Guideline for the investigation and management of red cell antibodies in pregnancy: A <scp>British Society</scp> for <scp>Haematology</scp> guideline

Abstract

This guideline was compiled according to the British Society for Haematology (BSH) process at [https://b-s-h.org.uk/media/lvdbh3p5/2023-11-14-bsh-guidelines-development-process-updated-nov-2023-1.pdf?cf=638356449664970000]. Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org and are also summarised in an appendix of the full BSH process guidance above. A search of published literature was undertaken using the Cochrane Library, Pubmed, MedLine and internet searches using the following key words and relevant MeSH terms: anti-D, anti-D Ig immune globulin, pregnancy, red blood cell antibodies in pregnancy, maternal red blood cell antibodies, antenatal anti-D prophylaxis, rhesus, RhD, haemolytic disease of newborn, erythroblastosis fetalis. This search covered the period 1999 to March 2022 and was restricted to manuscripts written in English, describing studies carried out in humans, and only including article types: clinical studies, clinical trials, comparative studies, evaluation studies, guidelines, meta-analysis, observational studies, systematic reviews and validation studies. Review of the manuscript was performed by the BSH Guidelines Committee Transfusion Task Force, the BSH Guidelines Committee and the Transfusion sounding board of BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by Royal College of Obstetricians and Gynaecologists; these organisations do not necessarily approve or endorse the contents. The purpose of the guideline is to make evidence-based recommendations for the application of blood grouping and red cell antibody testing in pregnancy. The aim is to predict the potential for, and where possible, prevent, haemolytic disease of the foetus and newborn (HDFN). The blood group and antibody status of a pregnant woman should be tested at booking and at 28 weeks' gestation to identify the ABO and D group and to detect red cell antibodies that have the potential to be clinically significant. Some antibodies (including anti-D, anti-K and anti-c) are associated with significant foetal and neonatal risks, such as anaemia, jaundice and perinatal loss. There are antibodies that are unlikely to significantly affect the foetus but that can cause neonatal anaemia and hyperbilirubinaemia, and others that may cause problems for the screening and timely provision of appropriate blood for the woman or baby. This guideline updates the previous British Society for Haematology (BSH) guidance published (2016) and is intended to incorporate necessary scope from the prior Royal College of Obstetricians and Gynaecologists (RCOG) Green-top Guidelines (2014) for the management of women with red cell antibodies during pregnancy. The testing protocols recommended here are designed to provide clarity for practice in order to protect pregnant women and their babies. Information about the implications of a blood test should be provided and informed consent obtained prior to samples being taken.1 It is essential that request forms are accurately completed and samples from pregnant women are correctly identified. Misidentification at the time of sampling could lead to an incorrect blood group being assigned to the transfusion record. This could result in errors in anti-D immunoglobulin (Ig) prophylaxis (missed or inappropriate administration of prophylactic anti-D Ig) and errors in the selection of blood components.2, 3 It is essential that the sample and request form conform to the requirements described in the BSH guidelines on the administration of blood components.4 In addition, it is essential that any previous administration of prophylactic anti-D Ig in the current pregnancy, including date and dose, is recorded on the laboratory request form. A clinical history, particularly of HDFN, miscarriages, previous transfusions and historical antibodies, is essential information and should where known be stated on the request form. Recommendation It is essential that the sample and request form conform to the requirements described in the guidelines on the administration of blood components (GRADE 1C).4 Recommendation Samples should be dated, labelled and signed by the person taking them, in the presence of the pregnant woman who should, whenever possible, be asked to state their full name and date of birth. Sample labels pre-printed away from the phlebotomy procedure or taken from the notes for example, ‘addressograph’ labels should not be used (GRADE 1C).4 Recommendation All laboratory testing procedures should be validated in compliance with published guidelines (GRADE 1C).5 A record of the pregnant woman's ABO and D type performed at booking is useful as confirmation of any subsequent testing performed on another sample taken at the point of need, should the woman or her baby blood transfusion at a Recommendation ABO and D grouping should be performed in with the guidelines for procedures in blood transfusion (GRADE 1C).5 Recommendation are not obtained in D the woman should be as D the D