Anti-K in OB patients

[cbaldwin]

I recently read that because anti-K can cause severe HDN it is becoming common practice for girls and women of child-bearing age to be transfused only with K- red cells and, if I understand this correctly, in the Netherlands K negative units are always given to women under 45.

What is the policy at your facility? How frequently is HDN caused by anti-K seen? I would like to hear opinions on this!

[Malcolm Needs ☆]

For some years now in the UK (at least since the 1996 BCSH pre-transfusion testing guidelines), it has been common practice in the UK that no K- female below the age of 60 is transfused with K+k+ or K+k- blood, unless they are exsanguinating, and there is no alternative.

As I said in a different post, it used to be common practice to advise Obstetricians to perform MCA DOppler/ultrasound (or whatever was around before these were available!) to monitor all anti-K pregnancies, although these are less predictive in early, rather than late pregnancy in cases of anti-K, and to consider referral to a Specialist Foetal Medicine Unit, depending upon the results. With the inprovement in the competency of individuals to carry out titrations, culminating in greater precision (if not accuracy) with results, we are less cautious, but still worry about an anti-K with a titre anything around 16 to 32.

Not all high-titre anti-K's seem to cause severe HDNF, whilst others with comparatively low levels sometimes cause extremely severe HDNF. It is not known why. Caine and Mueller-Heubach suggested that this may be due to how the K- lady was sensitised to produce anti-K in the first place (Caine ME, Mueller-Heubach E. Kell sensitization in pregnancy. Am J Obstet Gynecol 1986; 154: 85-90) suggested that, if the anti-K was produced as a result of a transfusion, HDNF tended to be less severe than if it was produced as a result of a previous pregnancy, but Leggat et al disputed these findings (Leggat HM, Gibson JM, Barron SL, Reid MM. Anti-Kell in pregnancy. Br J Obstet Gynecol 1991; 93: 667-673.

In 2005, a paper published by Chiaroni et al showed that that there is an association between HLA-DRB1 polymorphism and the production of anti-K. (Chiaroni J, Dettori I, Ferrera V, Legrand D, Touinssi M, Mercier P, de Micco P, Reviron D. HLA-DRB1 polymorphism is associated with Kell immunisation. Brit J Haematol 2005; 132: 374-378). They showed that the combined frequencies of the two HLA-DRB1 alleles (HLA-DRB1*11 and HLA-DRB1*13) was 83% in K immuniaed patients, when compared with 52% in healthy controls (Pc<0.001). One of my own staff members, who is taking an MSc, is going to do her project on the HLA-DRB1 types of lady's with anti-K in pregnancy, to see if there is an association between this polymorphism and the severity of HDNF with K+ babies.

At one time it was thought that anti-K interfered with foetal erythroiesis (Vaughan JI, Warwick R, Letsky E, Nicolini U, Rodeck CH, Fisk NM. Erythropietic suppression in fetal anemia because of Kell alloimmunization. Am J Obstet Gynecol 1994; 171(1): 247-252, and Vaughan JI, Manning M, Warwick RM, Letsky EA, Murray NA, Roberts IAG. Inhibition of erythroid progenitor cells by anti-Kell antibodies in fetal alloaimmune anemia. 1998; 338: 798-803), because the K/anti-K combination interfered with zinc ion transport across the cell membrane, but Daniels et al (Daniels GL, Hadley AG, Green CA. Fetal anaemia due to anti-K may result from immune destruction of early erythroid progenitors [Abstract]. Transf Med 1999; 9 (Suppl.): 16.) showed this not to be the case.

Hope this helps a bit.

:blahblah::blahblah:

[Deny Morlino]

Educational as always Malcolm! Thanks for the lesson!!

[cbaldwin]

Thank you for this very thorough explanation. The association with HLA-DRB1 polymorphism is interesting--wonder what's behind that and what your staff member will find in her research!

And, I still wonder if there is a growing trend in the US to transfuse K negative units to K negative women of child-bearing age!

[Eagle Eye]

At our facility (very busy OB with lots of high risk patients)...we do not type OB patients for K nor we give K- units.

[cbaldwin]

Aakupaku! Thank you for your feedback!

[L106]

We only have about 1,000 births a year, but we do not type OB patients for the K antigen nor give K Negative donor units. I do not recall ever having a case of HDN at our facility during the last 30 years due to Anti-K.

