Guideline for blood grouping and red cell antibody testing in pregnancy

Abstract

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 fetus 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 group and D status 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 fetal and neonatal risks, such as anaemia, jaundice or perinatal loss. There are antibodies that are unlikely to significantly affect the fetus but that can cause neonatal anaemia and hyperbilirubinaemia, and others may cause problems for the screening and timely provision of appropriate blood for the woman or baby. This guideline updates the previous guidance published in BCSH et al. (2007) and takes into account recent developments in fetal medicine, such as the widespread use of non-invasive monitoring for fetal anaemia by middle cerebral artery (MCA) Doppler ultrasound scanning, together with the facility to determine the relevant genotype of the fetus from DNA in maternal blood samples in many potential cases of HDFN as described in the recent Royal College of Obstetricians and Gynaecologists (RCOG) Green-top Guidelines (2014) for the management of women with red cell antibodies during pregnancy. Information from these investigations has changed the requirement for ongoing serological monitoring of red cell antibodies identified in pregnancy, and this has been taken into consideration in developing updated recommendations. The National Institute for Health and Care Excellence, (NICE, 2010) Guideline 62, ‘Antenatal Care’ was reviewed and re-published in 2010, but updated recommendations for blood grouping and antibody screening were however not included. The challenges flagged in the BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn (BCSH, 2014) of distinguishing between passive and immune anti-D are now covered in detail. The annual Serious Hazards of Transfusion (SHOT) reports continue to highlight errors in the administration of anti-D immunoglobulin (anti-D Ig) prophylaxis, some of which can be attributed to shortcomings in the clinical information provided with screening samples. The testing protocols recommended here are designed to provide clarity for practice in order to protect pregnant women and their babies. This guideline was developed in accordance with the British Committee for Standards in Haematology (BCSH) methodology. The guideline group was selected to be representative of medical and scientific experts. A search of published literature was undertaken using the Cochrane Library, Pubmed, MedLine, Embase and internet searches using the following key words and relevant MeSH terms: anti-D, anti-D Ig immune globulin, pregnancy, antibodies in pregnancy, antenatal prophylaxis, rhesus, RhD, RhD haemolytic disease, erythroblastosis fetalis. This search covered the period 1999 to July 2014 and was limited to the English language and humans. In addition, appropriate non-published literature, published policy documents and knowledge from experts in the field were incorporated and utilised. The papers included were subjected to critical reading by the authors using the CASP appraisal tool (CASP website) and were ranked according to the hierarchy of evidence. This approach took account of the National Institute for Health and Care Excellence's (NICE) systematic review (Chilcott et al., 2003) and the NICE Health Technology Assessment report published in 2007. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Transfusion Task Force of the British Committee for Standards in Haematology. The guideline was reviewed by a sounding board of UK haematologists, the British Committee for Standards in Haematology (BCSH) and the British Society for Haematology (BSH) Committee as well as representatives from the Royal College of Obstetrics and Gynaecology. Reviewers' comments were incorporated where appropriate. Criteria used to assign levels of evidence, and grades of recommendations are as outlined by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group (www.gradeworkinggroup.org), as outlined in Table 3. Providing information about any blood test and obtaining consent is a clinical responsibility, and informed consent should be obtained and documented prior to samples being taken (NICE, Guideline 62, 2008). It is essential that samples from pregnant women are correctly identified and that request forms are accurately completed. 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 Ig prophylaxis (missed or inappropriate administration of prophylactic anti-D Ig) and errors in the selection of blood components (SHOT, 2011; BCSH, 2014). It is essential that the request form and sample conform to the requirements described in the guidelines on the administration of blood components (BCSH, 2009a,b). 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 previous children who were affected by HDFN and of previous transfusions, is essential information and should be stated on the request form. Pre-printed labels should not be used to label pre-transfusion blood sample tubes for compatibility testing or antenatal screening. Samples should be hand-labelled, or labels that are printed ‘on demand’ (at the patient's bedside) are acceptable as an alternative to handwritten labels. All laboratory testing procedures must be validated in compliance with published guidelines (BCSH, 2012b). Wherever possible, testing should be performed on automated equipment, which ensures positive sample identification, and with electronic transfer of results to the Laboratory Information Management System (LIMS). A record of the pregnant woman's ABO and D type performed at booking is useful as confirmation of any subsequent testing on another sample taken at the point of need should the woman or her baby require blood transfusion at a later date. Maternal D typing is also undertaken to identify women who require anti-D Ig