Blood, 15 March 2003, Vol. 101, No. 6, pp. 2078-2080
Photochemical pathogen reduction: improved safety for the
blood supply?
Safety of the blood supply depends on an increasingly intense
donor-screening process and a series of serologic or nucleic acid-based
tests for HIV1/2, HTLVI/II, hepatitis B, hepatitis C, and
syphilis. There are, however, no tests for myriad other disease agents that could threaten the blood supply, including bacteria, malaria, babesiosis, Chagas disease, and emerging agents such
as West Nile virus. Pathogen reduction (PR) technology is a new
approach that places a PR compound in the donor blood bag ready to be
activated after blood collection. Several technologies are separately
being developed for platelets, red cells, and plasma. The common
approach taken by the various methodologies is to disrupt pathogen DNA
or RNA polymerase activity and interfere with pathogen nucleic
acid replication and, thus, disease transmission. The key is for the PR
technology to prevent pathogen transmission but preserve functional
activity of transfused cells and plasma proteins.
van Rhenen and colleagues (page 2426) report on the first randomized
double-blind clinical trial in European patients using one such
technology. Their system exposes bags of buffy-coat-prepared platelets
containing a synthetic psoralen compound (amotosalen) to UVA light.
Once photoactivated, the amotosalen intercalates and crosslinks
pathogen nucleic acid bases, preventing replication. van Rhenen's
protocol randomized thrombocytopenic oncology patients to receive
either untreated control (n = 51 patients; 256 transfusions) or
photochemically treated (PCT; n = 52 patients; 311 transfusions) platelet products. The estimated effect of PCT treatment on the mean
1-hour posttransfusion corrected count increment (CCI), one primary
endpoint, was a decrease of 1800 (P = .11) in the platelet count. The mean 24-hour CCI for the PCT arm, however, was 3200 lower
than that for the control arm (P = .02). Blinded,
clinically assessed bleeding events were equivalent between the 2 groups, speaking to preservation of platelet hemostatic function. There were no reported differences in adverse events between the 2 groups.
While data from this first reported clinical trial are very
promising, more data on in vivo platelet function would be useful. Further, any long-term adverse effects on recipients exposed to platelets treated by the amotosalen and UVA light procedure remain to
be determined. Clearly, this paper presages the future focus on PR
methods for ensuring the safety of the blood supply from known, as well
as emerging, pathogens. This study reports on buffy-coat-prepared platelets, a technology used widely in Europe but not in the United States, where platelets are prepared by apheresis or from whole blood
as platelet-rich plasma. Studies on these products and future reports
on red cell PR systems are awaited. At least in the US for the short
term, PR technology might be used in addition to, not in lieu of,
existing blood screening maneuvers. The important role to be
played by PR in the future remains to be defined.
Edward L. Snyder
Yale University School of Medicine
