Anti-D for the prevention of HDfN (bsh 2013)
N.B. This 2018 FAQ from NHSBT is a goldmine of facts and figures
key summary
125IU IM neutralizes 1ml of FMH
<12 weeks = 250 IU if ectopic, molar, TOP or heavy, repeated uterine bleeding
12-20 weeks = 250 IU all cases
>20 weeks = 500 IU all cases + test for FMH
15% of population RhD-
60% of RhD- mothers will carry a D+ baby
Intro
HDFN = Haemolytic Disease of the Fetus and Newborn
FMH = FetoMaternal Haemorrhage
RAADP = Routine Antenatal Anti-D Ig Prophylaxis
Reduction in RhD alloimmunisation in RhD neg women over time:
Prior to availability of Anti-D IgG, RhD alloimmunisation occurred in 16% of Rh D- women following two deliveries of Rh D+ infants.
Fell to 1% following the introduction of routine postpartum Anti-D administration
Now 0.35% with the use of routine prophylaxis at 28 weeks (RAADP)
—> has led to a corresponding reduction in HDFN mortality
Potentially Sensitising Events Requiring Anti-D Prophylaxis
15% = Probability of women having a potentially sensitising event during pregnancy (taken from a 2013 UK national audit of anti-D prophylaxis)
Pregnant D- women with no immune anti-D should be offered prophylactic anti-D Ig for potentially sensitizing events, and this must be given with 72 hours of the event.
If 72 hours has passed, anti-D can still be given up to 10 days post the event to some effect.
Sensitising events include:
Ectopic pregnancy, molar pregnancy, intrauterine death, termination of pregnancy
Stillbirth, miscarriage, threatened miscarriage
Amniocentesis, chorionic villous sampling, cordocentesis
Abdominal trauma (sharp / blunt, open / closed)
Delivery, External cephalic version
Intra-operative cell salvage
Occurring at less than 12 weeks gestation
Lab tests
G&S to determine or confirm maternal Rh D group and check for presence of anti-D
Anomalous Rh D typing results treated as Rh D- until confirmatory testing.
Do NOT need to test for FMH
Prophylaxis
250 IU Anti-D within 72 hours for any of indications above
Do NOT need to give anti-D when:
Spontaneous complete miscarriage confirmed by scan + uterus is not instrumented
Mild, painless PV bleeding
Occurring between 12 and less than 20 weeks
Lab tests
G&S to determine or confirm maternal Rh D group and check for presence of anti-D
If anti-D detected —> further history to determine whether immune or passive (i.e. previous anti-D injection). If not clear, assume passive and continue to offer anti-D.
Anomalous Rh D typing results treated as Rh D- until confirmatory testing.
Do NOT need to test for FMH
Prophylaxis
250 IU Anti-D within 72 hours for any of indications above
Repeat at 6 weekly intervals if continual uterine bleeding
Occurring between 20 weeks and term
Lab tests
G&S to determine or confirm maternal Rh D group and check for presence of anti-D
If anti-D detected à further history to determine whether immune or passive (i.e. previous anti-D injection). If not clear, assume passive and continue to offer anti-D.
Anomalous Rh D typing results treated as Rh D- until confirmatory testing.
Fetomaternal haemorrhage (FMH) testing is required
If FMH >4ml, a repeat sample is required 48 hours later if IV Anti-D was used (72 hours if IM) to ensure clearance of fetal cells
Prophylaxis
500 IU Anti-D IgG within 72 hours of the event, regardless of whether RAADP already given
Repeat at 6 weekly intervals if continual uterine bleeding that is considered part of the same sensitizing event. FMH testing 2 weekly
100 IU per ml of fetal blood (125 IU if IM) should be given if the two weekly FMH is positive.
Each new sensitising event should be treated as above regardless of the timing or dose of previous anti-D administration
Routine Antenatal Anti-D Prophylaxis (RAADP)
A routine G&S is taken at 28 weeks as the second (confirmatory) G&S in pregnancy
If anti-D is identified, determine whether immune or passive (i.e. previous Anti-D injection)
Two options (NICE says use cheapest):
1500 IU given once between 28-30 weeks
2 x 500 IU given at 28 and 34 weeks
Give regardless of any previous doses administered for potential exposure events.
Prophylaxis following birth of a Rh D+ child or intrauterine death (IUD)
Lab tests
Cord blood should be taken immediately following birth for ABO and Rh D type of baby.
Alternative is heel prick test. If no sample taken for whatever reason, assume Rh D+
DAT – Not routine. Perform is suspect HDN
Maternal G&S + FMH – Perform in all D- women delivering D+ infants to determine if additional doses of anti-D required. Take 30-45min post delivery (time for FMH to disperse in circulation)
Administration
500 IU within 72 hours of delivery if baby found to be Rh D+
1500 IU minimum dose if intraoperative cell salvage used. Monitor FMH
500 IU if intrauterine death, within 72 hours of IUD diagnosis (not delivery)
Management of transfusion of D+ blood components to D- girls/women of childbearing age
D+ Platelet transfusion
Wherever possible D- platelets should be transfused.
If time/circumstances demand use of D+ platelets:
250 IU will cover up to 5 adult units given within a 6 week period
Give SC if platelet count <30
Inadvertent transfusion of D+ blood
Less than 15ml transfused --> 125 IU IM per ml blood transfused
More than 15ml transfused --> Give IV Anti-D 1500-2500 IU and assess D+ cells by flow cytometry after 48 hours. Give further doses as required until no detectable D+ cells.
More than one unit of blood transfused --> Offer red cell exchange to patient. Discuss risk vs benefit. Single volume exchange will remove 65-70% D+ cells. Double volume 85-90%.
Passive Anti-D may be detectable for many months after large dose administration.
Cell free fetal DNA testing (cffDNA)
RAADP means that approx. 40% of D- women carrying a D- child will be given routine anti-D prophylaxis unnecessarily, equal to around 40,000 women per year in UK.
cffDNA first piloted in UK in 2013
cffDNA Screening Test from 11+2 weeks
Automated DNA extraction, Batched, high-throughput screening of fetal D type with 99% accuracy.
False negative (missing a D+) is <0.1%.
Tests for RHD exons 5 and 7
Cannot be run on women who are serologically positive for anti-D (need diagnostic test instead)
cffDNA Diagnostic Test from 16 weeks
Rh C, c, E, e and Kell can also be determined using manual DNA extraction
(Kell testing is from 20 weeks)
Principles and Safety of Anti-D IgG
Polyclonal anti-D IgG is prepared from pooled plasma of non-UK blood donors who carry high levels of anti-D due either to previous sensitization or intentional immunization.
Precise mechanism by which anti-D prevent alloimmunisation is unknown, but may include the rapid clearance of anti-D coated D+ red cells by macrophages, and down-regulation of antigen-specific B cells.
Plasma is screened for HBsAg, anti-HIV and HCV RNA
Viral inactivation performed due manufacturing
Adverse events
TTI - risk is essentially zero (no cases in UK history) but mindful of new emerging infections
Allergic reaction – rare but includes severe hypersensitivity and anaphylaxis
Giving certain IM preparations intravenously carries risk of anaphylaxis (due to trace quantities of IgA)
Dosing / Preparation
1 microgram of anti-D equivalent to 5 IU
Give into deltoid muscle. If gluteal to be used, ensure gets into muscle
Traceability – DoH requires that traceability records are kept for all anti-D products. So it makes sense for transfusion lab to store and issue products, however this is not a requirement and local practice may vary. Information must be stored on transfusion lab computer either way, and include:
Recipient name, DOB, Hospital number
Date & location of injection
Name of GP + Obstetrician if possible