Original Article In vitro evaluation of pathogen-inactivated buffy coat-derived platelet concentrates during storage: psoralen-based photochemical treatment step-by-step Mélanie Abonnenc, Giona Sonego, Julie Kaiser-Guignard, David Crettaz, Michel Prudent, Jean-Daniel Tissot, Niels Lion Vaudois Regional Blood Transfusion Service, Lausanne, Switzerland

SI M

TI

Se

rv

iz

iS rl

Background. The Intercept Blood SystemTM (Cerus) is used to inactivate pathogens in platelet concentrates (PC). The aim of this study was to elucidate the extent to which the Intercept treatment modifies the functional properties of platelets. Material and methods. A two-arm study was conducted initially to compare buffy coat-derived pathogen-inactivated PC to untreated PC (n=5) throughout storage. A four-arm study was then designed to evaluate the contribution of the compound adsorbing device (CAD) and ultraviolet (UV) illumination to the changes observed upon Intercept treatment. Intercept-treated PC, CAD-incubated PC, and UV-illuminated PC were compared to untreated PC (n=5). Functional characteristics were assessed using flow cytometry, hypotonic shock response (HSR), aggregation, adhesion assays and flow cytometry for the detection of CD62P, CD42b, GPIIb-IIIa, phosphatidylserine exposure and JC-1 aggregates. Results. Compared to fresh platelets, end-of-storage platelets exhibited greater passive activation, disruption of the mitochondrial transmembrane potential (∆Ψm), and phosphatidylserine exposure accompanied by a decreased capacity to respond to agonist-induced aggregation, lower HSR, and CD42b expression. The Intercept treatment resulted in significantly lower HSR and CD42b expression compared to controls on day 7, with no significant changes in CD62P, ∆Ψm, or phosphatidylserine exposure. GPIIbIIIa expression was significantly increased in Intercept-treated platelets throughout the storage period. The agonist-induced aggregation response was highly dependent on the type and concentration of agonist used, indicating a minor effect of the Intercept treatment. The CAD and UV steps alone had a negligible effect on platelet aggregation. Discussion. The Intercept treatment moderately affects platelet function in vitro. CAD and UV illumination alone make negligible contributions to the changes in aggregation observed in Intercepttreated PC.

Introduction

©

Keywords: Intercept Blood SystemTM, pathogen-reduction technology, platelet storage lesion.

The emergence of new pathogens and the risk of bacterial contamination of platelet concentrates (PC) remain major concerns when trying to guarantee the safety of platelet transfusions1,2. Pathogen-reduction technologies have been developed over the last few decades to tackle these risks and include the Intercept Blood SystemTM (Cerus, Concord, CA, USA), the Mirasol technique3 (TerumoBCT, Lakewood, CA, USA), and THERAFLEX UV-Platelet4 (MacoPharma, Mouvaux, France). The Intercept technique utilises a combination of ultraviolet (UV) A light (320-400 nm) and amotosalen hydrochloride, an aminoethoxymethyl derivative of psoralen. Amotosalen intercalates into the helical regions of DNA and, upon UVA activation, cross-links to pyrimidine bases, thereby preventing the replication

of susceptible pathogens. After illumination, residual amotosalen is removed by adsorption to guarantee a final concentration below 2 µM in PC. Intercept treatment of PC has been shown to be efficient against a broad range of viruses 5-10 , bacteria5,6,11,12, and parasites13-16, as well as contaminating leucocytes 17,18. To date, a number of clinical trials have compared the efficiency of Intercept-treated and conventional platelets19,20. Four meta-analyses have been performed, each with different results19,21-23. For example, in an Intercept-specific meta-analysis with reassignment of the reported bleeding scores into a single scale, Vamvakas showed that, compared to untreated platelets, Intercept-treated platelets resulted in lower corrected count increments and higher rates of mild and moderate bleeding21. Conversely, Cid et al. found that

