Protein translation occurs in platelet concentrates despite riboflavin/UV light pathogen inactivation treatment

2016 ◽  
Vol 10 (8) ◽  
pp. 839-850 ◽  
Author(s):  
Peter Schubert ◽  
Brankica Culibrk ◽  
Simrath Karwal ◽  
Raymond P. Goodrich ◽  
Dana V. Devine
Keyword(s):  
Uv Light ◽  
Protein Translation ◽  
Pathogen Inactivation ◽  
Platelet Concentrates

scholarly journals Effects of use of riboflavin and ultraviolet light for pathogen inactivation on quality of platelet concentrates

2011 ◽  
Vol 68 (6) ◽  
pp. 489-494 ◽  
Author(s):  
Zoran Stanojkovic ◽  
Ana Antic ◽  
Miodrag Stojanovic
Keyword(s):  
Uv Light ◽  
Storage Period ◽  
Buffy Coat ◽  
Blood Products ◽  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Platelet Storage ◽  
Control Units ◽  
The Moment ◽  
Uv Rays

Background/Aim. Pathogen inactivation in blood and blood products is one of the major means to achieve a zero risk blood supply and improve transfusion safety. Riboflavin (vitamin B2) activated by ultraviolet (UV) light, produces active oxygen which damages cell membrane and prevents replication of the carrier of diseases (viruses, bacteria, protozoa) in all blood products. The aim of this study was to establish the influence of the process of pathogens photoinactivation using riboflavin and UV rays on the biochemical and functional characteristics of platelet concentrates prepared from ?buffy coat?. Methods. The examination included 80 platelet concentrates prepared from ?buffy coat?, which was separated from whole blood donated by voluntary blood donors around 6 hours from the moment of collection. Concentrates were pooled, filtered and separated unton two groups: one consisted of 10 control units and the other of 10 examined units (pooled platelet concentrates). Examined units of the platelets were treated by riboflavin (35 mL) and UV rays (6.24 J/mL, 265-370 nm) on Mirasol aparature (Caridian BCT Biotechnologies, USA) in approximate duration of 6 min. A total of 35 mL of saline solution was added to the control units. The samples for examining were taken from the control and examined units initially (K0, I0), after the addition of saline (K1) and riboflavin (I1), after illumination (I2), first day of storage (K3, I3) and the fifth day of storage (K4, I4). The following parameters were measured: platelet count and platelet yield, residual erythrocyte and leukocyte count, pH, pO2, pCO2 and bacterial contamination. Results. All the measured parameters showed a statistically significant decrease comparing to K0 and I0; all the results of the first day of platelet storage showed statistically significant decrease comparing to K1 and I1, and all the results of the fifth day of platelet storage (K4, I4) showed a statistically significant decrease comparing to K1 and K3 and to I1 and I3. There was no the mentioned difference in the measured parameters between K4 and I4 (the end of storage - the fifth day). All the platelet units were sterile till the seventh day, when the investigation ended. Conclusion. Platelet concentrates inactivated by riboflavin and UV rays (Mirasol PRT sistem, Caridian BCT, USA) keep all the characteristics assessed by the Guide to the preparation, use and quality assurance of blood components (Council of Europe), during the whole storage period (five days). The obtained data were correlated with existing up to date literature and demonstrated that Mirasol treated platelets were safe and could be incorporated effectively in the routine blood bank and transfusion setting.

Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets

2001 ◽  
Vol 20 (10) ◽  
pp. 533-550 ◽  
Author(s):  
V Ciaravino ◽  
T McCullough ◽  
A D Dayan
Keyword(s):  
Ex Vivo ◽  
Reproductive Toxicity ◽  
In Vivo Studies ◽  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Baxter Healthcare ◽  
Safety Margins ◽  
Toxicology Assessment

The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations-compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53- mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000 fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of in vitro and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system.

Generation of procoagulant collagen- and thrombin-activated platelets in platelet concentrates derived from buffy coat: the role of processing, pathogen inactivation, and storage

Transfusion ◽  
2018 ◽  
Vol 58 (10) ◽  
pp. 2395-2406 ◽  
Author(s):  
Debora Bertaggia Calderara ◽  
David Crettaz ◽  
Alessandro Aliotta ◽  
Stefano Barelli ◽  
Jean-Daniel Tissot ◽  
...  
Keyword(s):  
Buffy Coat ◽  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Activated Platelets ◽  
And Storage

scholarly journals Photochemical inactivation of pathogenic bacteria in human platelet concentrates

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2698-2706 ◽  
Author(s):  
L Lin ◽  
H Londe ◽  
JM Janda ◽  
CV Hanson ◽  
L Corash
Keyword(s):  
Platelet Function ◽  
Pathogenic Bacteria ◽  
Uv Light ◽  
Platelet Concentrates ◽  
Gram Positive ◽  
Plasma Protein Concentration ◽  
Transfusion Therapy ◽  
Gram Negative ◽  
Gram Negative Organisms

