ABO hemolytic disease of the newborn
Introduction
Introduction to neonatal ABO hemolytic disease Hemolytic disease (newborn), also known as fetal erythroblastosis, belongs to the same family of immuno-hemolytic anemia (iso-immunehemolyticanemia), which refers to immune hemolytic anemia caused by blood group antibodies. It is caused by the incompatibility of maternal and child blood types, and it is one of the most common causes of neonatal hyperbilirubinemia, and it has an early onset and rapid progress. In severe cases, it can cause jaundice, so it is a disease worthy of attention. . basic knowledge The proportion of illness: 0.02% Susceptible population: multiple newborns with mother-child ABO blood group incompatibility Mode of infection: non-infectious Complications: anemia, neonatal bilirubin encephalopathy, heart failure, neurological deafness
Cause
Causes of neonatal ABO hemolytic disease
Maternal factor (65%):
ABO hemolytic disease is the most common type of maternal and child blood type incompatibility, mainly in the mother O type, fetal type A or B type, other blood types are rare.
Body factor (35%):
Because the fetus receives the maternal (through the placenta) homologous immune antibody, the disease condition is that the mother has been stimulated by the heterologous antigen to produce the corresponding immune antibody, and the antibody produced by the mother enters the fetus through the placenta, and the fetus is immunosensitive to the antibody. Sexually ill.
Pathogenesis
Most of the mothers of the affected patients are O-type, with immune anti-A and anti-B antibodies; most of the infants are type A, especially in A1 followed by A2, and type B, more common in O-type mothers, due to mothers' anti-A, Anti-B antibody is not only a natural antibody belonging to IgM, but also an immune antibody against IgG. In the serum of type A(B), it is mainly anti-B(A)IgM, and very few anti-B(A)IgG, and IgM antibody. Can not pass the placenta, immune anti-A or anti-B antibody (IgG) can pass through the placenta, antibodies into the fetus, attached to the corresponding erythrocyte membrane of the fetus, and its antigen immunoreactivity and hemolysis, ABO hemolytic disease can be the first The incidence of fetal disease, this is because the mother produces immune IgG antibodies, in addition to stimulation by red blood cell antigens, can also be produced by a variety of non-specific stimuli, because blood group substances with ABO can exist in a variety of tissue cells and body fluids, such as serum , saliva, gastric juice, ovarian cyst fluid, semen, amniotic fluid, sweat, urine, tears, bile, milk; and immunity caused by intestinal parasite infection, injection of typhoid vaccine, tetanus or diphtheria toxoid Sex antibodies, There are so many in pregnant women can stimulate the production of antibodies, so pregnant women before pregnancy already have these antibodies, the first tread can be sick.
Mothers with immune antibodies, although their fetuses are not compatible with their ABO blood type, are not necessarily ill. This is due to the antibodies from the mother, which are bound by the blood type substances present in the fetal plasma and tissues, preventing the effects of antibodies on red blood cells, and also due to the fetus. The antigen density on the surface of the red blood cells is small, so the amount of bound antibodies is small and does not cause symptoms.
Women with immune antibodies in the case of a baby with ABO hemolytic disease after giving birth, after pregnancy, according to Mothan analysis of a large number of data found that about 1/3 of the newborn is more serious than the first child, one third of the newborn The child is similar to the first child, and the other 1/3 is lighter than the first child.
Prevention
Neonatal ABO hemolytic disease prevention
Pregnant women with a history of unexplained stillbirth, abortion, blood transfusion history or neonatal severe jaundice should be identified, identified as early as possible and actively treated, often turning the child into safety.
Complication
Neonatal ABO hemolytic disease complications Complications anemia neonatal bilirubin encephalopathy heart failure neurological deafness
Concurrent fetal edema is relatively rare, can occur anemia, hyperbilirubinemia, and often complicated by bilirubin encephalopathy, heart failure, cholestasis syndrome, bilirubin encephalopathy surviving children, can leave high frequency neurological deafness, hand , Xu Xudong and cerebral palsy.
