Hemolytic disease of the newborn

Hemolytic disease of the newborn and fetus is an isoimmune hemolytic anemia that occurs when the blood of the mother and fetus is incompatible with erythrocyte antigens, where the antigens are the fetal erythrocytes, and antibodies to them are produced in the mother's body. Hemolytic disease of the newborn is diagnosed in approximately 0.6% of children. Perinatal mortality is 2.5%.

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What causes hemolytic disease of the newborn?

The immune conflict underlying hemolytic disease of the newborn may occur if the mother is antigen-negative and the fetus is antigen-positive. When developing GBPN by the Rh factor, the mother's erythrocytes are Rh-negative and the fetus's are Rh-positive, i.e. they contain the O-factor. The conflict (development of GBPN) usually occurs during repeated pregnancies, since prior sensitization is necessary.

Hemolytic disease of the newborn due to group incompatibility develops with 0(1) blood group of the mother and A(II) or, less frequently, B(III) blood group of the fetus. The conflict can be realized already during the first pregnancy. GBPN can also occur due to incompatibility of other rare antigen systems: Kell, Lutheran, etc.

How does hemolytic disease of the newborn develop?

For hemolytic disease of the newborn to develop, antigen-positive fetal erythrocytes must enter the bloodstream of an antigen-negative pregnant woman. In this case, it is not so much the fact of transplacental transfer of fetal erythrocytes that is of great importance, but the amount of fetal blood entering the mother's body. Factors that contribute to isoimmunization, especially for the Rh factor, include:

• previous medical and non-medical abortions;
• previous spontaneous (one or more) miscarriages;
• previous ectopic pregnancy;
• previous births (premature and term);
• invasive diagnostic methods (amniocentesis, cordocentesis, chorionic villus sampling);
• threat of termination of pregnancy.

The disease is based on hemolysis (destruction) of red blood cells, caused by incompatibility of the mother's and fetus's blood in terms of Rh factor, blood group and other blood factors, which occurs in the 3rd-4th month of intrauterine development and increases sharply after birth.

When antigen-positive fetal erythrocytes enter the bloodstream of an antigen-negative woman, her body produces anti-Rhesus or group antibodies. If the antibodies belong to the IgG class, they transplacentally pass into the fetal bloodstream, bind to the antigen-positive fetal erythrocytes, causing their hemolysis.

The Rhesus antigen system consists of six main antigens: C, c, D, d, E and e. Rhesus-positive erythrocytes contain the D factor, while Rhesus-negative erythrocytes do not, although other antigens of the Rhesus system are often found in them. Fetal erythrocytes that have the D antigen and enter the bloodstream of an Rh-negative pregnant woman lead, during the first pregnancy, to the synthesis of Rh antibodies, which belong to class M immunoglobulins, which do not penetrate the placenta. Then, class G immunoglobulins are produced, which are able to overcome the placental barrier. Due to the small number of fetal erythrocytes and immunosuppressive mechanisms, the primary immune response in a pregnant woman is reduced. That is why the implementation of the conflict with Rh incompatibility during the first pregnancy practically does not occur, and the child is born healthy. During repeated pregnancies, the development of the conflict is possible, and the child is born with hemolytic disease of the newborn.

A- and B-antigens are located on the outer surface of the plasma membrane of the erythrocyte. Isoimmune anti-A and anti-B group antibodies belong to the IgG class, unlike natural group antibodies - calamus, which belong to the IgM class. Isoimmune antibodies can combine with the corresponding A and B antigens and fix on other tissues, including placental tissues. That is why hemolytic disease of the newborn according to the ABO system can develop already during the first pregnancy, but only in about 10% of cases.

When both conflict options can be realized, a conflict according to the AB(0) system most often occurs.

But the Rh factor is not the only cause of the disease. It can occur due to blood incompatibility and other factors. In addition, hemolytic disease of the fetus can occur due to a mismatch between the mother's and fetus's blood in the main blood groups of the ABO system. Antigens A and B, inherited from the father, can cause the mother with blood group 0 to form incomplete agglutinins, which, unlike normal α- and β-agglutinins, can pass through the placental barrier and cause hemolysis of fetal erythrocytes. Conflict due to mismatch in the ABO system occurs in 10% of cases and is usually benign. It should be noted that mismatch between the fetus and mother's blood does not always lead to the development of the disease. For example, Rh incompatibility occurs in 5-10% of pregnancies, and Rh conflict - in 0.8%.

