A colleague in the Western USA reports that upon conducting a Quality Assurance audit at a hospital-based donor center in January 2006, a file for a 63 year old femaie donor revealed that in 2002, she made a donation that tested repeat reactive for anti-HTLV I/II with an indeterminate Western Blot (viral bands were present for p24 and p26). It was the donor center's deferral policy during 2002 to not use an HTLV antibody reactive donation for transfusion, but the center's policy did allow the donor to make additional donations provided she did not again test repeat reactive for anti-HTLV I/II and she was otherwise qualified to donate. The policies and procedures for that center have since been modified, such that if a donor tests repeat reactive for anti-HTLV I/II with an indeterminate Western Blot, that donor would be indefinitely deferred. The donor in question has donated ten whole blood units since 2002, and with each donation she tested non-reactive for anti-HTLV I/II as well as non-reactive for all other transfusion-transmittable diseases.

Questions raised by this case are as follows:

1. Should the donor now be indefinitely deferred, since her prior record has been discovered?
2. Are the donated units that have been collected since the policy change subject to recall and Biological Product Deviation reporting? If so, should the recipients of the products be notified?

The following comments have been received.

ADDENDA February 21, 2006

1. Dr. Louis Katz, past president of America's Blood Centers (attribution used with permission) reports that the donor under discussion would be eligible in most facilities (including his own) according to current guidance. Deferral must occur if the HTLV I/II EIA is repeat reactive (RR) on a single donation using two manufacturer's licensed assays, or if the HTLV I/II EIA used in the collection facility is RR on two separate donations. The confirmatory ("additional, more specific") assays are investigational (i.e. unlicensed) and most facilities would no longer perform an immunoblot or RIPA until the donor was already deferred according to the EIA criteria above, and then basically to focus the counseling message to the deferred donor. In Dr. Katz's center, the donor under discussion would be eligible, and no Biological Product Deviation Report or consignee notification would be required. Dr. Katz adds that the relevant language is from the 1997 Guidance for Industry - Donor Screening for Antibodies to HTLV-II available at http://www.fda.gov/cber/guidelines.htm

D. DONOR DEFERRAL
Donors with repeatedly reactive donations should be permanently deferred whenever additional, more specific tests confirm that the donor has antibodies to HTLV-I or HTLV-II. At the present time, there are no FDA licensed additional, more specific tests for antibodies to HTLV-I or HTLV-II. Donors should be indefinitely deferred whenever their donations have repeatedly reactive screening tests for HTLV-I or HTLV-II antibodies on more than one separate donation or when a second, licensed screening test of a different type for anti-HTLV-I and anti-HTLV-II is repeatedly reactive on the same donation. (Additional, more specific tests may be negative or indeterminate).

E. DONOR NOTIFICATION AND COUNSELING
Utilization of investigational additional, more specific tests may be useful in notification and counseling of donors with repeatedly reactive screening tests for antibodies to HTLV-I or HTLV-II.

Guidelines for notification and counseling HTLV-seropositive individuals have been provided in detail by the Public Health Service.

2. Susan Stramer, Ph.D., executive scientific officer, American Red Cross (attribution used with permission) reports that she would not recommend deferral of a donor merely because of a single donation that tested repeat reactive for HTLV I/II antibodies by an FDA licensed EIA and indeterminate by a non-licensed Western blot, unless the donor tested repeat reactive on that donation by 2 different FDA licensed EIA tests, or the donation in question was the second donation to be repeat reactive for anti-HTLV I/II. She emphasizes that when testing donors for HTLV infection, an indeterminate Western blot using a research test does not cause deferral of a donor, however, a positive Western blot test would.

3. Debra Kessler RN, MS, Director, Regional Services - New York Blood Center (attribution used with permission) reports that when HTLV Western Blots (WB) were available, her center did not defer a donor with a single HTLV I/II EIA repeat reactive (RR) test result, unless the HTLV WB was positive. In keeping with FDA regulations, her center put donors with HTLV I/II EIA unconfirmed results on "surveillance". If a second separate blood donation was HTLV I/II EIA RR, the donor would then be deferred. If no subsequent blood donation was HTLV I/II EIA RR, those 'HTLV antibody negative' donations could be used for transfusion, provided all other tests were also negative. She adds that their policy today, in the absence of an available HTLV WB, is to use a second licensed HTLV I/II EIA by a different manufacturer for 'confirmation'. If either a 'confirmatory' HTLV I/II EIA is RR, or a subsequent blood donation is HTLV I/II EIA RR, the donor is indefinately deferred and reactive blood donations are not used for transfusion. Only if a donor has had a single donation with an unconfirmed HTLV I/II EIA is the donor placed on surveillance. However, the donated units from an unconfirmed HTLV I/II EIA donation would not be used for transfusion.

Ms. Kessler acknowledges that she would not go back and defer the donor under discussion who had a single HTLV I/II EIA RR/WB Indeterminate donation in 2002. Also, she does not believe the subsequent negative donations made by that donor need to be recalled, since her interpretation of the FDA guidance is that those subsequent donations are acceptable.

ADDENDA Feb. 23, 2006

4. According to Jed B. Gorlin MD, Medical Director, Memorial Blood Centers in Minnesota (attribution used with permission), the dilemma of managing donors with a repeat reactive screening result for anti-HTLV I/II serves as a wonderful lesson of what can happen when a donor screening test is mandated, but no licensed confirmatory test is available. In Dr. Gorlin's opinion, when following up on repeat reactive anti-HTLV I/II results, it is both more efficient and yields more timely donor counseling if an alternate EIA strategy is used for donor counseling and deferral status. Having said that, he thinks that blood bankers should encourage manufacturers to develop licensed confirmatory tests that can be done with reasonable TAT, i.e. at a blood center. He writes to share his concern that a future requirement to screen donors for Chagas disease might be mandated before a confirmatory test with a reasonable TAT is licensed. For example, the Radioactive Immunoprecipitation Assay (RIPA) which some labs use to 'confirm' the presence of Chagas antibodies, is neither timely, convenient, nor licensed. Hence, he urges readers to comment to the FDA on the need to license a confirmatory test for all mandated donor screening tests. Finally, he asks that colleagues encourage test kit manufacturers to support further studies to develop confirmatory tests.

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator