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Rhesus-conflict during pregnancy
Last reviewed: 23.04.2024
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[Causes of the rhesus-conflict during pregnancy
95% of all clinically significant cases of hemolytic disease of the fetus are due to the incompatibility of the Rh (Rh) -factor, 5% - according to the ABO system. Another sensitization is known for other erythrocyte antigens (Kell, Kidd, Duffy, Lutheran, Lewis, MNSs, Pp, etc.), but sensitization of the described antigens is extremely rare.
Rhesus factor is a system of allogeneic human erythrocyte antigens, independent of the factors that determine the blood group (the ABO system), and other genetic markers.
Pathogenesis
There are 6 main antigens Rh. Two nomenclatures are used to designate this system of antigens: the Wiener nomenclature and the Fischer-Reis nomenclature.
According to Wiener nomenclature, symbols denote Rh antigens Rh0, rh I, rh II, Nr0, hr I, hr II.
The classification of Fisher-Reis is based on the assumption that there are 3 sites in the Rh chromosome for 3 genes that determine the Rh factor. Currently, the designation of Fischer-Reus antigens is recommended by the WHO Expert Committee on Biological Standards. Each gene complex consists of 3 antigenic determinants: D or absence of D, C or c, E or e in various combinations. The existence of antigen d has not been confirmed to date, since there is no gene responsible for the synthesis of this antigen. Despite this, the symbol d is used in immunohematology to indicate the absence of D antigen on erythrocytes when describing phenotypes.
Often two nomenclatures are used simultaneously. In this case, the symbols of one of the notations are placed in parentheses, for example Rh0 (D).
Thus, there are 6 genes that control the synthesis of the Rh factor, and there are at least 36 possible genotypes of the Rh system. However, fewer antigens can be detected phenotypically (5, 4, 3), depending on the number of homozygous loci in the individual. Antigen Rh0 (D) - the main antigen of the rhesus system, which has the greatest practical significance. It is found on the red blood cells of 85% of people living in Europe. It is on the basis of the presence of the antigen Rh0 (D) on the erythrocyte, the Rh-positive blood type is isolated. The blood of people whose erythrocytes are devoid of this antigen is referred to as a Rh-negative type. Antigen Rh0 (D) in 1.5% of cases occurs in a weakly expressed genetically determined variant - variety Du.
Persons with Rh-positive blood can be homozygous (DD) and heterozygous (Dd), which has the following practical significance [2]:
- If the father is homozygous (DD), which is observed in 40-45% of all Rh-positive men, then the dominant gene D is always transferred to the fetus. Therefore, in Rh-negative women (dd), the fetus will be Rh-positive in 100% of cases.
- If the father is heterozygous (Dd), which is noted in 55-60% of all Rh-positive men, the fetus can be Rh-positive in 50% of cases, since it is possible to inherit both a dominant and a recessive gene.
Thus, in a woman with Rh-negative blood during pregnancy from a man with Rh-positive blood in 55-60% of cases, the fetus will have Rh-positive blood. Determining the heterozygosity of the father presents certain difficulties and can not be introduced into routine practice. Therefore, pregnancy in a woman with Rh-negative blood from a man with Rh-positive blood should be conducted as a pregnancy with a fetus with Rh-positive blood.
Approximately 1-1.5% of all pregnancies in women with Rhesus-negative blood the first pregnancy is complicated by erythrocyte sensitization in the course of gestation, after birth this percentage increases to 10%. This frequency is significantly reduced when using anti-Rh0 (D) -immunoglobulin.
Symptoms of the rhesus-conflict during pregnancy
Immune antiresus antibodies appear in the body in response to a Rh rhesus antigen, either after a transfusion of Rh-incompatible blood, or after a Rh-positive fetus. The presence of antiresus antibodies in the blood of Rh-negative individuals indicates sensitization of the body to the Rh factor.
The mother's primary response to getting into the bloodstream of Rh antigens is the production of IgM antibodies, which do not penetrate the placental barrier to the fetus because of the large molecular weight. The primary immune response after D-antigen enters the mother's bloodstream occurs after a certain time, which is from 6 weeks to 12 months. When rhesus antigens re-enter the sensitized mother's body, rapid and massive production of IgG takes place, which, due to the low molecular weight, can penetrate the placental barrier. In half the cases, 50-75 ml of erythrocytes are sufficient for the development of the primary immune response, and 0.1 ml for the secondary immune response.
The sensitization of the maternal organism increases with the continued action of the antigen.
Diagnostics of the rhesus-conflict during pregnancy
- If the mother and father have Rh-negative blood, there is no need for further dynamic determination of antibody levels.
- In the case when a pregnant woman with Rhesus-negative blood has a partner with Rh-positive blood, the next step is to determine the titer of antibodies in dynamics.
- The availability of information on previous antibody titers is necessary to decide whether there has been immunization to date or has developed in this pregnancy.
- A rare cause of sensitization (about 2% of all cases), called "grandmother's theory", is the sensitization of a woman with Rh-negative blood at birth, due to contact with Rh-positive red blood cells of her mother.
- Definition of the class of antibodies: IgM (complete antibodies) do not represent risk of fetal pregnancy, IgG (partial antibodies) can cause hemolytic disease of the fetus, so detection of antibody titer is necessary.
Rhesus-conflict during pregnancy - Diagnosis
Screening
It consists of the definition of blood type and Rh factor. It should be administered to all women planning a pregnancy. In a woman with Rh-negative blood, the blood group and the Rh factor of the partner are tested.
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Treatment of the rhesus-conflict during pregnancy
Management of unimmunized pregnant women
- The titer of antibodies should be determined monthly.
- In case of detection of Rh-anti-D-antibodies at any term of pregnancy, the pregnant woman should be kept as pregnant with Rh-immunization.
- In the absence of isoimmunization, the pregnant woman is administered anti-Rh 0 (D) -immunoglobulin at the 28th week of pregnancy.
- If in 28 weeks anti-D-immunoglobulin prophylaxis was carried out, the determination of antibodies in the blood of a pregnant woman is not clinically significant.
Rhesus-conflict during pregnancy - Treatment
The mechanism of action of anti-Rh0 (D) -immunoglobulin
It has been proved that if the antigen and its antibody are injected together, then there is no immune response, provided an adequate dose of antibodies is given. By the same principle, anti-Rh0 (D) -immunoglobulin (antibody) protects against an immune reaction when a Rh-negative woman is exposed to Rh (+) [D (+)] fetal cells (antigen). Anti-Rh0 (D) -immunoglobulin does not have a negative effect on the fetus and the newborn. Anti-Rh0 (D) -immunoglobulin does not protect against the sensitization by other antigens of the Rh system (in addition to those encoded by the D, C and E genes), but the risk of hemolytic disease of the fetus caused by antibodies to Kell, Duffy, Kidd and others antigens is much lower.
A dose of 300 micrograms of anti-Rh0 (D) -immunoglobulin administered in 28 weeks of gestation, reduces the risk of isoimmunization during the first pregnancy from 1.5 to 0.2%. Therefore, in 28 gestation, all Rhesus-negative unimmunized pregnancies (no antibodies), when the fetus's father is Rh-positive, should receive 300 μg of anti-Rh0 (D) -immunoglobulin prophylactically.