Pathogenesis of edematous form of hemolytic disease of the newborn

The edematous form, or fetal hydrops, occurs if hemolysis begins in utero, approximately from 18-22 weeks of pregnancy, is intense and leads to the development of severe fetal anemia. As a result, severe fetal hypoxia occurs, which causes profound metabolic disorders and damage to the vascular wall. Increased permeability of the vascular wall leads to the fact that albumin and water move from the fetal blood into the tissue interstitium. At the same time, albumin synthesis in the baby's liver decreases, which aggravates hypoproteinemia.

As a result, a general edematous syndrome is formed in utero, ascites develops, fluid accumulates in the pleural cavities, in the pericardial cavity, etc. A decrease in the drainage function of the lymphatic system aggravates the development of ascites and the accumulation of fluid in other cavities of the body. Hypoproteinemia, accumulation of fluid in cavities in combination with damage to the vascular wall lead to the development of heart failure.

As a result of erythroid metaplasia in the organs and pronounced fibrosis in the liver, hepato- and splenomegaly are formed. Ascites and hepatosplenomegaly cause the diaphragm to be high, which leads to pulmonary hypoplasia. The increased amount of indirect bilirubin formed during hemolysis is excreted from the blood and tissues of the fetus through the placenta into the mother's body, so there is no jaundice at birth.

Pathogenesis of the icteric form of hemolytic disease of the newborn

The icteric form of the disease develops if hemolysis begins shortly before delivery. As a result of the destruction of red blood cells, the concentration of indirect (unconjugated) bilirubin increases rapidly and significantly, which leads to the following changes:

• accumulation of indirect bilirubin in the lipid substances of tissues, which causes yellowish discoloration of the skin and sclera - jaundice, and also as a result of accumulation of indirect bilirubin in the nuclei of the base of the brain, which leads to its damage with the development of neuronal necrosis, gliosis and the formation of bilirubin encephalopathy (nuclear jaundice);
• an increase in the load on liver glucuronyl transferase, which leads to the depletion of this enzyme, the synthesis of which begins in liver cells only after birth, and as a result, hyperbilirubinemia is maintained and intensified;
• an increase in the excretion of conjugated (direct) bilirubin, which can lead to a disruption in the excretion of bile and the development of a complication - cholestasis.

Just as with the edematous form, hepatosplenomegaly develops.

Pathogenesis of the anemic form of hemolytic disease

The anemic form develops when small amounts of maternal antibodies enter the fetus's bloodstream shortly before birth. In this case, hemolysis is not intense, and the newborn's liver quite actively removes indirect bilirubin. Anemia dominates, and jaundice is absent or minimally expressed. Hepatosplenomegaly is characteristic.

Symptoms of hemolytic disease of the newborn

Hemolytic disease of the newborn and fetus has three clinical forms: anemic, icteric and edematous. Among them, the most severe and prognostically unfavorable is edematous.

Common clinical signs of all forms of hemolytic disease of the newborn: pale skin and visible mucous membranes due to anemia, hepatosplenomegaly. Along with this, the edematous, icteric and anemic forms have their own characteristics.

Edematous form

The most severe form of hemolytic disease of the newborn. The clinical picture, in addition to the above symptoms, is characterized by widespread edematous syndrome: anasarca, ascites, hydropericardium, etc. Hemorrhages on the skin, the development of DIC syndrome as a result of hypoxia, hemodynamic disorders with cardiopulmonary insufficiency are possible. Expansion of the heart borders, muffled heart sounds are noted. Respiratory disorders often develop after birth against the background of pulmonary hypoplasia.

Jaundice form of hemolytic disease

This is the most common form of hemolytic disease of the newborn. In addition to the general clinical manifestations, which include pale skin and visible mucous membranes, as a rule, very moderate and moderate enlargement of the spleen and liver, jaundice, mainly of a warm yellow hue, is also noted. At birth, the amniotic fluid, umbilical cord membranes, and vernix caseosa may be stained.

Early development of jaundice is typical: it occurs either at birth or in the first 24-36 hours of a newborn’s life.

