Anti-D prophylaxis and administration during pregnancy and postnatally

Maternal sensitisation to the Rh D antigen resulting in anti-D antibodies remains a significant cause of haemolytic disease of the fetus and Newborn (HDFN). The development of anti-D antibodies occurs as a result of feto-maternal haemorrhage (FMH) between a woman with Rh D negative blood type and a Rh D positive fetus. Sensitisation is permanent and irreversible. However, it can usually be prevented by appropriate administration of prophylactic anti-D immunoglobulin (Ig).

Maternity units and associated transfusion laboratories have a duty of care to deliver anti-D Ig for RAADP (Routine Antenatal Anti-D Prophylaxis) and prophylaxis for PSE’s (Potentially Sensitising Events) to Rh D negative women at the correct dose and the correct time. Within 72 hours of the sensitising event.

The organisation of maternity services should ensure that women are aware that they are eligible for anti-D Ig and that service delivery is matched to this requirement.

Post delivery anti-D prophylaxis is vital to prevent sensitisation and women who are eligible should have anti-D recommended and given within 72 hours of the birth of the baby. A robust plan should be in place for them to receive the anti-D Ig and any additional dose of anti-D Ig as indicated by the result of the Kleihauer test.

Midwife Formulary

Midwives are permitted under the Medicines Act 1968 to administer certain medications during the course of a woman’s pregnancy and in the puerperium. This includes all GSL and P medicines and a selected group of POM medicines. The Midwives Formulary details which of the medicines above may be supplied and administered in NHS Highland without a Doctor’s prescription and gives guidance on supply and administration.

Prescription requirements

The signature is that of the midwife and annotated RM. Names must be signed legibly and printed if required.
For information regarding interactions, cautions and contraindications for the administration of the immunoglobulin refer to most up to date BNF.

Exclusion to midwife exemption

The route of administration for the anti-D immunoglobulin to be given by a registered midwife under their exemption is by intramuscular injection (IM).

In this case the medication MUST be prescribed by a member of medical staff and then can be administered by subcutaneous injection or by intravenous injection.

A. Identification of blood group and antibody screening

A blood sample for blood group (ABO and Rh D) and antibody screen (2 x blue EDTA tubes) should be obtained at the booking or point of contact appointment.

Caution: if a woman books later in the pregnancy, they still require samples for the above. The results will be inputted into the woman’s electronic record. The woman should be informed of her blood group as soon as is practical.

Note: Prophylactic anti-D Ig given to prevent sensitisation is indistinguishable from immune anti-D antibody. If a woman has received any prophylactic anti-D Ig during her pregnancy the date, time, dose and reason (RAADP or PSE) should be stated on the group and screen sample request form. (This information should be available in the anti-D section of the Badger record). This will help with the laboratory interpretation as to whether any anti-D antibody identified is likely to be maternal immune antibody or passive anti-D Ig recently administered to reduce the risk of sensitisation. In some instances this differentiation between immune and passive anti-D may not be immediately possible and the woman would need monitoring over time to distinguish between the two. In certain cases the additional testing would be required (anti D quantitation performed in Glasgow SNBTS lab) and the blood bank in Raigmore has established ways to identify these cases.

B. Women who are Rh D positive

Women, who are Rh D positive and have no red cell antibodies, should have a further blood sample taken for routine antibody screen (1 x blue EDTA tube) at 28 weeks gestation at the same time of routine sampling for full blood count estimation.

Women who are Rh D positive and have red cell antibodies should receive care in line with the Scottish National Guidelines: Scottish-Red-Cell-Antibodies-in-Pregnant-Women-Guidance-Feb-2020-FINAL.pdf (nhs.scot)

C. Women who are Rh D negative

Women who have a Rh D negative blood group and who have not formed anti-D antibodies will be sent a letter and Rh D card from the hospital transfusion laboratory. The midwife should discuss the blood group and anti-D prophylaxis with the woman at the earliest opportunity.

If a woman with Rh D negative blood develops red cell antibodies other than anti-D antibodies at any time during her pregnancy, she should receive care in line with the Scottish National Guidelines: Scottish-Red-Cell-Antibodies-in-Pregnant-Women-Guidance-Feb-2020-FINAL.pdf (nhs.scot)

Rh D negative woman who have red cell antibodies other than anti-D, should be offered anti-D immunoglobulin prophylaxis to prevent formation of anti-D antibodies.

Caution: Rh D negative women who had developed immune anti-D antibodies should not be given anti-D immunoglobulin. If there is any doubt whether the anti-D being detected is immune or prophylactic in nature, this should be discussed with a transfusion specialist for advice on further management and follow up.

D. RhD Variants

Most people are either positive (D Positive) or negative (D Negative) for the D antigen However, a small proportion of people have a variant D antigen. The blood transfusion laboratory will carry out further testing on these individuals to determine the type of D variant.

Clinical Interpretation of D variant Investigations:

• Variants identified as Weak D Types 1, 2 and 3: Considered to be and reported as D Positive. These patients are NOT eligible for prophylactic anti-D.
• All other variants: Considered to be and reported as D negative. These patients ARE eligible for prophylactic anti-D.