status is (GRADE 1C).5 Recommendation All pregnant women to be D should be written information about their status and the of anti-D Ig prophylaxis the foetus is to be D by cell foetal or the foetal D type is D status should be recorded in the notes to for their of the to prophylactic anti-D (GRADE antibody screening is undertaken to detect clinically significant antibodies, affect the foetus newborn, and to detect antibodies that may cause problems with the provision of blood components for the woman and for the Recommendation The screening and used for red cell antibody screening should with the guidelines for procedures in blood transfusion (GRADE to a of and a of ABO haemolytic disease in a testing for a of immune in pregnant women is not There is in using an in antibody clinically antibodies be in only by are not clinically significant in of Recommendation The procedures used for and of red cell antibodies should with the guidelines for procedures in blood transfusion (GRADE red cell antibodies have been in pregnancy, clinically significant maternal should be whenever a sample is This that antibodies that have potential to cause are and timely provision of blood for the woman for the baby. The of for antibody screening and be by the and strength of the antibody and an transfusion has been Recommendation The of antibody of should be where is a should be antibody should be using (GRADE and antibody a for and and are the only antibodies that are and are as possible, sample should be tested in with the previous sample and the to identify significant in antibody is used to assess the of clinically significant red cell antibodies anti-D and in in of in are tested by an test using red with of the designed for in should be used where are be taken in for where antibody is (including prophylactic anti-D Ig and clinically to that the of the antibody of is for example, where anti-K and are and to is necessary to the in the and it is recommended that the anti-D be in as an to of The is the of the that a and the of taken as the point for should be in the for example, the a in of a previous of to a subsequent of is to be a significant and the of the previous sample in is recommended possible, to that the in is not to in the of the anti-D not for in in the cell used for testing antibodies Recommendation clinically significant maternal antibodies have been testing including or should be to predict the to current and This may be particularly relevant foetal is not for the red cell (GRADE It is to foetal and using from maternal blood the for foetal blood This is useful in in where clinically significant red cell antibodies are and as screening to anti-D Ig prophylaxis for women with immune It is to that the used for foetal in from used for screening of D women and the should not be used The for such have been to be on testing the is The a in the foetus has a and It is that are provided with on the blood group of the baby at to provide the of to for on the neonatal blood group may be that are not known about or by the laboratory It is that samples are not in as the levels of with of have been for at weeks' The for and performed at or weeks' gestation is with the laboratory in as for and and in the stated on the laboratory of errors in or on the of the baby. Recommendation foetal blood grouping using foetal from maternal in can be performed for or with a of should be at the gestation by the laboratory by or foetal who can the implications of the test undertaken testing at the appropriate gestation (GRADE the of foetal of D women in the have been anti-D Ig prophylaxis as a foetal for pregnant women has been in and the to of anti-D Ig This of women and their to a blood with in to the provision of anti-D Ig prophylaxis and to This is provided by and in and the in The of of foetal status was recommended by the for and in Recommendation using a in pregnant women who have not anti-D, as of a screening to anti-D Ig prophylaxis, is for from weeks' The of such testing is on provision at a point in the antenatal that not an (GRADE All pregnant women should have blood samples taken in pregnancy, at by of pregnancy, for ABO and D group and for screening for the presence of red cell an antibody is should be carried out to the antibody and All pregnant D or D should have a blood sample taken at the 28 for the ABO and D group and screening for red cell women are as as women to form antibodies in that women who are for antenatal anti-D Ig prophylaxis have the 28 antibody screening sample taken the of is Samples taken the could result in anti-D being may be for immune anti-D, and immune anti-D being for anti-D Recommendation All pregnant women should be ABO and D and for the presence of red cell antibodies in and at 28 weeks' In D women the sample should be taken the administration of (GRADE Recommendation In pregnant women with clinically significant red cell antibodies of at 28 weeks' antenatal blood grouping or antibody screening is necessary (GRADE and from guideline with Recommendation All pregnant women who have a baby by should be as as of weeks' gestation to a foetal for and