Depending on the severity of jaundice, there are three degrees of the icteric form of hemolytic disease of the newborn:

• mild: jaundice appears by the end of the first or the beginning of the second day of the child's life, the bilirubin content in the umbilical cord blood does not exceed 51 μmol/l, the hourly increase in bilirubin is up to 4-5 μmol/l, the enlargement of the liver and spleen is moderate - less than 2.5 and 1.0 cm, respectively;
• moderate: jaundice occurs immediately at birth or in the first hours after birth, the amount of bilirubin in the umbilical cord blood exceeds 68 μmol/l, the hourly increase in bilirubin is up to 6-10 μmol/l, the liver is enlarged to 2.5-3.0 cm and the spleen to 1.0-1.5 cm;
• severe: diagnosed based on ultrasound data of the placenta, the optical density of bilirubin in the amniotic fluid obtained by amniocentesis, the amount of hemoglobin and the hematocrit value of the blood obtained by cordocentesis. If treatment is started late or is inadequate, the icteric form may be accompanied by the development of the following complications.

Nuclear jaundice

Symptoms indicating damage to the nervous system are noted. First, in the form of bilirubin intoxication (lethargy, abnormal yawning, loss of appetite, regurgitation, muscle hypotonia, disappearance of phase II of the Moro reflex), and then bilirubin encephalopathy (forced body position with opisthotonus, "brain" cry, bulging of the large fontanelle, disappearance of the Moro reflex, convulsions, pathological oculomotor symptoms - the "setting sun" symptom, nystagmus, etc.).

Bile thickening syndrome, when jaundice takes on a greenish tint, the liver increases slightly in size compared to previous days, a tendency to acholia appears, and the color saturation of urine increases.

Anemic form of hemolytic disease of the newborn

The least common and mildest form of the disease. Against the background of pale skin, lethargy, poor sucking, tachycardia, hepatosplenomegaly are noted, muffled heart sounds and systolic murmur are possible.

Along with changes in the fetus's body, there are also changes in the placenta. This is expressed in an increase in its mass. If the normal ratio of the placenta mass to the fetus mass is 1: 6, then with a Rh conflict it is 1: 3. The increase in the placenta occurs mainly due to its edema.

But this is not the only pathology associated with Rh-conflict. In addition to the above, Rh-conflict is characterized by antenatal (prenatal) death of the fetus and repeated spontaneous abortions.

Moreover, with high antibody activity, spontaneous abortions can occur in the early stages of pregnancy.

Women who have experienced Rh-conflict are more likely to develop toxicosis of pregnancy, anemia, and impaired liver function.

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Classification

Depending on the type of conflict, hemolytic disease of the newborn is distinguished:

• in case of incompatibility of maternal and fetal red blood cells according to the Rh factor;
• in case of incompatibility according to the ABO system (group incompatibility);
• in case of incompatibility due to rare blood factors.

According to clinical manifestations, the following are distinguished:

• edematous form (anemia with dropsy);
• icteric form (anemia with jaundice);
• anemic form (anemia without jaundice and dropsy).

According to severity, the icteric form is classified as mild, moderate and severe.

In addition, a distinction is made between complicated (kernicterus, bile thickening syndrome, hemorrhagic syndrome, damage to the kidneys, adrenal glands, etc.) and uncomplicated forms of hemolytic disease of the newborn.

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Diagnosis of hemolytic disease of the newborn

Diagnosis of hemolytic disease of the newborn is based on immunological examination of the pregnant woman, ultrasound, Doppler ultrasound of the fetoplacental and uteroplacental blood flow, electrophysiological examination methods, examination of amniotic fluid (during amniocentesis), cordocentesis and examination of fetal blood.

An immunological study allows us to determine the presence of antibodies, as well as changes in their quantity (increase or decrease in titer). Ultrasound allows us to measure the volume of the placenta, determine an increase in its thickness, detect polyhydramnios, an increase in the size of the liver and spleen of the fetus, an increase in the size of the abdomen of the fetus compared to the size of the head and chest, and ascites in the fetus. Dopplerometry allows us to detect an increase in the systolic-diastolic ratio and the resistance index in the umbilical artery and an increase in the blood flow velocity in the middle cerebral artery of the fetus. Electrophysiological methods (cardiotocography with determination of the fetal condition indicator) allow us to detect a monotonous rhythm in moderate and severe forms of the disease and a "sinusoidal" rhythm in the edematous form of GBP. A study of amniotic fluid (during amniocentesis) allows us to determine an increase in the optical density of bilirubin in the amniotic fluid. Finally, cordocentesis and fetal blood tests can detect a decrease in hematocrit, a decrease in hemoglobin, an increase in bilirubin concentration, perform an indirect Coombs test, and determine the fetal blood type and the presence of the Rh factor.

