Mother's Immune System Destroys Baby's Red Cells.

Many of us have heard of blood group ABO and whether we are positive or negative for an antigen which is part of the Rh blood group system. I am A positive for example.

These are very clinically significant blood groups but did you know that there are a multitude of other blood group systems and antigens most of which you will never have heard of. They are however very important in blood transfusions and pregnancy.

In pregnancy, an investigation performed by Blood Transfusion laboratories is to identify whether a mother's immune system has been sensitised and created antibodies against one of these blood group antigens on their baby's red blood cells. If this is the case the antibody level needs to be monitored and assessment made regarding how much damage it could cause to the baby and how to manage this.

I haven’t seen a blood film like this on a neonate for a long time, but here is one that presented recently on my weekend shift. Haemolytic Disease of the Fetus or Newborn or HDFN for short.

The only clinical details I received were jaundiced since birth and hence the reason for my decision to make a blood film.

In a normal neonatal film you would expect to see features of the the organs being immature such as occasional echinocytes (spikey red cells  reflecting kidneys), Howell-jolly bodies (a bit of DNA left in the red cell, suggesting an immature spleen), target cells (red cells that look like ..well  a target...reflecting liver immaturity). The red cells are far bigger than an adults and occasional fragments, polychromasia and nucleated red cells are normal. Very occasional spherocytes may also be seen.

Look at this film however, marked spherocytosis (the very dense dark damaged red cells), increased polychromasia ( purple staining young red cells) and increased nucleated red cells (very immature red cells normally seen in the bone marrow). This is not in any way normal for a neonate and my immediate thought was haemolysis. 

So the key word here from a morphological perspective is  'marked' as opposed to  occasional. Neonatal films can be tricky but it is not normal to have 'marked' numbers of anything. 

It worth noting that neonates do not always present in the same way as adults morphologically with haemolysis, and if a blood film shows a dominate poikilocyte or bizarre shaped red cells it is worth considering.

It is also good to remember that premature babies will often have an increase in red cell fragments and morphological signs that their organs are more immature.

Looking at the blood transfusion records the mother had an anti-c antibody. This is likely to have developed during a previous pregnancy. The baby here had the c antigen on it’s red cells and the mother’s immune system was therefore sensitised and primed to destroy the foreign antigen. This in effect means the mothers immune system was destroying the babies red cells! The DAT was strongly positive which supports this.

This rapid destruction of red blood cells can cause an enlargement of the baby’s liver and spleen which quickly try and compensate by making more red blood cells. In severe cases the baby cannot cope with anaemia and heart failure occurs before birth.

After birth build up of bilirubin can lead to liver enlargement and brain damage. The billribun here was very raised at 289 umol/L which required phototherapy to try and clear it.

I’ve been reading the following guidelines:

Article title:	Blood Grouping and Antibody Testing in Pregnancy | British Society for Haematology
Website title:	B-s-h.org.uk
URL:	https://b-s-h.org.uk/guidelines/guidelines/blood-grouping-and-antibody-testing-in-pregnancy/

 

Anti-D, anti-c and anti-K are the antibodies most often implicated in destroying the babies red cells severely enough to need antenatal intervention.

Clinically significant red cell antibodies should have their concentration measured throughout pregnancy, in order to guide the management and invervention in pregnancy before the antibody causes harm to the baby.

The guidelines suggest that Anti-D and anti-c are the only antibodies currently quantified, whereas the other clinically significant antibodies are titrated.

The mother in this instance initially had the anti-c antibody at a very low level of 0.2 IU/ml. Three weeks later this had only slightly increased to 0.5 IU/ml.  Just under a month later however the antibody level had risen to 10.6 IU/ml.

The table below taken from the BCSH guidelines indicates that this level would give a moderate risk of haemolytic Disease of the Fetus or Newborn.

The guidelines indicate that before 28 weeks anti-D and anti-c should be serologically tested every 4 weeks, then every 2 weeks after 28 weeks until delivery.

An interesting case and as I said, one I haven't seen morphologically for some time. A number of laboratory disciplines were involved in this, demonstrating the importance of Pathology in every diagnosis.