of antibody or (GRADE anti-D Ig has been in the of to D but it has in anti-D in is to anti-D Ig prophylaxis as or for a or The associated with the of the of anti-D are anti-D Ig is as immune anti-D, anti-D Ig prophylaxis may be the women from immune anti-D is as anti-D appropriate of the antibody during may be and that be to HDFN, not The of Transfusion a the in immune anti-D and anti-D as where women with immune anti-D not as as should have been the anti-D was to be anti-D and in of these the with of anti-D Ig and immune anti-D be the of anti-D Ig with the of immune anti-D or is The of anti-D Ig in maternal samples anti-D Ig has been The of anti-D Ig of anti-D Ig in a in pregnant women was to and following anti-D Ig are the stated in the administration of an of anti-D a of anti-D Ig is and the blood is to The of anti-D Ig is 3 anti-D Ig can be by for by an at or following of and for where are used or following of anti-D anti-D to and a is of the of anti-D anti-D or anti-D Ig) on the strength of with is as with the and of the red have been by as a result of on the of the strength of using that have not been by an of antibody in All anti-D in should be by with to the anti-D or tested by a that has been validated and that a result that is in or can be to The only is where anti-D is for the time prior to or at the time of for example, in a group and in the sample not be for but the baby should be for of as to be on the of the of any anaemia The of are unlikely to have a on clinical at and are not as as of and anti-D may be performed at a necessary to on clinical management in The should be in the of the and of any D Ig the for the of administration and the antibody status at the time of The clinical and of the of previous laboratory testing are in clinical where anti-D is in pregnancy, and should be to anti-D Ig has been for a prior to 28 it be that anti-D at or 28 may be immune as levels can 28 and should be undertaken as the antibody may be immune anti-D is to anti-D Ig as in the BSH guideline for the of anti-D Ig to any of the following the antibody should be as for that at to 28 and at 28 by foetal has been and testing or anti-D is 28 weeks' where of the following testing should as for women that is for antibody testing 28 weeks' and anti-D Ig prophylaxis should to be in with the BSH guideline for the of anti-D Ig to with anti-D should not be with an antibody the of anti-D it is that the anti-D is immune is the cause of samples from pregnant women with immune anti-D should be tested at 28 gestation and to the of anti-D to the anti-D and to identify any antibodies that may anti-D has been to be immune an in of or with the previous a significant of the period of gestation as be a in a validated has been taken of previous of HDFN, the of anti-D in have been used to the management of In addition, the D status of the foetus of pregnant women with a significant of anti-D should be using from a maternal blood This has a of The result of test can be used as a to the and of is used to for, and foetal with to foetal women with an anti-D of or a anti-D a of previous by should be to a foetal for including the for is a anti-D the foetal is performed at the for is previous of the of history, in anti-D and of The of is to be a and as by in these The for is described in Society of in and of in It is that for of foetal anaemia, weeks' It should be that has also been with anti-D at the anti-D is that to the presence of anti-D but anti-D is to a foetal has been and is the of anti-D on subsequent samples is the is in the a a sample should be tested for the presence of red cell antibodies at 28 weeks' and whenever blood is for for example, for The including the laboratory should be informed of the testing to and for example, the laboratory samples in where the clinical have that are not at of should be at not weeks' gestation to the of to maternal blood group is to antibody levels or or transfusions have been transfusion may be the is The procedure is performed in a with in foetal blood sampling is carried out to assess the foetal with the necessary and in to to the on the at of foetal anaemia, may be do not weeks' the foetal on the of Recommendation A should antibody in women with D (GRADE women with should be with the as women with immune anti-D that at to 28 weeks' gestation and of is useful in any in the antibody Samples from pregnant women with should be with to the where possible, the previous sample should be tested in as for immune should be undertaken to or the presence of clinically significant In with any previous of HDFN, the of in are of the to to a foetal The status of the foetus of pregnant women with a significant of should be using from a maternal blood This has a of The result of test can be used as a to the and of women with an of or a a of by should be to a foetal for including The of is as described in to a foetal has been and are being the of on subsequent samples is the is in the a a sample should be tested for the presence of red cell antibodies at 28 weeks' and whenever blood is for transfusion for example, for The including the laboratory