Prevention of Rh Hemolytic Disease of the Newborn (HDN)

What is the Rh factor and why is it important during pregnancy?
The Rh factor is an antigen that is found on the surface of red blood cells. If you have these antigens on your red blood cells, you would be considered Rh positive. Those who do not are Rh negative.1

How can the Rh factor affect pregnancies?
When an Rh-negative woman has Rh-positive antibodies in her blood and the baby she is carrying is Rh-positive, the antibodies could possibly enter the baby's bloodstream, attack the baby's red blood cells and cause HDN.1

When is there a risk of blood exchange?
The exchange of blood usually occurs during delivery but can happen during a miscarriage, amniocentesis, or as a result of an injury or trauma. There have been instances, though, where women develop antibodies to Rh-positive blood cells during pregnancy for no apparent reason.1

What happens when a baby is born with HDN?
If a baby is born with HDN, the infant may suffer from jaundice, anemia, or have permanent damage to the brain and central nervous system. HDN can lead to mental handicaps, hearing loss, or cerebral palsy.1

Is there treatment for HDN?
Extensive medical assistance may be necessary, including an exchange transfusion, which is where the baby's blood is replaced. By transfusing all of the baby's blood, the destruction of its red blood cells should stop, giving the baby a chance to survive.1

Can HDN be prevented?
Yes, prevention is key to protection. HyperRHO S/D is an immune globulin that, when administered properly, can prevent HDN, assuming that the mother does not already have Rh-positive antibodies in her system. HyperRHO S/D has high levels of specific antibodies against Rh-positive blood cells. When injected, HyperRHO S/D destroys any Rh-positive red blood cells that may have entered the mother's body. The injection also prevents the mother's immune system from further production of Rh-positive antibodies, hence protecting the baby from contracting HDN.1

When should HyperRHO S/D be administered?
Since laboratory findings have shown the development of Rh-positive antibodies during the final weeks of pregnancy, your doctor may suggest a first dose be given at 28 weeks' gestation. HyperRHO® S/D Full Dose (RhO[D] immune globulin [human]) should be administered again within 72 hours of delivery of an Rh-positive baby. For women undergoing spontaneous or induced abortion of up to 12 weeks' gestation, HyperRHO® S/D Mini-Dose (RhO[D] immune globulin [human]) should be administered within 3 hours or as soon as possible following the abortion.1,2

QUICK FACTS

  • In the United States, the frequency of Rh-negative status varies. It's about 17% in Caucasian people and 7% in Hispanic and African American people. The frequency is lower in people of Asian descent, averaging about 2%3
  • Once a mother is sensitized, she can no longer receive immune globulin treatment for HDN. This is why it is crucial to have an Rh immune globulin such as HyperRHO S/D administered before the mother is exposed to Rh-positive red blood cells1
  • An Rh-negative woman must be treated with an Rh immune globulin during each pregnancy4
  • If an estimated 4 million births occur each year, approximately 4,000 of those infants will be victims of HDN5
Important Safety Information for HyperRHO® S/D Mini-Dose (RhO[D] immune globulin
[human])

HyperRHO® S/D Mini-Dose (RhO[D] immune globulin [human]) is recommended to prevent the isoimmunization of RhO(D) negative women at the time of spontaneous or induced abortion of up to 12 weeks' gestation provided the following criteria are met:

  1. The mother must be RhO(D) negative and must not already be sensitized to the RhO(D) antigen.
  2. The father is not known to be RhO(D) negative.
  3. Gestation is not more than 12 weeks at termination.

HyperRHO S/D Mini-Dose is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent that can cause disease. There is also the possibility that unknown infectious agents may be present in such products.

NEVER ADMINISTER HYPERRHO S/D MINI-DOSE INTRAVENOUSLY. INJECT ONLY INTRAMUSCULARLY. ADMINISTER ONLY TO WOMEN POSTABORTION OR POSTMISCARRIAGE OF UP TO 12 WEEKS' GESTATION. NEVER ADMINISTER TO THE NEONATE.

HyperRHO S/D Mini-Dose should be given with caution to patients with a history of prior systemic allergic reactions following the administration of human immune globulin preparations.

The attending physician who wishes to administer HyperRHO S/D Mini-Dose to persons with isolated immunoglobulin A (IgA) deficiency must weigh the benefits of immunization against the potential risks of hypersensitivity reactions. Such persons have increased potential for developing antibodies to IgA and could have anaphylactic reactions to subsequent administration of blood products that contain IgA.