Since the prognosis for the disease depends on the bilirubin content, in order to develop further medical tactics, a newborn with suspected hemolytic disease of the newborn must first undergo a biochemical blood test to determine the concentration of bilirubin (total, indirect, direct), protein, albumin, AST, ALT, and then conduct an examination to determine the etiology of hyperbilirubinemia. For this purpose, the newborn undergoes a general blood test, determines the Rh factor in case of possible Rh sensitization and the blood group in case of possible ABO sensitization, determines the antibody titer and the direct Coombs reaction.

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Differential diagnostics

Differential diagnostics of hemolytic disease of the newborn is carried out with other anemias. These include hereditary anemias caused by the following disorders:

• disturbance of erythrocyte morphology (microspherocytosis, elliptocytosis, stomatocytosis);
• deficiency of red blood cell enzymes (glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, pyruvate kinase);
• anomaly of hemoglobin synthesis (a-thalassemia).

To exclude these diseases, it is necessary to carefully collect anamnesis about the presence of other carriers of this pathology in the family and conduct the following studies:

• determination of erythrocyte morphology;
• determination of osmotic stability and diameter of erythrocytes;
• determination of the activity of erythrocyte enzymes;
• determination of hemoglobin type.

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Treatment of hemolytic disease of the newborn

First of all, if we are talking about Rh-conflict, it is necessary to diagnose the disease during the period of intrauterine development of the fetus, assess its severity and, accordingly, the prognosis of the disease and conduct treatment until the fetus reaches viability. All treatment and preventive methods used during this period of the fetus' life are divided into non-invasive and invasive.

Non-invasive methods

Non-invasive methods include plasmapheresis and the administration of intravenous immunoglobulin to the pregnant woman.

Plasmapheresis of pregnant women is performed for the purpose of detoxification, re-correction and immunocorrection.

Contraindications to plasmapheresis:

• severe damage to the cardiovascular system;
• anemia (hemoglobin less than 100 g/l);
• hypoproteinemia (less than 55 g/l);
• hypocoagulation;
• immunodeficiency state;
• history of allergic reactions to protein and colloidal preparations, anticoagulants.

Immunoglobulin for intravenous administration is used to inhibit the production of maternal antibodies and block Rh-associated antibodies during their placental transport. Immunoglobulin for intravenous administration is used at a dose of 0.4 g per kilogram of the pregnant woman's body weight. This dose is distributed over 4-5 days. The courses of administration must be repeated every 3 weeks until delivery. This method of treatment is not considered generally accepted, since in severe cases of the disease the outcome for the fetus improves only slightly.

Invasive methods

Invasive methods include cordocentesis and intrauterine transfusion of red blood cells. These procedures are performed only in case of Rh sensitization; at present, this is the only pathogenetic method for treating hemolytic disease of the fetus.

Indications for cordocentesis:

• burdened obstetric history (death of previous children from severe forms of hemolytic disease of the newborn);
• high antibody titer (1:32 and higher);
• ultrasound shows signs of hemolytic disease of the fetus;
• high values of optical density of bilirubin in amniotic fluid obtained by amniocentesis (zone 3 of the Lily scale).

The time period during which cordocentesis is performed: from the 24th to the 35th week of pregnancy.

Indication for intrauterine transfusion of red blood cells when a positive Rh factor is detected in the fetus is a decrease in hemoglobin and hematocrit values by more than 15% of the norm determined at a given gestational age. For intrauterine transfusion of red blood cells, only "washed" red blood cells of blood group 0(1) Rh-negative are used. Intrauterine transfusion of red blood cells is performed according to indications 1-3 times.

Treatment of hemolytic disease of the newborn, unlike therapy for hemolytic disease of the fetus, includes, first of all, treatment of hyperbilirubinemia, secondly, correction of anemia, and finally, syndrome therapy aimed at restoring the functions of various organs and systems. All newborns with this disease are not put to the breast, but are artificially fed in the first 5-7 days of life, since antibodies can penetrate with the mother's breast milk and be absorbed in the intestines of newborns, which leads to increased hemolysis.