should be informed of the testing to and for example, the laboratory samples in where the clinical have that are not at of should be at not weeks' gestation to the of to maternal blood group is to antibody levels or or transfusions have been antibodies to in the blood group should be and in the as as these have the potential to cause to anti-K is by but levels are not The foetal anaemia associated with anti-K may be to the of to of their immune It has been stated in that the of to anti-K is not with the of the antibody and prior to where of of have that is associated with antibodies with a of or a has a of samples from women with anti-K should be in the pregnancy, as for any clinically significant and should be undertaken 28 weeks' and to of anti-K should be to a foetal on of the to a management A of is a recommended point for are being the of anti-K on subsequent samples is the are in the The including the laboratory should be informed of the testing to and for example, the laboratory samples in where the clinical have that are not at of should be at not weeks' gestation to the of to maternal blood group is to antibody levels or or transfusions have been the of of anti-K in pregnant women the of previous transfusions in the The of anti-K can be by for transfusion to with potential for known to be should be for the of who are or type is transfusions should not be are not of the in may be particularly relevant for women with anti-K as of anti-K in pregnant women from previous transfusion and only of the are a of of women with anti-K are It that the transfusion of women with anti-K is the of the foetus should be to for the current and any the type is or is the pregnant woman should be to a foetal anti-K is for and the is and a samples are 28 weeks' gestation antibodies should be for women and any antibodies at 28 clinically significant antibodies in to should be according to their Recommendation Samples from pregnant women with immune anti-D or should be at to 28 weeks' gestation and at should be to a foetal the antibody the the is where of the for be (GRADE Recommendation women with anti-K or antibodies should be to a foetal the antibody is identified. the foetus is known or to be at on or foetal at to 28 weeks' gestation and at is (GRADE Recommendation In where of foetal is being performed and antibody levels are in the of antibody strength is unlikely to be of and can be at the of a foetal (GRADE Recommendation All women who have an in a previous pregnancy, for should be to the foetal in any subsequent at to (GRADE Recommendation possible, is performed at the of the to to the foetal for and of appropriate blood (GRADE It is only antibodies that are of the foetal and red cell antibodies with a significant are by and antibodies to have not been in In to anti-D, and the following are associated with and have been as the cause of antibody may be of may be in women of a such as in the and in the the a form of HDFN, to that by including of and are in In at 28 information to management of the pregnancy. The is for women with a previous of a baby with and a clinical should be The of the may the of has been a previous baby that significant anaemia or jaundice to at an to that for anti-D, or is with and of at weeks' to anti-D, and the are the for the of of antibody in is In the of a of HDFN, the of with antibodies of is that of anti-D, and example, in a of at of from at and was perinatal to The to be for such as or are and do not provide a of the of pregnant women with antibodies of the It is that in the of a previous of pregnant women with antibody or for anti-D, and not to be as as with a of and or the antibody anti-D, or it is to the for group and a of is being an management should be with a foetal be informed by the in antibody and the The on the of and the for be on the of previous for the and the and in the A has to be to the for anti-D, and with a in of being and a of with an of anaemia and The of and for antibodies anti-D, and are the and of taking a to pregnant women with such antibodies be information about antibodies and their to cause clinically significant HDFN, it is recommended that is from a transfusion in a red cell for antibodies that have been associated with are in the Transfusion guidelines, Royal College of Obstetricians and Gynaecologists (RCOG) guidelines and an antibody has been testing of and gestation samples should In is a that an antibody with a of or cause of HDFN, a and has not been Recommendation significant antibodies, anti-D, or should be by at the booking and at 28 weeks' necessary on a or and or a of HDFN, to a in foetal should be for (GRADE In to blood group and of any red cell the for the pregnant woman's antenatal of the of the antibodies, with to the of and potential in blood for should where the to the to the woman to a foetal The woman should be and written information about the clinical of the and it should be that has been in the record. Recommendation In to blood group and of any red cell the for the pregnant woman's antenatal of the of the antibodies, with to the of and transfusion (GRADE Recommendation women