Rh Immune Globulin

Rh immune globulin (RhIg) is a human plasma–derived product consisting of IgG antibodies to the D antigen.

It is used to

• prevent immunization to the D antigen in D-negative individuals and
• for the treatment of immune thrombocytopenia.

Each dose of RhIg suppresses the immune response for up to a certain amount of D-positive red blood cells. As the measurement of the amount of D-positive RBCs within the patient is imprecise, the final dose of RhIg recommended is necessarily greater than the exact dose calculated. New techniques, such as molecular testing and flow cytometry, are now being used to diminish unnecessary Rh immune globulin use. ¹

Anti-D Prophylaxis

Prevention of anti-D formation in females of child bearing potential is important because anti-D can cause severe, potentially fatal, hemolytic disease of the fetus and newborn. Exposure to as little as 0.03 ml of D positive erythrocytes can result in sensitization. Perinatal administration of RhIg has decreased the risk of forming anti-D in D-negative women carrying D-positive fetuses from approximately 13–0.1%, and substantially reduced the risk of HDFN. ³

Anti-D Ig should be given routinely as soon as possible after delivery (but always within 72 h) to women who are D negative who deliver babies that are D positive. It should also be given at times during pregnancy when sensitisation could occur, such as during medical or surgical therapeutic termination of pregnancy, chorionic villus sampling, amniocentesis and following any abdominal trauma. It should also be given for episodes of vaginal bleeding where the pregnancy remains viable. At delivery and for potentially sensitising events after 20 weeks gestation, it is necessary to screen for FMH using an acid elution method and estimate the degree of FMH if fetal cells are seen. The BCSH guidelines recommend confirming any FMH > 2 ml by flow cytometry so that additional anti-D Ig can be given if the standard dose in use is not sufficient for the estimated bleed.
It takes 125 iu of anti-D Ig to remove a bleed of 1.0 ml fetal cells and preparations containing 250 iu, 500 iu and 1500 iu are in routine prophylactic use.
Because of the risk of silent FMH in pregnancy, routine antenatal anti-D prophylaxis is being offered to women in some countries. In the UK, this has been the subject of an appraisal by the National Institute for Health and Clinical Excellence, which recommends that anti-D Ig should be given either as a single 1500 iu dose at 28 weeks or in two 500 iu doses at 28 and 34 weeks in addition to the postnatal dose and doses to cover any potentially sensitising events during pregnancy. Women can decline RAADP, e.g. if they know the baby’s father is D negative or if they do not want any further pregnancies. The typing of fetal DNA in the maternal circulation may be used in the future to select women with fetuses that are D positive who would benefit from this additional prophylaxis, but at the moment, it is not universally offered.
It is important to take the 28-week sample for blood group and antibody screen before administration of anti-D Ig to ensure the maternal antibody screen correctly reflects the maternal antibody status. If anti-D is detected it is important to establish whether prophylactic anti-D has already been given resulting in passive acquisition of anti-D. In the absence of a clear history of anti-D Ig administration it is difficult to distinguish passively acquired from low-level maternal anti-D using serological techniques alone. The consequence of misinterpreting passively acquired anti-D as a maternal immune response is that anti-D prophylaxis may be omitted, leaving the women unprotected from sensitisation. Conversely, if maternal anti-D is misinterpreted as passively acquired, a sensitised pregnancy might not be managed appropriately. Laboratories supporting maternity units should have a strategy for dealing with positive antibody screens in D-negative mothers at, or after, 28 weeks, firstly establishing that anti-D is the only detectable antibody and then proceeding to quantify the antibody.
If the anti-D level is < 0.2 iu/ml, with a negative antibody screen at 28 weeks and a record of anti-D Ig administration, anti-D prophylaxis should continue. In all other situations the case should be managed individually with close monitoring of the anti-D level as for sensitised pregnancies and with anti-D prophylaxis being continued until it is proven beyond doubt that the anti-D represents a maternal immune response. ⁴

Anti-D immunoglobulin is used as an alternative to intravenous immunoglobulin to treat idiopathic thrombocytopenic purpura. Patients treated with anti-D immunoglobulin (WinRho®), in contrast to earlier published reports, had more adverse reactions, particularly chills and rigors, despite pretreatment with paracetamol and diphenhydramine. Two patients needed treatment for severe anemia and one for severe hemoglobinuria. Pretreatment with glucocorticoids or the use of subcutaneous anti-D immunoglobulin may reduce transfusion-related adverse reactions. However, the manufacturer of WinRho® withdrew their licensing applications in Europe. ²

References:

1. Joseph S.A. Restivo DO, Matthew S. Karafin MD, MS, in Transfusion Medicine and Hemostasis (Third Edition), 2019
2. K.J. Velthove, P.F.W. Strengers, Side Effects of Drugs Annual, 2012
3. B.H. Shaz, ... J.K. Karp, Reference Module in Biomedical Sciences, 2014
4. Megan Rowley, ... Clare Milkins, Dacie and Lewis Practical Haematology (Twelfth Edition), 2017