Anti-D Prophylaxis

Anti-D immunoglobulin is human polyclonal IgG against the RhD antigen, prepared from plasma of RhD negative donors who have been immunised. It prevents RhD alloimmunisation in RhD negative people who are exposed to RhD positive red cells, by clearing the cells before the immune system reacts. It does not treat established alloimmunisation, and it does not help a woman who already has her own anti-D.

Mechanism. Passive anti-D coats RhD positive red cells and removes them from the circulation, suppressing the primary immune response. Protection lasts weeks, and the passive antibody may be detected on later antibody screens.

Products. Intramuscular and intravenous preparations exist. Doses are expressed in international units (IU) or micrograms, and 1 microgram is about 5 IU, so 300 micrograms is about 1500 IU. A dose of 300 micrograms covers about 15 mL of RhD positive red cells (about 30 mL of foetal whole blood), and the usual calculation is about 20 micrograms for each 1 mL of RhD positive red cells.

Storage. 2 to 8 degrees Celsius, and never frozen.

Special groups. Pregnant and postpartum RhD negative women are the main group. RhD negative girls and women of childbearing potential who receive RhD positive blood components are another. In East Africa, RhD negative status is uncommon but important, anti-D immunoglobulin is often limited or costly, and rapid access to RhD typing of mother and baby decides who needs it.

Indications in pregnancy and delivery.

• Routine antenatal prophylaxis at about 28 weeks (and in some regimens again at 34 weeks) in RhD negative women with no anti-D.

• Within 72 hours after birth of an RhD positive baby (confirmed on cord or neonatal blood), including stillbirth with an RhD positive or unknown foetus.

• After sensitising events: miscarriage, termination, ectopic pregnancy, molar pregnancy, chorionic villus sampling, amniocentesis, antepartum haemorrhage, abdominal trauma, external cephalic version, intrauterine death, and any invasive procedure in pregnancy.

Indications in transfusion. RhD negative girls and women of childbearing potential who receive RhD positive red cells or platelets when RhD negative products are not available. After exposure to RhD positive red cells, the blood bank calculates the dose from the volume transfused, or advises on red cell exchange for large volumes.

Not indicated.

• Women who are RhD positive, including those with weak D or partial D variants, depending on laboratory policy. Partial D is usually treated as RhD negative in pregnancy.

• Women who already have anti-D produced by their own immune response. Passive anti-D from earlier prophylaxis can look like immune anti-D, and the blood bank must interpret the antibody history.

• Delivery of an RhD negative baby.

• Men and women beyond childbearing age with RhD negative status who receive RhD positive blood in emergencies, unless there is a particular plan.

Contraindications and cautions. Previous severe reaction to immunoglobulin, IgA deficiency with anti-IgA, and thrombocytopenia or bleeding disorders (use the intravenous product or a subcutaneous route instead of intramuscular, as the manufacturer allows).

Dose. Local products and regimens differ. The most widely used adult doses are:

• Routine antenatal prophylaxis: 1500 IU (300 micrograms) once at about 28 weeks, or 500 to 750 IU (100 to 150 micrograms) at 28 and 34 weeks as the product specifies.

• Postpartum: 1500 IU (300 micrograms) within 72 hours of delivery if the baby is RhD positive. Lower regimens of 500 IU (100 micrograms) are used where products and fetomaternal haemorrhage testing allow.

• Sensitising event before 12 weeks: at least 250 IU (50 micrograms), and in many places 1500 IU is used when only one dose size is stocked.

• Sensitising event at or after 12 weeks (and especially from 20 weeks): at least 500 IU (100 micrograms), and 1500 IU where that is the stocked dose.

• Transfusion of RhD positive platelets: at least 250 IU (50 micrograms), within 72 hours, covering a single adult dose, with the blood bank advising on larger exposure.

• Transfusion of RhD positive red cells: calculate about 100 IU (20 micrograms) for each 1 mL of RhD positive red cells, and use the intravenous product for large doses, as the blood bank directs.

Fetomaternal haemorrhage testing. After birth, and after sensitising events from about 20 weeks, an acid elution test or flow cytometry measures the volume of foetal cells in the maternal circulation. If it exceeds the amount covered by the usual dose, give extra anti-D in line with the calculated volume.

Timing. Give as soon as possible and within 72 hours of the event. Late doses still give some protection, and many units give a dose up to 10 days after the event, and even up to 28 days, when the earlier window was missed. Verify with local practice.

Route and administration. Deep intramuscular into the deltoid (not the buttock, which may reduce absorption), with the intravenous product used when the dose is large, when the patient has thrombocytopenia, or when the manufacturer states. Pregnant women need no change in dose for weight. Check identity of the patient and product and the RhD type before administration.

Monitoring. Observe for 15 to 20 minutes after the injection. Record the dose, batch, route and date in the patient's record, and tell the woman that passive anti-D may be detected on future screening.

Special groups.

• Breastfeeding: acceptable, with no change in the dose.

• Renal and liver impairment: no adjustment.

• Neonates: not given to the baby.

• Children and girls: weight does not alter the usual minimum dose.

Adverse effects. Pain at the injection site, low grade fever, headache, malaise and rash. Allergic reactions and anaphylaxis are rare. Intravascular haemolysis is a risk when high dose intravenous anti-D is used in RhD positive patients with immune thrombocytopenia, which is a different use and not part of prophylaxis.

Transmission risk. Viral safety depends on donor screening and manufacture, and the risk is very low with licensed products.

Failure of prophylaxis. Causes include a missed or late dose, a large fetomaternal haemorrhage that exceeded the dose, wrong group testing, or sensitisation before the dose. Test for anti-D in the next pregnancy.

Follow up. In the next pregnancy, measure antibody screening and titre early. Passive anti-D from the 28 week dose may be seen in the late antenatal screen and is expected. Active anti-D with a rising titre needs foetal monitoring.

Referral and escalation. Obstetrician and foetal medicine specialist for established anti-D and for large fetomaternal haemorrhage, and haematology and the blood bank when RhD positive blood is given to an RhD negative woman of childbearing potential.