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Rh Immune Globulin for HDN

RhD hemolytic disease is caused by maternal immunization to the D antigen, followed by subsequent transfer of maternal IgG across the placenta resulting in immune hemolysis of fetal red blood cells. Anti-D is usually not detectable for 5 to 15 weeks after sensitization, which is much slower than the usual immune response to other foreign antigens such as microorganisms. The incidence of maternal alloimmunization in the United States and European Union remains at 1 to 1.5 percent of at risk D negative women despite the introduction of prophylactic RhD immune globulin.

RhD 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 woman is D-negative, the antibody screen is positive, and the antibody is not anti-D.
  • RhIg should not be given if a woman 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 or later
  • 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.

Intravenous RhIg (WinRhoTM,Rhophylac®) is also available. Dosage recommendations are the same as for IM RhIg. IV RhIg 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.

Since switching to Rhophylac, our laboratory has noted several instances where a positive antibody screen at 28 weeks was later determined to have been caused by Rhophylac injection immediately prior to drawing a blood specimen for the antibody screeen. Rhophylac appears to be much more quickly absorbed into the circulation than older IM formulations of Rho(D) Immune Globulin. Therefore, it is much more likely to be detected in the antibody screen. Much time and effort have been spent trying to determine if anti-D was actively or passively acquired. Misinterpretation of these results could potentially result in failure to give RhIg postpartum. For these reasons, the 28-week blood sample should always be drawn prior to administration of Rhophylac.

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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