with clinically significant red cell antibodies should be and written information with of antibody and potential for and in blood (GRADE any woman with an time for and blood should be taken the for transfusion is can be for women with anti-D, or antibodies, as are labelled with full and antibodies anti-D, and blood may to be obtained from a blood women with antibodies or antibodies and is essential to in A search for blood may be or blood may to be to time or blood may to be obtained from the in time to the The of is and be Recommendation women with antibodies or antibodies an of the of maternal for and of appropriate to the of including of any should as in as the and (GRADE Recommendation of should to blood and cell should be where This of taking of the of the and the of the is a and also are to to appropriate management of transfusion in the and the baby (GRADE for transfusion has the requirements as blood for neonatal that is to the to and it is to for is to order as it only has and a of an should be ABO with the and ABO from maternal or antibodies D the D group as the for the to the has an antibody and with the blood should be and the to the baby of transfusion blood It should be in with a of Recommendation or neonatal maternal antibodies anti-D, or are of at should be where to that blood of and for relevant is (GRADE should be ABO with the and ABO from maternal or antibodies D the D group as the and for the to the has an and with the blood Recommendation transfusion in a the baby has an as blood be to (GRADE Recommendation In of the of blood for blood with maternal antibodies anti-D, or may be blood for or but should be to transfusion whenever (GRADE Recommendation and transfusion laboratory should to blood is not on the of clinical a haemolytic transfusion with potential associated including (GRADE Recommendation and blood that is not for antibodies is used for in the of immunoglobulin The presence of maternal red cell antibodies has implications for blood components such as or A maternal sample and a blood sample should be The blood sample should be used to the D group it is not pregnant women who prophylactic anti-D There is evidence that foetal red the can cause maternal the of as D for samples is not as the of using the for the of a of D can be by anti-D In the presence of a of testing a should be to assess the of the D of This is not recommended as a It has been that following anti-D Ig can the the foetal and to foetal D of samples have been found to have a test and may result in anti-D Ig not cause significant of red the maternal has been found to an red cell the red from the should be tested for the A should be performed on the and the and levels should be in addition, the baby should be for clinical of A is in of the is and the baby of HDFN, a red cell may be to the red cell antibody ABO antibodies cause HDFN, and the baby has a ABO with the the should also be tested with for any the woman has of and is necessary and is not Recommendation All to women who have clinically significant antibodies should be for evidence of A should be performed on a blood sample and and should be (GRADE women with red cell antibodies at 28 weeks' blood grouping and antibody screening of maternal D is not necessary testing is of antibodies in not management of the current pregnancy, testing is undertaken and antibodies the woman should be informed as may be implications for In a or maternal sample is to predict neonatal transfusion requirements red cell antibodies the to be and for should neonatal transfusion be Recommendation women with immune anti-D should have an test at and testing in with BSH guidelines for of (GRADE with red cell antibodies, particularly is a of foetal anaemia or red for transfusion may be to should for with a with and of This is a foetal There is evidence that the of red cell are used for a with an and the red cell is not foetal may be and may lead to in antibody testing is not has There is a of the of or to as a result of the and should be with the the is and is not anti-D immunoglobulin should be following the of is described in of is by of by these are foetal is in of of neonatal and the potential of transfusion should be for the The presence of red cell antibodies not a for the but an antibody should be carried in the transfusion is to maternal antibodies may for a following birth. Some anaemia for are antibodies and The of in with is to the a of not in foetal anaemia with is associated with are for the of foetal This has the aim of at gestation is associated with a foetal The a potential on the clinical of the and the of to be in a of clinical and laboratory practice should be undertaken on a to compliance with these guidelines where or in to should be A for is as All to the The to who reviewed and on the The BSH transfusion members at the time of guideline The to them, the BSH sounding and the BSH guidelines for their in The BSH the during the of All have a of to the BSH and Task may be on The following has undertaken and The following members of the group and have of to

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