Potential and limitation of UVC irradiation for the inactivation of pathogens in platelet concentrates

Terpstra, Fokke G.; Wout, Angélique B. van ′t; Schuitemaker, Hanneke; Engelenburg, F.A.C. van; Dekkers, David W. C.; Verhaar, Robin; Korte, Dirk de; Verhoeven, Arthur J.

doi:10.1111/j.1537-2995.2007.01524.x

Cited by 45 publications

(45 citation statements)

References 31 publications

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“…It should be noted that the dose used in this study is significantly higher than required for inactivation of most pathogens 5,6 and thus one can expect the activation of only a minor part of total ␣IIb␤3 present. However, during storage further platelet activation can take place due to outside-in signaling after binding of fibrinogen present in the plasma.…”

Section: Uv-c Light Induces Photolysis Of Disulfide Bonds In ␣Iib␤3mentioning

confidence: 98%

“…Platelet concentrates (PCs) were prepared from whole blood-derived buffy coats essentially as previously described 6,10 except that buffy coats were not pooled and Composol-PS (Fresenius HemoCare, Emmer Compascuum, The Netherlands) was added as synthetic storage medium (lowering the residual plasma to 30%). The platelet concentrates were kept at a constant temperature of 22°C in a platelet incubator (Helmer PF96, Noblesville, IN) for 1 or 2 days before use.…”

Section: Preparation Of Platelet Concentratesmentioning

confidence: 99%

“…[2][3][4] Recently, the possibility of using UV-C light without the addition of an exogenous sensitizer has been explored. 5,6 This approach uses UV-C at a wavelength of 254 nm, which is highly absorbed by nucleic acids, resulting in cyclobutane pyrimidine dimer formation and DNA degradation. 7,8 Since no photosensitizer needs to be added to the platelet concentrate, UV-C-based pathogen inactivation should be easier to implement in existing blood bank procedures.…”

Section: Introductionmentioning

confidence: 99%

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UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin αIIbβ3

Verhaar

Dekkers

Cuyper

et al. 2008

Blood

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UV-C irradiation has been shown to be effective for pathogen reduction in platelet concentrates, but preliminary work indicated that UV-C irradiation of platelets can induce platelet aggregation. In this study, the mechanism underlying this phenomenon was investigated. Irradiation of platelets with UV-C light (1500 J/m 2 ) caused platelet aggregation, which was dependent on integrin ␣IIb␤3 activation (GPIIb/IIIa). This activation occurred despite treatment with several signal transduction inhibitors known to block platelet activation. UV-C also induced activation of recombinant ␣IIb␤3 in Chinese hamster ovary (CHO) cells, an environment in which physiologic agonists fail to activate. Activation of ␣IIb␤3 requires talin binding to the ␤3 tail, yet ␣IIb␤3-⌬724 (lacking the talin binding site) was activated by UV-C irradiation, excluding a requirement for talin binding. The UV-C effect appears to be general in that ␤ 1 and ␤ 2 integrins are also activated by UV-C. To explain these findings, we investigated the possibility of UV-C-induced photolysis of disulfide bonds, in analogy with the activating effect of reducing agents on integrins. Indeed, UV-C induced a marked increase in free thiol groups in platelet surface proteins including ␣IIb␤3. Thus, UV-C appears to activate ␣IIb␤3 not by affecting intracellular signal transduction, but by reduction of disulfide bonds regulating integrin conformation. (Blood. 2008;112:4935-4939) IntroductionViral and, especially, bacterial contamination of platelet concentrates remains an issue for platelet transfusions. 1 To minimize contamination of blood platelets, several pathogen reduction approaches have been developed that rely on irradiation with ultraviolet light (UV) in combination with a photosensitizer. [2][3][4] Recently, the possibility of using UV-C light without the addition of an exogenous sensitizer has been explored. 5,6 This approach uses UV-C at a wavelength of 254 nm, which is highly absorbed by nucleic acids, resulting in cyclobutane pyrimidine dimer formation and DNA degradation. 7,8 Since no photosensitizer needs to be added to the platelet concentrate, UV-C-based pathogen inactivation should be easier to implement in existing blood bank procedures.UV-based pathogen reduction in blood platelets has a few drawbacks, as some properties of platelets are affected by UV irradiation. Van Marwijk and colleagues observed that UV-B irradiation resulted in increased fibrinogen binding to platelets. 9 Furthermore, the UV-B-induced aggregation appeared to be dependent on PKC activation, signifying an important role for platelet signaling in UV-B-mediated activation of integrin ␣IIb␤3, the receptor binding fibrinogen.As a member of the integrin family, ␣IIb␤3 consists of a large type I transmembrane ␣/␤ heterodimer, which is capable of bidirectional signaling through the plasma membrane. On unstimulated platelets, ␣IIb␤3 resides in an inactive conformation on the plasma membrane, but it is rapidly switched to an "on" state when the platelet becomes activated after stimula...

