Alloimmunization and Red Cell Antibodies – Time to be Concerned?
Learning Objectives and CME/Disclosure Information
This activity is intended for healthcare providers delivering care to women and their families.
After completing this activity, the participant should be better able to:
1. Select the antigen which is responsible for the most cases of Rh alloimmunization that causes hemolytic disease in the newborn 2. Discuss potential severity of hemolytic disease based on antigen
Estimated time to complete activity: 0.25 hours
Susan J. Gross, MD, FRCSC, FACOG, FACMG
President and CEO, The ObG Project
Disclosure of Conflicts of Interest
Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.
The PIM planners and others have nothing to disclose. The OBG Project planners and others have nothing to disclose.
Faculty: Susan J. Gross, MD, receives consulting fees from Cradle Genomics, and has financial interest in The ObG Project, Inc.
Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.
Method of Participation and Request for Credit
Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from Dec 31 2017 through Dec 31 2021, participants must read the learning objectives and faculty disclosures and study the educational activity.
If you wish to receive acknowledgment for completing this activity, please complete the post-test and evaluation. Upon registering and successfully completing the post-test with a score of 100% and the activity evaluation, your certificate will be made available immediately.
For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service within 4 weeks.
Joint Accreditation Statement
In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Physician Continuing Medical Education
Postgraduate Institute for Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Continuing Nursing Education
The maximum number of hours awarded for this Continuing Nursing Education activity is 0.2 contact hours.
The care of patients with sensitization to antigens other than D, that are known to cause hemolytic disease, should be the same as that for patients with D alloimmunization. ACOG has provided updated guidance (March 2018) that includes the following recommendations:
In a center with trained personnel and when the fetus is at an appropriate gestational age, Doppler measurement of peak systolic velocity in the fetal middle cerebral artery is an appropriate noninvasive means to monitor pregnancies complicated by red cell alloimmunization
The initial management of a pregnancy involving an alloimmunized patient is determination of the paternal erythrocyte antigen status
Serial titers are not useful for monitoring fetal status when the mother has had a previously affected fetus or neonate
Antibody titers are not appropriate for monitoring Kell-sensitized patients because Kell antibodies do not correlate with fetal status
Anti-D immune globulin is indicated only in Rh-negative women who are not previously sensitized to D
In addition, The AABB working group addressed the work up and management of ‘weak D’ (formerly Du) in their joint statement that included representatives from ACOG, CAP, American Red Cross, Armed Services Blood Program
Persons with a weak D type 1, 2 or 3 can be managed safely as Rh-positive and such women, if pregnant, do not require Rh immune globulin. For more than 50 years, the recommended practice in the United States has been to Rh type patients using laboratory methods that interpret weak D phenotypes as Rh-negative. The intent of this practice has been to protect Rh-negative persons, particularly Rh-negative women of childbearing potential, from inadvertent exposure and alloimmunization to Rh-positive red blood cells. RHD genotyping methods are now available that can identify those persons with a weak D phenotype who can be managed as Rh-positive (weak D types 1, 2 or 3).
ACOG has responded to the AABB working group above and advises that for weak D (previously known as Du)
An attractive solution to this problem is to perform molecular genetic RHD typing in weak D phenotype individuals as suggested by the Work Group on RHD Genotyping.
Currently, there is a lack of comprehensive cost-benefit analysis for this clinical approach. Clinicians are advised to administer Rh D immune globulin to patients with weak D blood type in appropriate clinical situations, by the same rationale as that for Rh D typing blood donors, until further scientific and economic studies are available.
Antepartum or intrapartum fetal-maternal bleeding may stimulate an immune response in the mother when any fetal blood group factor inherited from the father is not possessed by the mother. Maternal antibodies may form (alloimmunization) and there may be transplacental passage of these antibodies into the fetal circulation. This transplacental passage of antibodies into the fetal circulation may lead to hemolytic disease in the fetus and newborn. The risk of hemolytic disease is determined by the degree of antigenicity and the amount and type of antibody involved. The AABB recommends that patients should undergo repeat screening before receiving anti-D immune globulin at 28 weeks, postpartum and at the time of any event in pregnancy.
Five major antigens can be identified for the Rh (C,D,E) blood group system, these are:
In addition to the 5 antigens of the Rh system, there are more than 30 red cell antigen groups that have been described and many of these can can cause hemolytic disease in the newborn and fetus
Most cases of Rh alloimmunization causing hemolytic disease are the result of incompatibility with respect to the D antigen
The red cell antigen groups and their association with hemolytic disease:
Blood Group System
Hemolytic Disease Severity
No proven risk
No proven risk
Severe including hydrops
Rh E and c (non-D)
Mild to severe (c and E can
lead to hydrops); e and C are rare
Mild to severe including hydrops
Not a known cause of HDN
Mild to severe
Mild to severe
Mild to severe
Mild to severe
Note: Mild only, with no risk to advance to a higher risk category, can be treated with routine obstetric care. Any risk of moderate or above requires referral for fetal assessment
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Disclosure of Unlabeled Use
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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