Rh incompatible hemolytic disease of the newborn

Introduction to neonatal Rh blood group incompatibility Neonatal RH blood group is not hemolytic disease, also known as neonatal maternal and child blood group incompatibility, refers to immune hemolytic anemia caused by blood group antibodies, it is caused by the maternal and child blood group incompatibility, is neonatal hyperbilirubin One of the most common causes of blood, and early onset, rapid progress, severe cases can cause nuclear jaundice. Neonatal hyperbilirubinemia caused by blood group antigens is often seen in several antigenic blood types, such as RH blood type. basic knowledge The proportion of illness: 0.002% Susceptible people: children Mode of infection: non-infectious Complications: neonatal bilirubin encephalopathy

Neonatal Rh blood group incompatibility cause of hemolytic disease

Cause:

Rh blood group incompatibility is an antibody produced by the fetal red blood cell antigen that is lacking during the hemolytic disease of the newborn, and the hemolytic anemia produced by the placenta is introduced into the fetus. There are 26 human red blood cell blood type systems, among which the hemolysis caused by Rh blood group incompatibility is more common, and the degree of hemolysis is heavier. Rh blood group antigen is derived from three pairs of closely linked alleles on the first pair of chromosomes, and there are six antigens, namely C, c, D, d, E, and e. Among them, D antigen is the earliest discovered and the antigenicity is the strongest. When there is D antigen, it is called Rh positive. The existence of the d antigen has not yet been identified, and is only theoretically speculated, so d is a lack of D. DD and dD are Rh positive, and dd means Rh negative.

Although the placenta acts as a barrier to prevent fetal blood from entering the maternal blood circulation, a small amount of infiltration (transfusion of the placenta) can occur. Once the fetal red blood cell antigen is not in contact with the mother, the mother produces the corresponding blood group antibody, which is input into the fetus through the placenta and acts on the fetal red blood cells, which may cause neonatal hemolytic disease.

Using acid solubilization techniques, fetal red blood cells appear in the blood circulation of about 1 in 15 pregnant women at 3 months of gestation. During normal pregnancy, the amount of fetal blood entering the maternal circulation is very small. Generally, 0.2 ml of fetal blood enters the maternal blood circulation, which can stimulate the mother to produce antibodies. A large number of transplacental blood loss can also be seen in automatic or artificial abortion, ectopic pregnancy, cesarean section, pregnancy-induced hypertension syndrome, placenta previa, placental abruption, etc., all of which are likely to cause maternal sensitization to fetal red blood cells. For parents with ABO blood group incompatibility, the incidence of progeny Rh hemolytic disease is low, because the main blood group antigen does not cooperate, so that fetal blood is quickly destroyed by anti-A or anti-B lectin in the mother, thereby reducing Rh antigen. Sensitization reduces the chance of Rh hemolysis.

Pathophysiology

The excretion of bilirubin is mainly in the form of binding to glucuronidase. The lack of glucuronyltransferase in neonates, especially premature infants, leads to a decrease in glucuronide bilirubin, and the lack of YZ2 transporter, which causes bilirubin to be transported from hepatocytes to the biliary system, which constitutes blood bilirubin. The reason for the increase in prime.

When the Rh blood type is incompatible, the fetal red blood cells entering the mother are first swallowed by macrophages. Under the action of macrophage conditioning and antigen presentation, it takes a considerable time to release a sufficient amount of Rh antigen, and then stimulate the corresponding lymphocytes. An anti-Rh antibody is produced. This secondary immune response develops slowly and takes 2 to 6 months. The first anti-DIgM produced by the mother is low in content, short in existence, unable to pass through the placenta, and does not pose a threat to the fetus. Only when the primary reaction is re-pregnant, secondary immunization can occur quickly to produce IgG antibodies, which cause hemolysis of the fetal red blood cells through the placenta. Among the four subtypes of IgG, anti-D antibodies of IgG1 and IgG3 are most common, and if they are present at the same time, hemolysis is often severe.

Rh hemolytic disease occurs in the first fetus. It is generally only seen in the mother who has received blood group incompatibility before the pregnant mother or pregnant mother Rh positive, so that the pregnant mother has an initial reaction against anti-Rh positive antibody in the fetus, when she is pregnant Rh In a positive fetus, a secondary immune response can occur quickly, resulting in fetal hemolysis, the so-called grandmother theory proposed by Taylor.

Rh blood group incompatibility is mainly seen when the fetus is Rh positive and the mother Rh is negative, but it can also occur when the mother is Rh positive. If the mother is ee, cc, and the fetus is E or C, the mother can produce anti-E or anti-C antibodies. Among the Chinese Han population, RhCCDeeCcDee accounts for about half, and the antigenicity of RhE is second only to D. Therefore, Shanghai reported that Rh-positive Rh hemolytic disease accounts for more than 1/3 of the entire Rh hemolytic disease. From 1974 to 1994, Beijing Children's Hospital treated 71 cases of Rh hemolytic disease in 20 years, accounting for 4.6% of neonatal hemolytic disease, including 1/4 of hemolytic diseases with positive mother Rh.