Maternal antibody screening is undertaken to detect clinically significant which affect the fetus and to detect antibodies that may cause problems with the provision of blood components for the woman and for the of pregnant women are to have clinically significant red cell antibodies et al., et al., et al., the is anti-D, the of anti-D Ig prophylaxis has the There has been an in the of positive antibody as a result of passive anti-D A recent has that is a between and et al., to in cases and a of disease in a UK testing for a of immune in pregnant women is not recommended et al., There is in using an in antibody screening clinically antibodies be in testing et al., a positive antibody is obtained and red cell antibodies are testing of maternal blood should be undertaken to determine the and to determine the of antibodies or a of and the of red cell antibodies have been identified in pregnancy, the should be with sample taken to identify or any clinically significant maternal as women who have developed an are at of developing This that antibodies that have potential to cause HDFN are and the timely provision of blood for the woman for the baby. The of for antibody screening and be by the and of antibody and an transfusion has been The of clinically significant red cell antibody is pregnancy, to the need for to a fetal and subsequently to management of the pregnancy, including investigations and 2014). and antibody a Institute for Standards and and are the antibodies that are and are as possible, sample should be tested in with the previous sample and the results to identify significant in antibody is used to the of clinically significant red cell antibodies anti-D and in in of in are tested by using red where possible, of the Care must be taken in for where antibody is (including prophylactic anti-D Ig and clinically to that the of is where are and to is to the in the and it is recommended that the anti-D be in as an to of results The is the of the that a positive and the of taken as the point for this should be in the 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 to that the in is not to in the from in results between and in use and and and this should be taken into consideration results from Assessment for Transfusion Laboratory reports of antibody and with July and a clinically significant antibody of HDFN is in a maternal the can provide useful information to predict the of the fetus the relevant red cell and for the It should be that in any pregnancy, the may not be the in cases where the has been by with from a the pregnant woman's not be the It is to testing and to fetal using where in order to of where 2014). DNA for by can be obtained by or such a of and may maternal antibodies It is now to determine fetal and at or weeks gestation using fetal DNA from maternal blood the need for fetal blood sampling et al., This is useful in HDFN in cases where clinically significant red cell antibodies are and as screening to anti-D Ig prophylaxis for women with immune The for such may be on testing et al., et al., 2014). the is well The a in the fetus has a particularly between 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 may be that are not about or by the laboratory It is that samples are not in as the levels of with the time of are in the blood This may and it is to that samples are taken and in accordance with the requirements of the laboratory the results of typing have been for at weeks gestation et al., The for and performed at or weeks gestation is et al., 2008). later weeks may be for by and it is to that guidance on the gestation for testing is sampling may need to be where this is by the laboratory fetal using cell fetal DNA should be performed in pregnant women who have a of HDFN or where or that the is at of investigations should be by or fetal who have the to and the of the test results in the of clinical and the of any test results may be used to the and of of women in the be anti-D Ig prophylaxis as are a fetal typing for pregnant women has been in and the to use of anti-D Ig This of women and their to a blood with in to the provision of anti-D Ig prophylaxis and to et al., et al., et al., This is now provided by in but not The NICE the clinical and of non-invasive of fetal status in order to make recommendations on use screening of pregnant testing for is from weeks gestation with of et al., et al., et al., 2014). It to test the fetal status using a and at a later gestation for pregnant women as described All pregnant women should have samples taken in pregnancy, at at weeks for ABO and D grouping and for screening for the of red cell and an antibody is should be to determine the antibody and All pregnant D positive or D should have a blood sample taken at 28 weeks gestation for the ABO and D group and screening for red cell clinical guidance 62, 2008). women are as as women to form antibodies in et al., et al., must that women who are for antenatal anti-D Ig prophylaxis have the antibody screening sample taken the of anti-D Ig is Samples taken the could result in passive anti-D being which may be for immune anti-D immune anti-D being for passive anti-D Ig et al., There is that antibodies 28 weeks gestation are to cause clinically significant HDFN et al., et al., and the of has in the of anti-D Ig in samples taken 28 weeks gestation from women et al., it is not to between prophylactic anti-D Ig and immune anti-D the has a in to the is the potential for between the et al., and anti-K are the antibodies in haemolytic disease to antenatal et al., 2008). in women with a previous of significant HDFN be at and to a fetal of the antibody In testing protocols are by the and of the antibodies of antenatal antibody should be performed to for the of prior to maternal or fetal Ig prophylaxis has been in the of to but it has in anti-D in is passive to