ࡱ> y 0ىbjbj 8{{_2%$$$8\X\$"uuu$#ՐN։uuuu։Ww"w"w"uw"uw"w"tH|S8\wHm0w#M *#H|H|#d8uuw"uuuuu։։w!uuuuuuu#uuuuuuuuu :  Rhessus iso-immunization /.G'D) 9(/'D:FJ 'D1'HJ 'DE1-D) 'D1'(9) 2017 Objectives: -To identify the high risk group of Rh  ve pregnant ladies -management of Rh-ve women during pregnany & possible complications that associated with Rh isoimmunisation Blood group is defined in 2 ways: ABO group (O, A, B, AB). Rhesus system (C, D, E antigens). The importance of these blood groups system is that a mismatch between the fetus & mother & when red cells pass across to the maternal circulation as they do to a greater extent during labor or lesser extent during pregnancy, sensitization of the maternal immune system to these fetal foreign red cells may occur & subsequently give rise to hemolytic disease of the fetus & newborn. ABO blood group iso-immunization may occur when the mother is blood group O & the baby is blood group A, B or AB. Anti A & anti B antibodies are present in the maternal circulation naturally & hence dont require prior exposure & thus sensitization can occur at first pregnancy. ABO incompatibility causes mild hemolysis & anemia because most of anti-A or anti-B antibodies are mainly IgM & do not cross the placenta.In addition.A&B antigens are not fully developed in the fetus. The rhesus system is more commonly associated with severe hemolytic disease. Of all antibodies the D antigen is associated more commonly with severe hemolytic disease, this can only occur if the mother is D rhesus negative & the baby is D rhesus positive. The percentage of Rh-negative around 15% of Caucasians (RhD negative). The etiology of Rhesus disease: The occurrence of hemolytic disease of fetus and newborn (HDFN) as a result of Rhesus isoimmunization involves three key stages: First, a Rhesus negative mother must conceive a baby who has inherited the Rhesus positive phenotype from the father. Second, fetal cells must gain access to the maternal circulation in a sufficient volume to provoke a maternal antibody response. Finally, maternal antibodies must gain transplacental access & cause immune destruction of red cells in the fetus. Why are most first pregnancies unaffected by hemolytic/Rh disease of the newborn? The initial maternal immunoglobulin M (IgM) antibody response is short-lived with molecular weight that is too large to cross the placenta 2. The mothers antibody response mounts slowly (over 26 months). Exposure during pregnancy is mostly likely to occur after 28 weeks gestation, meaning that a first child will likely be delivered before he or she is affected. In addition, transplacental fetomaternal hemorrhage is most common at delivery. Thereafter IgG antibodies are produced and these can cross the placenta. Maternal IgG crosses the placenta and attaches to fetal erythrocytes that have expressed the paternal red cell antigen. These cells are then sequestered by macrophages in the fetal spleen where they undergo extravascular hemolysis producing fetal anemia Once Rh-isoimmunity has been initiated the individual produces large amounts of antibodies (secondary response) in response to small amounts of fetal Rh-positive blood leakage through the placenta in a subsequent pregnancy. The incidence of antepartum primary sensitization in the course of 1st Rh incompatible pregnancy in less than 1%. Only 10 15 % of Rh-negative mother who have Rh-positive husbands become sensitized at delivery. If the father of the fetus is Rhesus negative, the fetus cannot be Rhesus positive. Signs of fetal anemia: Clinical & ultrasound features of fetal anemia do not usually become evident unless fetal hemoglobin is more than 5g/dL less than the mean for gestation. Usually the features are not obvious unless the fetal hemoglobin is less than 6g/Dl. 1. polyhydramnios. 2. Enlarged fetal heart 3. Ascites and pericardial effusions 4. hyperdynamic fetal circulation (can be detected by Doppler ultrasound by measuring increased velocities in the middle cerebral artery or aorta) 5. reduced fetal movements. 6. Abnormal CTG with reduced variability. Fetal hydrops is defined as having fluid within at least two areas in the fetal-placental unit. These fluid collections used in the definition of hydrops include pericardial effusion, pleural effusion, abdominal ascites, skin edema, increased amniotic fluid, or placentomegaly. Severe anemia causes increased production of red blood cells in the fetal liver and spleen, which disrupts the portal venous circulation leading to hepatomegaly, ascites, edema of the placenta, and hyperbilirubinemia Potential sensitization events for Rhesus disease: Miscarriage. Termination of pregnancy. Antepartum haemorrhage. Invasive prenatal testing (CVS, amniocentesis & cordocentesis). Delivery. Rhesus disease gets worse with successive pregnancies. Approximately 97% of cases of erythroblastosis fetalis are caused by maternal immunization against the Rh (D) antigen present in the fetal red cells. The remaining cases caused by other fetal Ag groups such as C,c, E,e ;K(Kell), FY (Duffy) & JK(Kidd). Maternal iso-immunization