Rhogam crossing the placenta

[Mary]

The other day, we had an A Negative mom deliver who had received prenatal Rhogam 2 months ago. It was still circulating because we had a type and screen on her and the anti-D was still in her plasma (assuming it was the Rhogam).

On testing the cord blood, the baby was A Positive with a positive direct coombs. Although it is not our ordinary procedure, an eluate was performed on the cord which was identified as anti-D.

Any thoughts?

[BSIPHERD]

We see this occasionally. When we get a weakly pos DAT on an Rh Pos baby with an Rh Neg Mom who has received RhIG recently, we just report it is probably due to RhIG (or if there is also an ABO incompatibility, we report it may be due to one or the other). If both are true, our comment is "The baby has serologic evidence of ABO HDN. This is shown by a positive DAT and ABO incompatibility between the mother's plasma and the baby's cells. The baby's positive DAT could also be secondary to the administration of antepartum Rh Immune Globulin to the mother. This would not be expected to be clinically significant."

[janet]

A weak DAT could be due to the Rh immune globulin but if it was any more than weak I might suspect the mother made an allo anti-D. We had 2 women in 2006 that were given the usual prenatal care (ab screen at the beginning of pregnancy, ab screen and Rh immune globulin at 28 weeks, both ab screens were negative and patient did not report any bleeds) At delivery both presented with what we thought may be a passive anti-D; until the baby was born with a 3+ DAT. Both women received Rh Immune Globulin again since we couldn't prove passive or allo D at that time. 6 months later they still have an Anti-D. That rare chance Rh immune globulin doesn't work!?!

[rcurrie]

For extra peace of mind you could do a titer. Anti-D due to RHIG usually doesn't titer (titer = 0). We have also had a patient who received prenatal RHIG but still developed an anti-D. Her titer was 64 at birth. There was no apparent HDN, though, so the antibody must have developed late in the game.

BC

[jhaig]

We wouldn't rule out the possibility of HDN in a case like this because of the Rh incompatibility and the positive DAT. I've only seen this happen once before and in that case there was no clinical evidence of HDN (hemolysis, etc.) so we sent the final report out with a comment stating that the infant's anti-D is most likely due to passive anti-D from the mother's Rhogam injection and that due to the lack of clinical symptoms of HDN that the anti-D is most likely clinically insignificant.

It is possible for the anti-D to be detected for up to 24 weeks after administration in the mother, but I'm not sure whether that would apply to the infant as well.

Check the AABB Technical Manual 15th ed. pg 548 for more info on Rhogam and antepartum administration.

[Lcsmrz]

I vaguely remember -- sorry, I vaguely remember just about everything nowadays -- that the RhIg contains the immunoglobulin classes that can be transported across the placenta. We see that every once in a while, too, and assume passive antibody until we can easily test otherwise.

[rcurrie]

Here's the way it works at most of my hospital's 30+ clinics:

Nurse: Okay, Mary, this is your RHIG shot. Now go on down to the lab and have your prenatal lab work drawn.

I don't even bother trying to explain it any more.

BC

[Malcolm Needs ☆]

Since the introduction of routine antenatal anti-D prophylaxis in the UK (RAADP), as sanctioned by the National Institute for Health and Clinical Excellence (formally the National Institute for Clinical Excellence or NICE - sometimes known as the National Institute for Curbing Expenditure [not by me, of course!]), we see this all the time.

It is clinically benign.

:):)

[DebBB]

We often find Anti-D (presumed passive) when doing elutions for ABO incompatibility in Rh neg mums with Rh pos babes.

[GilTphoto]

We have also had this happen within the past year. The anti-D was titered and was 8, which is 1 tube higher than quoted in Technical Manual (4 or less) for the usual reactivity of passive RhIG. Because this patient received 2 shots of ante-partum RhIG due to a vaginal bleed during preg, we took the safer route. We assumed it was passive, gave her a postpartum shot, and told the doctor of the possibility of immune D, and to recheck her antibody status after 6 months.

The baby's Bilirubin rose slightly, but dropped after 4 days.

[L106]

The baby's Bilirubin rose slightly, but dropped after 4 days.

And, of course, that slight rise in the baby's bilirubin may not have had anything to do with the Rhogam.

[Malcolm Needs ☆]

From the number of studies performed before routine antenatal anti-D immunoglobulin prophylaxis was introduced in the UK Donna, I would be absolutely amazed if it was the Rhogam had caused the rise in the baby's bilirubin.

:eek:

[Annadele]

Out of curiosity:

What exactly does "passive" mean in the case of Rhogam? I know that RhIg is made from human plasma containing anti-D (so I'm assuming that it's the very same IgG1 that when naturally produced can cross the placenta and cause HDN) but is it manipulated in some way to prevent it from crossing over the placenta and causing significant hemorrhage or is any resulting hemolysis from crossing over just insignificant because of the small dose issued? I had read somewhere that occasionally it can even cause a positive DAT in the neonate (without other evidence of hemolysis) so I'd lean toward the latter but I saw a reference to a study elsewhere online that suggested that Rhogam avoids causing hemolysis even when given in high doses (I'm not sure if those high doses were warranted due to large fetal-maternal hemorrhage or not).

[ejsommers]

Annadele

I am going to assume that your question is more than the answer I am going to give but here goes:

"Passive" simply means that the Anti-D present in the Mother is due to the injection of RhIG rather than the Mother having a "real" Anti-D due to Rh sensitization.

[Liz]

Exactly, it is when you introduce the antibody to a person rather than have them form it, which would be active formation of the antibody. I too feel that your question is more loaded than this answer. You can elaborate if you wish and we'll give it another shot.

[galvania]

If the baby has other signs of HDN, you should consider the possibility that the mother has an antibody against a 'low frequency' antigen that is present on the father's cells

[Annadele]

Thanks All!

What I'm really wondering is what it is about passive antibodies that makes them clinically innocuous. Is it that the dose is so small that any rbc removal is inconsequential? Do they vary structurally in some way - perhaps so that they coat fetal rbcs in the mother's circulation without actually prompting their removal?

[Malcolm Needs ☆]

No Annadele, there is nothing "magic" about the structure of the anti-D immunoglobulin. It is straightforward IgG (or, at least, most of it is IgG, with a tiny bit of IgM, but that is inconsequencial). You are right in assuming that it is all down to the dose being small enough not to cause problems to the baby, but large enough (in most cases) to prevent the mother making her own immune anti-D.

[Mabel Adams]

And if the mother were actively making the antibody there would be more produced every day to cross the placenta and continue to do damage. The passive antibody is just a one-time (usually) bolus that should dissipate over time.

[L106]

You explained that very clearly, Mabel. Thanks!

Donna