31.     In the Prophylaxis of Rhesus Disease.  

(See also MCQ Paper 9, question 18.)

The origin of prophylaxis was the realisation that women who would automatically reject their babies’ blood on the ABO system were less likely to develop Rhesus antibodies. 

For example, a woman who has blood group O and delivers a baby with blood group B, is unlikely to develop Rhesus antibodies. 

Blood group O comes with naturally occurring anti-B antibodies.

These natural anti-B antibodies destroy the fetal cells which have got into the maternal circulation before they can evoke an immune response. 

It was realised that anti-D could do the same job. 

When I was a lad, anti-D was in very short supply.

ABO incompatibility between mother and baby was used to define which patients should have anti-D.

Fortunately this no longer has to apply.

Routine prophylaxis after delivery was introduced in 1969. 

Deaths from haemolytic disease of the newborn attributable to RhD have fallen:

    from 46/100,000 births before 1969,

    to 1.6/100,000 in 1990.

The amount of fetal blood transfused to the mother may exceed the neutralising capacity of the administered anti-D.

So, the Kleihauer test  (see MCQ 4, question 25) should be done to quantify the bleed.

Recommended doses of anti-D when feto-maternal transfusion may have occurred:

    e.g. miscarriage,

    ectopic pregnancy,

    trauma to the abdomen,

    amniocentesis,

    external version,

    manual removal of placenta etc.

    are as follows:

Whether anti-D should be given in early pregnancy has been a matter of some debate. 

The majority of sensitisations occur after 28 weeks and we do not know the gestation below which sensitisation is impossible. 

However, expert opinion is that anti-D is not required for threatened or complete miscarriage under 12 weeks.

The reasoning is that the total amount of blood in the fetus and placenta is so small that sensitisation is extremely unlikely. 

If instrumentation of the uterus is performed, anti-D should still be given. 

The main practical problem is that the gestation of the individual pregnancy is often not known for certain. 

If in doubt, give anti-D.

Hughes et al looked at women giving birth to babies with haemolytic disease due to Rh D between 1985 and 1990.

The population came from the SE of Scotland and the investigators wanted to know how they had become sensitised.

Some had been sensitised before prophylaxis became routine.

Some had been sensitised due failure to follow guidelines for prophylaxis using anti-D.

But the biggest group had been sensitised late on in apparently normal pregnancies.

They concluded that this was "due to failure of the current guidelines to provide adequate protection".

This gave impetus to providing routine antenatal prophylaxis.

Ante-natal prophylaxis has been recommended by NICE since 2002.

It is thought that feto–maternal bleeds without obvious cause or symptoms are a major source of sensitisation.

Most hospitals are excellent at giving anti-D at other times of risk:

    delivery,

    ante-partum haemorrhage,

    amniocentesis etc.

So it is not surprising that this latent sources of sensitisation is such a big proportion of the problem.

To deal with this, you have to give all Rhesus negative mothers anti-D in the third trimester to cover unrecognised feto-maternal bleeds.

Except the obvious exclusions:

    those with antibodies,

    those with proven homozygous Rh negative husbands,

    those planning sterilisation etc.

The practical problems are availability of anti-D and cost, but it should now be routine practice. 

Work is being done on manufactured monoclonal anti-D.

This should resolve the problem of availability and the theoretical risk of infection such as CJD. 

No case of maternal infection has been attributed to anti-D.

But it is currently being obtained from the USA to deal with the theoretical risk from UK sourced supplies. 

Interestingly, there has been a lot of research looking for fetal DNA in maternal blood. 

This has reached the point of practicality. (See MCQ12, question 19).

It is likely that in the next few years all Rh negative mothers will have their baby's Rhesus group checked in early pregnancy this way. 

If the baby is Rhesus negative, the mother will not need prophylactic anti-D. 

Similarly, the mother with anti-D antibodies will be able to be checked.

She will be able to see if her baby is Rhesus positive and liable to Rhesus induced haemolytic disease.

Clever stuff!

I don’t think you would really be expected to know that 25% of failures to provide prophylaxis occur in cases of miscarriage.

I included it as it is a salutary reminder.

It is recommended that anti-D be given within 72 hours of the potentially sensitising event.

But it should not be withheld at 72 hours as it may still have some effect up to 10 days.