II. Hemolytic disease of the newborn



treatment goals :

1. stopping vitamin K deficiency,

2. stop bleeding,

3. treatment of manifestations of HrDN.

Treatment regimen :

Mandatory treatment : Vikasol.

Adjuvant treatment : fresh frozen plasma, thrombin, epsilon aminocaproic acid, concentrated prothrombin complex preparation (PPSB), sodium bicarbonate solution, adroxon, packed red blood cells.

Indications for hospitalization : All children with or suspected HRD should be hospitalized.

Diet . Children with HRD are fed with expressed breast milk 7 times a day in accordance with age requirements, which is due to the presence of thromboplastin in human milk.

The introduction of vitamin K intramuscularly or intravenously (preferably) at a dose of 1-2 mg (vitamin K1), but you can enter a 1% solution of vikasol (vitamin K3) at a dose of 0.1-0.15 ml / kg (5 mg full-term and 2- 3 mg preterm).

In our country, so far, vikasol (vitamin K3) is predominantly prescribed – a water-soluble derivative of menadione, but less effective than phylloquinone (vitamin K1). Vikasol causes the effect not by itself, but by the phylloquinone and menadione formed from it in the liver. Considering that only a small percentage of vikasol is converted into phylloquinone and menadione, vikasol is administered 2 times a day, sometimes even 3 times. High doses of vikasol (more than 10 mg) or its long-term administration are dangerous because of the possibility of the formation of Heinz bodies in erythrocytes, the development of hyperbilirubinemia due to increased hemolysis .

With continued heavy bleeding, the simultaneous administration of fresh frozen plasma at the rate of 10-15 ml / kg intravenously or a concentrated preparation of the prothrombin complex (PPSB) at a dose of 15-30 U / kg intravenously is indicated . Rapid blood loss of 10-15% of the circulating blood volume leads to the development of shock, while the introduction of PPSB is contraindicated, as it can cause DIC.

With the development of hypovolemic shock due to posthemorrhagic anemia, red blood cell transfusion is carried out at the rate of 5-10 ml/kg (after transfusion of fresh frozen plasma at a dose of 20 ml/kg).

Local therapy for melena : 50 ml of a 5% solution of ε-aminocaproic acid + 20 mg of dry thrombin + 1 ml of a 0.025% solution of adroxon – 1 tsp each. 3 times a day and 0.5% sodium bicarbonate solution, 1 tsp. 3 times a day. In case of bleeding from the umbilical stump – ligation of the umbilical residue, hemostatic sponge, thrombin solution locally.

Prevention of HRD includes the administration of vitamin K. For this purpose, a 1% solution of vikasol is administered intramuscularly once to children at risk for the development of HrDN at the rate of 0.1 ml/kg during 2-3 days of life.

Hemolytic disease of the newborn

Treatment .

Treatment objectives : maintaining pregnancy until the fetus reaches viability, reducing the severity of hemolysis, correcting anemia and hyperbilirubinemia, treating pulmonary heart failure, preventing kernicterus and severe anemia.

I. Hemolytic disease of the fetus

Non-drug treatment : plasmapheresis, rheocorrection, immunocorrection. Drug treatment : cordocentesis with intrauterine transfusion of erythrocyte mass at 24-35 weeks of gestation.

Indications for cordocentesis are: a burdened obstetric history, a positive fetal Rh factor, positive ultrasound signs of fetal hemolytic disease, an increase in the level of bilirubin in the amniotic fluid, the presence of an antibody titer of 1:32 and above, a decrease in Hb and Ht by more than 15% of the norm for a given gestational age. Use only “washed” erythrocytes of the 0 (I) blood group, Rh – negative.

II. Hemolytic disease of the newborn

Treatment goals : treatment of hyperbilirubinemia, correction of anemia and post-syndromic therapy aimed at restoring the functions of various organs and systems. In the maternity hospital, newborns are transferred to the intensive care unit for treatment.

Non-drug treatment . The issue of breastfeeding is decided individually, studying the severity of anemia, the general condition of the child and mother. The mismatch of the blood of the mother and child by group or Rh factor is not a contraindication to early breastfeeding if the antibody titer was determined during pregnancy. Long-term weaning of a child with a mild form of HDN is not justified, because the amount of antibodies obtained with mother’s milk in the first days of life, as a rule, is insignificant due to the small volume of milk, and subsequently the natural destruction of antibodies begins.

The main treatment for hyperbilirubinemia in HDN is phototherapy . Phototherapy is based on the ability of bilirubin molecules under the action of light energy to change the chemical structure and associated physicochemical properties. Bilirubin absorbs light energy mainly in the blue region of the visible spectrum (wavelength 450-460 nm). Under the influence of light in the skin, toxic forms of bilirubin are converted into less toxic forms (15% lumibilirubin and 85% water-soluble indirect bilirubin isomers), which are removed from the body in the urine.