Blood Transfus 2015; 13: 255-64 DOI 10.2450/2014.0082-14 © SIMTI Servizi Srl

All rights reserved - For personal use only No other use without premission

255

Abonnenc M et al

iS rl

Intercept process (study 1) In study 1, we compared platelets treated with the Intercept process to untreated platelets. On day 1, two ABO-matched PC were pooled and split into two identical products, each coming from 10 donors. One untreated PC was kept under agitation at 22 °C for up to 7 days after collection (container of filtration kit R7013, 1,300 mL, PL2410 plastic). The other paired PC was processed with the Intercept kit for large volumes (INT2203B, Cerus). A total of 17.5 mL amotosalen hydrochloride 3 mM solution was added sterilely to the PC and the mixture further illuminated with the Intercept illuminator (INT100, Cerus) at 3.9 J/cm2. After illumination, the Intercept-treated PC was transferred to the CAD container and kept under agitation for 14 hours to remove residual amotosalen. The treated PC was then transferred to the final storage bag (1,300 mL, PL2410 plastic) under agitation at 22 °C.

iz

Intercept process step-by-step (study 2) In study 2, we aimed to evaluate the contribution of each step of the Intercept process, i.e. incubation with the CAD or UV illumination only, to the changes observed in Intercept-treated platelets. On day 1, three ABO-matched PC were pooled and split into four identical products. One untreated PC served as a control (untreated unit). The second PC was treated with the complete Intercept process as described above (Intercept unit). The third PC was directly incubated with the CAD for 14 hours under agitation at 22 °C and then transferred to the storage bag (CAD unit, no UV, no amotosalen). The fourth PC was treated with UVA only at 3.9 J/cm2 in the absence of amotosalen and stored under agitation at 22 °C (UV unit, no amotosalen, no CAD).

SI M

TI

Se

rv

clinical trials of Intercept were too heterogeneous with regards to 1 hour corrected count increments to reach any conclusion, whereas the 24-hour corrected count increments were homogenously lower for Intercepttreated platelets. However, a reassessment of the bleeding rates did not show any difference between Intercepttreated and control platelets23. Routine experience tends to indicate a lack of adverse events, no differences in platelet transfusion requirements, and a significantly lower incidence of acute transfusion reactions with Intercept-treated PC than with standard platelets24-26 or gamma-irradiated PC27, as shown by haemovigilance programmes. In addition, several groups have investigated the effect of Intercept treatment on in vitro platelet function28-33. Because of differences in the preparation of PC, storage media, and the protocols used for in vitro assays, there are discrepancies in the published data. The studies showed metabolic changes, impaired mitochondrial function, accelerated passive activation, and altered in vitro platelet aggregation in response to agonistinduced activation in Intercept-treated platelets. Recently, the impact of Intercept treatment on platelets was assessed at the protein level using proteomic methods; the treatment induced an acceleration of storage lesions, even though the majority of proteins remained intact32,34-36. Here, we evaluated the effect of the Intercept treatment on platelet function during storage. This study has the advantage of comparing PC prepared and analysed strictly in the same way. In addition, the influence of the different steps in Intercept treatment, particularly incubation with the compound adsorbing device (CAD), on the increase in storage lesions has been questioned; we, therefore, evaluated the contribution of incubation with the CAD and UV illumination alone to the changes in platelet aggregation observed in Intercept-treated PC.

©

Materials and methods

Preparation of the platelet concentrates Whole blood was obtained from regular donors who gave their consent to the use of their blood components in research. Whole blood units (450±50 mL +63 mL citratephosphate-dextrose) were collected (day 0) in a quadruple bag system (NGR6428B, Fenwal, Lake Zurich, IL, USA) and kept at 22 °C overnight. After centrifugation of the whole blood at 3,500×g for 14 minutes, red blood cells and plasma were expressed on Optipress II (Fenwal). Five ABO-matched buffy coats (60 mL, haematocrit 0.4, from donors who had not been taking non-steroidal anti-inflammatory drugs) were manually pooled with 280 mL of Intersol additive solution (Fenwal) and centrifuged at 500×g for 10 minutes. Platelets were expressed on a manual plasma extractor and filtered to remove leucocytes (R7013, Fenwal).

