Handling Nonspecific Antibody Panel Reactions

Note: this is an updated version of a previous post.

Anyone reviewing antibody panels, especially in the Middle East/Gulf region, encounters many panels for which no antibody specificity is identified.  As a transfusion medicine physician who often got called during the night for release of RBCs for patients with “nonspecific” pattern, this was a big headache.

Is it “nonspecific” because there isn’t a clinically significant antibody OR the technologist did not perform the testing or its interpretation correctly?  Does it need further testing?  Do I release blood components at this time?

In general, I do not routinely use polyspecific AHG for routine testing.  My first choice is for a gamma heavy-chain specific AHG but this is not available for gels or glass beads.  Then, I select the IgG AHG even though it does react with light chains and can detect IgM cold antibody reactions.

In general, with nonspecific reactions, I recommend the following:

  1. Repeat with a gamma heavy-chain specific reagent if the initial workup was made with another type of AHG (polyspecific or whole molecule IgG).
  2. Always do enzyme panels, sometimes with both papain and ficin reagents:  many Rh antibodies are optimally detected only at enzyme (example:  R1R1 patient with only anti-E at AHG phase but anti-E and anti-c at enzyme).
  3. Perform an extended Rh/Kell/Duffy/Kidd/Kell/MNSs/P1 phenotype and specifically check for those negative typing results AND for dosage (could the antibody only be detected in homozygous cells like many anti-M are?).
  4. Perform classical room temperature, 37C, and finally AHG phase testing.  Routinely I do not do this since antibodies not detected at 37C are unlikely to be clinically significant.  Sometimes, the AHG phase reactivity is a cold antibody of high-thermal amplitude.
  5. If the Jka or Jkb antigen typings are negative, repeat using a polyspecific AHG reagent.
  6. Use additional panels from multiple manufacturers.  Some reagents detect more nonspecific reactions than others.
  7. Try other potentiators than LISS such as PEG.
  8. Check the outdate of the panel and reagents:  if less than 1 week remaining, consider repeating with fresh reagents and getting a new patient sample.

Finally, if you still cannot define the specificity, consider repeating the testing after several days.  Maybe it is a newly emerging or an anamnestic response.

I emphasize as a physician, I do not care to see all possible antibodies present in the specimen but rather only those likely to be clinically significant.  In general, there is a shortage of labor in the blood banks so I want to eliminate unnecessary work.