Anti-D for the prevention of HDfN (bsh 2013)

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 D-

60% of D- 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

Prior to availability of Anti-D IgG, RhD alloimmunisation occurred in 16% of Rh D- women following two deliveries of Rh D+ infants.

Now 2% following the introduction of routine postpartum Anti-D administration

Further fall with the use of routine prophylaxis in 3rd trimester

Lead to a corresponding reduction in HDFN mortality

 

Potentially Sensitising Events Requiring 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):

  1. 1500 IU given once between 28-30 weeks

  2. 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)

 

Currently 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 can be taken from 11+2 weeks for high-throughput screening of fetal D type with 99% accuracy. False negative (missing a D+) is <0.1%.

Rh C, c, E, e and Kell can also be determined using diagnostic test from 16 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

  • 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