Hemolytic disease of the newborn

Introduction to neonatal 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. . The incidence rate of the first child accounts for 40% to 50%. basic knowledge The proportion of illness: 0.001% Susceptible people: seen in newborns Mode of infection: non-infectious Complications: jaundice, neonatal bilirubin encephalopathy, hemolytic anemia

Causes of neonatal hemolytic disease

Rh blood group incompatibility (5%):

The incidence of neonatal hemolysis caused by Rh blood group incompatibility is low in China. Usually, the mother is Rh-negative, the fetus is Rh-positive and the blood type is inconsistent, and causes hemolysis. Generally, the first fetus does not occur, but the disease from the second fetus However, if a Rh-negative mother received a Rh-positive blood transfusion before the first fetus, the first fetus may also develop.

ABO blood group incompatibility (60%):

The disease is most common with ABO blood group incompatibility, the most common is that the mother is O type, the fetus (or baby) is type A or type B, the first child can be ill, the more the number of births, the higher the incidence rate, and once More serious than once, it can be seen that the mother is type A, the fetus (or baby) is type B or type AB, the mother is type B, and the fetus (or baby) is type B or type AB, but rare, fetus (or baby) For type O, the disease can be ruled out.

Genetics (20%):

The hereditary dominant antigen is just missing from the mother. The fetal blood enters the mother for some reason. The mother produces the corresponding IgM antibody. When the fetal blood enters the mother again, the mother has a secondary immune reaction, which produces a large amount of IgG antibodies and enters through the placenta. Fetus, so that the fetus, neonatal hemolysis, as long as 0.1 ~ 0.2ml of fetal red blood cells into the maternal circulation is enough to make the mother sensitized.

1.Rh blood group incompatibility hemolytic disease: Most mothers are Rh negative, but Rh-positive mother babies can also be ill, the first child incidence rate is very low, because the first immune response to produce IgM antibody takes 2 to 6 months, and Weak, can not enter the fetus through the placenta, and the majority of fetal red blood cells into the mother occurs at the end of pregnancy or at the time of labor, so the first child is often in the latent stage of the primary immune response, when the second immune response occurs in the second pregnancy, only need to count It can appear in the day, mainly the antibody that IgG can pass through the placenta, and it can increase rapidly. Therefore, the second child is often ill. The antibody of Rh system can only be caused by human red blood cells. If the mother has had a history of blood transfusion, and the Rh blood type is different. The first child can also be ill, the mother's mother (grandmother) is Rh-positive, the mother has been sensitized before birth, the first child can also be ill, this is the grandmother's theory.

2. ABO blood group is not hemolytic disease: most are mother O type, fetal type A or B type; a few are mother type A, fetal type B or AB type, or mother type B, fetal type A or type AB, because A Or natural anti-A or anti-B antibodies of type B mothers are mainly IgM antibodies that cannot pass through the placenta, while alloantibodies present in type O mothers are mainly IgG, so ABO hemolytic disease is mainly found in O-type mothers, A or B. Type of fetus, BO hemolytic disease can occur in the first child, because food, Gram-negative bacteria, intestinal parasites, vaccines, etc. also have A or B blood type substances, continuous immune stimulation can make the body produce IgG anti-A or Anti-B antibody, such antibodies can cause hemolysis after entering the fetus through the placenta after pregnancy. Since A and B antigens are also present in many tissues outside the red blood cells, only a small amount of anti-A or anti-B antibodies through the placenta are combined with red blood cells, and the rest are It is neutralized and absorbed by soluble A and B blood group substances in other tissues and plasma, so although the maternal and infant ABO blood group incompatibility is very common, the incidence is only a minority.

Neonatal hemolytic disease prevention

1. The fetal period can be diagnosed in the fetal period.

(1) Early delivery: Rh-negative pregnant women have a stillbirth, a history of miscarriage, can take the mother's blood for immunological examination, such as detecting positive antibody, pregnant women should be followed up monthly to check the change in antibody titer, Rh antibody effect in this pregnancy The price rises from low to 1:32 or 1:64, the amniotic fluid bilirubin value is increased, and the amniotic phosphatidylcholine/sphingomyelin ratio is >2 (indicating that the fetal lung is mature), and early delivery can be considered to alleviate Fetal involvement.

