Description- Rh ("Rhesus factor") is a glycoprotein with antigenic properties that can be present on red blood cell (RBC) membranes. Individuals
- With Rh antigen are denoted Rh positive (or their blood type followed by a positive; for example, A+, B+, AB+, O+)
- Without Rh antigen are denoted Rh negative (or their blood type followed by a negative; for example, A-, B-, AB-, O-)
- In 1940, Drs. Karl Landsteiner and Alexander S. Wiener described an antiserum that was produced by immunizing rabbits with RBCs from Rhesus macaque; it agglutinated about 85% of human RBCs. The antigen that induced this immunization was named Rh factor to indicate that Rhesus blood was the donor for the production of the serum
- The Rh blood group is the second most immunogenic and clinically significant blood group system after ABO.
- The Rh blood group system consists of more than 45 antigens, among which the D, C, c, E, and e are most important.
- Agglutinins (antibodies) develop spontaneously in the plasma to the ABO blood group system, whereas antibodies to the Rh system are produced either through blood transfusion or placental transfer from the fetus during pregnancy.
- Rh antigen is determined as follows
- Homozygous Rh positive, antigen DD (Rh+)
- Heterozygous Rh positive, antigen Dd (Rh+)
- Homozygous Rh negative, antigen dd (Rh–)
- D antigen is wildly prevalent and more antigenic in the population than E or C. However, even in Rh negative individuals, E and C antigens may present and can cause a mild transfusion reaction.
The genes encoding the Rh proteins (RHD) are present on the short arm of chromosome 1.
Physiology/Pathophysiology- Rh incompatibility
- Low incidence in the general population.
- When an Rh negative person receives Rh positive blood, anti-Rh agglutinins develops slowly over a period of 6 weeks to 4 months.
- The slow development of Rh antibody will not produce any immediate transfusion reactions on first exposure. However, should the same person be exposed to Rh positive blood a second time, there will be an enhanced transfusion reaction against the transfused RBCs (hemolysis occurs at a slower rate compared to acute hemolytic reactions from ABO incompatibility).
- Hemolytic disease of the newborn (HDN)
- A serious and potentially fatal disease produced by hemolysis of Rh positive fetal RBCs. When an Rh negative mother becomes pregnant with an Rh positive baby, the fetal Rh positive RBCs enter the maternal circulation during delivery and initiate an immune response in the mother. In subsequent pregnancies, the Rh antibodies enter the fetal circulation through the placenta. If the second baby is also Rh positive, then these antibodies lyse the fetal blood cells.
- Severity: Can range from mild (fetus is minimally anemic) to moderate and severe (profoundly anemic and an excessive amount of bilirubin will be produced). In extremely severe conditions, the fetus develops erythroblastosis fetalis that is characterized by ascites, edema, pleural and pericardial effusions, high output cardiac failure, and extramedullary hematopoiesis.
- Fetal bilirubin: Transported to the mother through the placental circulation and metabolized by the maternal liver. Immediately after the birth, the excess bilirubin cannot be metabolized by the immature fetal liver and the baby becomes extremely jaundiced. The excess bilirubin crosses the blood–brain barrier and reaches the CNS and produces a condition called kernicterus. Kernicterus is characterized by the loss of reflexes, posturing, inactivity, poor feeding, bulging fontanelles, and seizures. Later, the infant may develop hearing loss, and mental retardation.
- RBCs. ABO and Rh compatibility should be performed and confirmed prior to any blood transfusion. In an emergency situation, patients should receive O Rh Negative blood (O-). Men and postmenopausal women may receive O+ blood.
- Fresh-frozen plasma (FFP). ABO compatibility is preferred, but may not be necessary in an emergency. Because FFP may contain only a small amount of RBCs, sensitization to Rh is unlikely; thus, donor FFP may be administered regardless of the recipient's Rh status. No prophylaxis is typically required; however, if administered to a woman of childbearing potential, there is some evidence to support prophylaxis.
- Platelets. Platelets possess ABO antigens, but not Rh. ABO and Rh typing are not necessary, but incompatibility can decrease post-transfusion counts (mainly from ABO incompatibility). Because platelets contain only a small amount of RBCs, sensitization to Rh antigen is unlikely; thus, donor platelets may be administered regardless of the recipient's Rh status. No prophylaxis is typically needed; however, if administered to a woman of childbearing potential, there is some evidence to support prophylaxis.
- Cryoprecipitate. ABO compatible units are preferred when large volumes are needed; however, Rh compatibility does not appear to be necessary.
- Rh incompatibility following blood transfusion in the general population creates difficulties in finding future compatible donors.
- Risk factors for Rh isoimmunization during pregnancy.
