Rh Immune Globulin for Prevention of Hemolytic Disease of the Newborn

Fetal RBCs cross the placenta during pregnancy and at the time of delivery, and may stimulate the mother to synthesize antibody to antigens inherited from the father. Most commonly, there is Rh incompatibility between fetus and mother. Although the primary immune response is IgM, the majority of Rh-negative women quickly convert to IgG anti-D production. IgG anti-D traverses the placenta and may cause hemolysis of fetal RBCs.

Rh immune globulin (RhIg) is a concentrated solution of IgG anti-D derived from human plasma. A 1 mL full dose vial is sufficient to counteract the immunizing effects of 15 mL of Rh positive red cells. It was developed to prevent immunization of Rh-negative women to the D antigen and thereby prevent hemolytic disease of the newborn (HDN) caused by anti-D.

The following is a summary of RhIg administration guidelines:

RhIg should be given at 26 to 28 weeks gestation if a 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.
RhIg should be given if a women is D-negative, the antibody screen is positive, and the antibody is not anti-D.
RhIg should not be given if a women is D-negative, the antibody screen is positive and the antibody is anti-D.
RhIg should not be given if a woman is D-positive, regardless of the antibody screen result.
RhIg is not necessary for women who are weak D positive.

RhIg Administration Guidelines

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

D-negative women who have received RhIg antenatally often have subsequent positive antibody screens due to passively acquired anti-D. 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.

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 fetal maternal hemorrhage (FMH).

If the delivering facility has a verified record of a negative antibody screen during the current pregnancy, repeat maternal testing is not required at the time of delivery 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. Either the Kleihauer Betke or flow cytometry method can be utilized. An appropriate dose of RhIg should be administered.

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).

Vials of RhIg = % fetal cells x 50/30

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.

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.

RhIG therapy should also be considered for Rh-negative women of child bearing age (or female children) who inadvertently or necessarily are exposed to Rh-positive red cells through platelet or red cell transfusions. Dose is based on the estimated packed red cell volume of the component transfused. RhIG therapy should be started as soon as possible after the transfusion event, but may be administered over several days if a large number of vials are needed.




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