In this issue of Blood, Verhaar and colleagues report that, although UV-C irradiation is an attractive method to minimize microbial contamination of platelet concentrates, it directly activates platelet αIIbβ3 by reducing critical extracellular disulfide bonds, resulting in the aggregation of stored platelets.

With the largely successful advent of viral testing, bacterial contamination has become the major infectious complication of transfusion. This is particularly relevant for platelets that must be stored at 20°C to 24°C to preserve platelet function, unfortunately resulting in a permissive environment for growth of bacterial contaminants. In fact, microbiologic testing of platelet products has revealed contamination rates of between 1 in 2000 and 1 in 40001  as well as a risk of clinical sepsis from apheresis platelets that can be as high as 1 in 15 000 infusions.2  Accordingly, platelet storage has been limited to 5 days to minimize the extent of bacterial growth.

Bacterial contamination of blood products can result from inadequate skin cleansing, from a small core of skin that sometimes enters the phlebotomy needle, and from contaminated blood collection packs.3  Thus, obvious ways to reduce contamination are to improve skin disinfection, to discard the first 15 to 30 mL of collected blood, and to culture or otherwise screen platelet products for the presence of bacteria.3  Another approach is to inactivate the contaminating bacteria.

Photodynamic and photochemical methods using ultraviolet (UV) light have been developed to inactivate bacteria in platelet products by damaging their DNA and RNA. Thus, irradiating platelet concentrates containing psoralen derivatives with UV-A light (wave length 315-400 nm) induces pyrimidine crosslinks in bacterial DNA and RNA, preventing subsequent replication and transcription. In the SPRINT trial, transfused platelets that had been irradiated with UV-A in the presence of the psoralen amotosalen were as hemostatically effective as control platelets. However, the photochemical treatment resulted in lower platelet increments and shorter intervals between transfusions, suggesting that it had caused mild platelet injury.4  Although UV-B irradiation (wave length 280-315 nm) has been used primarily to prevent HLA sensitization and platelet refractoriness, it has been combined with the dye thionine and yellow light in a 2-step procedure to inactivate bacteria in platelet concentrates.5  Enthusiasm for UV-B as a decontaminant, however, must be tempered by the report by van Marwijk Kooy et al, which found that UV-B irradiation causes platelet aggregation via oxygen radical-induced activation of protein kinase C.6 

In contrast to UV-A and UV-B, UV-C irradiation (wave length 100-280 nm) reduces bacterial growth in platelet concentrates without the need for photosensitizing additives. However, Terpstra et al observed that when platelets suspended in 10% plasma were irradiated with UV-C light, there was dose-dependent LDH release, P-selectin expression, and phosphotidylserine exposure that was mitigated to some extent by increasing the plasma concentration to 30%.7  In the work reported in this issue of Blood, the same group of investigators has studied the mechanism responsible for the decrease in platelet count that occurs during storage of UV-C–treated platelets. They found that relatively high-dose UV-C irradiation (1500 J/m2) caused immediate, αIIbβ3-dependent, platelet aggregation, implying that aggregate formation was the cause for the decreased platelet counts. Interestingly, UV-C–induced platelet aggregation was independent of platelet signal transduction. For example, it was unaffected by increasing platelet cAMP with forskolin, but it was associated with a marked increase in free thiol groups on the platelet surface, including free thiols in αIIbβ3. Incubating platelets with the reducing agent dithiothreitol has been known for decades to induce platelet aggregation, presumably by reducing critical but, as yet, unidentified disulfide bonds in αIIbβ3.8  Thus, the authors speculate that disulfide bond photolysis induced by UV-C irradiation was responsible for the platelet aggregation they observed.

The bacteriocidal properties of UV-C radiation would make it seem an ideal solution for the infectious complications of platelet transfusion. But the chemistry responsible for its bactericidal properties also has unexpected but unavoidable novel consequences on platelet function. It's not easy to mess with Mother Nature.

Conflict-of-interest disclosure: The author declares no competing financial interests. ■

REFERENCES

REFERENCES
1
Bryant
BJ
Klein
HG
Pathogen inactivation: the definitive safeguard for the blood supply.
Arch Pathol Lab Med
2007
, vol. 
131
 (pg. 
719
-
733
)
2
Alter
HJ
Klein
HG
The hazards of blood transfusion in historical perspective.
Blood
2008
, vol. 
112
 (pg. 
2617
-
2626
)
3
Hillyer
CD
Josephson
CD
Blajchman
MA
, et al. 
Bacterial contamination of blood components: risks, strategies, and regulation: joint ASH and AABB educational session in transfusion medicine.
Hematology
2003
(pg. 
575
-
589
)
4
Murphy
S
Snyder
E
Cable
R
, et al. 
Platelet dose consistency and its effect on the number of platelet transfusions for support of thrombocytopenia: an analysis of the SPRINT trial of platelets photochemically treated with amotosalen HCl and ultraviolet A light.
Transfusion
2006
, vol. 
46
 (pg. 
24
-
33
)
5
Mohr
H
Redecker-Klein
A
Inactivation of pathogens in platelet concentrates by using a two-step procedure.
Vox Sang
2003
, vol. 
84
 (pg. 
96
-
104
)
6
van Marwijk Kooy
M
Akkerman
JW
van Asbeck
S
, et al. 
UVB radiation exposes fibrinogen binding sites on platelets by activating protein kinase C via reactive oxygen species.
Br J Haematol
1993
, vol. 
83
 (pg. 
253
-
258
)
7
Terpstra
FG
van 't Wout
AB
Schuitemaker
H
, et al. 
Potential and limitation of UVC irradiation for the inactivation of pathogens in platelet concentrates.
Transfusion
2008
, vol. 
48
 (pg. 
304
-
313
)
8
Zucker
MB
Masiello
NC
Platelet aggregation caused by dithiothreitol.
Thromb Haemost
1984
, vol. 
51
 (pg. 
119
-
124
)