Anti-D Immunoglobulin

Anti-D immunoglobulin is a targeted immunoprophylactic treatment given to Rhesus D negative pregnant women. It aims to prevent maternal alloimmunisation against the Rhesus D antigen after exposure to Rhesus D positive fetal red blood cells.

It is one of the most successful, well established preventive interventions in obstetric practice. It has dramatically reduced the incidence of Rhesus D alloimmunisation and its associated haemolytic disease of the fetus and newborn, addressed in detail in the preceding entry.

This has been achieved through systematic implementation of routine antenatal administration and administration following specific, recognised sensitising events.

Mechanism of action and rationale

• Anti-D immunoglobulin comprises purified, exogenous anti-Rhesus D antibody. It binds to and clears any Rhesus D positive fetal red blood cells that have entered the maternal circulation. This happens before the mother's immune system can recognise the foreign antigen and mount its own, endogenous sensitising response.
• It thereby prevents the initial alloimmunisation event that would place any subsequent pregnancy carrying a Rhesus D positive fetus at risk of haemolytic disease of the fetus and newborn.
• The approach is preventive rather than therapeutic. It is given to Rhesus D negative women who are not already sensitised, confirmed by a negative antibody screen.
• It has no benefit, and is inappropriate, in a woman who has already developed Rhesus D sensitisation, because the exogenous antibody cannot reverse established maternal sensitisation.
• Fetomaternal haemorrhage, and thereby maternal exposure to fetal Rhesus D positive red cells, can occur at various points in pregnancy beyond delivery alone. Full prophylaxis protocols therefore incorporate routine, scheduled antenatal administration and additional administration following specific, recognised potential sensitising events at any stage of pregnancy.

• This entry addresses a preventive intervention rather than a clinical condition. The relevant clinical context is identification of Rhesus D negative status in a pregnant woman through routine antenatal blood group testing, with a negative antibody screen confirming the absence of pre-existing sensitisation.
• Specific, recognised potential sensitising events warrant additional, event-specific anti-D immunoglobulin beyond the routine, scheduled antenatal doses. Each carries potential for fetomaternal haemorrhage. They include:
  • antepartum haemorrhage
  • invasive prenatal diagnostic procedures (chorionic villus sampling or amniocentesis)
  • external cephalic version
  • significant abdominal trauma
  • miscarriage or termination of pregnancy (beyond a specific, relevant early gestational age threshold, according to local protocols)
  • ectopic pregnancy
• Delivery is the single most significant, common sensitising event, because of the substantial fetomaternal haemorrhage that characteristically occurs. Postnatal anti-D immunoglobulin is therefore a standard requirement for any Rhesus D negative woman who delivers a Rhesus D positive infant.

• Routine antenatal blood group and antibody screening is performed at initial booking and repeated at defined intervals during pregnancy. It identifies Rhesus D negative status and confirms the absence of pre-existing sensitisation, the essential foundation for prophylaxis planning.
• After delivery, testing the infant's blood group determines whether the infant is Rhesus D positive. This directly informs the need for postnatal maternal anti-D immunoglobulin.
• Non-invasive antenatal fetal Rhesus D genotyping using cell-free fetal DNA, where performed, may inform the anticipated need for postnatal maternal prophylaxis in advance of delivery.
• A Kleihauer test quantifies the volume of fetal red cells in the maternal circulation after a potential sensitising event or delivery. It supports determination of the anti-D immunoglobulin dose needed to clear the fetal cells present.
• This is particularly relevant after delivery or a significant sensitising event, where a larger than typical fetomaternal haemorrhage is possible.

• Routine antenatal anti-D immunoglobulin prophylaxis follows established, local protocol. It is commonly either a single, larger dose around 28 weeks gestation, or two smaller doses at approximately 28 and 34 weeks, according to the protocol used.
• It is offered to all Rhesus D negative, non-sensitised pregnant women. Silent, clinically inapparent fetomaternal haemorrhage can occur spontaneously in the antenatal period even without an identified sensitising event.
• Give postnatal anti-D immunoglobulin as promptly as possible after delivery (generally within 72 hours) to any Rhesus D negative woman confirmed to have delivered a Rhesus D positive infant. Adjust the dose according to Kleihauer test results where a larger than standard fetomaternal haemorrhage is identified or suspected.
• Give event-specific anti-D immunoglobulin promptly after the relevant sensitising event. Dose and timing follow established, local protocol guidance for the particular event and the gestational age at which it occurred.
• Full patient education on the rationale for and importance of this intervention is essential. Clear, systematic clinical protocols and documentation ensure appropriate, timely administration of both the routine, scheduled antenatal doses and any additional, event-specific doses.
• This underpins effective implementation of a highly successful preventive intervention. It directly supports the ongoing reduction in the incidence of Rhesus D alloimmunisation and its associated haemolytic disease of the fetus and newborn.