(2) repeated plasma exchange: for patients with severe Rh hemolytic disease prenatal monitoring blood Rh antibody titration is increasing, can be given repeated plasma exchange treatment, in exchange for antibodies, reduce fetal hemolysis.

(3) intrauterine blood transfusion: fetal edema, or fetal Hb <80g / L and the lung is not mature, feasible intrauterine blood transfusion, directly with the pregnant women serum non-aggregated concentrated red blood cells under the B-ultrasound into the umbilical blood vessels.

(4) Drugs: From the 4th month of pregnancy, oral Chinese herbal medicine motherwort, angelica, white peony, guangmuxiang, one dose per day, until delivery, pregnant women with ABO blood group incompatibility can give prevention of traditional Chinese medicine such as Yinchen, Pregnant women were given phenobarbital 90 mg/d 1 to 2 weeks before the expected date of birth to induce fetal glucuronyltransferase production.

(5) Termination of pregnancy: comprehensive treatment should be given to pregnant women to reduce the antibody producer and terminate the pregnancy if necessary.

2. After birth: Rh-negative women should be intramuscularly injected with anti-RhD IgG 300g as soon as possible within 72h of delivery of Rh-positive infants to avoid sensitization; 300g intramuscular injection at 29 weeks of the next pregnancy, the effect is better.

For Rh-negative women with abortion, prenatal bleeding, amniocentesis or ectopic pregnancy when Rh-positive blood is transfused, the same dose should be administered intramuscularly.

Neonatal hemolytic disease complications Complications jaundice neonatal bilirubin encephalopathy hemolytic anemia

There may be complications such as jaundice, hyperbilirubinemia, bilirubin encephalopathy, bile sticky syndrome, hemolytic anemia and respiratory and circulatory failure.

Symptoms of hemolytic disease in newborns Common symptoms Angle arch reversal maternal ABO blood group incompetent skin ecchymosis Physiological jaundice twitching liver splenomegaly edema edema hypoproteinemia ascites

The clinical manifestations of hemolytic disease in newborns vary in severity. Depending on the strength of the antigen, the immune response of the individual, the compensatory capacity of the fetus, and the prenatal interventions, the clinical manifestations of Rh hemolytic disease are more serious and progress faster. The clinical manifestations of ABO hemolytic disease are mostly mild, Rh hemolytic disease generally does not occur in the first child, and ABO hemolytic disease can occur in the first child.

1. Fetal edema: severe cases of fetal edema, mainly in Rh hemolytic disease, a large number of red blood cells destroyed in the fetal period, children with systemic edema, pale, skin ecchymosis, pleural effusion, ascites, low heart sound, fast heart rate, Difficulty breathing, hepatosplenomegaly, placenta also obvious edema, the ratio of placental weight to neonatal weight can reach 1: (3 ~ 4), severe cases can occur stillbirth, the cause of fetal edema and heart failure caused by severe anemia, Hypoproteinemia due to liver dysfunction is associated with increased capillary permeability secondary to tissue hypoxia.

2. Astragalus: The jaundice of children with hemolytic disease appears early, usually jaundice occurs within 24 hours after birth, and develops rapidly. Serum bilirubin is mainly unconjugated bilirubin, but there are also a few children who combine bile during the recovery period. The erythropoietin is obviously elevated, and there is a bile sticky syndrome. Some ABO hemolytic disease jaundice is lighter and similar to physiological jaundice.

3. Anemia: Children with hemolytic disease have different degrees of anemia, Rh hemolytic disease is more obvious, such as the persistence of blood group antibodies can lead to hemolysis continue to occur, children with obvious anemia 3 to 5 weeks after birth (Hb <80g / L ), called late anemia, more common in untransformed and premature infants who have undergone blood transfusion.

