Anti D from FFP?

[tbostock]

Has anyone ever seen a patient making anti-D from receiving two units of Rh Pos FFP? Patient is 81 years old, and she is A Neg. She was here in April of 2009, Ab screen neg, and we gave her two units of A Pos FFP. The patient insists she has not been at any other hospital and received any blood products this year other than the plasma in April. She's too old for RhIg. And she's Rh Neg, so WinRho is out of the picture. Hmmm...could this be an IVIG thing?

I saw a patient make an Anti-D from a unit of apheresis platelets once, but never from plasma. Any ideas?

[Malcolm Needs ☆]

I have never seen it myself, but have read about it in the earlier editions of Mollison.

Apparently, there can be red cell membranes in the FFP that have intact RhD antigens. They are insufficient in number to cause primary response, but can be in sufficient numbers to cause a secondary response.

If your patient had already been sensitised to the RhD antigen, either by pregnancy or by a previous transfusion (even many years ago), the anti-D may well have become serologically undetectable in the screen, but the memory cells in her circulation would still be sensitive to a second (or subsequent) immunological challenge by the RhD antigen.

By no means am I saying that this is the case with your patient, but it may be the answer.

:confused:

[David Saikin]

I agree with Malcolm . . . have read about it but never seen it.

[AMcCord]

I read a case study somewhere (maybe Transfusion????) about a young woman with anti-D who had never been pregnant or transfused but had a nice strong anti-D. After investigation of her medical history, they discovered that she had received FFP after a tonsilectomy at age 11. This was the only exposure to 'foreign' RBC antigens they could come up with. The authors noted that it is possible to find RBC stroma in FFP units (they were not talking about pheresis collection) because red cells can sneak by during plasma separation. Since freezing would not destroy the D antigen on the RBC stroma, stimulus could occur. Seems possible but it must be quite rare - or maybe not as rare as we think...has a study been done?

[Malcolm Needs ☆]

I read a case study somewhere (maybe Transfusion????) about a young woman with anti-D who had never been pregnant or transfused but had a nice strong anti-D. After investigation of her medical history, they discovered that she had received FFP after a tonsilectomy at age 11. This was the only exposure to 'foreign' RBC antigens they could come up with. The authors noted that it is possible to find RBC stroma in FFP units (they were not talking about pheresis collection) because red cells can sneak by during plasma separation. Since freezing would not destroy the D antigen on the RBC stroma, stimulus could occur. Seems possible but it must be quite rare - or maybe not as rare as we think...has a study been done?

How long ago was this? The reason I ask is because the seperation of plasma from red cells is much better controlled now than back in the days of yore, when quite a substancial amount of red cells could creep into the FFP.

[AMcCord]

The case study was probably within the last 5- ish years and the young woman in question was in her late teens so the FFP in question could have been separated with a casual disregard, shall we say, to having a few red cells sneaking into the product. I remember my student rotation at the blood center - not saying how many years ago - and watching FFP processed. Some of those units were definitely pinkish. You don't see that anymore.

I have seen a patient make anti-D after a unit of single-donor platelets, leukoreduced pheresis collection. There can't be many RBCs in those. That patient was into antibodies in a big way - the anti-D was her 4th, so she was obviously a super responder.

Edited October 2, 2009 by AMcCord

[Malcolm Needs ☆]

Thanks for that.

[TimOz]

Here are 2 referrences from Mollison:

Adverse effect of plasma exchange on anti-D production in rhesus immunisation owing to removal of inhibitory factors.

G R Barclay, M A Greiss, S J Urbaniak

Br Med J 1980;280:1569-1571 (28 June), doi:10.1136/bmj.280.6231.1569

Rhesus alloimmunization following intensive plasma exchange.

McBride JA, O'Hoski P, Barnes CC, Spiak C, Blajchman MA.

Transfusion. 1983 Jul-Aug;23(4):352-4.

[David Saikin]

I have seen the spectrum of Rh antibodies (D-C-E) from a neg patient getting Rh+ plts. The guy was one of those "super-responders" - he made another antibody every other day for about a week.

[adiescast]

Here are 2 referrences from Mollison:

Adverse effect of plasma exchange on anti-D production in rhesus immunisation owing to removal of inhibitory factors.

G R Barclay, M A Greiss, S J Urbaniak

Br Med J 1980;280:1569-1571 (28 June), doi:10.1136/bmj.280.6231.1569

Rhesus alloimmunization following intensive plasma exchange.

McBride JA, O'Hoski P, Barnes CC, Spiak C, Blajchman MA.

Transfusion. 1983 Jul-Aug;23(4):352-4.

