Titers of non-D antibodies and managing pregnancy

[Kip Kuttner]

There are guidelines for docs to use in order to manage pregnancies when anti-D is identified in the mom and titers a known. I have read (somewhere) that the significance of doing titers for non-D antibodies is not known. Does anyone have a differing opinion? For example if anti-S or anti-Wra is identified in a mom to be, would following serial titers provide useful information? Another way of asking the question is "If the titer of a non-D antibody goes up one, two or three-fold, is it significant?

Thanks in advance for the feed-back.

[Malcolm Needs ☆]

Hi Kip,

At the top of the page, you will see a tab marked Library. If you click on this, and then click on BloodBankTalk Library, you will see a list. If you go down this list to the bit that has the British Union Flag (sometimes, wrongly, called the Union Jack), you will see a bit called BCSH Guidelines. If you click on that, you will find a Guideline specifically devoted to testing during pregnancy, and this includes antibodies other than anti-D, anti-c or anti-K.

Although, of course, these Guidelines only apply to the UK, I would be very surprised if there are any significant differences throughout the world (except for the fact that we measure anti-D and anti-c in International Units per mL).

A couple of things that I would say is that titration is a test that is poorly carried out in many places. If you give ten people the same plasma from a single source, taken at the same time, the range of titres that you will get can be immense. This is one of the reasons why it was thought that there was little corrolation between titre and severity of HDFN, particularly in the case of anti-K. Things in the UK are now (slowly) getting better, since there is now a titration exercise included in our National External Quality Assurance Scheme, but are still not great.

The other thing is that you are wise to look at the literature, to see which antibodies are likely to cause HDFN, and which are not. For example, is the antibody usually IgM, IgG or a mixture, are the antigens well developed in utero, does the antibody cross the placenta, or is it adsorbed onto the apical surface, the father may not carry the gene encoding the antigen, etc?

In my opinion, I would overly worry about an anti-S, as this specificity rarely causes severe HDFN, and, of course, anti-Wra will only cause HDFN if the father has the DI3 gene and passes tis on to the baby.

I hope that is of some help, but I'm sure others could (and will) put it better!

:handshake:handshake:handshake:handshake:handshake

[David Saikin]

I titer abs which have clinical significance and are IgG . . . Fy, Jk, Ss, K, . . . your OB staff and Med Dir should provide guidance. And speaking of titers, I totally disagree with the AABB/CAP method which is actually a 1:3 initial dilution, ie, 1 volume of cells and 2 volumes of plasma/serum. But that is besides the point.

[Kip Kuttner]

Thanks for the replies. Yes, we would do titers on abs that have shown to be clinically significant. I would hope that the same lab would receive samples for further titer so the method for getting the titer would remain consistent. A rise in titer suggests increasing sensitization. How much of a rise is cause for concern may debatable. For Rh, the critical titer is 16 or 32 depending on the facility (and I hope the actual titer procedure. Would others agree that a difference of two dilutions regardless of the antibody involved, indicates on-going sensitization?

Malcom, I do not know if you are the site expert. However I am having difficulty downloading the BCSH guidelines. I get an error message "0.4 of 179KB - Operation could not be completed. Connection reset by peer" could there be an FTP server that is feeling ill?

Thanks to both David an Malcom

[Malcolm Needs ☆]

Sorry Kip, but I am, by far and away, the site IT idiot!!!!!!!!!!!!

The only think I can suggest is that you put "BSCH Guidelines" into your particular search engine, then go for the Transfusion Guidelines, and look for the one on testing during pregnancy. Sorry I can't be more helpful than that, but I am useless with computers.

[Kip Kuttner]

Silly me... I can do the net search.

I appreciate your help.

[rravkin@aol.com]

Kip,

I think that it is important to keep in mind that titer test results are utilized in conjunction with other findings to determine fetal health and developement. This is why they are performed and the importance of the titer in of itself is not messurable without the other data.

[GilTphoto]

At our hospital, we never get workups on mothers during pregnancy, and only see them when they come in to deliver.

A mother with an anti-D (titer=256) and anti-C (titer=128) delivered a baby who was positive for both antigens, but the bilirubin never got higher than 8.

Bilirubin was 3 at birth, 5 on day one, 8 on day two, then started dropping on day 3. The baby was discharged.

In the 8 years I have worked here, we have had many mothers with significant antibodies, but not one required anymore intervention other than time under the bili light.

So it doesn't really seem that you can correlate titer with outcome of the baby.

[Kip Kuttner]

GilTphoto I think what you are seeing is most consistent with reality. However the OBs should be following their patients using doppler ultrasound when they know the patient is a high risk pregnancy. I am working on the best advice to provide the OBs for follow-up based on the lab work we do when a potentially clinically significant Ab is detected during pregnancy. I can tell them to follow with serial titers, and that is easy for anti-D and even anti-K because there are published cut-offs but as you have illustrated above, titers are not always predictive even for well characterized antibodies.

And... as was mentioned above one titer is not often comparable to another.