may also be a result of blood transfusion of Rh +ve to Rh-ve female. Prevention of rhesus iso-immunization: Only RhD alloimmunization can be prevented through the use of a specific immunoglobulin (RhIg). By intramuscular administration of a 300 g dose of RhIG to Rh-ve mother during pregnancy at 28 and/or 34 weeks prophylactically even without exposure. At the time of the delivery of an RhD negative patient, cord blood should be tested for RhD typing. If the neonate is determined to be RhD positive, a second dose of 300 g should be administered within 72 h of delivery. And it can be given up to 14 to 28 days after delivery During pregnancy a dose RhIg to be given preferably within 72 hours of exposure to fetal red cells after any sensitizing events(already mention above). Indication for administration of antiD 1. Spontaneous or elective abortion 2. Ectopic pregnancy 3. Hydatidiform mole 4. Genetic amniocentesis, chorion villus biopsy& fetal blood sampling. 5. APH:Placenta previa with bleeding or Suspected abruption 6. Intrauterine fetal demise 7. Blunt trauma to the abdomen (includes motor vehicle accidents) 8. At 28 weeks gestation, unless father of fetus is RhD negative 9. Amniocentesis for fetal lung maturity 10. External cephalic version 11. within 72 hours of delivery of an RhD-positive Infant 12. after administration of RhD-positive blood components Dose of antiD: Standard dose of Rh-immune globulin used, the 300 g dose cover 30 mL of fetal blood or 15 mL of D-positive red cells (only 1% of women have e"5 mL of fetal blood mixing with maternal blood after delivery). Kleihauer test is a test of maternal blood to determine the proportion of fetal cells present .Fetal erythrocyte contain Hb F which is more resistant to acid or alcohol denaturation than adult Hb A, so after exposure to acid only fetal cells remain.it will allow calculation of the amount of extra anti-D immunoglobulin required should a large transfusion have occurred. When should a larger amount of fetomaternal hemorrhage be suspected (e"15 mL fetal red blood cells)? 1. Multiple gestation 2. Placenta previa with bleeding 3. Placental abruption 4. Manual extraction of placenta 5. Fetal death in the second or third trimester 6. Blunt abdominal trauma Management: -Take full obestetric hx.(hx of intrauterine fetal death due to fetal hydropes, hx of neonatal anemia and jaundice, hx of transfusion of blood and blood products) - send for blood group of the husband - Maternal indirect coomb's test thus if: Rh-negative non immunized patient. Rh-negative immunized patient. Group 1: Rh-negative non immunized patient. This group is formed by the primigravida & multigravida patients who are Rh-negative & dont have detectable iso-antibodies in the initial prenatal evaluation (indirect Coombs test was negative).  Negative no further testing Manage as normal pregnancy Father Rh Factor AB screening Manage as  Become +ve sensitized  Positive Antibody screening pregnancy At booking then 28 week AB screening give (D) IG  Remains -ve at 28 weeks & determine Eligibility of 2nd dose of (D) IG at delivery Criteria for post partum administration of Anti D: The newborn infant is Rh-positive. The mother is Rh-negative & not sensetize:direct Coombs test on umbilical cord blood is negative. To be given within 72 hours after delivery(though can be given up to 14-28 days. Group 2: Rh-negative immunized patient. If the father is Rhesus positive he may be a hetrozygote(50%likelihood that the baby is D Rhesus positive )or homozygote(100%likelihood) Obtain an antibody screen on all pregnant women at their first prenatal visit. If the antibody screen returns positive, this her first immunized pregnancy and no history of baby with erythroblastosis, follow up with antibody titer at first visit and every 2-4 weeks, if antibody titer remains below the critical value then can allow pregnancy to continue to term &delivery at (38-40 weeks) and expect normal or slightly affected baby.(titer simply refers to the number of times a sample has been diluted before the amount of antibody becomes undetectable) If antibody titer rise to acritical level(usually 32) there is a risk for fetal hydrops The fetus can be monitored for the development of anemia. In the past ,the bilirubin concentration of amniotic fluid was determined optically to give an indirect measure of fetal haemolysis . this involved an invasive procedure with the attendant risks of miscarriage/preterm labor and further boosting of the alloimmune response. Middle cerebral artery (MCA) Dopplers (peak velocity measurement) have been shown to correlate reliably with fetal anemia., this means that that the use of invasive tests to monitor disease progression(once a critical antibody level has been reached)have been replaced by non-invasive assessment using MCA Doppler. A fetus with raised MCA Dopplers has a high probability of anemia. In these cases treatment should be in, or guided by, tertiary fetal medicine centres.treatment options include: Delivery or fetal blood transfusion. 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