Treatment of hyperbilirubinemia

Treatment of hyperbilirubinemia involves the use of conservative and surgical therapy. They start with conservative treatment, and at critical bilirubin values they combine it with surgical treatment - replacement (exchange) blood transfusion (RBT).

Conservative therapy includes phototherapy (PT) and the use of immunoglobulin for intravenous administration. Infusion therapy, as recommended by the Russian Association of Perinatal Medicine Specialists (RASPM), is carried out in cases where it is impossible to adequately feed the child. Phenobarbital is currently practically not used due to the fact that the onset of the effect is significantly delayed from the moment of its use and against the background of its use, there is an increase in the syndrome of central nervous system depression.

Phototherapy

The mechanism of action of phototherapy is based on the fact that when it is carried out on irradiated areas in the skin and subcutaneous fat layer at a depth of 2-3 mm, as a result of photooxidation and photoisomerization processes, a water-soluble isomer of indirect bilirubin is formed - lumirubin, which then enters the bloodstream and is excreted with bile and urine.

Indications for phototherapy:

• yellowness of the skin at birth;
• high concentration of indirect bilirubin.

Principles of phototherapy:

• radiation dose - not less than 8 μW/(cm2xnm);
• the distance from the source to the patient specified in the device instructions must be maintained;
• the child should be placed in an incubator;
• the child's eyes and genitals should be protected;
• The child's position under the FT lamps should be changed every 6 hours.

Minimum values of indirect bilirubin concentration (μmol/l) at which phototherapy is indicated

Body weight, g	Age
	24 h	48 h	72 h	4-7 days
<1000	51	85	90	90-120
1000-1500	85	120	150	170
1500-2000	100	120	170	190
2000-2500	120	190	220	240
>2500	130	200	220	250

Phototherapy is carried out continuously with breaks for feeding the child for 3-5 days. FT should be discontinued when the indirect bilirubin content drops below 170 μmol/l.

Various reactions and side effects may occur during phototherapy.

Complications and side effects of phototherapy

Manifestations	Mechanism of development	Events
Tanned Skin Syndrome	Induction of melanin synthesis	Observation
Bronze Child Syndrome	Accumulation of photooxidation products of direct bilirubin	Cancel FT
Diarrhea	Activation of intestinal secretory function	Observation
Lactose intolerance	Serous lesions of the villous epithelium	Monitoring, if necessary - cancellation of FT
Hemolysis	Damage to circulating red blood cells due to photosensitivity	Cancellation of FT
Skin burns	Excessive lamp radiation	Cancellation of FT
Exicosis	Increased fluid loss	Increase the amount of fluid your child drinks
Skin rashes	Increased histamine production and release during photosensitivity	Monitoring, if necessary - cancellation of FT

If signs of cholestasis appear, as evidenced by an increase in the direct bilirubin fraction by 20-30% or more, an increase in the activity of AST and ALT, alkaline phosphatase, and cholesterol concentration, the duration of phototherapy should be limited to 6-12 hours/day or completely cancelled to avoid the development of “bronze child” syndrome.

Use of immunoglobulin

Intravenous immunoglobulin is used to block Fc receptors, which prevents hemolysis. Early administration of immunoglobulin is necessary (in the first 2 hours of life), which is only possible with antenatal diagnosis of the disease. Later administration of immunoglobulin is possible, but less effective.

Standard immunoglobulins for intravenous administration are used: sandoglobin, ISIVEN (Italy), polyglobin Np (Germany), etc.

Possible schemes for the administration of immunoglobulins:

• 1 g/kg every 4 hours;
• 500 mg/kg every 2 hours;
• 800 mg/kg daily for 3 days.

Regardless of the dose and frequency, a proven (95%) positive effect was obtained, which was manifested in a significant reduction in the frequency of SPC and the duration of phototherapy.

Infusion therapy

Infusion therapy is performed in cases where it is not possible to adequately feed the child while phototherapy is being performed. The daily volume of fluid administered to the child must be increased by 10-20% (in children with extremely low body weight - by 40%) compared to the physiological need.

When carrying out infusion therapy, it is necessary to monitor the child’s body weight, evaluate diuresis, electrolyte levels, blood glucose, and hematocrit.

