Is gamma irradiation (like that used to prevent GVHD) a feasible strategy to limit bacterial growth in platelet components?

A transfusion medicine physician in Detroit wonders if gamma irradiation (like that used to prevent GVHD) might be a feasible strategy to limit bacterial growth in platelet components. She and her blood bank staff are frustrated with a lack of good alternatives for detecting bacteria in platelet concentrates manufactured from platelet-rich plasma. At present her hospital uses low pH to detect bacterial contamination of platelet concentrates, but this test has a high false-positive rate which results in significant product wastage. In addition, they question the sensitivity of pH to detect units that are truly contaminated. She points out that AABB Standard 5.1.5.1 states that "the blood bank or transfusion service shall have methods to limit and detect bacterial contamination in all platelet components", and wonders if the irradiation of platelets with 25 Gy (or a higher dose) would be sufficient to meet the spirit of the AABB Standard to limit bacteria in platelet products. In one study (Huston, BM et al, Am J Clin Path 1998) bacterial kill was evaluated in spiked platelet products tested at doses of 0 to 75 Gy. The authors concluded that exposure of bacteria-contaminated platelet concentrates on storage day zero to gamma irradiation at levels up to 75 Gy is ineffective at sterilizing the platelet concentrates, but that higher levels of irradiation may be effective in sterilizing platelet concentrates. The authors suggested that the function, survival, and sterility of platelets after higher than conventional levels of irradiation need further study. In another study (Read EJ et al, Transfusion 1988) the authors concluded that irradiation of platelet concentrates up to 30 Gy has no effect on the in vivo recovery or survival of platelets, and that irradiation administered before storage of platelet concentrates does not interfere with their clinical efficacy (at a dose not exceeding 30 Gy). The Detroit physician wonders if any colleague has studied what might be the highest dose of irradiation that platelets can tolerate without their function or clinical efficacy being affected, and what would be the residual bacterial contamination risk at that irradiation dose?

The following comments have been received.

ADDENDA Dec. 28, 2004

1. A transfusion medicine physician in New Zealand reports that in his experience the difference in irradiation doses for preventing GVHD and for 'sterilizing' a product are orders of magnitude apart. Looking at the AABB Tissue Banking standards, he reports that to sterilize tissue (e.g., femoral heads) a dose of 15 kGy is required, roughly 500 times the dose used to prevent GVHD. He is of the opinion that irradiators in blood banks generally cannot generate such a dose. Even if they could, such doses cause some damage to bone according to the orthopedic surgeons who use it. Therefore, he would be very surprised if platelets were usable after such a dose.

ADDENDA Dec. 29, 2004

2. A colleague in the Midwest reminds us that it is important to remember that the size of the irradiated target is important. In general, when one compares cells and their size, the smaller the volume, the larger the required dose of irradiation to effect a 'kill'. Thus bacteria are but small fractions of the volume of white cells, the usual target of irradiation used for prevention of GVHD. Thus bacteriocidal doses would likely have to be much greater than what blood bank irradiators usually deliver in any sort of practical time period.

ADDENDA Dec. 30, 2004

3. A transfusion medicine physician in North Carolina reports that platelets appear to be extremely resistant to gamma irradiation. Studies with irradiation doses up to 750 Gy (normal conventional blood bank dose = 25 Gy) have found little, if any detrimental effect of irradiation on platelets. However conventional doses of irradiation are ineffective at sterilizing platelet concentrates. An inverse linear dose-related extinction of bacteria has been shown with a number of bacteria when suspended in platelets. However, even at levels up to 75 Gy, bacteria remain viable. Higher doses are not practically achievable (due to exposure time) with current blood bank irradiators. Use of photo-active pathogen reduction with a variety of nucleotide cross linking agents have been pursued but are not cleared for use in the United States. Even if such products were available, they may not be able to eradicate bacteria that have formed spores.

References:

• Huston BM. Brecher ME, Bandarenko N. Lack of efficacy for conventional gamma irradiation of platelet concentrates to abrogate bacterial growth. Amer J Clin Path 1998;109:743-747.
• Wong ECC, Brecher ME, Huston B, Kaplan A, Lehman K, Mitchell K, Bandarenko. Efficacy of high dose gamma irradiation on bacterial growth in apheresis platelets. Transfusion 1998;38 supplement S278
• Wong ECC, Brecher ME, Parker P, Sohier C, Korycka B, Bandarenko N. Effect of high dose gamma irradiation on platelet biochemistry and aggregation. Transfusion 1998;38 supplement S280
• Wong ECC, Brecher ME, Madden V, Bandarenko N. Ultrastructural changes of platelets irradiated at 30,000 cGy. Transfusion 1998;38 supplement S281

Submit comments to the e-Network Forum at enetworkforum@cbbsweb.org

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

W. Tait Stevens, MD
CBBS e-Network Forum Editor & Moderator

Elizabeth M. St. Lezin, MD
CBBS e-Network Forum Associate Editor & Moderator