Guidelines on the prophylactic use of Rh D immunoglobulin ...

1 Guidelines on the prophylacticuse of Rh D immunoglobulin (anti-D) in obstetricsGuidelines on theprophylactic useof Rh D immunoglobulin (anti-D)in obstetricsApproved by the National Health and Medical Research Council6 June 2003 Revision of Guidelines funded by theAustralian Government Department of Health and AgeingIssued by the National Blood Authority Commonwealth of Australia 2003 ISBN 0 642 82372 3 This w or k is cop yr ight. A par t fr om an y use as per mitted under theCop yr ight Act 1968, no par t ma y be r epr oduced b y an y pr ocess withoutpr ior wr itten per mission fr om the Commonwealth a v aila b le fr om theDepar tment of Communications, Inf or mation T ec hnolog y and the Ar and inquiries concer ning r epr oduction and rights should beaddr essed to the Commonwealth Cop yr ight Administration, IntellectualPr oper ty Br anc h, Depar tment of Communications, Inf or mationT ec hnolog y and the Ar ts, GPO Bo x 2154, Canber r a A CT 2601 or postedat.

2 Pub lication appro v al 3372 (JN 7965)Pub lications Pr oduction UnitA ustr alian Go v er nment Department of Health and Ag eingiiCONTENTSSUMMARYVSUMMARY OF RECOMMENDATIONSviiClinical indications and dosage Rh D immunoglobulinviiSummary of dosing recommendations for Rh D negative pregnantwomenviiGeneralviiSensitising events in the first trimesterviiiSensitising events beyond the first trimesterviiiAntenatal prophylaxisixPostpartumixPathology testingxSecuring supplyxiCommunication and educationxiINTRODUCTION1 Background1 Scope of this report11 BASIS FOR GUIDELINE Evidence base for use of Rh D Cost-effectiveness analysis112 SECURING SUPPLY MOVING TOWARDS SELF-SUFFICIENCYIN RH D Promoting the efficient use of Rh D Securing future

3 Supply of Rh D Staged implementation of antenatal prophylaxis183 COMMUNICATION AND EDUCATION21 APPENDICES23 ATerms of reference and membership of the Working Party23 BGuideline Development Process25C Literature review on the use of Rh D immunoglobulin inobstetrics search strategy and results27 ACRONYMS AND ABBREVIATIONS31 BIBLIOGRAPHY33iiiivSUMMARYIn 1999, the National Health and Medical Research Council publishedguidelines aiming to balance best practice in the use of Rh D immunoglobulinwith the limited supply. While the Working Party found that universalprophylaxis with Rh D immunoglobulin to Rh D negative women at 28 and 34weeks gestation is generally regarded as best practice, it was unable torecommend antenatal prophylaxis due to supply constraints at that the 1999 Guidelines were issued, there have been a number ofdevelopments which have increased the supply of Rh D immunoglobulin inAustralia, although self-sufficiency has not yet been reached.

4 A 250 IU (50 g)dose of Rh D immunoglobulin was introduced in May 2001, and its use inpotentially sensitising events in the first trimester should ensure more efficientuse of existing supply. In addition, an overseas product was approved for usein Australia in October 2002, to ease pressure on the domestic supply untilself-sufficiency can be reached, and additional funding was provided to theAustralian Red Cross Blood Service (ARCBS) to recruit more anti-D donors andto conduct primary immunisation and boosting of existing 2001 the Working Party was reconvened to review the Guidelines ,particularly in regard to antenatal prophylaxis. Based on the results of anupdated literature review and assessment of progress towards self-sufficiencyin Rh D immunoglobulin , a range of recommendations have been made forthe staged implementation of full antenatal prophylaxis.

5 The amendedguidelines will be used to implement a multi-faceted strategy for securingfuture supply, which includes measures to increase domestic production of RhD immunoglobulin , as well as wide - ranging communication and education topromote its most appropriate report is intended to update rather than replace the Guidelines released in1999. It aims to inform clinicians, other health professionals and policy makersabout changes to the previous Guidelines and new recommendations for useof Rh D immunoglobulin in Australia. These recommendations should bereviewed within five years, according to the availability of Rh OF RECOMMENDATIONSC linical indications and dosage Rh D immunoglobulinThe Working Party has made a range of recommendations on the clinicalindications for Rh D immunoglobulin , including postpartum administration,antenatal administration for indications, and the staged implementation of fullantenatal prophylaxis.