These D variants will be recorded in the Woman’s SCI Store record.

E. Anti-D immunoglobulin prophylaxis following a potentially sensitising event during pregnancy

Any woman who experiences a potentially sensitising event (PSE) during pregnancy should be offered prophylactic anti-D immunoglobulin (Ig).

In order to be effective, prophylactic anti-D Ig should be administered as soon as possible and always within 72 hours of a PSE. The Raigmore Hospital Blood Bank performs FMH for the whole of the NHS Highland region Monday- Sunday. If you are concerned that your patient will not receive anti-D within 72 hours of the PSE then please contact the Raigmore Hospital Blood Bank to discuss your patients care with the laboratory and SNBTS Transfusion Consultant.

If it is not possible to administer prophylactic anti-D Ig within 72 hours, it may still be effective when administered within 10 days. (The decision to administer anti-D Ig in this instance should be made by an obstetrician following consultation with a haematologist/transfusion specialist).

Prophylactic anti-D Ig offered following a PSE during pregnancy should be administered regardless of routine antenatal anti-D prophylaxis.

Irrespective of whether anti-D has already been given for PSE:

1. Obtain blood sample for Blood Group and Antibody Screen (1 x blue EDTA tube).
   Do NOT wait for results before administering prophylactic anti-D Ig.
2. Administer (with consent) 1500 units anti-D Ig at 28 to 30 weeks
   (Or administer at least 500 units anti-D Ig at 28 weeks and then administer again at least 500 units anti-D Ig at 34 weeks).
3. If the woman has received 500 units in the 6 weeks leading up to her RAADP anti-D dose at 28 weeks, send a Kleihauer to assess anti-D Ig PRIOR to this appointment and administering RAADP anti-D.
4. Document on electronic patient record (EPR).

<12 weeks gestation

1. Obtain blood sample for Blood Group and Antibody Screen (1 x blue EDTA tube).
   No Kleihauer sample is required.
   • The following information should be included on all PSE BTS request forms:
     • Gestation
     • When and dose of last anti-D administered
     • Type of PSE
     • Date and time of bleeding (if applicable)
     • If bleeding is recurrent (if applicable)
2. Await result of antibody screen, if possible.
   
   • If no anti-D antibodies present, administer (with consent) anti-D prophylaxis at a minimum dose of 250 units Ig* within 72 hours of event to:
     • All Rh D negative women who present with heavy vaginal bleeding and/or severe abdominal pain – if uncertain discuss with Obstetrician
     • Surgical management of miscarriage
     • Ectopic Surgical or Medical management
     • Evacuation of Molar pregnancy
   • *if minimum dose of 250 units Ig is not available, administer 500 or 1500 units Ig as appropriate.
   • This advice adheres to the guidelines from the British Society of Haematology, which differ slightly from the NICE guidelines on Miscarriage and Ectopic pregnancy, with respect to gestation cut off and medical management of ectopic pregnancy. This advice is consistent with the standards followed by the BTS lab.
3. Document on electronic patient record (EPR).

12 to 20 weeks gestation

1. Obtain blood sample for Blood Group and Antibody Screen (1 x blue EDTA tube).
   No Kleihauer sample is required.
   • The following information should be included on all PSE BTS request forms:
     • Gestation
     • When and dose of last anti-D administered
     • Type of PSE
     • Date and time of bleeding (if applicable)
     • If bleeding is recurrent (if applicable)
2. Await result of antibody screen, if possible.
   
   • If no anti-D antibodies present, administer (with consent) anti-D prophylaxis at a minimum dose of 250 units Ig within 72 hours of event.
   • This dose should cover up to 6 weeks for women with recurrent bleeding.
3. Document on electronic patient record (EPR).

20 weeks gestation to term

1. Obtain blood sample for Blood Group and Antibody Screen, and Kleihauer Test (2 x blue EDTA tubes).
   • The following information should be included on all PSE BTS request forms:
     • Gestation
     • When and dose of last anti-D administered
     • Type of PSE
     • Date and time of bleeding (if applicable)
     • If bleeding is recurrent (if applicable)
2. (First episode) Await result of antibody screen if possible.
   1. If no anti-D antibodies present, administer (with consent) anti-D prophylaxis at a dose of 500 units Ig within 72 hours of event.
   2. No need to wait for the Kleihauer result, but if the Kleihauer Test indicates that further anti-D is required, administer further dose of anti-D Ig as advised by BTS.

At Delivery

• Obtain maternal blood sample, within 45 minutes of birth for confirmation of Blood Group, Rh D type, Antibody Screen and Kleihauer Test (2 x blue EDTA tubes).
• Also obtain cord blood sample (1 x blue EDTA tube).

The following information should be included on all delivery forms:

• When and dose of last anti-D administered.
• Add Baby’s CHI to additional notes on the maternal request form.
• Add Maternal CHI to additional notes on the Baby’s request form.

1. Administer (with consent), to previously non-sensitised women, at least 500 units of anti-D within 72 hours of delivery to the woman, if baby is confirmed Rh positive. If Kleihauer Test indicates that further anti-D is required, administer a further dose of anti-D as advised by BTS.
2. Document on electronic patient record (EPR).