Thanks Tim. These were interesting articles.

[heathervaught]

I don't know that plasma separation has necessarily changed in all blood center settings over the last 20 years. At my facility, we use spring-loaded manual expressors, and apply a hemostat to tubing when all of the plasma has been expressed. We perform a visual inspection of the plasma to ensure that it does not appear to be contaminated with RBCs, but that does not guarantee that it is absolutely free of RBCs (we haven't had our eyes calibrated recently ). Some blood centers are using automated expressors like the Compomat, but I would suggest that those blood centers are certainly in the minority.

[Malcolm Needs ☆]

I don't know that plasma separation has necessarily changed in all blood center settings over the last 20 years. At my facility, we use spring-loaded manual expressors, and apply a hemostat to tubing when all of the plasma has been expressed. We perform a visual inspection of the plasma to ensure that it does not appear to be contaminated with RBCs, but that does not guarantee that it is absolutely free of RBCs (we haven't had our eyes calibrated recently ). Some blood centers are using automated expressors like the Compomat, but I would suggest that those blood centers are certainly in the minority.

These sorts of automated expressors (I'm not sure of the actual type) are used universally within the NHSBT.

[John C. Staley]

If I were so bold as to venture a guess I would tend to agree with Malcolm's earlier post and consider this a likely secondary response. Her anti-D from many years ago had dropped below detectable levels and there was enough antigen in the FFP to produce a response. I know of at least 2 "older" ladies who's anit-D had dropped below detection.

Malcolm, I hope this agreeing with you is not becoming a habit!!!

[Malcolm Needs ☆]

It doesn't bother me in the least John - but it might get others talking!!!!!!!!!!!!!!!!!!!!!!!!!

[BSIPHERD]

I've seen a couple of cases in my blood bank career that we attributed to plasma because we were able to verify that the red cell units transfused were Rh negative (D and weak D).

However, with the recent discussion of Rh Del, I think there is another possible explanation that would need to be explored. If the red cell unit was a Del (types as Rh negative and weak D negative, will adsorb Anti-D and it can be eluted, and can stimulate production of Anti-D in Rh negative patients), that could also be an explanation. I think this would have to be ruled out before we could assume that the FFP from an Rh positive person had stimulated the Ant-D.

[Malcolm Needs ☆]

I've seen a couple of cases in my blood bank career that we attributed to plasma because we were able to verify that the red cell units transfused were Rh negative (D and weak D).

However, with the recent discussion of Rh Del, I think there is another possible explanation that would need to be explored. If the red cell unit was a Del (types as Rh negative and weak D negative, will adsorb Anti-D and it can be eluted, and can stimulate production of Anti-D in Rh negative patients), that could also be an explanation. I think this would have to be ruled out before we could assume that the FFP from an Rh positive person had stimulated the Ant-D.

True, this explanation cannot be ruled out without proof, but even in the Far East where Del is more common, Del is extremely rare, and the stimulation of anti-D by Del is even rarer.

[TimOz]

Here is a more recent reference with anstract (and an Australian one from my friends in the West):

Immunohematology. 2005;21(4):149-51. Case report: immune anti-D stimulated by transfusion of fresh frozen plasma.

Connolly M, Erber WN, Grey DE.

Transfusion Medicine Unit, The Western Australian Centre for Pathology and Medical Research, PathCentre, QEII Medical Centre, Western Australia 6009.

FFP has occasionally been reported to generate an immune response to RBC antigens (e.g., anti-D and anti-Fya). The Council of Europe requires that each unit of FFP have less than 6 x 10(9)/L RBCs. However, there is considerable variation internationally in the method of production and the level and assessment of RBC contamination of FFP. This study reports the case of a 63-year-old group B, D- man who received multiple transfusions of D- blood products over a 4-month period. Seven months later the patient's antibody screen remained negative and he was transfused with seven units of D- RBCs and six units of FFP, four of which were D+. Two months later anti-D, -E, and -K were detected in his plasma. Although the anti-E and anti-K could have resulted from transfusion of antigen-positive RBCs, the anti-D could have resulted only from transfusion of the D+ FFP. The D status of FFP is currently not considered when selecting products for transfusion even though the D antigen is highly immunogenic and the level of RBC contamination of FFP is not always known. This case highlights that transfusion of FFP is a stimulus for RBC antibodies and that when a patient has had a recent transfusion of FFP, consideration should be given to obtaining a sample for pretransfusion testing within 3 days before a scheduled RBC transfusion. In addition, the D status of FFP should be considered before administering FFP to premenopausal D- women.