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No notes for slide. Enfermedad hemolitica perinatal 1. Flint Porter, MD. The infor- the mother, antepartum or intrapartum fetal—maternal bleeding may stimulate mation is designed to aid prac- an immune reaction in the mother.

Maternal immune reactions also can occur titioners in making decisions from blood product transfusion. These guide- these antibodies into the fetal circulation.

Depending on the degree of anti- lines should not be construed as genicity and the amount and type of antibodies involved, this transplacental dictating an exclusive course of passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed treatment or procedure. Vari- and untreated, alloimmunization can lead to significant perinatal morbidity ations in practice may be war- and mortality. Advances in Doppler ultrasonography have led to the develop- ranted based on the needs of the ment of noninvasive methods of management of alloimmunization in pregnant individual patient, resources, women.

Together with more established protocols, Doppler ultrasound evalua- and limitations unique to the tion may allow for a more thorough and less invasive workup with fewer risks institution or type of practice. Prevention of alloimmunization is addressed in another Practice Bulletin 1.

Five major antigens can be identified with known typing sera, and there are many variant antigens. Of the numerous nomenclature systems that have been developed, the Fisher—Race nomenclature is best known and most compatible with our understanding of the inheritance of the Rho or D antigen and the clinical management of Rh alloimmunization 2.

The antigens produced severity of fetal anemia 4. These patients may benefit by these alleles originally were identified by specific from more aggressive fetal assessment, such as measure- antisera and have been lettered C, c, D, E, and e. Anti-C, anti-c, anti-D, anti-E, and anti-e designate specific antibodies directed against their Incidence of Rh-Incompatible respective antigens.

Pregnancy An Rh gene complex is described by the three appro- The incidence of Rh incompatibility varies by race and priate letters. Eight gene complexes are possible listed in ethnicity. The genotype CdE has never been demonstrated in vivo 2. Causes of Rh Alloimmunization Most of the cases of Rh alloimmunization causing Rh alloimmunization can occur only if a sufficient num- transfusion reactions or serious hemolytic disease in the ber of erythrocytes from an Rh-positive fetus gain access fetus and newborn are the result of incompatibility with to the circulation of its Rh-negative mother.

The volume respect to the D antigen. For this reason, the designation necessary to cause alloimmunization varies from patient Rh positive usually indicates the presence of the D anti- to patient and is probably related to the immunogenic gen and Rh negative indicates the absence of D antigen capacity of the Rh-positive erythrocytes and the immune on erythrocytes.

Specific fied. Among these are the Cw antigen and the Du antigen, clinical factors such as cesarean delivery, multifetal ges- which is now referred to as weak D.

The latter is a het- tation, bleeding placenta previa or abruption, manual erogeneous group of clinically important D antigen vari- removal of the placenta, and intrauterine manipulation ants. Some weak D-positive patients are capable of may increase the volume of fetomaternal hemorrhage. In producing the anti-D antibody, although alloimmuniza- most cases, though, excessive fetomaternal hemorrhage tion rarely occurs. The volume of fetal blood entering the maternal circulation is Other Antibodies 0.

Like most cold tion is caused by antepartum fetomaternal hemorrhage agglutinins, Lewis and I antigens do not cause erythro- In contrast, Kell anti- of patients during the third trimester 5. Detectable feto- bodies anti-K can produce erythroblastosis fetalis. A maternal hemorrhage resulting in alloimmunization may more complete list of antibodies and their effects can be occur in first-trimester spontaneous and induced abortion found in Table 1.

Often, Kell alloimmunization is caused Alloimmunization also has been reported after by prior transfusion because Kell compatibility was not threatened abortion and ectopic pregnancy 14, Care of Several obstetric procedures may lead to fetomaternal patients with sensitization to antigens other than D that hemorrhage and, in turn, maternal alloimmunization. A possible mination, amniocentesis, and external cephalic version exception is Kell sensitization, in which amniotic fluid 16— Table 1.

Irregular antibodies causing hemolytic disease of the newborn: a continuing problem. Clin Obstet Gynecol ; Anti-D Immune Globulin to Prevent with a history of a previously affected fetus or neonate, Alloimmunization serial titer assessment is inadequate for surveillance of fetal anemia.

Titer values are reported as the integer of Anti-D immune globulin is not indicated for patients pre- the greatest tube dilution with a positive agglutination viously sensitized to D. However, it is indicated for reaction.

Variation in titer results from different laborato- patients who might be sensitized to other blood group ries is not uncommon, so titers should be obtained in the antigens. A critical titer is that titer associated with a significant risk for severe Clinical Considerations and erythroblastosis fetalis and hydrops, and in most centers Recommendations this is between and For patients with alloimmu- detecting alloimmunization in women?

The American Association of Blood Banks also recommends repeated antibody screen- tion of maternal antibodies to diagnose ing before administration of anti-D immune globulin at hemolytic disease in the fetus? Patients who are weak D Du posi- Determination of Paternal Genotype tive are not at risk for alloimmunization and should not The initial management of a pregnancy involving an receive anti-D immunoprophylaxis.

A positive result is deter- development of noninvasive methods to assess the degree mined by agglutination caused by the cross-linking of the of fetal anemia. Doppler was used to measure the peak antibody with the corresponding antigen. Moderate or severe ane- that each pregnancy will have an Rh-negative fetus that is mia was predicted by values of peak systolic velocity in not at risk of anemia.

Given that the genes coding for the the fetal middle cerebral artery above 1. Correct technique is a critical identify a number of minor antigens C, c, E, and e. This procedure should be used only by those with Table 1 should be performed in the same manner. Studies have reported a good correlation between the Determination of Fetal Genotype peak systolic velocity in the fetal middle cerebral artery and hemoglobin in fetuses that have undergone two pre- The fetal antigen type should be assessed when the pater- vious transfusions, expanding the clinical use of this nal genotype is thought to be heterozygous or is Doppler test 27, Amniocentesis is the primary modality used to There are some limitations of this technology.

In ic fluid. The sensitivity and specificity of PCR typing are addition, as with any new technology, the measurements reported as In a center with trained purpose, but its use should be discouraged because dis- personnel and when the fetus is at an appropriate gesta- ruption of the villi may result in unnecessary fetomater- tional age, middle cerebral artery Doppler measurements nal hemorrhage and worsening alloimmunization If seem to be an appropriate noninvasive means to monitor the fetus is found to be negative for the erythrocyte anti- pregnancies complicated by red cell alloimmunization.

Detection of fetal D by molecular analysis of mater- positive for non-D antigens at the first nal plasma or serum can be assessed in the second prenatal visit? This The use of anti-D immune globulin to prevent red cell is possible because of high concentrations of fetal DNA alloimmunization has led to a relative increase in the found in maternal plasma It should be noted, how- number of non-Rh-D alloimmunizations causing fetal ever, that this is not a widely used clinical tool.

Overall, antibodies to the accepted method of assessing the severity of eryth- minor antigens occur in 1. In general, care of the pregnant patient with Queenan curve for earlier gestational ages 19—25 antibodies to one of the clinically significant minor anti- weeks. The current trend is management with middle gens is similar to care of Rh-D alloimmunized pregnant cerebral artery Doppler ultrasonography. An important exception involves alloimmuniza- VOL. Hemoglobin concentrations in healthy fetuses and fetuses that underwent cor- docentesis.

The reference range in the healthy fetuses was between 0. Values for the fetuses that underwent cordo- centesis are plotted individually.

Solid circles indicate fetuses with hydrops. Noninvasive diagnosis by Doppler ultra- sonography of fetal anemia due to maternal red-cell alloimmunization. N Engl J Med — All rights reserved.


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