Recommendation grades (A-C) and levels of evidence (Ia-IV) are defined at the end of the "Major Recommendations" field.
Administration of Anti-D Immunoglobulin
- Documentation accompanying the injection must include a report containing the following details:
- Identity of the patient to include surname, forename, date of birth and a unique ID number with the date when the injection is to be given. (Level IIa, Grade B).
- Identity and address of the general practice (GP) surgery/antenatal clinic administering the injection. (Level IIa, Grade B).
Details of the injection will include batch number and strength of dose and route of administration.
- The details of the administration of anti-D must be recorded in the antenatal record. It is also important that these details are centrally recorded in the hospital blood bank computer so that this information is readily available should pre-transfusion testing be required.
Prevention of Antibody Formation
- If the pregnancy is non-viable and no sample can be obtained from the baby, prophylactic anti-D should be administered to the woman, if she is D-negative. (Level IV, Grade C).
- Following sensitising events anti-D should be injected as soon as possible and certainly within 72 hours of the event. However if this deadline cannot be met due to exceptional circumstances, some protection may be offered up to 10 days after the sensitising event (Lee et al., 1999; Royal College of Obstetricians and Gynaecologists [RCOG], 2002). (Level III Grade B).
- It is essential to assess the volume of feto maternal haemorrhage (FMH) to calculate the appropriate anti-D dosage for administration. (Level IIb, Grade B).
Management of a Routine Prophylaxis Scheme
- The routine antenatal anti-D prophylaxis (RAADP) scheme should be regarded as supplementary to any anti-D administered for the following sensitising episodes (RCOG, 2002). (Level IIb Grade B):
Amniocentesis
Cordocentesis
Other in-utero therapeutic intervention/surgery (e.g., intrauterine transfusion, shunting)
Ante partum haemorrhage (APH)
Chorionic villus sampling
Ectopic pregnancy
External cephalic version
Fall/abdominal trauma
Intrauterine death
Miscarriage
Termination of pregnancy
- It is important that the 28-week antibody screening sample is taken prior to the first routine prophylactic injection being given. This forms the second screen required in pregnancy in the National Guideline Clearinghouse (NGC) summary of the British Committee for Standards in Haematology (BCSH) Guidelines for Blood Grouping and Red Cell Antibody Testing in Pregnancy. (Gooch et al., 2006) (Level III, Grade B).
Pretransfusion Antibody Screening
- The specificity of anti-D detected post-injection should be confirmed using a panel of D negative reagent cells. This test should also be used to establish the presence or absence of any other clinically significant antibodies, especially in transfused patients. See the NGC summary of the BCSH Guidelines for Blood Grouping and Red Cell Antibody Testing in Pregnancy. (Gooch et al., 2006) (Grade B).
- If there is a record of anti-D injection within the past eight weeks and the level is below 1 international unit per milliliter (iu/mL) a further sample should be tested at 28 weeks and prophylaxis should continue. If there is no record of anti-D injection the antibody should be monitored as for immune anti-D i.e., at four weekly intervals to 28 weeks and at fortnightly intervals thereafter. If the anti-D level is falling, it is probably passive whereas if it is steady or rising it is probably immune. Prophylactic anti-D should continue in either case unless it is established that the anti-D is immune. (Gooch et al., 2006) (Level IIb, Grade B).
Prevention of Anti-D Formation in the Event of Recurrent Uterine Bleeding in D- Negative Women During Pregnancy
Recurrent Uterine Bleeding Before 12 Weeks Gestation
Anti-D immunoglobulin is not necessary in women with threatened miscarriage with a viable fetus where bleeding completely stops before 12 weeks gestation. However, it may be prudent to administer 250 iu anti-D Immunoglobulin where bleeding is heavy or repeated or where there is associated abdominal pain, particularly if these events occur as gestation approaches 12 weeks (Level IV, Grade C recommendation). The period of gestation should be confirmed by ultrasound.
Recurrent Uterine Bleeding Between 12 and 20 Weeks Gestation
D-negative women with recurrent PV bleeding between 12 and 20 weeks gestation should be given 250 iu anti-D immunoglobulin at a minimum of 6 weekly intervals (Level IV, Grade C).
Recurrent Uterine Bleeding after 20 Weeks Gestation
Anti-D immunoglobulin 500 iu should be given at a minimum of 6 weekly intervals. Estimation of FMH by acid elution technique should be carried out at 2 weekly intervals. If the 2 weekly FMH is positive, additional dose of anti-D immunoglobulin (500 iu minimum, more if FMH exceeds 4 mLs) should be offered regardless of the presence or absence of passive anti-D in maternal plasma, and FMH should be retested after 72 hours (Level IV, Grade C).
Management of Transfusion of D-Positive Blood Components
D Positive Platelet Transfusions
Whenever possible, D negative platelets should be transfused to D negative pre-menopausal women who need a platelet transfusion. Occasionally, if the appropriate product is not available or would cause unacceptable delay, it may be necessary to transfuse D positive platelets. In these circumstances, prophylaxis against possible Rh alloimmunisation by red cells contaminating the platelet product should be given (Menitove, 2002).
