Journal of Obstetrics and Gynaecology (1997) Vol. 17, No. 4, 420± 421

Royal College of Physicians of Edinburgh/RoyalCollege of Obstetricians and Gynaecologists:Consensus Conference on Anti-D Prophylaxis7 & 8 April 1997

Final Consensus StatementAt a conference convened by the Royal College ofPhysicians of Edinburgh and the Royal College ofObstetricians and Gynaecologists, a consensus panelconsidered speci® c issues relating to anti-D prophy-laxis in the UK. This statement is based on presenta-tions given at the meeting, published research andexpert opinion .

The panel reached the following conclusions:

Overview(1) Perinatal deaths due to RhD alloimmunisationhave fallen a hundred-fold since the introduction in1969 of a policy to administer anti-D IgG to RhD-negative women after sensitising events in pregnancyand the birth of RhD-positive infants. In the 1990spregnancy loss and death in the ® rst week afterdelivery due to RhD alloimmunisation is in the orderof 50 per year in the UK.

(2) RhD alloimmunisation still occurs. One to two ofevery 100 RhD-negative women at risk still becomesensitised. This appears to be for two main reasons:(1) some women do not receive the bene® t of thecurrent policy, and (2) women are sensitised by smallbleeds from the fetus, mainly in the last twelve weeksof pregnancy, which go undetected.

Current guidelines on anti-D prophylaxisÐ arethey effective, can they be improved?

(3) The panel is concerned that there is abun-dant evidence that the guidelines are not beingfully applied

(4) The generally accepted UK guidelines are Recom-mendations For The Use Of Anti-D Immunoglobulin(National Blood Transfusion Service Immunoglobu-lin Working Party, 1991) . The panel recommends thatthese should at present remain the reference standardfor good clinical practice and that there should be nochange to the dosage principle of 500iu for 4ml offetal red blood cells. We are reassured to learn thatthere is an expert group currently undertaking reviewand revision of the current guidelines, with particularattention being given to the use of anti-D IgG in the® rst trimester of pregnancy. Failures of complianceare particularly common following potentially sensi-tising events during pregnancy, both in respect of theadministration of anti-D IgG and the estimation of

size of feto-maternal haemorrhage (FMH) by Klei-hauer, or alternative, tests.(5) Awareness of the need for anti-D IgG and aKleihauer (or alternative) test is essential among staffinvolved in the care of pregnant women in obstetricand midwifery units, and also in A&E departmentsand in primary care.

(6) It is recommended that information lea¯ ets aboutthe guidelines should be given to RhD-negativewomen and their partners, and relevant health profes-sionals.

Antenatal anti-D prophylaxisÐ is it worthwhile,and can we afford it?(7) A current recommendation is that anti-D IgGshould be given after events signalling the possibilityof FMH. The panel believes that routine antenatalanti-D prophy laxis is of proven bene® t and that thiswould signi ® cantly reduce levels of RhD alloimmuni-sation. The currently available studies however makeit dif ® cult to estimate the scale of the reduction.

(8) The panel proposes that because all RhD-negativepregnant women are at risk from hidden bleeds, theyshould be given anti-D IgG prophylactically.

(9) A paucity of recent cost-effectiveness studiesmakes it dif ® cult to make de® nite and accurate state-ments regarding the ef® ciency of extending the cur-rent policy to include routine antenatal prophylaxis.The cost of offering routine antenatal prophy laxis willdepend on dose and frequency. Estimates of cost perdose vary.

(10) Evidence to date suggests that antenatal prophy-laxis has the potential over time to save moreresources than it costs if restricted to primigravidae(for this purpose we include multigravid women with-out a living child), although this will involve a mod-est degree of preliminary investment in order toincrease the supply of anti-D IgG. Increasing theprogramme to include all RhD-negative pregnantwomen will have a positive net cost which might beconsiderable, but the cost per life year saved is stilllikely to compare favourably with other NHS inter-ventions.