[cbaldwin]

My source for the information regarding the "growing trend" ("becoming common practice" is the exact wording) is Geoff Daniel's "Human Blood Groups". I wonder if it is a growing trend in Europe, but not in the United States. It is just something I wonder about...

Okay, so here is my next question...It seems that anti-K in OB patients is treated as a more serious issue in the Netherlands and in the UK than in the US. Am I correct about that and is there an explanation?

Sorry, I can't help but wonder about this, and I have no practical knowledge or experience in this matter....my information comes from books.

I am looking forward to whatever instruction is available! Thank you!

[Malcolm Needs ☆]

There is no doubt that anti-K in pregnancy is treated as potentially serious. In the 1994 paper I quoted in the long post above, it was stated that 7% of the cases requiring an IUT involved anti-K.

Now, it has to be remembered that this particular paper was written before our guidelines said that K- blood should be given to K- females under 60 years of age, and that this figure may have dropped since then. However, in a study by the NHSBT, currently underway, of the 39 pregnancies involving anti-K, with a K+ baby, 1 required repeat IUTs (titre 1000), two involved still births (titres 512 and, frighteningly, 32) and one involved an IUD (titre, terrifyingly, 16).

Of the 35 live births, 2 others had to have IUTs, and 27 others had to have delivery or post-delivery intervention (early delivery, "top-up" transfusions, phototherapy or exchange transfusions).

This data is in the raw state at the moment (I probably shouldn't even be quoting it yet), but, as you can see from this, there is a real and present danger from anti-K in pregnancy.

Edited January 10, 2012 by Malcolm Needs

[adiescast]

We have not at this point had a case of HDN due to anti-K. We do not routinely give K negative blood to women of child bearing years.

I wonder if there is a difference in the transfused population between the U.S. sites and the UK and European sites that could account for their seeing a higher incidence of immunization with K in women of child bearing years? Medicine is practiced differently in the regions. Is there some factor they have that we do not have or something we have that they do not? K is historically known to be very immunogenic, second only to D possibly, yet we do not see it enough to warrant a policy like our very stringent D policies.

All speculation, of course...

Edited January 11, 2012 by adiescast
clarification

[YorkshireExile]

We are a large maternity hospital in the UAE and for the last couple of years we routinely give K negative blood to our ladies. On average we have 1-2 cases per year of HDFN caused by anti-K. The last one required numerous top-up transfusions.

[Malcolm Needs ☆]

We have not at this point had a case of HDN due to anti-K. We do not routinely give K negative blood to women of child bearing years.

I wonder if there is a difference in the transfused population between the U.S. sites and the UK and European sites that could account for their seeing a higher incidence of immunization with K in women of child bearing years? Medicine is practiced differently in the regions. Is there some factor they have that we do not have or something we have that they do not? K is historically known to be very immunogenic, second only to D possibly, yet we do not see it enough to warrant a policy like our very stringent D policies.

All speculation, of course...

It may be to do with the ethnic mix of your donors (e.g. K+ is about 9% in Caucasian populations, 2% in Black populations, rare in Oriental populations, 12% in Iranian Jews, as high as 25% in Arabs - figures taken from Reid and Lomas-Francis), the ethnicity of the patients and, of course, the ethnicity of partners.

In addition, of course, most K- mums will never have been transfused.

Therefore, it is a bit of an "accident", if you like, that a K- mum will have been transfused with K+ blood, possibly, has the "right" HLA-DRB1 gene to make anti-K (see one of my posts above), that she "chooses" a K+ male partner, and that the baby inherits the fathers KEL1 gene from him. If the ethnic mix in your area makes this less likely than in other areas, then HDNF due to anti-K will also be less likely.

Edited January 11, 2012 by Malcolm Needs

[webersl]

I would say that most Transfusion Services in the US do not consider K an issue when transfusing women of child bearing potential. (Unless she has anti-K, of course.)

Some transfusion services respect C, E, K (and sometimes Fya) in Sickle Cell Disease patients, who will be frequently transfused, in order to PREVENT the eventual production of these common antibodies - to make it easier to find compatible blood if there should be an emergency later down the road.

[JOANBALONE]

I work in a large hospital system in the midwest USA. I have seen several severe HDFN cases due to anti-K in the last few years. Some physicians are beginning to request K negative blood for females of child bearing potential. Eventually, I think it will be routine to give K negative blood to females of child bearing potential.

JB

[Malcolm Needs ☆]

Well, it's such an easy thing to do that I don't know why it isn't done as a matter of course.