Aggregometry Aggregometry was performed with an APACT 4004 aggregometer (LABiTec, Ahrensburg, Germany). Briefly, 120×106 platelets were centrifuged for 5 minutes at 500×g, suspended in 300 µL of AB group fresh-frozen plasma (FFP, previously centrifuged at 120,000×g to remove microparticles) and agitated for 5 minutes. The platelet suspension (250 µL) was transferred to a cuvette with 2 µL of 0.1 M calcium chloride and equilibrated for 2 minutes at 37 °C before being measured in the presence of: thrombin receptor activator peptide 6 (TRAP; Endotell [Allschwil, Switzerland], 8-60 µM), adenosine diphosphate (ADP; Sigma [Buchs, Switzerland], 8-60 µM), collagen (Nycomed [Zurich, Switzerland], 2-7.5 µg/mL), and arachidonic acid (AA; Endotell, 0.38-0.7 mg/mL). Volumes of agonist ranged from 5 to 20 µL depending on the final concentration required. FFP-diluted platelets were set at 0% aggregation before addition of the agonist, and 300 µL AB-group FFP was set at 100% aggregation. Blood Transfus 2015; 13: 255-64 DOI 10.2450/2014.0082-14

256

All rights reserved - For personal use only No other use without premission

Characteristics of pathogen-inactivated PC

Hypotonic shock response The hypotonic shock response (HSR) was measured with the aggregometer. Aliquots of platelets (3-5 mL) were diluted to 0.9×106 platelets/µL with AB-group FFP and agitated for 5 minutes at room temperature and then 250 µL of the diluted platelets were transferred to a cuvette. The diluted platelets were set at 0% aggregation, and distilled water set at 100% aggregation. Two hundred microlitres of distilled water or sodium chloride were injected 120 seconds after the start of monitoring, which continued for a total of 10 minutes.

Results

iS rl

Statistical analysis Data were expressed as the mean ± standard deviation (SD). Each experiment was performed on five different preparations of buffy coat-derived PC. Comparisons were made using analysis of variance (ANOVA) with repeated measures and post-hoc comparisons (R software, version 2.15.1). Differences were considered statistically significant when the p value was 13 days)58,64,65. This concept is consistent with our findings that apoptosis markers appear late during storage. The contribution of incubation with the CAD to greater passive platelet activation observed in photochemically treated PC has long been questioned. Some studies have reported higher initial platelet activation upon prolonged CAD exposure, even though no significant correlation has been found between CAD duration and initial platelet activation29,44. Our results indicate that incubation with the CAD, or UV illumination alone, does not contribute to, or at least plays a minor part, in the aggregatory changes observed with Intercept treatment.

©

SI M

TI

Se

rv

Platelet activation induces inside-out signalling leading to rapid conversion of the GPIIb-IIIa into its active conformation 53, which promotes fibrinogen binding. We showed that, upon Intercept treatment, platelets exhibit a higher capacity to adhere to fibrinogen compared to untreated platelets. Similarly, Lozano et al. observed a slight increase in platelet coverage under flow conditions for Intercept-treated platelets compared to control platelets, although the difference did not reach statistical significance33. Our observation is in agreement with the expression of PAC-1, a marker of active GPIIb-IIIa, which is higher on the surface of Intercept-treated platelets. The higher expression of active GPIIb-IIIa in treated platelets may partly be the result of greater passive activation, as observed in Intercept-treated platelets based on the increase in P-selectin expression and α-granule secretion. Although not yet demonstrated with UVA irradiation, some groups have reported that UVB irradiation of platelets mediates platelet aggregation via protein kinase C signalling and subsequent activation of GPIIb-IIIa54,55. UVC irradiation also activates GPIIbIIIa via a reduction of the disulphide bonds regulating integrin conformation56. The HSR reflects platelet membrane integrity and normal energy metabolism in vitro, which has been correlated with in vivo platelet recovery57. We observed a significant decline throughout the storage period in all units, with a reduced HSR of Intercept-treated platelets on day 7. However, the measured HSR decreased to the level of that of fresh platelets (50-90%) and end-of-storage platelets (40-80%) and, therefore, remained in the acceptable range57. The mitochondria-dependent apoptosis pathway is induced in platelets in response to either intrinsic chemical triggers or high shear stress58,59. Disruption of the ∆Ψm, one of the intrinsic chemical triggers of apoptosis, is considered to be an early sign of apoptosis upstream of caspase activation, phosphatidylserine exposure, and terminal loss of platelet function. We observed a loss of the ∆Ψm in a relatively small fraction of platelets during storage. In agreement with other studies31,32, but in contrast with Picker et al.29,42, we did not observe an influence of Intercept treatment on ∆Ψm. The exposure of platelets to phosphatidylserine can be the result of: (i) a caspase-dependent apoptotic pathway independent of platelet activation, which may play a role in the clearance of ageing platelets59,60, or (ii) the conversion of activated platelets to a procoagulant state induced by strong agonists in combination with a sustained high intracellular concentration of Ca2+ and loss of mitochondrial membrane potential61,62. Thus far, the different mechanisms underlying the activation of