6 The recommendations take into account the results ofan updated literature review and the current and projected future supply of RhD immunoglobulin . The recommended doses aim to ensure that all Rh Dnegative women are adequately protected from immunisation against Rh Dpositive of dosing recommendations for Rh D negativepregnant womenRh D immunoglobulinObstetric conditionsSensitising events in the first trimester250 IU (50 g)Sensitising events beyond the first trimester625 IU (125 g)PregnancyAntenatal prophylaxis (28 and 34 weeks for first pregnancy)625 IU (125 g)Postpartum600 IU (120 g)** In the shor t to medium term, impor ted pr oduct should be used for this indication to ease thepr essur e on the domestic supply of Rh D immunoglobulin .

7 At the time of writing, the onl yimpor ted pr oduct r eg ister ed f or use in A ustr alia is pr esented as a 600 IU [120 g] pr epar For successful immunoprophylaxis, Rh D immunoglobulin should beadministered as soon as possible after the sensitising event, but alwayswithin 72 hours (level I evidence). If Rh D immunoglobulin has not beenoffered within 72 hours, a dose offered within 9 10 days may provideprotection. Blood should be taken from the mother before administrationof the Rh D immunoglobulin to assess the magnitude of fetomaternalhaemorrhage (FMH). Where FMH quantitation shows that FMH greaterthan that covered by the dose already administered has occurred,administration of an additional dose/s sufficient to provideimmunoprophylaxis must be administered and preferably within 72 events in the first trimester A dose of 250 IU (50 g) Rh D immunoglobulin should be offered to everyRh D negative woman with no preformed anti-D to ensure adequateprotection against immunisation for the following indications up to andincluding 12 weeks gestation (level IV evidence): miscarriage; termination of pregnancy; ectopic pregnancy; and chorionic villus sampling.

8 A dose of 250 IU (50 g) Rh D immunoglobulin is sufficient to preventimmunisation by a fetomaternal haemorrhage of ml of fetal red cells(5 ml whole blood) (level IV evidence). The Working Party strongly recommends that women undergoingtermination of pregnancy be tested to determine whether they are Rhesusfactor positive or negative, to avoid unnecessary use of Rh Dimmunoglobulin. There is insufficient evidence to support the use of Rh D immunoglobulinin bleeding prior to 12 weeks gestation in an ongoing pregnancy, althoughif the pregnancy then requires curettage Rh D immunoglobulin should begiven. If miscarriage or termination occurs after 12 weeks gestation, 625 IU(125 g) Rh D immunoglobulin should be events beyond the first trimester Although some of the recent evidence related to the use ofimmunoprophylaxis is based upon studies of potentially sensitising eventsoccurring up to 20 weeks gestation, for practical purposes the WorkingParty recommends that a dose of 250 IU (50 g) be used for the firsttrimester events (up to and including 12 weeks gestation) and 625 IU(125 g) be used beyond first trimester.

9 Future revisions of theseguidelines may, in the face of further evidence extend the use of the 250IU (50 g) dose beyond 12 weeks gestation. A dose of 625 IU (125 g) Rh D immunoglobulin should be offered toevery Rh D negative woman with no preformed anti-D to ensure adequateprotection against immunisation for the following indications after 12weeks gestation (level IV evidence): genetic studies (chorionic villus sampling, amniocentesis andcordocentesis); abdominal trauma considered sufficient to cause fetomaternalhaemorrhage;viii each occasion of revealed or concealed antepartum haemorrhage(where the patient suffers unexplained uterine pain the possibility ofconcealed antepartum haemorrhage should be considered, with a viewto immunoprophylaxis); external cephalic version (performed or attempted); and miscarriage or termination of pregnancy.

10 As evidence for the efficacy of this dose for these indications is notavailable, it is recommended that the magnitude of fetomaternalhaemorrhage be assessed and further doses of Rh D immunoglobulinadministered if required, especially where transplacental access orpuncture of fetal blood vessels prophylaxis Universal prophylaxis with Rh D immunoglobulin to Rh D negativewomen with no preformed anti-D antibodies at 28 and 34 weeks gestationis generally regarded as best practice (level II evidence). With current availability of Rh D immunoglobulin the Working Party is ableto recommend administration of 625 IU (125 g) Rh D immunoglobulin at28 and 34 weeks in all Rh D negative primigravidae with no preformedantibodies. It is anticipated that full antenatal prophylaxis will be able tobe implemented when domestic supplies of Rh D immunoglobulinincrease sufficiently to cover that increased Rh D immunoglobulin should be offered to every Rh D negative womanfollowing delivery of an Rh D positive baby (level I evidence).