Infusion therapy mainly includes transfusion of 10% glucose solution4. Infusion therapy is performed intravenously or intragastrically through a gastric tube. Intragastric administration of fluid can be started from the 3rd-4th day of life; to prevent the development of cholestasis, a 25% solution of magnesium sulfate at a rate of 5 ml/kg, no-shpa - 0.5 ml/kg, 4% potassium chloride solution - 5 ml/kg can be added to the drip. With intragastric administration of fluid, there is no need to reduce the volume of feedings.

Surgical therapy - replacement blood transfusion

A distinction is made between early (in the first 2 days of life) and late (from the 3rd day of life) ZPK.

An indication for late IPC is the concentration of indirect bilirubin equal to 308-340 μmol/l (for a full-term newborn).

Indications for late exchange transfusion in newborns depending on birth weight

Body weight, g	Concentration of indirect bilirubin, µmol/l
<1500	220*-275
1500-1999	275*-300
2000-2499	300*-340
>2500	340-375

1 * Minimum bilirubin values are an indication for the initiation of appropriate treatment in cases where the child's body is exposed to pathological factors that increase the risk of bilirubin encephalopathy (anemia; Apgar score at the 5th minute less than 4 points; Pa02 less than 40 mm Hg lasting more than 1 hour; arterial blood pH less than 7.15 lasting more than 1 hour; rectal temperature less than 35 °C; albumin concentration less than 25 g/l; deterioration of neurological status against the background of hyperbilirubinemia; generalized infectious disease or meningitis).

When the first symptoms of bilirubin intoxication appear, immediate ZPK is indicated, regardless of the bilirubin concentration.

Selection of drugs for exchange blood transfusion

In case of isolated Rh conflict, Rh-negative red blood cell mass of the same group as the child's blood and plasma are used, but it is possible to use plasma of blood group AB(IV). In case of isolated group conflict, red blood cell mass of group 0(1), which coincides with the Rh factor of the child's red blood cells, and plasma of AB(IV) or the same group as the child's blood group are used. If both Rh incompatibility and ABO incompatibility can develop, as well as after intrauterine blood transfusions for ZPK, Rh-negative red blood cell mass of blood group 0(1) and plasma of AB(IV) or the same group as the child's blood group are used.

In case of hemolytic disease of the newborn with a conflict of rare blood factors, donor blood that does not have a “conflict” factor is used.

Calculation of the volume of drugs for replacement blood transfusion

The total volume is 1.5-2 BCC, i.e. for a full-term baby about 150 ml/kg, and for a premature baby - about 180 ml/kg.

The ratio of red blood cell mass to plasma depends on the initial hemoglobin concentration before the operation. The total volume consists of the volume of red blood cell mass required to correct the anemia and the volume of red blood cell mass and plasma required to achieve the volume of the ZPK. The volume of red blood cell mass required to correct the anemia is calculated using the formula:

Volume of red blood cell mass (ml) = (160 - child's hemoglobin in g/l) x 0.4 x child's weight in kg.

The volume of red blood cell mass required to correct anemia should be subtracted from the total volume; the remaining volume is replenished with red blood cell mass and plasma in a ratio of 2:1. The following ratio of red blood cell mass, depending on the child's hemoglobin concentration, roughly corresponds to the above.

Red blood cell mass	Plasma
120 g/l < Hb <150 g/l = 2	1
100 g/l < Hb <120 g/l = 3	1
80 g/l < Hb <100 g/l = 4	1

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Replacement blood transfusion technique

The ZPK is performed through one of the large vessels (umbilical vein, subclavian vein). Before the ZPK, blood is taken to determine the concentration of bilirubin, compatibility of the blood of the donor and recipient. The ZPK is performed in a "pendulum manner", i.e. by alternately removing and introducing a portion of blood at a rate of up to 5-7 ml per kilogram of the child's weight. Before the ZPK, plasma can be administered at a rate of 5 ml/kg. The ZPK begins with the removal of blood. Before the ZPK and during it, the catheter is washed with a solution of sodium heparin.

If the initial hemoglobin concentration is below 80 g/l, the ZPK begins with correction of anemia, i.e. with the introduction of only red blood cell mass under the control of the hemoglobin content. After reaching the hemoglobin concentration of 160 g/l, red blood cell mass and plasma are introduced. For this purpose, the red blood cell mass can be diluted with plasma, or two syringes of red blood cell mass and one syringe of plasma can be introduced alternately.

