Medical brain notes 42

  Isoimmunization When any fetal blood group factor inherited from the  father is not possessed by the mother, antepartumor intrapartum fetal–maternal bleeding may stim-ulate an immune reaction in the mother. Maternal immune  reactions also can occur from blood product transfusion.  The formation of maternal antibodies is called  isoimmuniza-tion.  It can lead to various degrees of transplacental passage ofthese antibodies into the fetal circulation, causing an  anti-body response  sufficient to destroy fetal red cells. Althoughearly exposures to maternal antigens during pregnancy may occur in the same pregnancy, isoimmunization more commonly occurs in a subsequent pregnancy. The bind-ing of maternal antibodies to fetal red blood cells leads to  hemolytic disease  in the fetus or newborn, characterizedby  hemolysis, bilirubin release,  and  anemia.  The sever-ity of the illness encountered by the fetus or newborn is d...

  NATURAL HISTORY   Any of the many blood group antigen systems can lead to isoimmunization, but the number of antigens involved in fetal and neonatal hemolytic disease is limited. The most common antigen involved is part of the  Rh (CDE) sys-tem,  specifically the  D antigen.   The Rh system is a complex of five antigens—including the  C, c, D, E,  and  e antigens —each of which elicits a unique immune response. These antigens are inherited together in distinctive patterns reflecting the underlying genotypic makeup of the parents. C and c are alternate forms of the same antigen, as are E and e, but there is nod antigen. The D antigen is either present or absent.  Patientswith the D antigen are termed  Rh D-positive,  and those lacking this gene, and hence the antigen, are said to be  Rh D-negative. Approximately 15% of whites, 5% to 8% of African Americans, and only 1% to 2% of Asians and Native Americans are Rh D-negativ...

  DIAGNOSIS   All pregnant women should be tested at the time of the first pre-natal visit for ABO blood group and Rh-D type and screened for the presence of erythrocyte antibodies. These laboratory assessments should be repeated in each subsequent pregnancy.  Repeated anti-body screening is also recommended before administration of anti-D immunoglobulin at 28 weeks of gestation, post-partum, and the time of any event in pregnancy. Patients who are weak-D positive are not at risk for isoimmunization and should not receive anti-D immunoprophylaxis.   Any antibodies potentially associated with fetal hemo-lysis found during this routine screening are further eval-uated based on the strength of the antibody response, which is reported in titer format (1:4, 1:8, 1:16, etc.), with higher numbers indicative of a more significant antibody response. Although often encountered during the process of antibody screening, anti-Lewis and Anti-I antibodies are not associated with fe...

  ASSESSMENT   Although antibody titers reflect the strength and the amount of the maternal antibody response, their utility in pregnancy management is limited.  Titers provide no information aboutfetal status.  In an initial sensitized pregnancy, serial antibodytiter values can assist in determining when the maternal anti-body response is strong enough to represent a risk of fetal anemia. A  critical titer  is that titer associated with a signif-icant risk for severe fetal hemolytic disease and hydrops fetalis. In most centers, this is between 1:8 and 1:32. If the initial antibody titer is 1:8 or less, the Rh D-negative patient can be monitored with titer assessment every 4 weeks. In a first-sensitized pregnancy, titers are generally performed every 4 weeks. With a history of an affected fetus or infant, titers are not helpful in predicting fetal hemolytic disease and further evaluation is warranted.   Evaluation for possible fetal anemia is usually u...

  MANAGEMENT   Previously, blood was transfused into the fetal abdomi-nal cavity, where absorption of the red cells could take place over several days through the lymphatic channels.     Currently,  transfusion  of antigen-negative red blood cells (depending on the blood group involved) to the fetus is indicated when PUBS determines that the fetus has mod-erate or severe anemia with a hematocrit less than 30%.  Direct transfusion under ultrasound guidance into the umbilical vein has become the preferred technique.  The procedure has a1% to 3% risk of complications, including fetal death and preterm delivery, which must be weighed against the pre-dicted course of the fetus if left untreated or delivered. The volume of red blood cells to be transfused can be calculated based on the gestational age, estimated fetal weight, the hematocrit of the unit of blood, and the differ-ence between the current fetal hematocrit and the desired hematocrit. Because...

  PREVENTION   Maternal exposure and subsequent sensitization to fetal blood usually occurs at delivery, but it can occur at any time during pregnancy. In the late 1960s, it was discovered that an antibody to the D antigen of the Rh system could be prepared from donors previously sensitized to the antigen. Administration of the  anti-D immune globulin  soon after delivery prevents an active antibody response to the D anti-gen by the mother in most cases.   Anti-D immune globulin is effective only for the D antigen of the Rh system. It is not effective in preventing sensitiza-tion to other Rh antigens or any other red cell antigens. It is now standard for Rh D-negative women who deliver Rh D-positive infants to receive a dose of 300  μ g of anti-D immune globulin within 72 hours of delivery (Box 19.2). This practice reduces the risk of sensitization to the D antigen from around 16% to approximately 2%. The residual 2% risk is believed to result from sensitiz...

  MANAGEMENT OF ISOIMMUNIZATION TO OTHER RED CELL ANTIGENS   Although the routine use of Rh immune globulin has decreased isoimmunization due to the D antigen,  iso-immunization due to other blood group antigens has propor-tionally increased.  The frequency of these antibodies varies depending on the frequency of the antigen in the general population and in various ethnic groups. In addition, the likelihood that these antibodies will result in significant fetal hemolytic disease depends on several factors, includ-ing the size of the sensitizing antigenic stimulus, the rela-tive potency of the antigen, and the isoform (IgG or IgM) of antibody response.   Sensitization to any of these antigens can occur in any exposed women lacking the particular antigen, regardless of her ABO or Rh type. An antibody screen will detect the presence of these antibodies.  The most important cause ofhemolytic disease of the fetus not associated with the D antigen is isoimmunizat...