Indications for the beginning of phototherapy are set out in Table. 2.25.

Tab. 2.25. Indications for phototherapy in newborns depending on the level of indirect bilirubin, BW and age (Formular system)

Body weight, g NB level, µmol/l
24 hours 48 h 72 h 4-7 days
<1000 120-170

The exception is children who develop jaundice during the first day of life, including as a result of hemolytic disease of the newborn. Phototherapy in this category of children, regardless of their gestational age, should begin with the onset of jaundice. The most commonly used light source is blue light fluorescent lamps. For home treatment, “photo blankets” can be used. In the latter case, light is transmitted to the child’s skin from powerful halogen lamps using light guides.

The principles of phototherapy are as follows :

1. The radiation dose must be at least 8 μW/cm2/nm;

2. You must not violate the requirements of the instructions for the device on the recommended distance from the light source to the child;

3. During phototherapy, the child must be in an incubator or ORS (every 2 hours, body temperature should be measured if the incubator does not support automatic skin temperature control);

4. When carrying out phototherapy, it is necessary to protect the eyes and genitals (in boys);

5. Every 2-6 hours it is necessary to change the position of the child relative to the light source, turning the baby up with his stomach or back;

6. It is advisable to carry out phototherapy continuously, taking breaks only for feeding and hygienic care for the newborn, lasting at least 3-5 days. Since the reaction of the conversion of the water-insoluble isomer of indirect bilirubin into water-soluble isomers is reversible when the phototherapy session is stopped.

7. The daily volume of liquid administered to the child must be increased by 1 ml/kg/hour (in children with very low body weight – by 0.5 ml/kg/hour) in comparison with the physiological need of the child.

8. In cases where children are on partial or total parenteral nutrition, the use of fat emulsions should be limited until the threat of bilirubin encephalopathy is eliminated.

All children receiving phototherapy should have a daily biochemical blood test for bilirubin (if there is a threat of bilirubin encephalopathy, every 6-12 hours).

It should be remembered that phototherapy may be accompanied by side effects : maculopapular rash on the skin, frequent stools, the appearance of a bronze skin tone, exsicosis. In experiments on laboratory animals, the potential damaging effect of bright light on the retina and testicles was shown, which necessitated the protection of the eyes and genitals during light therapy sessions.

The indication for stopping phototherapy is the absence of signs of a pathological increase in bilirubin, while the concentration of total bilirubin in the blood serum should be below the values that served as the basis for starting phototherapy.

12 hours after the end of phototherapy, a control study of blood bilirubin is necessary. Phototherapy must be combined with additional fluid administration (additional drinking or infusion therapy if it is impossible to drink the child). The composition of infusion media includes 10% dextrose solution, according to indications (hemorrhagic syndrome, hypoalbuminemia), fresh frozen plasma, 5% albumin solution can be administered.

An exchange transfusion operation (ERT) is indicated for the edematous form of HDN and for the ineffectiveness of phototherapy for the treatment of the icteric form. There is an early OZPK, which is performed in the first two days of life, and later OZPK – from the third day of life.

Indications for early OZPK are :

1. the level of bilirubin in the cord blood is above 68 µmol/l;

2. hourly increase in bilirubin in full-term babies is more than 9 µmol/l;

3. in premature babies – more than 8 µmol / l.

An indication for late OZPK is a critical level of bilirubin :

in a full-term ≥342 µmol / l, in a premature baby, the critical level of bilirubin depends on body weight at birth and age (see Table 2.26).

Tab. 2.26. Indications for FPC in preterm infants depending on the level of NB, BW and age*

MT, g NB level, µmol/l
3rd day 4th day 5th day 6th day 7th day

* In the presence of risk factors for the development of bilirubin encephalopathy, PZK should be carried out at lower numbers of indirect bilirubin: Apgar score at the 5th minute ≤3 points; serum protein < 50 g/l (serum albumin ≤25 g/l); blood glucose level below 2.2 mmol/l; the presence of generalized infectious diseases or meningitis; PaO2 < 40 mmHg Art. duration >1 hour; arterial pH < 7.15 for > 1 hour; rectal temperature ≤35 °C; deterioration of the neurological status against the background of hyperbilirubinemia.

In severe congenital HDN (pallor, icteric staining of the umbilical cord, skin, edema), the technique of partial OZPK is used.

Before determining the blood group and Rh factor, erythrocytes 0 (I), Rh – are administered at the rate of 45 ml / kg. In case of an isolated Rh-conflict for OZK, a Rh-negative erythrocyte mass of the same group as the child’s blood and fresh frozen plasma are used (AB (IV) plasma can be used.

In an isolated group conflict, an erythrocyte mass is used that matches the mother’s blood group (most often 0 (I) groups), which matches the child’s blood in Rh and AB (IV) plasma, or one group with the child’s blood group.

