Hemolytic disease

гемолитическая болезнь фото Hemolytic disease of the newborns is a nonphysiological development of hemolytic anemia of the isoimmune type, which arises as a result of the incompatibility of the erythrocyte antigens of the fetus and the mother's blood, which contains a high concentration of antibodies to these antigens. Level diagnosis of such a pathology as "hemolytic disease of the newborn" is 0.6%, and the perinatal mortality rate according to the world statistics does not exceed 2.5%.

Causes of hemolytic disease of newborns

The basis of the etiopathogenetic mechanism of the development of hemolytic disease of the newborn is the development of an immune conflict that occurs under the condition of "antigen-negativity" of the mother and the "antigen-positivity" of the unborn child. In order to develop a classical hemolytic disease of the fetus, an obligatory condition is the preliminary sensitization of the mother's organism, that is, the available fact of repeated pregnancy. In a situation where hemolytic blood disease develops in terms of group incompatibility, the fact of mother's sensitization does not matter, and anemia develops even during the first pregnancy.

The pathogenetic mechanism of the development of hemolytic disease of newborns is triggered when antigen-positive erythrocyte blood cells enter the body of an antigen-negative pregnant woman. The most important is the volume of fetal blood that enters the mother's blood. There is a whole range of non-modifiable risk factors that promote the development of hemolytic disease in newborns in the form of previous abortions and miscarriages, the presence of an ectopic pregnancy in history, the use of invasive diagnostic techniques and the threat of termination of pregnancy in the past.

The basis of the disease is erythrocytic intracellular hemolysis, occurring in the second trimester of pregnancy and dramatically progressing after delivery. After the entry of antigen-positive erythrocyte cells of the fetus through the fetoplacental barrier, the mechanisms of enhanced production of antiresusive or anti-group antibodies are activated in the mother's body. The produced antibodies of the IgG group freely re-enter the fetal bloodstream, and as a result of their contact with the fetal antigens, active intracellular erythrocyte hemolysis develops.

During the first pregnancy erythrocytic hemolysis does not occur because of insufficient number of red blood cells of the fetus, as well as as a result of immunosuppressive mechanisms of the mother's body, however, the process of sensitization of the mother, which is important in the development of hemolysis in subsequent pregnancies, is launched.

The percentage of possible development of hemolytic disease in a newborn child according to the ABO system is 10%, but the complexity of this disease lies in the fact that erythrocytic hemolysis is formed already at the first pregnancy. Despite this, this form of the disease is characterized by a more favorable course and a minimal risk of complications.

For edematous hemolytic disease of a newborn is characterized by the development of erythrocyte hemolysis at the stage of intrauterine development of the fetus from the 20th week of pregnancy . As a result of progressive anemia, the fetus develops a total hypoxic lesion of all structures and tissues, accompanied by severe metabolic disturbances and damage to the vascular walls. As a result of damage to the walls of the vessels, conditions are created for the excess water and albumin release from the blood plasma in the interstitial interstitium of the fetus with a simultaneous decrease in protein production in the liver parenchyma.

Long-term hypoproteinemia inevitably leads to the formation of diffuse edematous syndrome even in the prenatal period, as well as severe heart failure . Due to the fact that the resulting bilirubin as a result of erythrocyte hemolysis penetrates the mother's body through the fetoplacental barrier, the newborn child does not develop jaundice of the skin.

The icteric variant of the course of hemolytic disease of a newborn develops when the erythrocytic hemolysis develops in the last weeks of pregnancy or immediately before delivery. In connection with the fact that as a result of intensive destruction of a large number of erythrocyte cells, a large concentration of bilirubin is released. The skin of a newborn child acquires icteric color as a result of excessive accumulation of bilirubin in their structures. More severe complications arise in the situation when the indirect fraction of bilirubin accumulates in neurons of the brain, as in this situation irreversible bilirubin encephalopathy develops. As a result of excessive excretion of direct bilirubin by bile-excreting pathways, conditions are created for stagnation of bile and development of signs of a cholestatic syndrome.

An anemic variant of hemolytic disease of newborns is considered the most favorable, since in the pathogenesis of its development, the minimum volume of antibodies arrives in the bloodstream just before the onset of labor, and therefore the erythrocytic hemolysis is of a low intensity.

Symptoms and signs of hemolytic disease of newborns

The most unfavorable course is accompanied by a swollen version of the hemolytic disease of the newborn, and the anemic version of the course may be completely asymptomatic. Despite the fact that each of the clinical forms of this pathology is characterized by the development of specific pathognomonic symptoms, there are a number of clinical manifestations characteristic of any variant of the course of hemolytic disease in the newborn. To such clinical symptoms should be attributed pronounced pallor of the mucous membranes and hepatosplenomegaly.

With edematous hemolytic disease of the newborn there is a rapid progression of the edematous complex, manifested in the accumulation of a large amount of exudate in the natural cavities in the form of exudative pleurisy, pericarditis , ascites. Due to prolonged hypoxic damage to the fetus, conditions are created for the development of DIC syndrome , hemodynamic disorders and respiratory disorders. In a situation where a child is born viable, visually marked sharp diffuse puffiness, pastose skin. An objective examination of a newborn reveals a sharp expansion of absolute cardiac dullness, muffled heart tones, a lack of vesicular breathing over a large extent of pulmonary fields.

