Saturday, March 07, 2009

The last dance? Musings on the continued relevance of red cell serology to transfusion

As someone who previously has bemoaned the relative lack of serologic articles relevant to routine immunohematology practice in the AABB journal Transfusion, I was delighted to see two such articles in the March 2009 issue, as well as an editorial featuring one of the papers. They are not strictly serology but discussing red cell antibodies is close enough for me.

This blog discusses these antibody-focussed papers and some of their interesting findings, including language tidbits - musings on the continued relevance of red cell serology to transfusion.

RBC serology has been disappearing from the transfusion world for some time now.

  • Could this be its last dance? (Right click and choose "open in new tab" - you can listen and continue to read)
Paper #1
Schonewille H, de Vries RRP, Brand A.
Alloimmune response after additional red blood cell antigen challenge in immunized hematooncology patients. Transfusion 2009 Mar;49(3):453-7.

The Schonewille study retrospectively investigated the frequency with which already immunized hematooncology patients develop additional RBC antibodies when further transfused.
Using 24 years of data, they found that immunized hematooncology patients (despite receiving significant immunosuppressive therapy) retain an ability to form additional antibodies with a rate (21.7%) comparable to nonimmunosuppressed presensitized individuals (20-25%).
The authors conclude:
  • "To avoid extensive RBC alloimmunization, preventive extended antigen matching may be considered in hematooncology patients, who have shown to be capable of antibody formation."
Extended RBC phenotyping of donors for select patient groups is a subject that Schonewille and colleagues have broached before:

Further reading for those interested in transfusion-related RBC antibody production:

Extended matched RBC phenotyping is the topic discussed by Pomper and Simpson in their editorial:
  • Pomper GJ, Simpson MB. The prevention of alloimmunization: a balance of precaution, expectation, and outcome. Transfusion 2009 Mar;49(3):406-8.
The authors note that preventing alloimmunization in multi-transfused patients with hemoglobinopathies such as sickle cell disease has some acceptance, given that alloimmunization rates are high (19-43% in patients with sickle cell disease) and that transfusion reactions can produce severe complications.

They then discuss the following:
  • Clinical consequences of additional antibody production on clinical outcomes in other patients, concluding that delayed hemolytic transfusion reactions (DHTR), caused by weak undetected antibodies, do not adversely affect most patients.

  • Difficulties of broadening extended antigen phenotyping beyond sickle cell patients

  • Need for research to identify at-risk patients
Editorial's "so what" statements:
  • Clearly, avoiding RBC alloimmunization will be a benefit to any patient.

  • However, there is a balance to be considered between the expectations for improved patient outcome through an extended antigen matching program and the effect of the program on RBC inventory, donor collections, and other necessary functions vying for resources.
Ah ha! More potential for clinical outcomes research and also cost-effectiveness studies....

Paper #2
Tormey CA, Stack G. The persistence and evanescence of blood group alloantibodies in men. Transfusion 2009 Mar;49(3):505-12.

This paper retrospectively examined the disappearance of RBC antibodies in more than18,000 transfused military veterans. Antibodies were categorized as "preexisting" (detected in first antibody screen) or "hospital-acquired" (detected after initial negative antibody screen).
Main results
  • Records revealed that a total of 407 antibodies disappeared (follow-up testing ranged from less than 1 yrs to 10 yrs)

  • Disappearance of hospital-acquired antibodies (108/222; 48.6%) was significantly higher (p less than 0.0001) than that of preexisting antibodies (36/185; 19.5%).
  • Half (54/108) of disappearing, hospital-acquired alloantibodies disappeared within 6 months of detection;all disappeared by 10 years.
  • 2.2% of antibodies disappeared and reappeared one or more times without known antigenic reexposure

  • Among common alloantibodies, disappearance varied with antigenic specificity

  • About two-thirds of alloantibodies disappeared within 5 years of formation, a rate higher than previously reported in mixed-sex populations
Spot quiz
For those serologists out there, can you guess which hospital-acquired antibody had the highest rate of disappearance? I'm betting that you can. [Answer below]

The authors provide an interesting discussion of why some common antibodies have varying disappearance rates, including these possible factors:
  • Patient age when antibodies were produced
  • Antigen dose (e.g., Rh incompatible RBC vs platelets for anti-D)
  • Antigen density on RBC
  • Relative foreignness of antigen at molecular level (e.g, no. of amino acid differences between various antigen epitopes)
Their conclusions
  • We believe that the data support the need for regional, multi-institutional data sharing on patients who form BG antibodies, so that DHTRs can be avoided.

  • In addition, questions remain as to why preexisting antibodies are more persistent than newly acquired antibodies.
  • Also, it is not known why certain individuals make more persistent antibodies and why BG antibodies with certain specificities persist longer than others.
For some time now I have been amused by the gradual appearance in transfusion papers of words and phrases seldom heard or seen. I mean, who'd a thunk you would see a paper featuring Rapa Nui in Transfusion?

Here are 3 such words from the papers mentioned in this blog:
  • Paucity (Just kidding! These days this one is used in every other paper in Transfusion. Unfortunately no dearth or plethora appeared to round out the troika of increasingly common words.)

  • Evanescence

  • Inhomogeneity
Answer - Spot Quiz

Nearly 90 percent of hospital-acquired anti-Jka disappeared, 75% (6/8) within 3 months. Many other antibodies also disappeared within 3 months, including 30% (10/24) of anti-K and 23% (7/22) of anti-E.

So there you have it. So long as people make RBC antibodies, red cell serology goes on to dance another day. And when antibodies evanesce, the dance gets more challenging. As the genie once said, "Gotta fade...."
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