Abstract Platelet concentrates (PC) may be infrequently contaminated with low levels of bacteria that can cause septicemia and death in patients receiving transfusion therapy. We evaluated the efficacy of a photochemical decontamination (PCD) technique using 8-methoxypsoralen (8-MOP) and long wavelength UV light (UVA) to inactivate bacteria in standard therapeutic PC. Twelve phylogenetically distinct pathogenic bacteria, 5 gram-positive and 7 gram-negative organisms, were seeded into PC to a final challenge dose ranging from 10(5) to 10(7) colony- forming units (CFU)/mL. Contaminated PC were treated with 8-MOP (5 micrograms/mL) and 5 J/cm2 of UVA, a PCD treatment regimen found to adequately preserve in vitro platelet function. Greater than 10(5) CFU/mL of all 5 gram-positive (Staphylococcus aureus, Streptococcus epidermidis, Streptococcus pyogenes, Listeria monocytogenes, and Corynebacterium minutissimum) and 2 of the gram-negative (Escherichia coli and Yersinia enterocolitica) organisms were inactivated. The remaining 5 gram-negative organisms were more resistant, with less than 10(1) to 10(3.7) CFU/mL inactivated under these conditions. The inactivation efficiency for this resistant group of gram-negative organisms was improved when PC were resuspended in a synthetic storage medium with reduced plasma protein concentration (15%) and an increased 8-MOP concentration (23.4 micrograms/mL). Illumination with 3 J/cm2 of UVA in this system inactivated greater than 10(5) CFU/mL of 4 resistant gram-negative organisms (Salmonella choleraesuis, Enterobacter cloacae, Serratia marcescens, and Klebsiella pneumoniae) and 10(4.1) CFU/mL of the most resistant gram-negative organism (Pseudomonas aeruginosa). This level of PCD treatment did not adversely affect in vitro platelet function. These results demonstrate that PCD using 8-MOP (5 to 23.4 micrograms/mL) effectively inactivated high levels of pathogenic bacteria in PC with adequate preservation of in vitro platelet properties.

Vitamin K3 Is a Potential Ultraviolet Photosensitizer for Pathogen Reduction of Human Platelets and Plasma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3434-3434
Author(s):  
Fei Xu ◽  
Jaroslav Vostal
Keyword(s):  
Bacterial Growth ◽  
Uv Light ◽  
Human Platelets ◽  
Uvb Radiation ◽  
Platelet Concentrates ◽  
Vitamin K3 ◽  
E Coli ◽  
Uva Irradiation ◽  
Pathogen Reduction ◽  
The Impact

Abstract Abstract 3434 Human platelets are stored up to 5 days at room temperature and may support bacterial growth before transfusion. Transfusion of bacterially contaminated platelets remains the highest transfusion transmitted infectious disease risk today. One approach to reducing this risk is the development of safe and effective pathogen reduction methodologies. We evaluated UV light (A and B) with vitamin K3 (VK3) as a photosensitizer for efficacy in reducing bacterial growth in platelet concentrates and plasma. Six species of bacteria, including Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae and Escherichia coli, were spiked respectively into phosphate buffered saline (PBS) buffer and exposed to UVA irradiation before bacterial growth was determined. As shown in Figure 1, the bacterial colony forming units (CFU) were reduced with increasing VK3 concentrations and UVA dosages. The VK3 at 400 uM plus UVA-radiation (2.88 J/cm2) significantly reduced the bacterial CFU in PBS spiked with bacteria. The same six-bacteria panel were spiked respectively into platelet concentrates (PCs) diluted with platelet additive solution and mixed with 400 uM VK3 before the UVA irradiation. As shown in Fig 2a, the bacteria CFU were reduced with increasing dosage of UVA but efficacy declined with lower dilution of PCs. At VK3 concentration of 400 uM and PC diluted to 20% a UVA-dose of 5.76 J/cm2 significantly reduced bacterial CFUs in PCs spiked with E coli, K pneumoniae, P aeruginosa and S epidermidis respectively. Similar results were obtained with the same six-bacteria panel spiked into plasma as shown in Fig 2b. UVB and VK3 combination had a biphasic inhibitory effect as shown in Fig 3. The VK3 at 200 uM plus UVB-radiation (0.015 J/cm2) also significantly reduced the CFU from the same six-bacteria panel spiked into PBS. However higher concentrations of 1600 uM VK3 could partially reverse the bacterial growth inhibition under UVB-radiation at 0.0038, 0.0075, and 0.015 J/cm2 for E coli, K pneumoniae and S aureus bacterial organisms. These findings suggest that VK3 may serve as an effective UVA photosensitizer for pathogen reduction of human platelets. With UVB light, lower concentrations of VK3 are effective at inhibiting bacterial proliferation but higher concentrations of VK3 may serve as a weak UVB blocker. Additional studies will need to be conducted to determine the impact of UV light and VK3 on platelet in vitro and in vivo performance. “This abstract reflects the views of the author and should not be construed to represent FDA's views or policies.” Disclosures: No relevant conflicts of interest to declare.

scholarly journals The clinical and biological impact of new pathogen inactivation technologies on platelet concentrates

Blood Reviews ◽  
2014 ◽  
Vol 28 (6) ◽  
pp. 235-241 ◽  
Author(s):  
Julie Kaiser-Guignard ◽  
Giorgia Canellini ◽  
Niels Lion ◽  
Mélanie Abonnenc ◽  
Jean-Claude Osselaer ◽  
...  
Keyword(s):  
Pathogen Inactivation ◽  
Platelet Concentrates ◽  
Biological Impact
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