Is it permissible to release for transfusion a blood component that shows icteric plasma, drawn from a donor who is otherwise acceptable and whose hepatitis tests are negative?

A blood banker in Alaska was curious for input regarding the observation of icteric plasma noted in platelet pheresis components, and blood components in general. Apparently there is a critical shortage of platelet pheresis components and a recently drawn unit is decidedly more icteric than "normal". All testing is acceptable and the donor is well and healthy. Thoughts on causes?

Editor's NOTE:  The information at a previous e-Network discussion might be of interest, particularly response numbers 3 and 4.

The following responses have been received.

ADDENDA Feb. 10, 2003

1. Chris Gresens, MD of BloodSource in Sacramento (name and institution used with permission) reports they see no reason to discard components that appear icteric, provided all other safety criteria (e.g., donor answered all questions appropriately; all infectious disease marker testing is nonreactive, etc.) are acceptable. Because icteric or greenish-tinged units are neither uncommon nor specific for blood-transmissible problems, it would be inappropriate to discard such components based solely upon this type of insignificant discoloration. Dr. Gresens adds that after changing their SOP to accept such units several years ago, they have saved dozens of units from discard each year.

ADDENDA Feb. 11, 2003

2. Ronald Domen, MD, Professor of Pathology, Medicine and Humanities and Medical Director, Blood Bank and Transfusion Medicine at the Milton S. Hershey Medical Center Penn State University College of Medicine (name and institutional affiliation used with permission) sees no reason why icteric plasma, that is otherwise safe, should be discarded and not used. However, he says that many facilities do discard the plasma that appears to be icteric, from donors with Gilbert's Syndrome, for example. His personal experience has been that transfusing physicians are more likely to be aesthetically "put-off" by a unit of icteric plasma infusing into their patient rather than necessarily having concerns about the unit being "infectious." The same holds for plasma that might be "discolored" because the donor was taking certain medications (e.g., birth control pills), or vitamins (e.g., high doses of vitamin A or large quantities of carrot juice).
   
   
3. J. Lawrence Naiman, MD, retired ARC Medical Director, CBBS webmaster, Instructor in the Transfusion Service at Stanford Medical Center, and lead author of the 1996 Transfusion paper and subsequent study cited in the earlier e-network discussion ('Icteric plasma suggests Gilbert's syndrome in the blood donor') offers these additional comments:
   
   "Our study showing elevated total bilirubin levels in stored sera from 7.7 percent of 298 healthy blood donors (whose plasma had not been observed to be icteric) indicated that Gilbert's syndrome was common and usually overlooked in the donor population. A subsequent study in Spain by Salazar, F et al (Med Clin (Barc) 2000;115:540-1) using PCR to screen 100 blood donors for the promoter region encoding the UGT-1 gene revealed the homozygous 7/7 genotype of Gilbert's syndrome in 9 percent of subjects, reinforcing our impression that the elevated bilirubin levels in our study were a result of Gilbert's syndrome.
   
   One of the major obstacles both then and now to releasing blood components whose plasma is icteric is the Code of Federal Regulations (21CFR Part 606, Section 640.11 (b) that states: 'Inspection. The product shall be inspected immediately after separation of the plasma, periodically during storage, and at the time of issue. The product shall not be issued if there is any abnormality in color or physical appearance or if there is any indication of microbial contamination.' AABB Standards on this issue (J. 3000) is more liberal, allowing release of the product if 'specifically authorized by the medical director', but remains inconsistent with the CFR.
   
   I certainly agree with the rationale behind the practice cited by Dr. Gresens (response #1 above), especially since nucleic acid testing for hepatitis C has been included in the screening of donated blood in this and other countries. However, until the regulatory paradox in the US can be resolved, those who release products whose plasma is icteric are theoretically at risk of citation. It should not be difficult to develop a simple protocol for evaluating these products and their donors, which could then be used as a basis for modifying the language in the CFR to permit release of these products. The contribution to preserving the healthy donor base justifies the efforts in tackling this vexing issue. If and when this should this occur, attention will need to be directed, as Dr. Domen suggests, to reassuring the transfusing physician about the benign nature of this common color anomaly."

ADDENDA Feb. 13, 2003

4. Chris Gresens, MD responds to Dr. Naiman's well-thought-out comments re icteric plasma (verbatim) "As a point of clarification, I want to emphasize that we, too, seriously considered the section he cited from the CFR when we changed our policy to allow the use of icteric blood components. Ultimately, we determined that our approach would not be in opposition to the CFR. Our (very reasonable, I believe) rationale for this was that icteric plasma neither is very uncommon nor is it, when identified in a healthy individual, at all likely to be an "abnormality." Moreover, it is not indicative of "microbial contamination." Therefore, it is our assertion that our policy in no way parts from what is required by the FDA. I hope that the above assists with any debate over this matter."
   
   
5. Dr. Naiman agrees that Dr. Gresens' reasoning appears sound, but wonders what those at the FDA have to say on this, since they are the 'final arbiters' when it comes to interpreting the existing code during field inspections.

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