4. Liver, splenomegaly: severe cases of extramedullary hematopoiesis, liver, splenomegaly.

5. bilirubin encephalopathy (bilirubin cerebritis): bilirubin encephalopathy can occur in hemolytic disease of newborns, bilirubin in full-term children exceeds 18 mg/dl, and bilirubin in preterm infants exceeds 12-15 mg/dl. The encephalopathy begins to manifest as a godsickness, the sucking reflex and the hug reflex are weakened, and the muscle tension is low. It lasts for half a day to one day. If the disease progresses, there is fever, two eyes gaze, increased muscle tension, convulsions, angulation, etc. Death due to respiratory failure or pulmonary hemorrhage.

Examination of neonatal hemolytic disease

[Laboratory Inspection]

1. Blood biochemical examination: red blood cell reduction, hemoglobin reduction, reticulocyte significantly increased, nucleated red blood cells are seen in the smear, white blood cell count, together with nucleated red blood cells can be greatly increased, these blood changes also with hemolysis Different.

2. Blood type examination: When the maternal Rh blood type is incompatible, the horse blood serum can be used to identify the ABO blood type, and the ABO blood type may be misclassified. Because the horse is stimulated by human red blood cell surface antigen, when the anti-A (B) antibody is produced, Anti-IgG antibodies are produced, so when there are unexplained doubts, it should be thought that the disease may be switched to human serum to identify the ABO blood group.

3. Specific antibody examination: There are immune antibodies, blood stasis and jaundice index increase, bilirubin increased, due to different methods of operation, the results can differ by more than 3 times, urine, urinary biliary excretion increased, and biliary tract in the biliary tract When blocked, it can be grayish, bilirubin can be found in urine, erythrocyte acetylcholinesterase activity is significantly reduced in ABO hemolytic disease, plasma albumin prothrombin and fibrinogen may be reduced, which can cause bleeding symptoms, severe cases Available thrombocytopenia, prolonged bleeding time, poor blood clot systolic, a small number of DIC.

4. Serum bilirubin: mainly unbound bilirubin, children with hemolytic disease gradually deepened after birth, bilirubin levels showed dynamic changes, need to be followed up 2 to 3 times a day.

diagnosis

1. X-ray examination: see the soft tissue of the fetal head outside the skull to form a transparent band, the body shape becomes fat, the hands and feet can not flex or have the placenta shadow increased.

2. Ultrasound examination: It is helpful for the diagnosis of severe edema of the fetus with ascites. Ultrasound examination such as fetal skin thickness exceeding 5mm means fetal edema, ultrasound monitoring can detect hepatosplenomegaly and peripheral edema, and can be used to detect bile by amniocentesis. The presence of erythropoietin in amniotic fluid, the increase of bilirubin in amniotic fluid, especially combined with ultrasound to confirm hepatosplenomegaly or edema, suggesting that the prognosis is critical, and it is necessary to infuse red blood cells through the abdominal wall under ultrasound guidance, if the fetus is close to full term, as soon as possible End the pregnancy.

Diagnosis and diagnosis of hemolytic disease in newborns

diagnosis

1. History: Any pregnant woman with a history of unexplained stillbirth, abortion, blood transfusion history, neonatal severe symptom history, or early post-natal manifestation, should be tested for specific antibodies. :

1 test tube should be clean and dry to prevent hemolysis.

2 prenatal blood group antibody test, blood samples to the mother and her husband; newborn test to send newborn blood samples, father and mother blood samples supplemented (such as maternal blood can not be timely buckled, you can only send newborn blood samples).

3 neonatal blood draw 3ml (not anticoagulation); maternal blood 5ml (not anticoagulation); husband blood 2ml (anticoagulation, the use of general anticoagulant).

4 If the local can not be tested, the maternal serum can be separated and sent to the nearby inspection unit, and the other dance music 2ml anticoagulation. When the weather is hot, the blood sample bottle can be placed in the big mouth bottle with ice cubes. Sterile).