(11) The panel considers there to be no effectiveargument against protecting all RhD-negativewomen, as opposed to just primigravidae. While thegreatest cost bene® ts of routine anti-D IgG prophy-laxis have been demonstrated in primigravidae, itcannot be ethically or economically justi ® ed to limitthe policy to this group of women.

0144-3615/97/040420-02 $9.50 ã Institute of Obstetrics and Gynaecology Trust, 1997

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Consensus Statement on Anti-D Prophylaxis 421

(12) It is expected that UK blood transfusion centreswill be able to meet requirements for supply ofpolyclonal anti-D at least for a programme in primi-gravidae. In the long term however, it is reasonable toexpect supply will be suf ® cient to protect all RhD-negative women routinely. Until a safe monoclonalproduct is available the principal source of donorswill have to be sensitised men and women. No seri-ous adverse reactions have been reported in womenreceiving intramuscular anti-D IgG, but it is import-ant that the viral and other safety issues raised bychanges in product manufacture are kept under rigor-ous review.

(13) It remains to be decided which dosage andschedule of prophy laxis is the most effective. Thereare two main optionsÐ a dose of 500iu at 28 and 34weeks, or alternatively a single larger dose early inthe third trimester. Both seem to work.

(14) In introducing antenatal prophylaxis we suggestthat health authorities should ® rst check on compli-ance with current guidelines. If initially there isinsuf ® cient anti-D IgG for all women at risk, primi-gravidae should be given priority. Early consultationwith professionals in primary care will be essential.

Monoclonal anti-DÐ is it safe, will it work andcan it replace polyclonal anti-D?(15) In 1991 the guidelines authors hoped that aneffective monoclonal anti-D would soon be availableto supplement polyclonal anti-D and that there wouldbe suf ® cient quantities to allow antenatal prophy laxisto be started. In 1997 it appears that:

· Monoclonal preparations, of which supply wouldbe theoretically limitless, could in principlereplace polyclonal anti-D.

· Only Phase I trials are at present complete onmonoclonal preparations. It is not yet certain ifthese preparations will be safe and ef® cacious,reliable or affordable. There may be advantagesfrom an intravenous preparation that can also begiven intramuscularly.

· It is also uncertain how long it will be before

monoclonal products are available in suf ® cientquantity, and whether they will be acceptable toregulators.

· The process of introducing monoclonal productsand possibly phasing out polyclonal anti-D willneed to be agreed nationally, and will require acomparative trial. Polyclonal products should notbe phased out until the monoclonal supply hasbeen shown to be secure.

Should anti-D be used for the treatment ofimmune-mediated thrombocytopenia?(16) The panel accepts that anti-D IgG may have aplace in the treatment of RhD-positive non-splenec-tomised patients, especially children, with chronicimmune thrombocytopenia, and that in these patientsit may have a similar role to high-dose intravenousimmunoglobulin. However with current UK practiceit is only likely to be used in a small number ofpatients. In the UK there is an imported anti-D IgGpreparation available for use in immune-mediatedthrombocytopenia on a named-patient basis.

Ethical considerations of anti-D provision fromimmunised volunteers

(17) The donor should be empowered to make a fulland free informed choice before consenting to theimmunisation procedure. Voluntary consent to thisprocedure must be genuine and explanation geared tocapacity to understand and act on what is required. Acomprehensive information lea¯ et should be madeavailable for prospective donors.

(18) It is likely there will continue to be a need forimmunised donors well into the 21st century, anduntil the safety, ef® cacy and quality of monoclonalanti-D is established to the standard of Europeanregulatory requirements.

(19) The question of compensation for non-negligentharm is vexed but clearly some effective and trans-parent arrangement to compensate volunteers is desir-able.

S. J. Urbaniak on behal f of the Organisin g Committee, Royal College of Physician s, 9 Queen Street, Edinburg h EH12 1JQ,UK

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