With a combination of Rh-conflict and conflict in the blood group, Rh-negative erythrocyte mass of group 0 (I) and plasma AB (IV) or one group with the child’s blood are used.

If the blood of the mother and the blood of the fetus are incompatible due to rare factors, the child needs to be transfused with blood from an individually selected donor.

In children who do not have signs of hemolytic disease, the exchange transfusion operation is performed with a freshly prepared donor erythrocyte mass of the same group and Rh factor as the blood group and Rh factor of the child, and with donor plasma of the same blood group.

The risk group includes children with : morpho-functional immaturity, cephalohematomas in need of resuscitation, hereditary hemolytic anemia

Tab. 2.27. Tactics of treatment of newborns with hemolytic disease by blood group in the first 24 hours of life

Indicator Phototherapy under continuous supervision Phototherapy and preparation for exchange transfusion Exchange transfusion
The concentration of hemoglobin in the capillary blood of a newborn in the first 24 hours of life, g/l. >140 120 – 140 <120
Change in the concentration of bilirubin in the capillary blood of a newborn in the first 24 hours of life, µmol/l per hour <6.8 6.8 – 8.5 >8.5

The replacement of two volumes of the child’s circulating blood (160–180 ml/kg in term infants and 180 ml/kg in preterm infants) is required for PBRP. The ratio of red blood cells to plasma depends on the initial level of hemoglobin before the start of PZK, usually being 2: 1.

For OZKK, it is necessary to use only freshly prepared erythrocyte mass (shelf life is not more than 72 hours).

OZKP is carried out through the umbilical vein, where the catheter is inserted. The catheter is inserted into the vein of the umbilical cord filled with saline containing 0.5-1 U / ml of heparin. At the age of more than 4 days and / or in the presence of contraindications for umbilical vein catheterization, PZK is performed through any other central vein, to which reliable and safe access can be provided. Before OZPK, the level of bilirubin is examined, the compatibility of the blood of the donor and the child is determined. OZKK begins with the removal of blood. Fractional portions of 10-20 ml (for very premature and seriously ill newborns – 5-10 ml) slowly remove the child’s blood and replace it alternately with erythromass and donor plasma in an equivalent amount (every 2 syringes of injected erythromass, one plasma syringe is injected). During the operation, calcium preparations, 10% glucose are administered. At the end of the OZPK, blood is examined for bilirubin. At the very end of the operation, a broad-spectrum antibiotic is injected into the umbilical catheter (half the daily dose).

A child who has undergone POP is at risk for hypoglycemia, hypocalcemia, hyperkalemia, metabolic acidosis, bacterial infections, and hemodynamic disorders. In this regard, the observation of such children should be carried out in the conditions of the post (ward) of intensive care.

To prevent reactive hypoglycemia in children who have satisfactorily tolerated OZK, it is necessary to start drinking 5% glucose solution as soon as possible (within the next 0.5-1 hour), and children in serious condition continue intravenous administration of 10% glucose solution.

Umbilical vein catheterization and OZPK increase the risk of infection, which requires strict adherence to the rules of asepsis and antisepsis during the operation and in the care of the umbilical wound in the postoperative period. If there is a threat of umbilical sepsis, antibiotic therapy is indicated.

After POP, serum bilirubin levels rise (due to transfer from the tissues), which may require a second POP.

All children after PPO require continued phototherapy.

Medical therapy . To prevent and stop hemolysis, use standard immunoglobulin for intravenous administration in the first 2 hours of life or later, but immediately at the diagnosis of HDN, at the rate of 1 g / kg every 4 hours; or 500 mg/kg every 2 hours during the day; or 500 mg/kg daily for 3 days, or 800 mg/kg once a day for 3 days.

The use of phenobarbital for the treatment of TTH is not currently recommended (late effect, CNS depression).

In severe anemia caused by HDN (venous blood Hb level less than 120 g/l), early exchange transfusion is performed.

With the development of late anemia, epoetin alfa is used (taking into account the level of reticulocytes), which is administered 3 times a week at a dose of 200 IU/kg subcutaneously for 2-3 weeks. With iron deficiency against the background of epoetin, iron preparations of 2 mg / kg are added orally.

Complications: bile thickening syndrome, nuclear jaundice, late anemia.

The most severe complications develop during or after OPPK: arrhythmias, cardiac arrest, thromboembolism, thrombosis, thrombocytopenia, hyperkalemia, hypocalcemia, hypoglycemia, acidosis, development of viral and bacterial infection, hypothermia, necrotizing enterocolitis.


With the edematous form of HDN, perinatal fetal death still most often develops. In the icteric form, the prognosis depends on the timeliness of the OZPK and the degree of CNS damage. With an anemic form, the prognosis is the most favorable. Perinatal mortality in HDN is 2.5%. In 4.9% of children after TTH, there is a lag in physical development. CNS pathology develops in 8% of children.

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