As with all preparations administered by the intramuscular route, bleeding complications may be encountered in patients with thrombocytopenia or other bleeding disorders.

Although systemic reactions to immunoglobulin preparations are rare, epinephrine should be available for treatment of acute anaphylactic symptoms.

Other antibodies in the HyperRHO S/D Mini-Dose preparation may interfere with the response to live vaccines such as measles, mumps, polio or rubella. Therefore, immunization with live vaccines should not be given within 3 months after HyperRHO S/D Mini-Dose administration.

Animal reproduction studies have not been conducted with HyperRHO S/D Mini-Dose. It is also not known whether HyperRHO S/D Mini-Dose can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HyperRHO S/D Mini-Dose is not indicated for use during pregnancy and it should be administered only postabortion or postmiscarriage.

Safety and effectiveness in the pediatric population have not been established.

Reactions to HyperRHO S/D Mini-Dose are infrequent in RhO(D) negative individuals and consist primarily of slight soreness at the site of injection and slight temperature elevation. While sensitization to repeated injections of human globulin is extremely rare, it has occurred.

Please see full Prescribing Information for HyperRHO S/D Mini-Dose.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.


Important Safety Information for HyperRHO® S/D Full Dose (RhO[D] immune globulin
[human])

HyperRHO® S/D Full Dose (RhO[D] immune globulin [human]) is indicated for prevention of Rh hemolytic disease of the newborn (HDN) and the prevention of isoimmunization in RhO(D) negative individuals who have been transfused with RhO(D) positive red blood cells.

HyperRHO S/D Full Dose is made from human plasma. Because this product is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Never administer HyperRHO S/D Full Dose intravenously. Inject only intramuscularly. Never administer to the neonate.

RhO(D) immune globulin (human) should be given with caution to patients with a history of prior systemic allergic reactions following the administration of human immunoglobulin preparations. Such persons have increased potential for developing antibodies to IgA and could have anaphylactic reactions to subsequent administration of blood products that contain IgA.

As with all preparations administered by the intramuscular route, bleeding complications may be encountered in patients with thrombocytopenia or other bleeding disorders.

A large fetomaternal hemorrhage late in pregnancy or following delivery may cause a weak mixed field positive DU test result. If there is any doubt about the mother's Rh type, she should be given RhO(D) immune globulin (human). A screening test to detect fetal red blood cells may be helpful in such cases.

If more than 15 mL of D-positive red blood cells are present in the mother's circulation, more than a single dose of HyperRHO S/D Full Dose is required. Failure to recognize this may result in the administration of an inadequate dose.

Although systemic reactions to human immunoglobulin preparations are rare, epinephrine should be available for treatment of acute anaphylactic symptoms.

Administration of live virus vaccines (eg, MMR) should be deferred for approximately 3 months after RhO(D) immune globulin (human) administration.

HyperRHO S/D Full Dose should be given in pregnant women only if clearly needed because animal reproduction studies have not been conducted.

Reactions to RhO(D) immune globulin (human) are infrequent in RhO(D)-negative individuals and consist primarily of slight soreness at the site of injection and slight temperature elevation. While sensitization to repeated injections of human immunoglobulin is extremely rare, it has occurred.

Elevated bilirubin levels have been reported in some individuals receiving multiple doses of RhO(D) immune globulin (human) following mismatched transfusions. This is believed to be due to a relatively rapid rate of foreign red cell destruction.

Please see full Prescribing Information for HyperRHO S/D Full Dose.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.


References:

  1. HyperRHO® S/D Full Dose (RhO[D] immune globulin [human]) Prescribing Information. Grifols.
  2. HyperRHO® S/D Mini-Dose (RhO[D] immune globulin [human]) Prescribing Information. Grifols.
  3. Dean L. Blood groups and red cell antigens. Hemolytic disease of the newborn. National Center for Biotechnology Information website. http://www.ncbi.nlm.nih.gov/books/NBK2266/. Accessed May 18, 2016.
  4. March of Dimes. Rh disease. March of Dimes website. http://www.marchofdimes.org/complications/rh-disease.aspx. Updated December 2009. Accessed May 18, 2016.
  5. Mari G; Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. New Engl J Med. 2000;342:9-14.