Conclusion

In summary, compared to controls, PC treated for pathogen inactivation with the Intercept Blood SystemTM exhibit increased passive activation accompanied by moderate changes in adhesion and aggregation. Whether these in vitro changes translate into altered in vivo haemostatic function is still to be determined. Importantly, our experiments indicated that incubation with the CAD and illumination with UVA during Intercept treatment does not contribute to the changes in aggregation observed in vitro in Intercept-treated PC.

Acknowledgements

This work was supported by the Research Commission of the Swiss Red Cross Blood Transfusion Service.

Source of support

MA and GS are supported by a grant from the Research Commission of the Swiss Red Cross Blood Transfusion Service.

Authorship contributions

MA and MP designed the experiments. MA, GS, JKG and DC performed the experiments. MA, MP, JDT and NL reviewed the results and the manuscript.

Blood Transfus 2015; 13: 255-64 DOI 10.2450/2014.0082-14 262

All rights reserved - For personal use only No other use without premission

Characteristics of pathogen-inactivated PC

©

SI M

TI

Se

1) Alter HJ, Klein HG. The hazards of blood transfusion in historical perspective. Blood 2008; 112: 2617-26. 2) Vamvakas EC, Blajchman MA. Blood still kills: six strategies to further reduce allogeneic blood transfusion-related mortality. Transfus Med Rev 2010; 24: 77-124. 3) Goodrich RP, Edrich RA, Li J, Seghatchian J. The Mirasol PRT system for pathogen reduction of platelets and plasma: an overview of current status and future trends. Transfus Apher Sci 2006; 35: 5-17. 4) Seghatchian J, Tolksdorf F. Characteristics of the THERAFLEX UV-Platelets pathogen inactivation system an update. Transfus Apher Sci 2012; 46: 221-9. 5) Lin L, Cook DN, Wiesehahn GP, et al. Photochemical inactivation of viruses and bacteria in platelet concentrates by use of a novel psoralen and long-wavelength ultraviolet light. Transfusion 1997; 37: 423-35. 6) Knutson F, Alfonso R, Dupuis K, et al. Photochemical inactivation of bacteria and HIV in buffy-coat-derived platelet concentrates under conditions that preserve in vitro platelet function. Vox Sang 2000; 78: 209-16. 7) Lin L, Hanson CV, Alter HJ, et al. Inactivation of viruses in platelet concentrates by photochemical treatment with amotosalen and long-wavelength ultraviolet light. Transfusion 2005; 45: 580-90. 8) Pinna D, Sampson-Johannes A, Clementi M, et al. Amotosalen photochemical inactivation of severe acute respiratory syndrome coronavirus in human platelet concentrates. Transfus Med 2005; 15: 269-76. 9) Jauvin V, Alfonso RD, Guillemain B, et al. In vitro photochemical inactivation of cell-associated human T-cell leukemia virus type I and II in human platelet concentrates and plasma by use of amotosalen. Transfusion 2005; 45: 1151-9. 10) Sawyer L, Hanson D, Castro G, et al. Inactivation of parvovirus B19 in human platelet concentrates by treatment with amotosalen and ultraviolet A illumination. Transfusion 2007; 47: 1062-70. 11) Lin L, Dikeman R, Molini B, et al. Photochemical treatment of platelet concentrates with amotosalen and long-wavelength ultraviolet light inactivates a broad spectrum of pathogenic bacteria. Transfusion 2004; 44: 1496-504. 12) Brecher ME, Hay S, Corash L, et al. Evaluation of bacterial inactivation in prestorage pooled, leukoreduced, whole blood-derived platelet concentrates suspended in plasma prepared with photochemical treatment. Transfusion 2007; 47: 1896-901. 13) Van Voorhis WC, Barrett LK, Eastman RT, et al. Trypanosoma cruzi inactivation in human platelet concentrates and plasma by a psoralen (amotosalen HCl) and long-wavelength UV. Antimicrob Agents Chemother 2003; 47: 475-9. 14) Castro E, Girones N, Bueno JL, et al. The efficacy of photochemical treatment with amotosalen HCl and ultraviolet A (INTERCEPT) for inactivation of Trypanosoma cruzi in pooled buffy-coat platelets. Transfusion 2007; 47: 434-41. 15) Grellier P, Benach J, Labaied M, et al. Photochemical inactivation with amotosalen and long-wavelength ultraviolet light of Plasmodium and Babesia in platelet and plasma components. Transfusion 2008; 48: 1676-84.