2. Blood type: The fetal BO blood type is determined by amniotic fluid during pregnancy. If the mother and the same type are confirmed, the disease may be immune to the disease, but the Rh blood type blood-free substance needs to be taken from the fetal blood to be stereotyped, and the newborn O type can exclude ABO hemolytic disease. It is not possible to rule out hemolytic disease in other blood group systems.

3, specific antibody examination: including mother, infant, paternal blood type, antibody titer, anti-human globulin test (indirect method before birth, direct method after birth), release test and free test, which is the diagnosis of this disease The main basis.

The anti-human globulin indirect test uses red blood cells with known antigens to check the presence or absence of incomplete antibodies in the serum of the subjects; direct test positive indicates that the baby red blood cells have been sensitized by blood group antibodies, the release test is positive, and the diagnosis is established because of sensitized red blood cells. The antibody is released by heating, and the specificity of the antibody in the release solution must be determined by standard red blood cells. The free test is to find unconjugated antibodies in the neonatal serum, but the red blood cells have not been sensitized, and the positive indicates that it may be harmed.

In the diagnosis of pregnancy may be the disease, should strive to test the antibody once every month within 6 months of pregnancy, once every half month from July to August, once a week after 8 months or as needed, the antibody titer is low To the high, the undulations or sudden changes from high to low indicate that the condition is unstable, there is a possibility of aggravation, and the potency remains unchanged, indicating that the condition is stable or the maternal and child blood types are consistent. The antibody is only caused by the legacy, and after the exclusion of the remaining factors, Generally, the severity of the disease is directly proportional to the antibody titer, but the ABO system is naturally similar to the anti-A (B) substance relationship, and some unmarried women have a titer of 1024. Usually, the ABO hemolytic disease has a titer of 64 as a suspected case, but individual There is also a report of the onset when the titer is 8.

4, amniotic fluid examination of bilirubin content: it is not like the antibody titer left by the previous one, so amniotic fluid bilirubin content has a guiding significance for estimating the condition and considering the termination of pregnancy time, normal amniotic fluid is transparent and colorless, severe hemolysis In the early morning, the water was yellow.

Liley found that the increase in optical density at 450 mm is proportional to the severity of fetal hemolytic disease. Since the concentration of bilirubin in normal fetal amniotic fluid decreases with increasing gestational age, the optical density at 450 mm measured at different gestational weeks. The number of rises has different meanings. The results obtained by Liley from immunized women's amniotic fluid from 101 Rh, the optical density increase of 450 mm is plotted on the ordinate, and the gestational age is plotted on the abscissa, which is divided into three areas, amniotic fluid. The increase in optical density at 450mm is in the upper area, the condition is serious, and it is generally about to die. In the middle area, the moderate disease is severe. In the lower area, it may be a Rh-negative child or a Rh-positive child with extremely mild anemia. 10% need to change blood.

5, imaging examination: systemic edema in the X-ray film visible soft tissue widened transparent band limbs curvature is poor, B-ultrasound is more clear, hepatosplenomegaly, chest and abdominal effusion can be reflected in the screen.

6, other laboratory tests: the same value for the diagnosis of this disease.

Differential diagnosis

1, systemic edema: to be differentiated from the hereditary globin peptide chain synthesis of alpha-thalassemia Hb Bant s fetal edema and congenital malformation, other should also consider maternal diabetes, congenital nephropathy, placental dysfunction, fetal One child or one fetal blood transfusion, intrauterine infection and other factors can be identified by clinical examination serology.

2, jaundice: physiological jaundice appeared late, slow progress, mild, no anemia and hepatosplenomegaly, sepsis has symptoms of poisoning, fever, specific antibody negative, blood culture helps identify, other such as giant cell inclusion disease, Poisonous worm disease, intracranial hemorrhage, G-6-PD deficiency and other congenital hemolytic diseases should be considered for identification.

3, anemia: mainly related to various causes of hemorrhagic anemia, G-6-PD deficiency is more common in the South, other congenital hemolytic anemia, nutritional anemia are rare.

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