- Spontaneous abortion
- Placenta previa
- Placental abruption
- Ectopic pregnancy
- Abdominal/pelvic trauma
- Intra uterine fetal death
- Amniocentesis
- Cordocentesis
- Chorionic villous biopsy
- Routine pregnancy
- Rh typing is performed in every pregnant patient via a serum blood draw. If the mother is Rh negative, Rh typing is performed on the father.
- Fetal Rh typing can be done from amniocentesis or chorionic villus sampling (CVS).
- In Rh negative mothers with a second Rh positive fetus, serial measurements of maternal antibody titers are performed during pregnancy. Additionally, frequent ultrasonography is performed to monitor the fetal well-being and to detect anemia and signs of hydrops, like the diameter of the umbilical vein, placental thickness, and pericardial effusion.
- Color-flow Doppler: Measuring the peak systolic middle cerebral artery (MCA) velocity by ultrasound has proved to be a reliable method to detect fetal anemia. Peak systolic velocity is measured by using the pulsed Doppler. Measurements can be started as early as 18 weeks of gestation and are to be repeated at 1- to 2-week intervals until 35 weeks.
- Anti-D IgG prophylaxis coats and destroys Rh positive fetal cells when they enter the maternal circulation, thereby preventing maternal sensitization. It is administered in the following situations
- Rh incompatible transfusion in women with childbearing potential
- Rh negative mothers with an Rh positive fetus (regardless of antibody levels). It is given as either a single injection of 300 µg IM (1,500 UI) at the 28th week of gestation or two injections of 100–125 µg (500–625 UI), at the 28th week and 34th week of pregnancy. Additionally, because the half-life of IgG is 17–21 days, an additional 300 µg is administered within 72 hours of delivery. Prophylaxis does not appear to have any side effects on the fetus and can decrease the risk of alloimmunization of an Rh negative gravid women to 0.2% during that pregnancy, as well as the probability of immunization in subsequent pregnancies.
- As a "booster" dose in Rh negative mothers with an Rh positive fetus
- Threatened abortion
- Hydatidiform mole
- Ectopic pregnancy
- Fetal death
- Blunt trauma to the abdomen
- Placenta previa
- Placental abruption
- Amniocentesis
- External cephalic version.
- Fetal intraperitoneal blood transfusions are considered to correct fetal anemia and prevent hydrops fetus. It involves delivering blood (fresh, packed, Type O, Rh negative, cross-matched with maternal serum, gamma irradiated to prevent graft-versus-host reaction) in 10 mL aliquots to raise hematocrit levels to 40%. If blood has been stored, the additive can be removed by washing. If antigen-compatible allogenic blood is unavailable, then maternal RBCs may be utilized (it does not have to be ABO matched). A Tuohy needle is introduced into the peritoneal cavity of the fetus under ultrasound guidance and an epidural catheter is threaded. Specific indications include
- A mother who has a history of previous perinatal loss.
- Previous need for neonatal exchange transfusion.
- High antibody titer.
- MCA Doppler suggests anemia.
- Ultrasound evidence of fetal hydrops
- Fetal intrauterine intravenous transfusion (IVT) is used to treat hydrops fetalis and may require repeat procedures. Anesthesia for the mother is required (sedation or neuraxial). for the fetus, a needle is inserted under ultrasonographic guidance into an umbilical vein and neuromuscular blockade is administered (vecuronium 0.1 mg/kg). Subsequently, blood that is packed, fresh, Type O, Rh negative, cross-matched with maternal serum, and gamma irradiated to prevent graft-versus-host reaction is injected. Maternal blood may be used if antigen-compatible allogenic blood is unavailable (does not require ABO matching). The amount needed is calculated as follows: fetal weight (g) × 0.14. The mother is subsequently admitted to the hospital for 24 hours of observation with continuous monitoring of the fetus. The procedure can be repeated every 10 days for 3 weeks, depending on the severity of the fetal anemia. Complications include transient fetal bradycardia, cord hematoma, umbilical vein compression, and fetal death.
- Management of the sensitized newborn
- Mild hemolytic disease (mildly anemic with Hg >14 g/dL and bilirubin <4 mg/dL): Treated with early phototherapy.
- Moderate hemolytic disease: Although the newborn has some degree of anemia and is not jaundiced at birth, he or she can rapidly develop hyperbilirubinemia in the first 24 hours. This can lead to kernicterus and permanent neural damage. The neonate can receive an exchange transfusion with type-O Rh-negative blood along with intense phototherapy.
- Severe hemolytic disease: These newborns are either stillborn or hydrops fetus at birth
- Use of IVIG in doses of 0.5–1 g/kg in single or multiple dose regimens have been able to effectively reduce the need for exchange transfusion in the baby.
- Emerging treatment methods: Serial plasmaphereses followed by weekly IV immune globulin to the mother is a recent advance.