iS rl

References

iz

NL received conference honoraria on two occasions from Cerus, the provider of the Intercept Blood SystemTM. JDT received an honorarium from TerumoBCT (European customer panel). The other Authors declare that they have no conflicts of interest.

16) Eastman RT, Barrett LK, Dupuis K, et al. Leishmania inactivation in human pheresis platelets by a psoralen (amotosalen HCl) and long-wavelength ultraviolet irradiation. Transfusion 2005; 45: 1459-63. 17) Grass JA, Hei DJ, Metchette K, et al. Inactivation of leukocytes in platelet concentrates by photochemical treatment with psoralen plus UVA. Blood 1998; 91: 2180-8. 18) Irsch J, Lin L. Pathogen inactivation of platelet and plasma blood components for transfusion using the INTERCEPT blood system. Transfus Med Hemother 2011; 38: 19-31. 19) Butler C, Doree C, Estcourt LJ, et al. Pathogen-reduced platelets for the prevention of bleeding. Cochrane Database Syst Rev 2013; 3: CD009072. 20) Prowse CV. Component pathogen inactivation: a critical review. Vox Sang 2013; 104: 183-99. 21) Vamvakas EC. Meta-analysis of the studies of bleeding complications of platelets pathogen-reduced with the Intercept system. Vox Sang 2012; 102: 302-16. 22) Vamvakas EC. Meta-analysis of the randomized controlled trials of the hemostatic efficacy and capacity of pathogenreduced platelets. Transfusion 2011; 51: 1058-71. 23) Cid J, Escolar G, Lozano M. Therapeutic efficacy of platelet components treated with amotosalen and ultraviolet A pathogen inactivation method: results of a meta-analysis of randomized controlled trials. Vox Sang 2012; 103: 322-30. 24) Osselaer JC, Cazenave JP, Lambermont M, et al. An active haemovigilance programme characterizing the safety profile of 7437 platelet transfusions prepared with amotosalen photochemical treatment. Vox Sang 2008; 94: 315-23. 25) Osselaer JC, Doyen C, Defoin L, et al. Universal adoption of pathogen inactivation of platelet components: impact on platelet and red blood cell component use. Transfusion 2009; 49: 1412-22. 26) Cazenave JP, Isola H, Waller C, et al. Use of additive solutions and pathogen inactivation treatment of platelet components in a regional blood center: impact on patient outcomes and component utilization during a 3-year period. Transfusion 2011; 51: 622-9. 27) Sigle JP, Infanti L, Studt JD, et al. Comparison of transfusion efficacy of amotosalen-based pathogen-reduced platelet components and gamma-irradiated platelet components. Transfusion 2013; 53: 1788-97. 28) Apelseth TO, Bruserud O, Wentzel-Larsen T, et al. In vitro evaluation of metabolic changes and residual platelet responsiveness in photochemical treated and gammairradiated single-donor platelet concentrates during long-term storage. Transfusion 2007; 47: 653-65. 29) Picker SM, Speer R, Gathof BS. Functional characteristics of buffy-coat PLTs photochemically treated with amotosalenHCl for pathogen inactivation. Transfusion 2004; 44: 320-9. 30) van Rhenen DJ, Vermeij J, Mayaudon V, et al. Functional characteristics of S-59 photochemically treated platelet concentrates derived from buffy coats. Vox Sang 2000; 79: 206-14. 31) Jansen GA, van Vliet HH, Vermeij H, et al. Functional characteristics of photochemically treated platelets. Transfusion 2004; 44: 313-9. 32) Hechler B, Ohlmann P, Chafey P, et al. Preserved functional and biochemical characteristics of platelet components prepared with amotosalen and ultraviolet A for pathogen inactivation. Transfusion 2013; 53: 1187-200. 33) Lozano M, Galan A, Mazzara R, et al. Leukoreduced buffy coat-derived platelet concentrates photochemically treated with amotosalen HCl and ultraviolet A light stored up to 7 days: assessment of hemostatic function under flow conditions. Transfusion 2007; 47: 666-71.

