Rh Immune Globulin (RhIG)
Prevention of Hemolytic Disease of the Newborn Due to Anti-D
Routine testing and appropriate use of Rh Immune Globulin (RhIG) during pregnancy and immediately after delivery or termination of pregnancy can successfully prevent most cases of hemolytic disease of the newborn (HDN) caused by alloimmunization to the D antigen. RhIg timing and dosage depend on the gestational date and on whether any events that increase the risk of fetomaternal hemorrhage (FMH) have occurred. Antepartum administration of Rho Immune Globulin (RhIG) is indicated between 26 and 28 weeks of gestation in all pregnant Rh negative women who have not already developed anti-D. RhIG is also recommended after invasive procedures such as amniocentesis, periumbilical blood sampling (PUBS), intrauterine transfusions, pregnancy termination, amniocentesis or other obstetrical complications.
Prenatal/Perinatal Testing and Rh Immune Globulin Administration
I. Initial visit
All women should have ABO and D testing performed as early as possible during each pregnancy. D typing should include a test for weak D, if initial typing appears to be D negative. ABO and D types must match historical records. Discrepant results must be fully investigated and resolved.
All pregnant women should be tested at least once during each pregnancy for unexpected alloantibodies, preferably at their first prenatal visit. The antibody screen should include an antiglobulin phase using anti-IgG following 37C incubation. If the antibody screen is positive, antibody identification must be performed. Once an antibody has been identified, repeat identification is not necessary. A selected cell panel should be performed to exclude the presence of other antibodies. Titration of clinically significant alloantibodies found early in pregnancy might be appropriate to establish a baseline for comparison to subsequent samples. Samples should be retained for repeat subsequent testing.
1. RhIg should be given at 26 to 28 weeks gestation if the woman is D-negative and the antibody screen is negative for anti-D. If the first prenatal visit is earlier than 26 weeks gestation, the antibody screen should be repeated at 26 weeks prior to administration of RhIg.
2. RhIg should be given if the women is D-negative, the antibody screen is positive, and the antibody is not anti-D.
3. RhIg should not be given if the women is D-negative, the antibody screen is positive and the antibody is anti-D.
4. RhIg should not be given if the woman is D-positive, regardless of the antibody screen result. RhIg is not necessary for women who are weak D positive.
| Rh Type | Antibody Screen |
RhIg Administration |
| D negative | Negative |
Yes |
| D negative | Positive with anti-D |
No |
| D negative | Positive with other antibody |
Yes |
| D positive | Negative |
No |
| D positive | Positive with other antibody |
No |
II. Follow-up visits
Repeat ABO and Rh testing is not necessary. A repeat antibody screen should be considered only for D-negative women at 26 to 28 weeks gestation whose initial visit was too early to receive RhIg. RhIg should be given if the antibody screen remains negative for anti-D. If the repeat antibody screen is positive for anti-D, RhIg should not be given and the pregnancy should be managed as high risk.
A selected cell panel should be run to exclude clinically significant alloantibodies other than anti-D. If no other clinically significant alloantibodies are found, except passive anti-D, these pregnancies do not need to be handled as high risk.
Most women who receive antepartum RhIG will develop a positive antibody screen due to passively acquired anti-D. The half-life of RhIG , in the absence of significant fetomaternal hemorrhage, is 21 to 30 days. Therefore, when a patient has received a standard 300 ug dose of RhIG, anti-D is often detectable up to 12 weeks later. In some reported cases, anti-D has remained detectable for as long as 6 months. For this reason, it is important to notify the laboratory that a patient has received RhIG, whenever an antibody screen is ordered. If the laboratory is not aware of this pertinent history, passively acquired anti-D may be misinterpreted as Rh sensitization. This misinterpretation could result in further unnecessary serological testing or in failure to give RhIG postpartum.
RhIg should be administered to all D-negative women with no evidence of anti-D within 72 hours of any event that may increase the risk of FMH such as:
- Pregnancy termination at >/=13 weeks gestation
- Amniocentesis
- Chorionic villus sampling
- PUBS
- External version
- Suspected placental pathology
If the pregnancy is at or after 26 weeks gestation, the need for additional doses of RhIg should be determined by testing maternal blood for the presence of excessive FMH.
Once an antibody has been identified, it need not be re-identified. A selected cell panel should be run to exclude the presence of other clinically significant alloantibodies. Identification of any new alloantibodies is indicated. Periodic repeat titration of clinically significant alloantibodies may be appropriate during the continuation of pregnancy. Each new sample should be tested in parallel with the immediately preceding sample or with the original sample.
III. At delivery
A. Mother: If the delivering facility has a verified record of a negative antibody screen during the current pregnancy, repeat maternal testing is not required unless a question of HDN arises.
If the delivering facility has a verified record of immunization to D, RhIg should not be given.
If the mother is known to be D-negative and not immunized to D and the cord blood types as D negative, RhIg should not be given and no further testing is necessary.
If the mother is known to be D-negative and not immunized to D and the cord blood types as D positive (including weak D), a test for excessive FMH should be performed to determine RhIg dosage. An appropriate dose of RhIg should be given.
If the mother is known to be D-negative and not immunized to D and the cord blood is not tested, a test for excessive FMH should be performed to determine RhIg dosage. An appropriate dose of RhIg should be administered.
B. Infant: No cord blood testing is required except to establish candidacy of mother to receive RhIg or to investigate suspected HDN. If a question of HDN arises when the mother has clinically significant alloantibodies, ABO and Rh typing and direct antiglobulin testing should be performed on infants cord blood. In the absence of a maternal sample, eluate testing may be useful to confirm an antibody implicated in HDN.
RhIg Dose for Fetal Maternal Hemorrhage
The amount of fetal maternal hemorrhage is calculated by multiplying the percent fetal cells by 50 (maternal blood volume is typically 5 liters or 50 deciliters). This product is then divided by 30, which is the volume of fetal blood neutralized by a single vial of RhIg (300 ug dose).
For example, if the percent of fetal hemorrhage is 2%, then the volume of fetal hemorrhage is 100 mL. Dividing 100 mL by 30 mL/vial yields 3.3 vials. This number is rounded down to 3 and 1 vial is added for insurance. The required dose is 4 vials.
RhIg is very safe and has a very low risk of viral transmission, especially of enveloped viruses. A potential risk of anaphylaxis exists in IgA deficient patients. No more than 5 vials should be injected into each buttock at one time. Large doses should be given at 12-hour intervals over a 72-hour period. Cost for a single 300 ug vial is approximately $80.
WinRho (IV RhIg)
An intravenous form of anti-D Ig (WinRhoTM) became available in 1995. It is prepared with a solvent detergent treatment that inactivates lipid-enveloped viruses. WinRho is packaged in vials containing either 120 ug (600 IU) or 300 ug (1500 IU) RhIg that require reconstitution with 0.9% sodium chloride. Dosage recommendations are the same as for IM RhIg. WinRho is preferrable to IM RhIg when large doses are required. Advantages include its rapid effect, less patient discomfort, and larger allowable single dose. The major disadvantage is increased cost. References American Association of Blood Banks Bulletin #98-2. Prevention of Hemolytic Disease of the Newborn. February 16, 1998.
Harwell, EA. Use of Rh Immune Globulin. Am J Clin Pathol 1998; 110:281.
