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.
|Blood Group System||Antigen||Hemolytic Disease Severity|
|Lewis||No proven risk|
|I||No proven risk|
|Kell||K||Severe including hydrops|
|Rh E and c (non-D)||c
| Mild to severe (c and E can
lead to hydrops); e and C are rare
|Duffy||Fya||Mild to severe including hydrops|
|Fyb||Not a known cause of HDN|
|Kidd||Jka||Mild to severe|
|Mild to severe|
|P||PP1pk(Tja)||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
ACOG Practice Bulletin No. 192: Management of Alloimmunization During Pregnancy
ACOG Practice Bulletin No. 181: Prevention of Rh D Alloimmunization
Dean L (NCBI): Blood Groups and Red Cell Antigens
AABB: Joint Statement on Phasing-In RHD Genotyping for Pregnant Women and Other Females of Childbearing Potential with a Serologic Weak D Phenotype
Rh D alloimmunization can be prevented with the administration of anti-D immune globulin. ACOG recommends administration of anti-D immune globulin to unsensitized Rh D-negative women as follows
ACOG language in (” “)
All pregnant women are currently tested at the time of the first prenatal visit for ABO blood group and Rh D type and screening for red cell antibodies. The potential volume of fetal–maternal hemorrhage that can cause Rh D alloimmunization is extremely variable and ranges from 0.1 mL to 30 mL. Data is limited when it comes to many of the potential sensitizing events and therefore some of the recommendations are based on consensus and expert opinion.
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.
Previous administration of human anti-Rho(D) immune globulin (RhoGam) does not generally interfere with an immune response to rubella vaccine and is not a contraindication to postpartum vaccination. However, women who have received anti-Rho immune globulin should be serologically tested 6–8 weeks after vaccination to ensure that seroconversion has occurred.
ACOG Practice Bulletin 181: Prevention of Rh D Alloimmunization
ACOG Practice Bulletin 192: Management of Alloimmunization During Pregnancy
CDC: Epidemiology and Prevention of Vaccine-Preventable Diseases – Rubella
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