rv

Conflict of interests

Blood Transfus 2015; 13: 255-64 DOI 10.2450/2014.0082-14 All rights reserved - For personal use only No other use without premission

263

Abonnenc M et al

iz

iS rl

52) Johnson L, Loh YS, Kwok M, Marks DC. In vitro assessment of buffy-coat derived platelet components suspended in SSP+ treated with the INTERCEPT blood system. Transfus Med 2013; 23: 121-9. 53) Shattil SJ, Kim C, Ginsberg MH. The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol 2010; 11: 288-300. 54) 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; 83: 253-8. 55) Zhi L, Chi X, Gelderman MP, Vostal JG. Activation of platelet protein kinase C by ultraviolet light B mediates platelet transfusion-related acute lung injury in a two-event animal model. Transfusion 2013; 53: 722-31. 56) Verhaar R, Dekkers DW, De Cuyper IM, et al. UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin alphaIIbbeta3. Blood 2008; 112: 4935-9. 57) Holme S, Moroff G, Murphy S. A multi-laboratory evaluation of in vitro platelet assays: the tests for extent of shape change and response to hypotonic shock. Biomedical Excellence for Safer Transfusion Working Party of the International Society of Blood Transfusion. Transfusion 1998; 38: 31-40. 58) Leytin V. Apoptosis in the anucleate platelet. Blood Rev 2012; 26: 51-63. 59) Li J, Xia Y, Bertino AM, et al. The mechanism of apoptosis in human platelets during storage. Transfusion 2000; 40: 1320-9. 60) Schoenwaelder SM, Yuan Y, Josefsson EC, et al. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood 2009; 114: 663-6. 61) Jobe SM, Wilson KM, Leo L, et al. Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis. Blood 2008; 111: 1257-65. 62) Heemskerk JW, Bevers EM, Lindhout T. Platelet activation and blood coagulation. Thromb Haemost 2002; 88: 186-93. 63) Perrotta PL, Perrotta CL, Snyder EL. Apoptotic activity in stored human platelets. Transfusion 2003; 43: 526-35. 64) Leytin V, Allen DJ, Mutlu A, et al. Platelet activation and apoptosis are different phenomena: evidence from the sequential dynamics and the magnitude of responses during platelet storage. Br J Haematol 2008; 142: 494-7. 65) Cookson P, Sutherland J, Turner C, et al. Platelet apoptosis and activation in platelet concentrates stored for up to 12 days in plasma or additive solution. Transfus Med 2010; 20: 392-402.

