Effects of a new pathogen‐reduction technology (Mirasol PRT) on functional aspects of platelet concentrates

Pérez-Pujol, Sı́lvia; Tonda, Raúl; Lozano, Miguel; Fusté, Berta; López-Vílchez, Irene; Galán, Ana M.; Li, J.; Goodrich, Raymond P.; Escolar, Ginés

doi:10.1111/j.1537-2995.2005.04350.x

Cited by 101 publications

(126 citation statements)

References 41 publications

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“…Values obtained from other studies (n = 18) after initial prolonged resting time (study II/II/IV) showed non-significant increases in p-selectin expression in T-PC compared to C-PC. In addition, we found higher baseline expression of CD62p throughout storage, which is comparable to published results on PRT-treated platelets [4,[10][11][12]. Values observed in these studies range from 35% (day 1) up to 60% (day 5), which is comparable to our values of 23% (day 1) to 35% (day 5) in series I and of 28% (day 1) to 45% (day 6) in series IV.…”

Section: Discussionsupporting

confidence: 81%

Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol®)-Treated Platelets Collected by Plateletpheresis

Janetzko¹,

Hinz²,

Marschner³

et al. 2009

Transfus Med Hemother

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Background: The Mirasol® pathogen reduction technology (PRT) for platelet concentrates (PC) uses riboflavin and UV light (270–360 nm). We evaluated the impact of PRT on platelets in comparison to standard single-donor PC. Material and Methods: Platelets were resuspended in autologous plasma. After 2 h rest without agitation, PC were split into an untreated control unit (C-PC) and an immediately treated unit (T-PC) (series I). In series IV, split PC were stored under agitation over night before PRT was carried out. Platelet quality was assessed by pH, glucose consumption, lactate production rate, LDH, soluble sCD62p and CD62p expression with and without TRAP (thrombin receptor-activating peptide) over 7 days. Results: Series I: On day 5, pH values were lower for T-PC (6.8 ± 0.2 vs. 7.4 ± 0.1, C-PC), accompanied by a higher glucose consumption rate of 0.069 ± 0.016 vs. 0.035 ± 0.006 mmol/10¹² platelets/h and lactate production rate of 0.126 ± 0.031 vs. 0.063 ± 0.011 mmol/10¹² platelets/h. CD62p using TRAP was lower for T-PC (50 ± 11 vs. 62 ± 14%). Baseline activation was higher in T-PC (35 ± 12 vs. 28 ± 15%). Longer initial rest time had no impact on these results (series II/III/IV). Conclusion: PRT leads to an increase of platelet metabolism and activation independent of the length of the initial rest times. PC resuspended in autologous plasma should be stored at maximum up to day 5.

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Section: Discussionsupporting

confidence: 81%

Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol®)-Treated Platelets Collected by Plateletpheresis

Janetzko¹,

Hinz²,

Marschner³

et al. 2009

Transfus Med Hemother

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“…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.…”

mentioning

confidence: 99%

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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“…However, shearinduced adhesion is maintained in Mirasol-treated platelets [41][42][43], and mitochondrial function is preserved [44,45]. De- Overview of the Mirasol ® Pathogen Reduction Technology System 13 tween the Mirasol-treated and control group were detected for mean number of days between transfusions, mean number of platelet transfusions per patient and dose of platelets transfused.…”

Section: Mirasol Prt System For Plateletsmentioning

confidence: 99%

Pathogen Reduction Technology Treatment of Platelets, Plasma and Whole Blood Using Riboflavin and UV Light

Marschner¹,

Goodrich²

2011

Transfus Med Hemother

183

186

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Bacterial contamination and emerging infections combined with increased international travel pose a great risk to the safety of the blood supply. Tests to detect the presence of infection in a donor have a ‘window period’ during which infections cannot be detected but the donor may be infectious. Agents and their transmission routes need to be recognized before specific tests can be developed. Pathogen reduction of blood components represents a means to address these concerns and is a proactive approach for the prevention of transfusion-transmitted diseases. The expectation of a pathogen reduction system is that it achieves high enough levels of pathogen reduction to reduce or prevent the likelihood of disease transmission while preserving adequate cell and protein quality. In addition the system needs to be nontoxic, non-mutagenic and should be simple to use. The Mirasol® Pathogen Reduction Technology (PRT) System for Platelets and Plasma uses riboflavin (vitamin B2) plus UV light to induce damage in nucleic acid-containing agents. The system has been shown to be effective against clinically relevant pathogens and inactivates leukocytes without significantly compromising the efficacy of the product or resulting in product loss. Riboflavin is a naturally occurring vitamin with a well-known and well-characterized safety profile. The same methodology is currently under development for the treatment of whole blood, making pathogen reduction of all blood products using one system achievable. This review gives an overview of the Mirasol PRT System, summarizing the mechanism of action, toxicology profile, pathogen reduction performance and clinical efficacy of the process.

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Effects of a new pathogen‐reduction technology (Mirasol PRT) on functional aspects of platelet concentrates

Abstract: PLT function was well preserved in PCs treated with 6.2 J per mL Mirasol PRT and stored for 5 days.

Cited by 101 publications

References 41 publications

Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol®)-Treated Platelets Collected by Plateletpheresis

Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol®)-Treated Platelets Collected by Plateletpheresis

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

Pathogen Reduction Technology Treatment of Platelets, Plasma and Whole Blood Using Riboflavin and UV Light

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Effects of a new pathogen‐reduction technology (Mirasol PRT) on functional aspects of platelet concentrates

Abstract: PLT function was well preserved in PCs treated with 6.2 J per mL Mirasol PRT and stored for 5 days.

Cited by 101 publications

References 41 publications

Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol&reg;)-Treated Platelets Collected by Plateletpheresis

Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol&reg;)-Treated Platelets Collected by Plateletpheresis

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

Pathogen Reduction Technology Treatment of Platelets, Plasma and Whole Blood Using Riboflavin and UV Light

Contact Info

Product

Resources

About

Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol®)-Treated Platelets Collected by Plateletpheresis

Evaluation of Different Preparation Procedures of Pathogen Reduction Technology(Mirasol®)-Treated Platelets Collected by Plateletpheresis