The most common clinical variant of the hemolytic disease of the newborn is icteric, the pathognomonic symptom of which is a change in the coloration of not only the skin of the newborn child, but also the original grease, amniotic fluid and the umbilical cord. Most often, the above changes are observed immediately after delivery or during the first day of the child's life. Given the severity of clinical and laboratory changes, it is common to separate the icteric form of a newborn's hemolytic disease by the severity level.

An easy degree of icteric syndrome is established in the case when the skin is icteric no earlier than two days after birth, and the bilirubin index in the blood collected from the umbilical cord does not exceed 51 μmol / l. In this condition, there is no significant increase in the parameters of the spleen and liver, and in some situations, their dimensions remain normal.

Jaundice of moderate severity differs early debut (immediately after delivery) and a significant concentration of bilirubin in cord blood exceeding 68 μmol / l. Moderately severe jaundice is always accompanied by a significant increase in the size of the liver and spleen.

Diagnosis of hemolytic disease of newborns, accompanied by severe icteric syndrome, consists in the production of ultrasound of the placenta, the study of amniotic fluid for determining the optical density of bilirubin. In a situation where a severe form of hemolytic disease is not subject to timely medication correction, serious complications develop in the form of nuclear jaundice.

Symptoms that indicate the development of nuclear jaundice include intoxication syndrome in the form of lethargy, pathological yawning, lack of appetite and regurgitation, muscle hypotension. Severe intoxication of the structures of the central nervous system is characterized by the development of the forced position of the child in bed with opisthotonus, the appearance of a "cerebral" scream, the bulging of the large fontanel, the disappearance of congenital reflexes, increased convulsive readiness and pathological oculomotor symptoms.

Unfortunately, the isolated anemic form of hemolytic disease of newborns is among the rarest. With this clinical variant, the child does not have severe health disorders and is more likely to be diagnosed after a placenta study that is large in size due to the development of edema.

In a situation in which a critically large number of antibodies are produced in the mother's blood and subsequently fed into the bloodstream of the fetus, antenatal fetal death at any term of pregnancy is observed. In general, women who have suffered Rh-conflict, note the severe course of pregnancy due to the development of toxicosis and damage to the structures of the hepato-biliary system.

For the timely diagnosis of hemolytic disease of the newborn, a comprehensive examination of a woman during pregnancy, including immunological analysis, ultrasound with dopplerometry of the fetoplacental blood flow, amniocentesis with further study of amniotic fluid, cordocentesis and subsequent analysis of the fetal blood is of utmost importance.

Immunological analysis allows not only to determine the presence of antibodies in maternal blood, but also to analyze their concentration, as well as the dynamics of titer growth. When carrying out an ultrasound, the volume and placental area must be measured, its possible local thickening is visualized, polyhydramnios detected, and in the early stages the accumulation of fluid in the abdominal cavity of the fetus is determined, which is determined in the form of a significant increase in the size of the abdomen. The amniotic fluid is examined for the purpose of determining the increase in the optical density of bilirubin, which is the case with intracellular erythrocytic haemolysis of the fetal blood.

Forms of hemolytic disease of newborns

The basis for the division of hemolytic disease of the fetus's blood into categories is based on a variety of pathogenetic variants of the formation of the disease. The main category of patients with hemolytic disease are newborns, which are incompatible with erythrocyte antigens with their mother, in particular, Rh-related. The second category of patients consists of newborn patients who develop a clinical picture of hemolytic anemia as a result of group incompatibility with the mother's blood. Hematology distinguishes another specific form of hemolytic disease of the fetus, the emergence of which develops as a result of incompatibility with rare hematological factors (Lutheran, Kell).

Depending on the specificity of the clinical course of the disease and the prevalence of certain clinical and laboratory syndromes, the hemolytic disease of children is divided into three main forms:

1. The edematous variant is a combination of the main anemic symptom complex with massive edematous syndrome.

2. In icteric variant of hemolytic disease of newborns, the icteric symptom complex in combination with pronounced anemia syndrome comes to the fore.

3. Anemic form is considered the most favorable with respect to the impact on the health of the child and at the same time the most difficult to diagnose.

In a situation where measures are taken to treat the child in time, an uncomplicated variant of the hemolytic disease course is observed, and with the complications of the underlying disease, a complicated form is observed, characterized by an extremely severe progressive course and a high risk of lethal outcome.

Treatment of hemolytic disease of newborns

In the situation of the existing Rhesus conflict, the early setting of the diagnosis of hemolytic disease in the early antenatal period, with the concomitant assessment of severity and prognosis for the viability of the child, is of paramount importance. Possible effective therapeutic measures are divided according to the principle of invasiveness.

Non-invasive methods for correcting hemolysis are plasmapheresis and immunoglobulin therapy of a pregnant woman. Despite the fact that plasmapheresis has a good detoxification and immunocorrecting action, there is a whole spectrum of absolute contraindications to its use in the form of severe heart pathology, severe anemia and hypoproteinemia, immunodeficiency and allergic reaction to injected colloid preparations.