Neonatal Rh blood group incompatibility prevention

1.Rh negative women

(1) If blood transfusion is required, the Rh blood type should be tested first, and Rh blood should be transfused. If the blood type is different, immediately intramuscular Rh(D) IgG is administered, and 20 g of blood is input according to the input of 1 ml of blood.

(2) After induction of labor or delivery of Rh-positive infants after 8 weeks of pregnancy, intramuscular injection of anti-Rh(D) IgG 300 g within 3 days, if there is a special condition that causes fetal blood to flow into the mother, such as multiple births, placenta previa, etc., the dose is doubled. .

(3) After amniocentesis, intramuscular injection of anti-Rh (D) IgG 100 g.

(4) Rh-negative pregnant women start taking phenobarbital 1 to 2 weeks before the expected date of birth, 30-60 mg per day, orally 2 to 3 times.

(5) intrauterine blood transfusion, when B-ultrasound or amniotic fluid measurement found that the fetus is seriously affected, the fetus is less than 33 weeks, can do intrauterine blood transfusion to save the fetus, lose Rh negative "O" type concentrated red blood cells to the fetal abdominal cavity, 20 Lose 20ml in ~22 weeks, 40ml in 24 weeks, 100ml in 32 weeks, and lose once every 1.5~3 weeks.

(6) Determine the ratio of amniotic fluid L/S. If the lung is mature, consider giving the baby a delivery in advance.

2. Rh-positive women: Those who have had severe jaundice in the newborn and have an anemia history should be examined for other Rh blood group antibodies other than D antibody.

3. Prevention of bilirubin encephalopathy: Actively take various measures to reduce free bilirubin in the blood, prevent premature birth and intrauterine growth and backwardness. Be careful to keep warm after birth, correct hypoxia, acidosis, and prevent infection. Avoid using drugs that cause hemolysis and inhibit liver enzyme activity. Avoid hyperosmotic drug infusion. Prevent excessive free fatty acids when feeding nutrients.

Neonatal Rh blood group incompatibility complications Complications neonatal bilirubin encephalopathy

Bilirubin encephalopathy (nuclear jaundice)

The main complication of neonatal hemolytic disease is encephalopathy caused by unconjugated bilirubin toxicity to the central nervous system. Unbound bilirubin, which is degraded by heme, is a polar compound that is insoluble in water and can enter the brain. The damage of bilirubin to the brain is caused by its deposition in the brain, depending on the following three mechanisms: 1 bilirubin can continuously pass through the blood-cerebrospinal fluid barrier even in "physiological hyperbilirubinemia". But most do not cause permanent nerve damage. 2 Under pathological conditions, plasma free bilirubin increased significantly, resulting in a significant increase in bilirubin entering the central nervous system, bilirubin combined with nerve cells, resulting in deposition of brain tissue. 3 Some factors such as sepsis, hypoxia, fever and acidosis can further damage the blood-cerebrospinal fluid barrier and increase the penetration of bilirubin into the brain. The term nucleoside is derived from the basal ganglia and the cerebellum stained yellow by bilirubin. The clinical symptoms of encephalopathy often appear 2 to 5 days after birth, and may also occur in later periods. Early symptoms include anorexia, restless sleep, decreased muscle tone, apnea, and hug reflexes. As the disease continues to develop, there may be loud screams, paralysis, and angulation, followed by irregular breathing and pulmonary hemorrhage, often leading to death. Survivors may have persistent sequelae such as sensorineural deafness, dyslexia, language problems, severe cerebral palsy, mental retardation, ataxia, and acromegaly. From hyperbilirubinemia to bilirubin encephalopathy can be divided into 4 phases: 1 aura. 2 period. 3 recovery period. 4 sequelae. Bilirubin encephalopathy in premature and low birth weight infants often lacks typical sputum symptoms.

Other: thrombocytopenic purpura, disseminated intravascular coagulation in a few cases.

Severe children may have lower blood sugar

It is related to the increase of insulin in blood. Hypoglycemia can increase damage to the central nervous system and increase the toxic effects of bilirubin, which should be monitored regularly and appropriate treatment should be taken.

Neonatal Rh blood group incompatibility symptoms of hemolytic disease Common symptoms Skin pale coagulopathy jaundice edema Fetus edema intracranial hemorrhage ascites hepatosplenomegaly pericardial effusion pleural effusion

All clinical manifestations depend on the rate of fetal red blood cell destruction and the degree of compensatory erythropoiesis. Lighter patients have only a small amount of hemolysis, and severe cases can show fetal edema syndrome leading to intrauterine death. Generally, the heavier the anemia, the more severe the clinical manifestations, and the greater the risk of brain damage caused by hyperbilirubinemia.