anti-D Ig prophylaxis as or for a or The associated with the of the of anti-D are passive anti-D Ig is as immune anti-D, anti-D Ig prophylaxis may be the women from immune anti-D is as passive anti-D appropriate of the antibody during may be and that be to HDFN not The annual report included a the in between immune anti-D and passive anti-D Ig as were cases where women with immune anti-D were not as as should have been the anti-D was to be passive anti-D and in of these the were with some of HDFN (SHOT, anti-D Ig and immune anti-D be The of passive anti-D Ig with the of immune anti-D or is The of passive 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 the following anti-D Ig et al., are on the stated in the administration of an of anti-D a of anti-D Ig is and the blood is The of passive anti-D Ig is weeks et al., anti-D Ig can be by serological for by an test at weeks or following of and for weeks where are used or following of anti-D anti-D weeks to and a weeks is et al., of the of anti-D anti-D or passive anti-D Ig) on the of with is as this with the and of the red have been affected by HDFN as a result of on the of the of using that have not been validated (SHOT, 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 anti-D et al., et al., The is where anti-D is for the time prior to or at the time of in a group and in which the sample need not be for but the baby should be for of HDFN as need to be on the of the of any anaemia The results of are unlikely to have a on clinical at this and are not as as of and Maternal anti-D may be performed at a later The results should be in the of the and of any anti-D Ig the for the of administration and the antibody status at the time of The clinical and knowledge of the results of previous laboratory testing are in clinical where anti-D is in pregnancy, and should be to this anti-D Ig has been for a prior to 28 it must be that anti-D at or 28 weeks may be immune as levels can between 28 weeks and monitoring should be undertaken as the antibody may be immune anti-D is to anti-D Ig as in the BCSH guideline for the use of anti-D Ig to HDFN (BCSH, 2014). with anti-D should not be with an antibody the of anti-D it is that the anti-D is is the cause of samples from pregnant women with immune anti-D should be tested at 28 weeks gestation and weeks 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 as this be a in a validated test (BCSH, account has been taken of previous of the of anti-D in Table have been used to the management of and Doppler can be used to detect and fetal anaemia et al., 2014). women with an anti-D of or a anti-D a of affected by HDFN should be to a fetal for including It should also be that HDFN has also been with anti-D at et al., the anti-D is that to the of passive anti-D but anti-D should be weeks 28 weeks gestation and weeks to a fetal has been and are being the of anti-D on subsequent samples is the is in the 2014). a however a sample should be tested for the of red cell antibodies at 28 weeks gestation and blood is for for The including the should be informed of the testing to and the laboratory samples in cases where the clinical have that are not at of HDFN should be at weeks gestation to the of to maternal blood group antibodies 2014). The D status of the fetus of pregnant women with a significant of anti-D should be using from a maternal blood This has a of et al., The result of this test can be used as a to the and of ongoing monitoring the sample in which anti-D is is for antenatal antibody screening or is screening selected to provide red cell as for screening in the BCSH compatibility guidelines (BCSH, can be useful to detect or the of of this approach is the of using such a screening for in and an immune anti-D should be A of antibodies with but not with can be by serological to be or et al., who have produced or but not anti-D, at of immune anti-D and should be anti-D Ig prophylaxis in accordance with the BCSH guideline for the use of anti-D Ig to HDFN 2014). It is to identify these cases to appropriate and to anti-D Ig prophylaxis, and a should of is the of the may be useful as of testing at a women with should be with the as women with immune anti-D, at to 28 weeks gestation and weeks of is useful in monitoring 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 of clinically significant In with any previous of the of in Table are of the requirement to to a fetal et al., to a fetal has been and are being the of on subsequent samples is the is in the 2014). a a sample should be tested for the of red cell antibodies at 28 weeks gestation and blood is for transfusion for The including the should be informed of the testing to and the laboratory samples in cases where the clinical have that are not at of HDFN should be at weeks gestation to the of to maternal blood group antibodies 2014). The status of the fetus of pregnant women with a significant of should be using from a maternal blood This has a of et al., The result of this test can be used as a to the and of ongoing monitoring It is to that may cause anaemia in the baby. antibodies to in the blood group should be and in the as anti-K as these have the potential to cause HDFN et al., 2014). HDFN to anti-K is by but levels are not The fetal anaemia associated with anti-K may be to the of et al., to the of their immune et al., It has been stated in some that the of HDFN to anti-K is not with of the and prior to where HDFN of recent of affected that HDFN is associated with antibodies with a of at et al., et al., samples from women with anti-K should be the antibody is identified in the pregnancy, and should be undertaken weeks 28 weeks gestation and to a fetal has been and are being the of anti-K on subsequent samples is the are in the 2014). The including the should be informed of the testing to and the laboratory samples in cases where