[Rh-fan]

Although the numbers are not as big as in the UK, we see the same kind of HDN as Malcolm stated. We see childeren at 16 weeks pregnacy in need of a transfusion and as Malcolm also stated with different titers (and als the lower titers).

We also do ADCC testing during pregnancy (a test with monocytes to predict the severity of the HDN, expressed in a percentage). Above 50 there is a great change of HDN, this is largely validated for anti D antibodies (1980's). But because of the lower number of anti K pregnacies a good review of those is only made a few years ago and there we see that above 30 almost every (K+) child is in need of IUT.

Peter

[webersl]

Well, it's such an easy thing to do that I don't know why it isn't done as a matter of course.

$$ - I'm just saying.

[Steven Jeff]

It was only last week that I sent a sample from the hospital I work in, to Malcolm’s RCI laboratory on a lady who is 16 weeks pregnant with an anti-K. Malcolm’s laboratory has reported back an anti-K titre of 16000 with a request for repeat samples at 20 weeks, samples from the partner and advice to refer the lady to a specialist fetal/maternal unit. If I remember correctly (telephone report so far) the samples will be sent to the International Blood Group Reference laboratory in Bristol

I suspect we will have little to do with the further management of this patient, because I am sure she will be referred and rightly so.

Steve

:)

[Mabel Adams]

Now they can draw a sample from the mom and determine the actual K type of the baby by DNA testing so that removes some guesswork on whether the baby is K+. We don't test for K for transfused females but we do transfuse them a lot less frequently than we did in the pre-AIDS days. I have been around for some 33000 births and have never seen a case of anti-K HDFN. The babies were always K neg.

I wonder if the number of small hospitals is larger in the US due to our lower population density. It would ask a lot of them to keep anti-K for the occasional young woman being transfused and then if the only 2 O units they had happened to be K+ they would be scrambling. They are all generalists that would have to remember these special rules twice a year.

Very interesting about the HLA type. Both my workplaces have been near Indian reservations and we have had a surprising number of people sharing a surname that made anti-K in each community. This just might be the explanation behind it.

[cbaldwin]

Hi Mabel! What test would we request if we wanted DNA testing on the baby from the mom's sample? And how are the baby's RBCs separated from the mom's RBCs for testing? Catherine

[Rh-fan]

Hi Mabel! What test would we request if we wanted DNA testing on the baby from the mom's sample? And how are the baby's RBCs separated from the mom's RBCs for testing? Catherine

I am not mabel but I think I know it.

There is methode in wich you can isolate DNA from the plasma of the mother. The plasma contains also a percentage of fetal DNA. The mother is lacking the K allel so if you find a K allel in this DNA it must be from the mother. If you do not find the K allel you have to look for other DNA markers to confirm the presence of fetal DNA.

You need a lot of EDTA blood (30ml) and a very specific PCR test for the test. This test is developed for RhD but can now alos be performed for C, c, E, K and HPA1a.

Peter

[Malcolm Needs ☆]

I am not mabel but I think I know it.

There is methode in wich you can isolate DNA from the plasma of the mother. The plasma contains also a percentage of fetal DNA. The mother is lacking the K allel so if you find a K allel in this DNA it must be from the BABY. If you do not find the K allel you have to look for other DNA markers to confirm the presence of fetal DNA.

You need a lot of EDTA blood (30ml) and a very specific PCR test for the test. This test is developed for RhD but can now alos be performed for C, c, E, K and HPA1a.

Peter

Sorry Peter - everything else correct.

Geoff Daniels, who does this for us in the UK does not think the test is that reliable for the KEL1 gene until 20 weeks gestation.

[cbaldwin]

cbaldwin

Hi Mabel! What test would we request if we wanted DNA testing on the baby from the mom's sample? And how are the baby's RBCs separated from the mom's RBCs for testing? Catherine

Oops--RBCs don't have DNA! What company does this test?

[Mabel Adams]

Puget Sound Blood Center in Seattle does it. Probably others too. In CA you could check with Blood Centers of the Pacific.

[Rh-fan]

Sorry Peter - everything else correct. Oops. big mistake (shame)

Geoff Daniels, who does this for us in the UK does not think the test is that reliable for the KEL1 gene until 20 weeks gestation.

We rather do the K1 after 18 weeks but sometimes we try it sooner (before 16 weeks) in strong cases of HZFN because that is the time they can start with IUT.

Peter