The purpose of immunoglobulin therapy is to reduce the production of antibodies, for which intravenous Immunoglobulin is used at a calculated dose of 0.4 g per kg of weight of the pregnant woman. This dose is distributed for 5 days, which is one course. The frequency of course immunoglobulin therapy is once every three weeks during the entire pregnancy. This technique is used only in the case of an average course of the disease.

Greater efficacy in leveling the signs of hemolytic disease of the fetus is invasive techniques in the form of cordocentesis and antenatal transfusion of erythrocyte mass, which are pathogenetically appropriate for the elimination of intrauterine hemolysis. To apply the cordocentesis, there should be strict indications in the form of a burdened obstetric anamnesis (available reliable facts of fetal death from hemolytic disease of the fetus), high antibody titer exceeding 1:32, presence of ultrasound signs of hemolytic disease, high optical density of bilirubin in amniotic fluid. The optimal period for conducting a cordocentesis is the period of 24-35 weeks of pregnancy.

Intrauterine transfusion of erythrocyte mass is used only in case of critical parameters of hemoglobin and hematocrit, for which only Rh-negative washed erythrocytes of the first blood group are used. This procedure is carried out once.

The treatment of hemolytic disease after childbirth consists in the application of techniques aimed at eliminating hyperbilirubinemia , anemia, and the use of drug-induced symptomatic therapy. Newborn children suffering from hemolytic disease are subject to artificial feeding, since in the breast milk of the mother, a large number of antibodies are accumulated that can aggravate the course of the underlying disease.

For the purpose of correcting the hyperbilirubinemic syndrome, both conservative and operational methods are currently used. Conservative therapy implies the use of phototherapy and parenteral immunoglobulin therapy. The therapeutic effect of phototherapy is the formation of a water-soluble isomer of indirect bilirubin in the thickness of the skin and the subcutaneous fat layer under the influence of photo-irradiation of the skin. The synthesized lumirubin is subsequently eliminated from the body along with urine and bile. To achieve a good result in the form of eliminating the jaundice of the skin of a newborn baby and reducing the bilirubin index, it is necessary to carefully monitor the performance of all the technical components of phototherapy, that is, there must be an adequate loading dose, the child must be in a kouveze with superimposed protective equipment on the paraorbital area and genitals. The duration of the continuous phototherapy course is five days on average, but there is an absolute criterion for stopping the irradiation of a newborn child, which is a decrease in the bilirubin index of less than 170 μmol / l. To avoid the development of complications from the use of phototherapy, you should abandon this type of treatment if the child has signs of a cholestatic syndrome.

When conducting phototherapy, a mandatory condition is observance of the drinking regime of the child. In the case where oral rehydration is not possible and there is a risk of dehydration, it is necessary to carry out infusion therapy under mandatory daily diuresis control. For infusion therapy, 10% glucose solution is used in a volume that is 10% higher than the daily requirement of a newborn baby in the fluid.

The pharmacological effect of intravenous immunoglobulin is the blockade of specific Fc receptors and the prevention of erythrocyte hemolysis. The greatest effectiveness of immunoglobulin therapy in the case of its early use in the first hours of life of the newborn, which occurs in the diagnosis of hemolytic disease in the prenatal period of fetal development. The treatment regimen consists in the intravenous administration of Sandoglobin or Polyglobin at a calculated dose of 1 g per 1 kg of the child's weight multiples every 4 hours.

In a situation where conservative methods do not bring the desired effect, or the child has absolute contraindications to their use, it is necessary to resort to a replacement blood transfusion, which belongs to the category of surgical methods for treating a hemolytic disease of the newborn. Absolute clinical criteria, which is an indication for the use of a replacement blood transfusion, is the appearance in the child of signs of bilirubin intoxication and encephalopathy. The dose of the drug administered is calculated depending on the weight of the child (150 ml per 1 kg of weight). Venous access for the administration of the drug is via the umbilical vein. It should be borne in mind that the procedure of replacement blood transfusion may be accompanied by the development of both urgent and delayed complications, therefore it is necessary to follow the dynamic observation of the patient, including the evaluation of clinical and laboratory criteria.

Hemolytic disease of newborns

The most unfavorable variant of hemolytic disease of the fetus is edematous, since the severity of the defeat of all vital structures is critical. The prognosis for the recovery of a child suffering from icteric form of hemolytic disease depends not only on the timeliness of the provision of medicamental care, but also on the severity of the intoxication damage of the brain. The anemic variant is characterized by a mild clinical course and no complications.

Children who underwent hemolytic disease during the newborn period, in most cases, do not differ in physical and psychomotor backwardness from their peers, except for a complicated variant of the disease, in which mental retardation is recorded in 8% of cases. The level of prenatal mortality in this pathology does not exceed 2.5%, which is explained by the high level of early diagnosis of hemolytic disease of the fetus.

? Hemolytic disease of the newborn - which doctor will help ? The treatment of this disease deals with a children's hematologist.