At the end of the ZPK, blood is taken again to determine the bilirubin concentration. After the ZPK, conservative therapy is continued.

ZPK may be accompanied by the development of immediate and delayed side effects.

Complications of exchange transfusion

Manifestations		Events
Heart	Arrhythmia	Cardiac activity control
	Volumetric overload
	Heart failure
Vascular	Thromboemboia, air embolism	Compliance with blood transfusion technique
	Thrombosis	Flushing the catheter with sodium heparin solution
Coagulation	Sodium heparin overdose	Monitoring the dose of heparin sodium
	Thrombocytopenia	Platelet count monitoring
Electrolyte	Hyperkalemia	For prophylaxis, for every 100 ml transfused (red blood cell mass and plasma in total), administer 1-2 ml of 10% calcium gluconate solution
	Hypocalcemia
	Hypernatremia	Control
	Acidosis	Control of sewage treatment plants
Infectious	Viral	Donor control
	Bacterial	To prevent complications after ZPK and for the time the catheter is in a large vessel, antibacterial therapy is prescribed.
Other	Mechanical destruction of donor cells	Control
	Necrotizing enterocolitis	Observation, detection of clinical symptoms, appropriate therapy
	Hypothermia	Body temperature control, warming up
	Hypoglycemia	For prophylaxis, for every 100 ml transfused (red blood cell mass and plasma in total), administer 2 ml of 10% glucose solution4
Graft versus host disease		Transfuse blood products that have been exposed to radiation
		Do not use large volumes for ZPK

Late anemia develops 2-3 weeks after the IPC. It is usually hyporegenerative and hypoerythropoietic in nature. Recombinant erythropoietin is used to correct it (epoetin alfa subcutaneously 200 IU/kg once every three days for 4-6 weeks).

If iron deficiency is detected during treatment with recombinant erythropoietin, iron preparations are included in the therapy at a dose of 2 mg/kg orally based on the utilized iron.

Prevention

Prevention is designed for women with Rh-negative blood. Prevention of group incompatibility does not exist.

To prevent the development of Rh sensitization, all women with Rh-negative blood should be given one dose of anti-D-Rhesus immunoglobulin in the first 72 hours (preferably in the first day) after delivery if the newborn has Rh-positive blood or in the case of an abortion, both spontaneous and involuntary.

To prevent all the negative consequences of Rh-conflict and conflicts in other blood factors, it is necessary to determine the blood type of the expectant mother and, if it turns out that she has Rh-negative blood, it is necessary to find out whether this woman has been transfused with Rh-positive blood (and, in general, whether she has been transfused with any blood); to find out what the current pregnancy is (whether there have been any previous artificial or spontaneous abortions, intrauterine death of the fetus, premature birth or death of the newborn shortly after birth from jaundice). Information about the Rh-factor of the father of the future child is also important.

For the purpose of prevention, in addition to all of the above, anti-Rhesus immunoglobulin is used. This is done either after the birth of a Rh-positive child, or after the first artificial abortion. It is administered to the mother intramuscularly, once, no later than 72 hours after delivery. This specific prevention of Rh-conflict is possible only in non-sensitized women (sensitization is an increase in sensitivity), that is, in those who have not been transfused with Rh-positive blood, have not had abortions or miscarriages, and, in general, this is the first pregnancy.

In addition to specific prophylaxis, non-specific prophylaxis is also carried out. It includes various medications that reduce the body's sensitization and increase its immunobiological defenses. Sometimes, for the same purpose, a pregnant woman is transplanted with a skin flap from her husband.

Forecast

In the edematous form of GBPIN, the prognosis is the least favorable, which is due to the severity of the child's condition at birth. In the icteric form, the prognosis depends on the degree of damage to the central nervous system, the severity of bilirubin encephalopathy. In the anemic form, the prognosis is the most favorable.

Perinatal mortality in GBPN is 2.5%. Mental and psychomotor development of children who have suffered from such a condition as hemolytic disease of the newborn corresponds to age norms in the overwhelming majority. Physical developmental delays are noted in 4.9% of children. CNS pathology is detected in approximately 8% of children.

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