1. Astragalus : Even if there is a hemolytic disease in the newborn, there is no jaundice at birth. Once the newborn has jaundice on the first day of birth, the possibility of hemolytic disease of the newborn must be considered. Serological examination should be performed immediately to confirm the diagnosis. The jaundice of Rh hemolytic disease occurs early and to a greater extent.

2. Immunological hemolysis and anemia : phenobarbital increases glucuronyltransferase activity and increases bilirubin binding protein content. Prenatal or neonatal phenobarbital increases the rate of bilirubin clearance and lowers blood bilirubin.

The patient has immune hemolysis. The extent of anemia depends on the result of the hemolysis process and the red blood cell balance of the bone marrow. At birth, most newborns have only mild anemia, and the liver and spleen can be slightly enlarged. If the anemia is aggravated, the liver and spleen increase gradually. In severe anemia, congestive heart failure, edema, ascites, and pleural effusion can occur, which constitutes a fetal edema syndrome, most of which die several hours after birth, and the severe ones die in the uterus.

Examination of neonatal Rh blood group incompatibility

Peripheral blood

The degree of anemia, the increase in reticulocytes and the appearance of nucleated red blood cells are directly proportional to the degree of hemolysis. Blood smears showed polychromaticity, red blood cell size, and nucleated red blood cells. When Rh is hemolyzed, spherical red blood cells are rare. When hemolysis is severe, white blood cells increase and the left side of the nucleus is seen.

Bone marrow: mainly showing excessive proliferation of red blood cell lines.

Immunological examination

The main basis for postpartum diagnosis is the examination of serum-specific immune antibodies. Rh hemolytic disease is caused by IgG anti-Rh antibodies produced by the mother. The antibody is from the serum of the mother rather than the serum of the sick child. Therefore, mother's serum should be used for examination as much as possible. Specifically, it includes the following four aspects: 1 Check whether the mother Rh blood type is different. 2 Check if the baby's red blood cells are sensitized. Positive anti-human globulin test indicates that infant red blood cells are sensitized by blood group antibodies. Further release tests to find out which blood group antibodies are. 3 Check the presence and type of blood group antibodies in the serum of infants. Infant serum and various standard red blood cells were used as an anti-human globulin indirect test, and positive results indicated the presence of blood group antibodies and inferred the type of antibodies. 4 Check the presence or absence of Rh blood group antibodies in the maternal serum, and the positive ones have reference significance for diagnosis. Once the newborn Rh is positive and the mother Rh is negative and directly anti-human globulin test positive can be diagnosed. There are a few Rh hemolytic patients whose mother is Rh positive (D positive), but there are antibodies against E, c, C and so on.

Serum bilirubin test

In the fetal period, bilirubin can pass through the placenta, so umbilical cord blood bilirubin is not high. If it exceeds 3 mg/dl, intra-femoral anemia may occur. After birth, the ability of the placenta to clear bilirubin is lost, and the bilirubin content in the blood of newborns is rapidly increased. The increasing speed and absolute value of the newborns constitute an important indicator for predicting bilirubin encephalopathy. Therefore, serum bilirubin should be closely monitored. Changes in the content of the prime. According to Beijing Children's Hospital, high direct bilirubinemia can occur at the same time as indirect bilirubin increase, considering the result of cholestasis; while direct bilirubin >4mg/dl should be alert to the occurrence of ketosis after phototherapy Possible. Most of the direct bilirubin increased to normal in the short term.

Other auxiliary examinations: X-ray, B-ultrasound, electrocardiogram, biochemistry, etc. are selected according to the condition, clinical manifestations, symptoms and signs.

Diagnosis and differential diagnosis of neonatal Rh blood group incompatibility

diagnosis

According to clinical manifestations, laboratory tests can be diagnosed.

Differential diagnosis

1. Fetal edema: should be differentiated from non-immune fetal edema, especially -thalassemia, Hb Barts fetal edema syndrome, other should also consider congenital nephropathy, fetal-mother transfusion, intrauterine infection, congenital malformation, etc. Factors, these can be identified by clinical tests serological tests and the like.

2. Astragalus: Physiological jaundice appears late, slow progress, mild degree, no anemia and hepatosplenomegaly, rare nucleated red blood cells in peripheral blood, sepsis has symptoms of poisoning, unstable body temperature, positive blood culture helps identify, others Congenital hemolytic diseases such as G-6-PD deficiency should also be identified.

3. Anemia: It is mainly differentiated from blood loss anemia caused by various causes, such as fetal-female blood transfusion, fetal-fetal transfusion, intracranial hemorrhage and visceral rupture.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.