©

SI M

TI

Se

rv

34) Prudent M, Crettaz D, Delobel J, et al. Proteomic analysis of Intercept-treated platelets. Journal of proteomics 2012; 76 Spec No.: 316-28. 35) Thiele T, Sablewski A, Iuga C, et al. Profiling alterations in platelets induced by Amotosalen/UVA pathogen reduction and gamma irradiation--a LC-ESI-MS/MS-based proteomics approach. Blood Transfus 2012; 10 (Suppl 2): s63-70. 36) Prudent M, D'Alessandro A, Cazenave JP, et al. Proteome changes in platelets after pathogen inactivation - an interlaboratory consensus. Transfus Med Rev 2014; 28: 72-83. 37) Bellavite P, Andrioli G, Guzzo P, et al. A colorimetric method for the measurement of platelet adhesion in microtiter plates. Anal Biochem 1994; 216: 444-50. 38) Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods 1995; 184: 39-51. 39) Cardigan R, Turner C, Harrison P. Current methods of assessing platelet function: relevance to transfusion medicine. Vox Sang 2005; 88: 153-63. 40) Picker SM, Oustianskaia L, Schneider V, Gathof BS. Functional characteristics of apheresis-derived platelets treated with ultraviolet light combined with either amotosalen-HCl (S-59) or riboflavin (vitamin B2) for pathogen-reduction. Vox Sang 2009; 97: 26-33. 41) Picker SM, Schneider V, Oustianskaia L, Gathof BS. Cell viability during platelet storage in correlation to cellular metabolism after different pathogen reduction technologies. Transfusion 2009; 49: 2311-8. 42) Picker SM, Oustianskaia L, Schneider V, Gathof BS. Annexin V release and transmembrane mitochondrial potential during storage of apheresis-derived platelets treated for pathogen reduction. Transfus Med Hemother 2010; 37: 7-12. 43) Chavarin P, Cognasse F, Argaud C, et al. In vitro assessment of apheresis and pooled buffy coat platelet components suspended in plasma and SSP+ photochemically treated with amotosalen and UVA for pathogen inactivation (INTERCEPT Blood SystemTM). Vox Sang 2011; 100: 247-9. 44) Janetzko K, Lin L, Eichler H,et al. Implementation of the INTERCEPT blood system for platelets into routine blood bank manufacturing procedures: evaluation of apheresis platelets. Vox Sang 2004; 86: 239-45. 45) Wagner SJ, Skripchenko A, Myrup A, et al. Evaluation of in vitro storage properties of prestorage pooled whole blood-derived platelets suspended in 100 percent plasma and treated with amotosalen and long-wavelength ultraviolet light. Transfusion 2009; 49: 704-10. 46) Li Z, Delaney MK, O'Brien KA, Du X. Signaling during platelet adhesion and activation. Arteriosclerosis, thrombosis, and vascular biology 2010; 30: 2341-9. 47) Offermanns S. Activation of platelet function through G proteincoupled receptors. Circulation research 2006; 99: 1293-304. 48) Varga-Szabo D, Pleines I, Nieswandt B. Cell adhesion mechanisms in platelets. Arterioscler Thromb Vasc Biol 2008; 28: 403-12. 49) Ohto H, Nollet KE. Overview on platelet preservation: better controls over storage lesion. Transfus Apher Sci 2011; 44: 321-5. 50) Shrivastava M. The platelet storage lesion. Transfus Apher Sci 2009; 41: 105-13. 51) M iyaji R, Sakai M, Urano H, et al. Decreased platelet aggregation of platelet concentrate during storage recovers in the body after transfusion. Transfusion 2004; 44: 891-9.

Arrived: 24 March 2014 - Revision accepted: 22 July 2014 Correspondence: Niels Lion Unité Recherche & Développement Service Régional Vaudois de Transfusion Sanguine (SRTS VD) Route de la Corniche 2 1066 Epalinges, Switzerland  e-mail: [email protected]

Blood Transfus 2015; 13: 255-64 DOI 10.2450/2014.0082-14 264

All rights reserved - For personal use only No other use without premission

In vitro evaluation of pathogen-inactivated buffy coat-derived platelet concentrates during storage: psoralen-based photochemical treatment step-by-step.

The Intercept Blood SystemTM (Cerus) is used to inactivate pathogens in platelet concentrates (PC). The aim of this study was to elucidate the extent ...
1MB Sizes 0 Downloads 6 Views