A dose of 250 iu anti-D immunoglobulin should be sufficient to cover up to five adult therapeutic doses of D positive platelets given within a 6 week period (BCSH, 2003) (Grade B). In severely thrombocytopenic patients with platelet counts of less than 30 x 109/L, anti-D should be given subcutaneously to avoid the risk of haematoma following intramusculary (i.m.) injection. It is not necessary to administer anti-D immunoglobulin to D-negative females without childbearing potential, or males who receive D positive platelets (BCSH, 2003; Menitove, 2002).
Inadvertent Transfusion of D Positive Blood to D Negative Pre-Menopausal Females
When less than 15 mL have been transfused, the appropriate dose of anti-D immunoglobulin should be given. When more than 15 mL have been transfused, it is preferable to use the larger anti-D immunoglobulin i.m. preparation (2500 iu). The dose should be calculated on the basis that 500 iu of anti-D will suppress sensitisation by 4 mL of D positive red cells (RCOG, 2002).
When two units or more of D-positive blood have been transfused, a red cell exchange transfusion should be considered to reduce the load of D positive red cells in circulation and the dose of anti-D immunoglobulin required to suppress immunisation. In this situation, the patient should be counselled regarding the implications of both non-intervention (for future pregnancies) and of treatment, including any hazards from receiving donated blood, the exchange procedure itself and of larger doses of anti-D including intravenous anti-D (RCOG, 2002).
A single blood-volume red cell exchange transfusion will achieve a 65 to 70% reduction in D-positive red cells; a double volume exchange will achieve an 85 to 90% reduction. Shortly after the exchange transfusion, the residual volume of D-positive red cells should be estimated using flow cytometry. Intravenous anti-D Immunoglobulin is the preparation of choice, achieving adequate plasma levels immediately and being more effective microgram for microgram at clearing red cells. The dose to be administered should assume that 600 iu of anti-D i.v. will suppress immunisation by 10 mL fetal red cells. Intramuscular preparations of anti-D immunoglobulin must not be given intravenously. An appropriate combined dose of i.v. and i.m. anti-D should be determined in discussion with a specialist in Transfusion Medicine. Follow-up tests for D positive red cells should be undertaken every 48 hours and further anti-D given until there are no detectable D positive red cells in circulation.
Free anti-D in mother's serum does not necessarily reflect adequate prophylaxis and anti-D immunoglobulin treatment should be continued until D positive red cells are no longer detectable (RCOG, 2002).
Passive anti-D given in large doses may be detectable for up to 6 months or longer, and tests for immune anti-D may not be conclusive for several months.
Table: Recommendations for Antenatal and Postnatal Tests and the Prevention of Sensitisation
| Gestation |
Summary of Tests and Treatment |
| <12 weeks |
No action for uncomplicated miscarriage or painless vaginal bleeding.
In all other cases check ABO and D type to confirm D negativity. Confirm absence of anti-D.
Issue and administer 250 iu anti-D, intramuscularly (i.m.)
|
12 weeks
|
20 weeks
|
For all potentially sensitising episodes ABO and D type to confirm D negativity. Confirm absence of immune anti-D.
Issue and administer 250 iu anti-D, i.m.
|
| |
|
| 20 weeks |
For all potentially sensitising episodes ABO and D type to confirm D negativity. Confirm absence of immune anti-D.
Assess FMH.
Issue and administer at least 500 iu anti-D, i.m., depending on the size of FMH.
|
| |
|
| 28 weeks |
First RAADP
Issue and administer at least 500 iu prophylactic anti-D. The routine sample for blood group and antibody screen as required by BCSH Guidelines (see the NGC summary of the BCSH Guidelines for Blood Grouping and Red Cell Antibody Testing in Pregnancy) (Gooch et al., 2006) must be taken prior to this injection.
|
| |
|
| 34 weeks |
Second RAADP
Issue and administer at least 500 iu anti-D.
|
| |
|
| BIRTH |
TESTS ON BABY – Establish ABO and D type.
MATERNAL TESTS – Check ABO and D type.
Assess FMH if baby is D positive.
Issue and administer at least 500 iu anti-D to the mother if baby is D positive. More anti-D may be required depending upon the size of any FMH.
|
Definitions:
Level of Evidence
Ia Evidence obtained from meta-analysis of randomised controlled trials
Ib Evidence obtained from at least one randomised controlled trial
IIa Evidence obtained from at least one well-designed controlled study without randomization
IIb Evidence obtained from at least one other well-designed quasi-experimental study
III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case–control studies
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
Grade of Recommendation
Grade A (evidence levels Ia, Ib) Requires at least one randomised controlled trial as part of the body of the literature of overall good quality and consistency addressing the specific recommendation
Grade B (evidence levels IIa, IIb, III) Requires availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendation
Grade C (evidence level IV) Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates absence of directly applicable studies of good quality
