Long-standing Controversies

Monospecific anti-IgG vs Polyspecific AHG

Once upon a time in Bloodland all labs used polyspecific antiglobulin serum (AHG) for pretransfusion testing. This was in the bad old days (circa 1970s and early 1980s) when the villain "complement" reigned supreme. Back then we believed that terrible things would happen if somehow we missed an antibody that bound complement. The antibody could be a very weak IgG antibody or a clinically insignificant cold antibody that bound complement at RT before tests were incubated. Accordingly, we needed to do everything in our power to detect complement: things such as using clotted patient specimens (recall that C1qrs needs free Ca++ to hold it together); and using polyspecific AHG so that C3 binding would be detectable in the indirect antiglobulin test (IAT) phase.

The controversy posed two major questions:

  1. What was the risk of missing a clinically significant IgG antibody if antiglobulin serum lacked anti-C3?

  2. Which complement components were important in polyspecific antiglobulin sera?

See these Medline abstracts for an overview of the controversy and related research:

Today many labs use monospecific anti-IgG for routine pretransfusion testing. The advantage is that C3 (bound by cold clinically insignificant antibodies) will not be detected. A potential disadvantage is that very weak IgG antibodies may go undetected if they are so weak that they cannot be detected by routine (IATs). This is because it takes about 300 - 500 IgG antibody molecules per red cell to be detectable in the IAT. If these weak antibodies bind C3, (e.g., anti-Jka or anti-Jkb ), there may be an increased likelihood that they they would be detected by polyspecific antiglobulin serum (containing both anti-IgG and anti-C3), or so the theory goes. Blood banks who use anti-IgG may miss these weak antibodies, but this would be a rare event.

The practice of using anti-IgG, which has a small risk associated with it, is an example of "risk management," in which risks are compared to benefits. Many labs have decided that the risk is small and the advantages outweigh the risk. In this case the risk is the likelihood of missing a very weak antibody versus the benefit of not detecting C3 bound by cold antibodies. Not detecting clinically insignificant cold antibodies is more cost-efficient since it saves technologist time.

IAT Crossmatch with Donors vs Confirmation of Donor ABO Group

Once upon a time, not too long ago, most transfusion services did an IAT crossmatch with donors, even if the antibody screen was negative. Currently, for routine testing, many labs today do an ABO, Rh, and antibody screen followed by an immediate spin (IS) crossmatch with donors (for confirmation of donor and patient ABO compatibility). The IAT crossmatch with donors is omitted because the probability of detecting a clinically significant antibody in the crossmatch (i.e., one that was missed by the antibody screen) is very low. When the IAT crossmatch is omitted, it is important to ensure ABO compatibility between patient and donor. This can be done by an IS at RT or by doing an electronic crossmatch.

One of the more recent studies showing the relative safety of this protocol is that of

  • Heddle et al (1992).

    Prewarm Technique

    The accepted use of prewarm technique is to prevent cold-reactive alloantibodies or autoantibodies from reacting in the IAT phase by preventing them from binding complement at RT with subsequent detection by anti-C3 in the IAT, when using polyspecific AHG serum.

    Prewarm technique is somewhat controversial, because some transfusion services use it to determine the clinical significance of antibodies, something that it was never intended to do.

    Judd has cautioned that prewarm technique (which he has coined "prefried technique") was never meant to be used to determine the clinical significance of antibodies. Moreover, it is possible to prewarm away clinically relevant antibodies such as anti-D, -E, -c, -K, and -Fya.

    With this in mind, technologists should hesitate to prewarm unidentified antibodies. In particular, beware of prewarming unidentified antibodies that react solely in the antiglobulin phase and do not produce direct agglutination at RT.

    Enrichment activity #7

    Test rationalization involves deciding which diagnostics tests should be offered to physicians. Typically, the tests chosen are ones that are consistent with diagnostic value, patient safety, and cost effectiveness. In transfusion medicine, test rationalization includes the topics discussed earlier (clinical significance, prewarm tests, controversies). For example, over the years labs have had to decide whether to use polyspecific antiglobulin serum or monospecific anti-IgG for indirect antiglobulin tests (IATs); whether to do IAT crossmatches for patients with no unexpected antibodies; under which circumstances prewarm tests are appropriate and inappropriate, etc.

    Blood "scandals"

    In the aftermath of transfusion-associated AIDS in the 1980s, there have been so-called blood scandals in all developed countries with blood transfusion systems. The Canadian experience has been documented by the "Commission of Inquiry on the Blood System in Canada, " otherwise known as the Krever Commission. This investigation into Canada's blood system lasted from 1993 to 1997, cost over $14 million , and culminated in the Krever Report . [To view the Report, you will need Abobe Acrobat Reader, downloadable at Adobe .]

    There are 3 volumes, each over 1000 pages. Volume 3 of the Report reviews international responses to the risk of HIV in Canada, the USA, Australia, France, Germany, Japan, The Netherlands, and the United Kingdom. It's fascinating reading and perhaps one of the best sources of information on international blood systems.

    While it is not required reading for the course, I encourage you to browse various sections to obtain an appreciation of the blood tragedies that occurred in most countries.

    Enrichment activity #8

    Part of the Krever Report deals with tracebacks and lookbacks and the failure of blood systems to respond quickly to notifying recipients of infected products.

    Read this commentary from the Krever Report. Based on the commentary and on Tracking , answer the following questions. E-mail replies to Pat .

    1. Differentiate between lookbacks and tracebacks.

    2. Contrast the timing of lookbacks in Canada and the USA.

    3. By the summer of 1988 what percentage of documented lookback cases had been completed in Canada?

    4. List three difficulties of conducting lookbacks cited in the Report. Can you think of any others?

    5. Post a comment to the mailing list about current procedures for conducting tracebacks and lookbacks in your geographical area or about the status of such processes. If you cannot obtain access to this information, post a comment about any issue in the Krever commentary.

    Prewarm Technique Controversies Newer Methods