in the globin gene. Lead to changes in the composition of hemoglobin, the clinical symptoms of this group of diseases vary in severity, mostly manifested as chronic progressive hemolytic anemia.

3. Nutritional iron deficiency anemia: the disease is mainly characterized by anemia, pay attention to the identification of thalassemia and hereditary polycythemia. The red blood cell morphology of iron deficiency anemia showed no significant abnormal changes except for the expression of low heme small cells, and the serum iron and iron, serum iron and bone marrow cells decreased.

4. Jaundice hepatitis or cirrhosis: The disease is accompanied by hepatosplenomegaly and jaundice. In a few cases, liver function damage may also occur, so it is easily misdiagnosed as jaundice hepatitis or cirrhosis. However, it can be identified by medical history inquiry, family survey, red blood cell morphology observation, and hemoglobin electrophoresis.

5. Hemolytic uremic syndrome: This disease has hemolytic activity such as jaundice and anemia in the clinic, and sometimes it is easily misdiagnosed as hemolytic anemia. However, the disease also has thrombocytopenia and acute renal failure, which can be identified according to clinical symptoms and laboratory tests.

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