Symptom
Newborn ABO hemolytic disease symptoms Common symptoms Maternal and child ABO blood group incompetent jaundice jaundice stagnation severe anemia dead liver splenomegaly red blood cell life shortened
The symptoms of ABO hemolytic disease vary greatly. Mild jaundice is mild, and it is easy to be regarded as physiological jaundice and missed diagnosis. Some only show advanced anemia. In severe cases, stillbirth can occur, severe jaundice or severe anemia, liver enlargement. Nuclear jaundice can occur in severe cases, but splenomegaly is rare.
Compared with Rh hemolytic disease, the symptoms are mild, the clinical manifestations are mainly jaundice, jaundice appears earlier (24 ~ 36h) and deepens, serum bilirubin can reach 255mol / L (15mg / dl) or more, a few more than 340mol / L (20mg / dl), if not treated in time can also be complicated by bilirubin encephalopathy, anemia, hepatosplenomegaly is mild, and fetal edema is more rare.
1. Astragalus: It is the main symptom of ABO hemolytic disease, most of which occurs 2 to 3 days after birth, and jaundice occurs in the first day after birth, accounting for about 1/4. Similarly, severe jaundice is produced [refers to serum total bilirubin in It is also about 1/4 of 342 mol/L (20 mg/dl) or more.
2. Anemia: ABO hemolytic disease patients have varying degrees of anemia, but generally mild, severe anemia (referred to as hemoglobin below 100g / L) only accounted for about 5%.
Some mild cases of ABO hemolytic disease may not be as early as symptoms, but late anemia occurs 2 to 6 weeks after birth, or anemia is particularly severe during the period of 8 to 12 weeks after birth due to "physiological anemia". The antibody persists and is caused by chronic hemolysis. Blood group antibodies can shorten the lifespan of red blood cells. It is reported that the lifespan of such children's red blood cells is only about 35 days, and the daily hemoglobin decline is about 4 times that of normal children in the same period, and the destruction of red blood cells is increased. At this time, the bone marrow hematopoietic function is physiologically low and cannot be effectively compensated, resulting in neonatal late anemia.
Examine
Examination of neonatal ABO hemolytic disease
1. Hematological examination: Most of red blood cells and hemoglobin are in the normal range, only about 5% of hemoglobin is below 100g/L, reticulocytes are often increased, and heavy red blood cells can reach more than 10%. The shape of red blood cells is spherical. Red blood cells, and erythrocyte saline osmotic fragility and autolysis are increased.
2. Serological examination
(1) Determination of bilirubin: Because the degree of ABO hemolytic disease is quite different, the degree of serum bilirubin is also inconsistent, and serum total bilirubin is more than 1/4 of 342 mol/L (20 mg/dl). In short, the degree of jaundice in ABO hemolytic disease is relatively mild. The bilirubin value of 86 neonates with AO hemolytic disease is counted. The average value is (131.7±83.8) mol/L [(7.7±4.9) mg/dl]; BO hemolysis In 66 cases of neonates, the average bilirubin value was (126.5±71.8) mol/L [(7.4±4.2) mg/dl], and in serum bilirubin, the unconjugated bilirubin was mainly increased.
(2) Antibody assay: The detection of blood group antibodies against red blood cells in neonatal red blood cells or serum is the main experimental basis for the diagnosis of ABO hemolytic disease. Generally, three tests are performed: the first is to improve the Coombs test, which is The optimal dilution of the anti-human globulin serum detects antibodies attached to the red blood cells of the child; the second is the antibody release test, which uses heating to release the antibodies on the red blood cells of the child and then examine the release. The antibody in the liquid, any of the two tests positive, can be diagnosed as ABO hemolytic disease, and the positive rate of antibody release test is higher, and the third is the plasma free antibody assay, which is to check the antibody in the serum of the child. If only the free antibody is positive, it only indicates that the patient has antibodies in the body, which does not mean that it has been sensitized, so it can only be suspected as ABO hemolytic disease.
3. Regular X-ray, B-ultrasound examination, brain CT examination if necessary.
Diagnosis
Diagnosis and identification of neonatal ABO hemolytic disease
Diagnostic criteria
According to clinical manifestations and laboratory tests, maternal and infant ABO blood group incompatibility, plus a red blood cell sensitization index (improved direct Coombs test or antibody release test) positive, can be diagnosed.
