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Posted: June 14, 2004

Addenda: June 16 & 22; Sept. 15 & 21, 2004


Criteria for performing repeat antibody identification panel workups

A transfusion medicine physician in the Northeastern USA reports that at her hospital transfusion service laboratory the current protocol for triggering an antibody identification panel workup includes a newly positive antibody screen or a change in the strength or pattern of antibody screen reactivity suggesting that a new antibody may be present. Under this paradigm, if a patient has a known red cell antibody and their antibody screen reactivity is unchanged and consistent with the known antibody, a panel workup is not performed (regardless of transfusion history OR TIME SINCE LAST FULL ANTIBODY PANEL WORK-UP, WHICH MIGHT BE YEARS) to rule in or rule out other antibodies. She is curious to learn if other institutions follow a similar strategy, and if not, what do they do regarding the trigger and frequency of repeating patient work-ups to reconfirm known and/or identify new unexpected red cell antibodies (FOR INPATIENTS AND FOR OUTPATIENTS IF DIFFERENT)

The following responses have been received.

ADDENDA June 16, 2004

  1. A colleague in Louisiana whose facility is a level one trauma center reports that they have approximately 600 in-house patients and a very large outpatient population. Their protocol for repeat antibody identification workups is to perform an antibody workup on each sample that presents with a positive antibody screen. If an antibody has been previously identified, they run a "confirmatory panel" rather than a complete workup. The confirmatory panel consists of 1 cell positive for the offending antigen and just enough antigen negative cells to rule out the formation of other antibodies. The exception to the rule is for warm and cold autoantibodies which entail absorptions. Additional workups are not performed within the hospital stay UNLESS the patient receives blood, in which case the workup is repeated.

  2. A colleague in a sunbelt state reports that at their 350-bed children's hospital, they do not routinely perform additional antibody identification workups for a patient who has an antibody that has already been identified. However, when they receive a new sample for a patient with a known antibody, they routinely screen that patient's sample against selected cells that lack the antigen corresponding to the known antibody. If a selected cell screen lacking the corresponding antigen is reactive in the screening test, a new antibody identification workup is initiated, since such a finding strongly suggests the presence of an additional antibody.

  3. The transfusion service medical director who posed the original question has done a 'survey' of her New England community and has learned that at 11 of 19 hospitals the technologists repeat an antibody identification panel workup with every new sample (which may equate to a new panel workup as often as every 72 hours). Two of the 19 hospitals perform 'mini panels' to rule-out new antibodies, like anti-E and anti-Kell. The remaining 6 hospitals repeat the antibody workup at variable times such as every month, every 7 days, every 14 days, or every three months.

  4. A very experienced blood bank laboratorian in Northern California reports that she is an advocate of the 'selected-cell approach' to antibody identification workups, for patients who already have a previously identified red cell antibody. She has summarized her strategies for determining when it’s time to perform repeat antibody identification on sensitized patients as follows:

    "Laboratories may repeat the identification when they see an increase in the strength of the plasma reactions, unexpectedly incompatible with an “antigen-negative” unit, or a new or stronger direct antiglobulin test (DAT). However, all of these strategies have limitations. Judging the strength of plasma reactions is subjective, and it is impossible to evaluate an increase in reactivity if the reactions are 4+. The strategy of waiting for an “antigen-negative” unit to be incompatible fails to recognize a new antibody when the donor unit is negative for the antigen that corresponds with the new antibody. Finally, the DAT may be negative following a hemolytic transfusion reaction. In her experience testing selected cells (based on the patient’s phenotype) every three days in lieu of an antibody screen is an easy cost-effective way to insure that a new antibody is promptly recognized. It is her institution's policy to perform a complete phenotype on a pre-transfusion or cell-separated sample from all patients who will be receiving ongoing transfusions. Initial antibody identification is performed, and when clinically significant alloantibodies are identified, repeat identification of these antibodies is not performed. Instead, future testing is limited to selected cells that are homozygous (double dose) for antigens that correspond with clinically significant alloantibodies that can be made by the patient."