A direct anti-globulin test (DAT) on the cord blood sample is not routinely performed since it may be positive in a proportion of cases because of antenatal prophylaxis with anti‐D Ig. However, a DAT should be performed if haemolytic disease of the new-born is suspected or anticipated because of a low cord blood haemoglobin concentration &/or the presence of maternal immune red cell antibodies. A detailed plan for these women will be available in her Electronic Patient Record.

Summary list of potentially sensitising events (PSEs) by gestation and action

Women who are RhD negative, AND RhD antibodies are present, check advice on BTS report following sample. Discuss with medical staff.

Where intra‐operative cell salvage (ICS) is used during Caesarean section in Rh D negative, previously non‐sensitised women:

1. Obtain cord blood within 45 minutes of birth.
2. Obtain a maternal blood sample for confirmation of Blood Group, Rh D type, Antibody Screen and Kleihauer Test (2 x blue EDTA tubes) for estimation of FMH 30 to 45 minutes after reinfusion in case more anti-D Ig is indicated.
3. A minimum dose of 1500 units anti‐D Ig (in place of the normal 500 units Ig) should be administered following the re‐infusion of salvaged red cells.
   It is important that clinicians inform the transfusion laboratory, via the request form if ICS has been used to ensure that correct dose of anti-D Ig is issued.
4. Document on electronic patient record (EPR).

Note: diagnosis of IUD and delivery are 2 separate PSEs.

1. At diagnosis of IUD, obtain maternal blood sample for confirmation of Blood Group, Rh D type, Antibody Screen and Kleihauer Test (2 x blue EDTA tubes).
   • The following information should be included on all PSE BTS request forms:
     • Gestation
     • When and dose of last anti-D administered
     • Type of PSE
     • Date and time of bleeding (if applicable)
     • If bleeding is recurrent (if applicable)
2. Administer (with consent) 500 units Ig as soon as possible after diagnosis of IUD.
   If the Kleihauer test indicates further anti-D is required, administer as advised by BTS.
3. Further anti-D may be required, especially if delivery is more than 72 hours after diagnosis.
4. Repeat a Kleihauer test (2 x blue EDTA tubes) post birth and administer further anti-D as advised by BTS.
5. Document on electronic patient record (EPR).

The SNBTS Consultant should make the Neonatologist Consultant aware of any FMH bleeds determined to be >100mL in order to provide support to neonate.

In cases of large FMH and particularly if FMH is in excess of 100mL a suitable preparation of IV anti-D Ig should be considered. The dose of IV anti-D is 100 unit/mL of fetal red cells.

IM only preparations must NEVER be given intravenously.

This must be administered within a hospital setting and will be organised in discussion between the Consultant Obstetrician and SNBTS Transfusion Medicine Consultant.

Adverse events relating to the requesting and administration of anti-D immunoglobulin (Ig) to women of child-bearing potential are reportable to the Serious Hazards of Transfusion Report (SHOT).

Reporting adverse events on Datix as ‘Blood Transfusion - Anti D Errors’ will automatically send notification to specific members of the NHS Highland Hospital Transfusion Team who will contact the clinical area for further information and report the event to SHOT.

Anti-D clinical reportable events include:

• Omitted or late administration.
• Administered to a D-positive patient Administered to a patient with known immune anti-D.
• Administered erroneously to a D-negative mother of a D-negative baby.
• Administered to the wrong patient, failure of bedside check.
• Failure to perform a Kleihauer following PSE ≥20 weeks and at delivery.
• Handling and storage errors associated with anti-D Ig, including issue of expired anti-D Ig, inappropriately stored anti-D Ig, where batch numbers on the vials do not match with issue paperwork, or inappropriate route of administration.
• Inadequate follow up of fetal cell clearance post sensitising event or post delivery.

If the patient has a history of allergic reaction to Anti-D, then she should be individually counselled by the Consultant Obstetrician and Haematologist Team. Different preparations should be considered. Management should be planned by team of consultant Obstetrician, Haematologist and eventually Anaesthetist.

• BNF
• Grampian Medicines Management Group: Meds Guidelines and Policies
• NICE guideline [NG140] Abortion care. Published: 25 September 2019
• Quereshi et al. British Society for Haematology guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn.
• Scottish National Guidance for Pregnant Women with Red Cell Antibodies (SNBTS, 2013).
• SHOT (Serious hazards of Transfusion)

BNF: British National Formulary
DAT: Direct Antiglobulin Test
EDTA: Ethylenediaminetetraacetic Acid
FMH: Feto-Maternal Haemorrhage
GSL: General Sales List
HDFN: Haemolytic Disease of the Fetus and Newborn
ICS: Intraoperatic Cell Salvage
Ig: Immunoglobulin
IUD: Intra-uterine Death
P: Pharmacy medicine
POM: Prescription Only Medicines
PSE: Potentially Sensitising Event
RAADP: Routine Antenatal Anti-D Prophylaxis
RM: Registered Midwife
EPR: Electronic Patient Record (Badgernet record)