Prenatal diagnosis
(1) Determination of parental blood type: Any maternal woman with unexplained abortion, premature birth, stillbirth, stillbirth history, or neonatal severe jaundice should be alert to the presence or absence of maternal and child blood group incompatibility, determine the blood type of the mother and father, parents In case of blood type incompatibility, the mother's blood group antibody should be determined.
(2) Determination of maternal blood group antibody: pregnant women suspected of hemolytic disease in the fetus should be tested for anti-blood group antibodies. The first measurement is usually carried out in the fourth month of pregnancy, which can be used as the basic level of antibodies, and will be measured once a month. It is measured once every half month for 7-8 months of pregnancy and once a week after 8 months. If the antibody titer rises, the fluctuations may be high or the low may indicate that the child may be affected, when the antibody titer It should be used for amniocentesis at 1:32. Due to the presence of substances similar to A and B antigens in nature, there may be natural anti-A or anti-B antibodies in the mother. The antibody titer of ABO hemolytic disease is usually 1:64 as a suspicious case. The mother's antibody titer remained unchanged, suggesting that the condition is stable.
(3) amniocentesis: normal amniotic fluid is colorless and transparent, severe hemolytic disease amniotic fluid is yellow-green, the hemolysis of the fetus is heavier, the higher the amniotic fluid bilirubin content, so the amniotic fluid bilirubin content can be used to estimate the condition and decide to terminate the pregnancy. The optical density of amniotic fluid at a wavelength of 450 nm is proportional to the bilirubin content in amniotic fluid. The optical density of amniotic fluid at a wavelength of 450 nm can be determined by spectrophotometer to represent the level of bilirubin in amniotic fluid due to bilirubin in amniotic fluid. The content decreases with increasing gestational age, so the increase in optical density measured at different gestational weeks has different meanings.
(4) imaging examination: systemic edema of the fetus X-ray film visible soft tissue widened transparent band, limb curvature is poor, B-ultrasound showed fetal liver spleen, chest and abdominal effusion.
2. Postnatal diagnosis
(1) Clinical manifestations: Observe the hemolytic symptoms of neonates with anemia, edema, jaundice and hepatosplenomegaly, and if necessary, consider hemolytic disease of the newborn.
(2) Laboratory examination: for edema at birth, anemia, jaundice within 24 hours after birth and neonates with negative mothers should consider hemolytic disease of the newborn, blood routine, maternal and child blood type, serum bilirubin and Coombs test.
Differential diagnosis
1. Systemic edema: Causes of systemic edema in neonates, in addition to hemolytic disease, homozygous globin-forming anemia (thalassaemia), severe congenital heart disease, large arteriovenous malformations, congenital nephropathy, congenital Sexual hepatitis, intrauterine infection, and mother's diabetes can be identified by clinical manifestations and serological tests.
2. Physiological jaundice: mild mild jaundice in ABO hemolytic disease, easy to be regarded as physiological jaundice and need to be identified, physiological jaundice appears later than this disease, to a lesser extent, without anemia and hepatosplenomegaly, no Systemic symptoms, peripheral blood nucleated red blood cells and reticulocytes do not rise.
3. Infection: Septicemia can cause anemia, jaundice, liver and spleen, easy to be confused with hemolytic disease, but sepsis has symptoms of poisoning, body temperature changes, serum bilirubin is also increased, and no blood type antibodies can be identified.
Other infections in the uterus, such as cytomegalovirus, rubella virus, herpes simplex virus, etc. can also cause anemia, jaundice, liver spleen, but more with retinal choroiditis, intracranial calcification, serum corresponding IgM antibody positive, Coombs test negative.
4. Anemia: Hemorrhagic anemia is not associated with jaundice, blood type antibodies are negative, and often can find the cause of blood loss, easy to identify, mainly should be differentiated from other causes of hemolytic disease, including glucose-6-phosphate dehydrogenase deficiency , pyruvate kinase deficiency, hexokinase deficiency, spherocytosis, elliptic polycythemia, etc., the main point of identification for these diseases Coombs test negative, and the appearance of abnormal red blood cells.
5. Rh hemolytic disease.