ADDENDA June 22, 2004

  1. W. John Judd, FIBMS, MIBiol, Professor of Immunohematology in the Department of Pathology at the University of Michigan Medical Center (attribution used with permission) and colleagues have found that a negative indirect antiglobulin test (IAT) with donor and/or reagent RBCs lacking antigens to which a patient is known to have made antibodies serves to detect any additional, relevant antibodies. They published their findings in Transfusion 2002;42(S):20.

    The following is John Judd's summary of their work:

    "In this study, we reviewed a year's records of antibody studies. New antibodies found by repeat antibody identification (ABID) studies, using complete panels of untreated and ficin-treated RBCs, were categorized by relevance. We used the term "wanted" to define potentially significant antibodies against antigens required to be present on reagent RBCs used in screening tests for unexpected antibodies. All other antibodies were considered unwanted. The ability of IATs vs. R1R1 and R2R2 RBCs plus a 2-unit IAT-crossmatch with units negative with known antibodies to reveal new antibodies was determined from test results.

    Of 960 ABID studies, 385 (40%) were repeat investigations. These revealed 19 wanted new antibodies in 16 patients: E(6); K(5); Jka(2); Fya(2); Ce; c; CD; S. In 8 patients, the new antibodies were evident by screening tests. IAT-crossmatch would have found the wanted new antibodies in 7 of the 8 other cases if the donor cells carried the relevant antigens. The exception was an anti-S masked by a warm autoantibody. Repeat studies also found 26 unwanted new antibodies in 25 patients: 10 nonspecific; 5 auto; 3 cold alloantibody; 3 passive; 2 to low incidence antigens; 2 rouleaux; enzyme-only C. These were seen by screening tests in 5 cases, but only 2 more unwanted new antibodies would have been found by IAT-crossmatch.

    In light of these data, we no longer routinely perform repeat ABID studies, nor do we run exclusion tests, on prospective transfusion recipients, unless the known antibodies react with >90% random donor units. In the immediate six months following adoption of this policy we tested some 18,000 samples. Five new wanted antibodies were found in screening tests (Fya, K and Jkax3) and five by IAT crossmatch (Fya, Kx2 and Jkax2). For new antibodies found by IAT crossmatch we issue compatible units if time does not permit completion of ABID studies."

ADDENDA Sept. 15, 2004

  1. A transfusion medicine physician in NewYork states that the comments attributed to Dr. Judd in posting #5 above mention an exception to the study which he had published in Transfusion, involving a patient with an anti-S masked by a warm autoantibody. The criteria for repeating antibody identifications were effective and saved unnecessary effort, but were limited to patients not having warm autoantibodies. The New York physician has noticed a substantial increase in the number of patients with warm autoantibodies since they began using the sensitive gel methodology several years ago. He would therefore be interested to know how Dr. Judd manages warm autoantibody cases.

ADDENDA Sept. 21, 2004

  1. In response to the question posed in #6 above, John Judd replies that AABB Standards require tests for unexpected antibodies to be performed within three days of scheduled transfusion. However, prior to his arrival in Ann Arbor, he acknowledges that the policy at that institution was to repeat adsorption studies once a week (every 7 days), provided the patient had been transfused since the last investigation and more than 7 days had elapsed since that study. This policy there remains in effect today. In John's earlier response to this discussion (posting #5), he mentions that patients with autoantibodies meeting the above criteria would qualify for a repeat study every 7 days at his institution - since their serum/plasma reacts with >90% RBC samples. Because such patients have been transfused, his institution does an allogeneic adsorptiion with ZZAP-treated RBCs that are matched to the patient's Jk and Rh phenotypes. If necessary, they do a cell separation to determine their Jk and Rh status. They have phenotype information for the major blood group systems on most of their technical staff, who are generally willing to donate 10-20 mL of ACD-anticoagulated blood for these studies.

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