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Section: Uv-c Light Induces Photolysis Of Disulfide Bonds In ␣Iib␤3mentioning

confidence: 98%

Section: Preparation Of Platelet Concentratesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin αIIbβ3

Verhaar

Dekkers

Cuyper

et al. 2008

Blood

Self Cite

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“…Although the residual risk of STRs for RBCs is approximately one log phase below the residual risk of STRs for PCs, the absolute number of annually transfused RBCs is one log phase higher. Based on these assumptions, the ideal bacterial screening methods or pathogen reduction systems should include all blood products to reduce the risk for bacteria transmission significantly [34][35][36]. Therefore, new screening technologies or pathogen inactivation systems are eagerly awaited.…”

Section: Discussionmentioning

confidence: 99%

Screening of platelet concentrates for bacterial contamination: spectrum of bacteria detected, proportionof transfused units, and clinical follow-up

et al. 2009

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“…The storage of aliquots of platelet concentrates in a culture bottle with 5% CO 2 has been used in several studies on human platelets and results in similar storage conditions compared with storage in a standard platelet storage container. 19,20 Preparation of washed aged platelets and supernatant rat PLT products After 5 days of storage, rat PLTs products were separated into washed platelets and supernatant. The PLTs products were centrifuged for 15 minutes at 1250g and 22°C.…”

Section: Preparation Of Rat Plts Productsmentioning

confidence: 99%

Supernatant of stored platelets causes lung inflammation and coagulopathy in a novel in vivo transfusion model

Vlaar

Hofstra

Kulik³

et al. 2010

Blood

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100

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Transfusion-related acute lung injury is suggested to be a "2-hit" event resulting from priming and activation of pulmonary neutrophils. Activation may result from infusion of lysophosphatidylcholines (LysoPCs), which accumulate during storage of blood products. In the present study, we developed a syngeneic in vivo transfusion model to test whether storage of platelet concentrates (PLTs) results in lung injury in healthy rats as well as in a "2-hit" model using lipopolysaccharide-pretreated rats. In addition, the effect of washing of platelets was studied. In healthy rats, transfusion of aged PLTs caused mild lung inflammation. In LPS-pretreated rats, transfusion of aged PLTs, but not fresh PLTs, augmented pulmonary and systemic coagulopathy. When PLTs components were transfused separately, supernatant of aged PLTs, but not washed aged platelets, induced pulmonary injury in the "2-hit" model.

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Potential and limitation of UVC irradiation for the inactivation of pathogens in platelet concentrates

Cited by 45 publications

References 31 publications

UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin αIIbβ3

UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin αIIbβ3

Screening of platelet concentrates for bacterial contamination: spectrum of bacteria detected, proportionof transfused units, and clinical follow-up

Supernatant of stored platelets causes lung inflammation and coagulopathy in a novel in vivo transfusion model

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