the clinical have that are not The of cases of anti-K in pregnant women are the of previous The of anti-K can be by for transfusion to with potential for to be should be selected for the of who are or type is should not be are not (BCSH, 2012b). in may be particularly relevant for women with anti-K as of anti-K in pregnant women results from previous transfusion and of the are positive a of of women with anti-K are It is that the transfusion of women with anti-K should be and a sample from the of the fetus should be for the type is or is the pregnant woman should be to a fetal anti-K is identified 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 The status of the fetus of pregnant women with anti-K should be using from a maternal blood sample the is for the or status is This has a of et al., The result of this test can be used as a to the and of ongoing monitoring It is antibodies that are of the fetal 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 et al., et al., et al., 2008). been as the cause of antibody may be some of which may be in women of a such as in the et al., and in the et al., the a form of to that by including of In at 28 weeks gestation information to determine management of the pregnancy. A clinical should be the testing of women with a previous of children with The of may the of has been a previous baby who significant anaemia or monitoring to this at an to that for or be with Doppler monitoring and consideration of at weeks to and the are the for Doppler the of of antibody in is In the of a of the of developing with antibodies of is that of anti-D, and in a of pregnant women with and at and was perinatal to the antibodies et al., The to be for such as or some are and not provide a of a of pregnant women with antibodies of the et al., et al., et al., It is that in the of a previous of pregnant women with antibodies with and anti-D, and not need to be as as with a of HDFN the antibody or cases of significant anaemia be to be by Doppler monitoring at and weeks The on the of monitoring and the need for be on the of previous for the affected and the reports and in the A has to be between monitoring to the for and with a in of being and a of monitoring with an of anaemia and The of cases and for antibodies and are the and of a approach to monitoring pregnant women with such antibodies be information about antibodies and their to cause clinically significant it is recommended that is from a transfusion in a red cell for antibodies that have been associated with HDFN are in the guidelines and the on et al., et al., an antibody has been testing of and gestation samples should In is a that an antibody with a of or cause some of a between and HDFN has not been The of antibodies should be or and any clinically significant antibodies should be or on the In to blood group and of any red cell reports must the for the pregnant woman's antenatal of the of the antibodies with to the of HDFN and potential in blood for transfusion (NICE, should where the to the need to the woman to a fetal The woman should be and information about the clinical of the and it should be documented that has been in the record. of the of samples should also be A maternal sample and a blood sample should be The blood sample should be used to determine the D group it is not pregnant women who must prophylactic anti-D There is that fetal red the can cause maternal the use of as D for typing samples is not recommended as the of using the for testing the of a of D can be by anti-D (BCSH, This is not recommended as a It has been that following anti-D Ig can the the fetal and to fetal D of D positive samples have been to have a positive et al., and this may result in There is that prophylactic anti-D Ig not cause significant of red et al., the maternal sample has been 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 2014). In addition, the baby should be for clinical of jaundice guidance on neonatal A positive is in of the is positive and the baby of a red cell may be to the red cell antibody ABO antibodies cause and the baby has a ABO with the the should also be tested with for any which the woman has of and is and is not 2014). who have been in with for the prevention of HDFN to anti-D may type as D for et al., 2014). In this the and should be to of clinically significant red cell are into the women with red cell antibodies at 28 weeks blood grouping and antibody screening of maternal D is not pre-transfusion compatibility testing is of antibodies in not management of the current pregnancy, testing is undertaken and antibodies the woman should be informed as may be for In a or maternal sample is to predict neonatal transfusion requirements red cell antibodies the need to be and also for should neonatal transfusion be A test for should be performed on the maternal blood sample from women with immune anti-D to detect fetal in the maternal to the of in order to determine any requirement for anti-D Ig of clinical and laboratory practice should be undertaken on a to compliance with these where or in to compliance should be A for is included as reviewed the literature and the draft of the and the subsequent of the prior to and following and reviewed the literature and the the BCSH transfusion reviewed the literature and revised the The BCSH at the time of writing this guidance was and The BCSH the during the writing of this All authors have a of to the BCSH and Task Force which may be on The members of the writing group have of to the and information in these guidelines is to be and at the time of to the the British Society for Haematology the any for the of these BCSH guidelines have used the for levels of and recommendations in laboratory guidance is to clinical the of a test to clinical tool to compliance with the BCSH guidelines for blood grouping and red cell antibody testing in