Functional characteristics of buffy‐coat PLTs photochemically treated with amotosalen‐HCl for pathogen inactivation

Picker, Susanne M.; Speer, Relindis; Gathof, Birgit

doi:10.1111/j.1537-2995.2003.00590.x

Cited by 60 publications

(86 citation statements)

References 42 publications

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“…Culturing using the BacTec ® System (BD Biosciences, San Jose, CA, USA), residual WBCs and RBCs, LDH release, and p-selectin expression were performed as described previously [25]. Samples for cytokine analysis were centrifuged at 1,000 × g for 30 min at room temperature and the supernatants were frozen at -70 °C.…”

Section: Laboratory Methodsmentioning

confidence: 99%

Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Picker

Steisel

Gathof³

2009

Transfus Med Hemother

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Background: Soluble mediators in platelet concentrates (PCs) released from contaminating white blood cells (WBCs) and platelets (PLTs) themselves are supposed to promote allergic and non-hemolytic febrile transfusion reactions in the recipient. Pathogen reduction technologies (PRTs) prevent replication and proliferation of pathogens as well as of WBCs, and may reduce cytokine accumulation in PCs during storage and prevent adverse events after PLT transfusion. On the other hand, such treatments may also lead to increased cytokine production by stimulation of WBCs or PLTs due to the photochemical or photodynamical process itself. Material and Methods: 12 triple-dose PLT apheresis collections were leukoreduced by the process-controlled leukoreduction system of the Trima Accel machine and split into 3 units undergoing Mirasol-PRT treatment (M) or gamma irradiation (X) or remaining untreated (C). During storage for up to 7 days, PLT activation, WBC-derived Th-1/2, and inflammatory as well as PLT-derived cytokines were measured by cytometric bead array and enzymelinked immunosorbent assay, respectively. Results: Independent of treatment, all PLT products exhibited low levels of WBC-associated cytokines near or below assay detection limits. WBC-associated cytokines were not elevated by Mirasol-PRT treatment. PLT-derived cytokines were detected at higher levels and increased significantly during storage in all units. Most likely due to higher PLT activation, M units showed significantly higher levels of PLT-derived cytokines compared to untreated and gamma-irradiated units on day 5 of storage. Conclusion: In all PCs, PLTs themselves were the main source of cytokine release. Mirasol-PRT treatment was associated with a significantly increased PLT activation and accumulation of PLT-derived cytokines during storage, without affecting WBC-derived cytokines relative to controls.

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Section: Laboratory Methodsmentioning

confidence: 99%

Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Picker

Steisel

Gathof³

2009

Transfus Med Hemother

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“…release criteria up to 7 d of storage, this treatment results in considerable metabolic deterioration, increased platelet activation during storage and inconsistent findings by in vitro haemostatic assessment (Van Rhenen et al, 2000;Janetzko et al, 2004;Jansen et al, 2004;Picker et al, 2004;Apelseth et al, 2007;Lozano et al, 2007;van der Meer et al, 2009). Nevertheless, transfusion in thrombocytopenic patients corrected prolonged bleeding times .…”

mentioning

confidence: 99%

Clinical effectiveness of leucoreduced, pooled donor platelet concentrates, stored in plasma or additive solution with and without pathogen reduction

Kerkhoffs¹,

Putten²,

Novotny³

et al. 2010

Br J Haematol

153

309

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SummaryPathogen reduction (PR) of platelet products increases costs and available clinical studies are equivocal with respect to clinical and haemostatic effectiveness. We conducted a multicentre, open‐label, randomized, non‐inferiority trial comparing the clinical effectiveness of buffy‐coat derived leucoreduced platelet concentrates (PC) stored for up to 7 d in plasma with platelets stored in platelet additive solution III (PASIII) without and with treatment with amotosalen‐HCl/ultraviolet‐A (UVA) photochemical pathogen reduction (PR‐PASIII). Primary endpoint of the study was 1‐h corrected count increment (CCI). Secondary endpoints were 24‐h CCI, bleeding, transfusion requirement of red cells and PC, platelet transfusion interval and adverse transfusion reactions. Compared to plasma‐PC, in the intention to treat analysis of 278 evaluable patients the mean difference for the 1‐h CCI of PR‐PASIII‐PC and PASIII‐PC was −31% (P < 0·0001) and −9% (P = n.s.), respectively. Twenty‐seven patients (32%) had bleeding events in the PR‐PASIII arm, as compared to 19 (19%) in the plasma arm and 14 (15%) in the PASIII arm (P = 0·034). Despite the potential advantages of pathogen (and leucocyte) inactivation of amotosalen‐HCl/UVA‐treated platelet products, their clinical efficacy is inferior to platelets stored in plasma, warranting a critical reappraisal of employing this technique for clinical use.

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“…Prior to PRT treatment with the INTERCEPT BLOOD SYSTEM as described previously [19][20][21] [22][23][24]. Untreated C units were resuspended in 150 ml of InterSol plus 30 ml saline to compensate for the addition of photosensitizers.…”

Section: Prt Treatmentmentioning

confidence: 99%

Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

Picker

Oustianskaia

Schneider

et al. 2010

Transfus Med Hemother

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Background: In vitro function of stored platelet (PLT) con-centrates was analyzed after applying two different techniques of pathogen reduction technology (PRT) treatment, which could increase cellular injury during processing and storage. Methods: Nine triple-dose PLT apheresis donations were split into 27 single units designated to riboflavin-UVB (M) or psoralen-UVA (I) treatment or remained untreated (C). Throughout 8 days of storage, samples were analyzed for annexin V release, the mitochondrial transmembrane potential (ΔΨ) and some classical markers of PLT quality (pH, LDH release, hypotonic shock response (HSR)). Results: PLT count and LDH release of all units maintained initial ranges. All units exhibited a decrease in pH and HSR and an increase in annexin V release and ΔΨ disruption. Notably, throughout the entire storage period, annexin V release re-mained lowest in M units. Throughout 7 days of storage, M units remained comparable to C units (p > 0.05), whereas inferior values were observed with I units. Here, differences to C units reached significance by day 1 (pH: p < 0.0001), day 5 (annexin V release: p < 0.014), and day 7 (HSR, ΔΨ: p ≤ 0.003). After PRT treatment, annexin V release and ΔΨ disruption were significantly (p < 0.001) correlated with pH and HSR. Conclusion: During storage, all units showed a de-crease in HSR and an increase in acidity, annexin V release and ΔΨ disruption. While M units remained comparable to C units, I units demonstrated significantly inferior values dur-ing terminal storage. This could have resulted from differences in PRT treatment or simply be due to differences in storage media and should be analyzed for clinical relevance in future investigations.

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Functional characteristics of buffy‐coat PLTs photochemically treated with amotosalen‐HCl for pathogen inactivation

Cited by 60 publications

References 42 publications

Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets

Clinical effectiveness of leucoreduced, pooled donor platelet concentrates, stored in plasma or additive solution with and without pathogen reduction

Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction

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