Amotosalen/UVA pathogen inactivation technology reduces platelet activability, induces apoptosis and accelerates clearance

Hechler, Béatrice; Ravanat, Catherine; Gachet, Christian

doi:10.3324/haematol.2017.180539

Cited by 7 publications

(7 citation statements)

References 11 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The INTERCEPT technique also moderately increases platelet storage lesions, which may account for the reduced posttransfusion platelet recovery reported in some clinical trials, without altering the hemostatic clinical performance of the cells 12,13 . Some of these lesions nevertheless appear to be reversible, since we have shown that INTERCEPT‐treated platelets, once isolated from their storage medium by washing and resuspended in a physiological buffer, exhibit spontaneous activation and functional properties very similar to those of untreated platelets 14,15 . The storage medium is therefore an additional parameter susceptible to influence the development of storage lesions.…”

Section: Introductionmentioning

confidence: 81%

“…12,13 Some of these lesions nevertheless appear to be reversible, since we have shown that INTERCEPT-treated platelets, once isolated from their storage medium by washing and resuspended in a physiological buffer, exhibit spontaneous activation and functional properties very similar to those of untreated platelets. 14,15 The storage medium is therefore an additional parameter susceptible to influence the development of storage lesions.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Removal of citrate from PAS‐III additive solution improves functional and biochemical characteristics of buffy‐coat platelet concentrates stored for 7 days, with or without INTERCEPT pathogen reduction

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background: Deterioration in quality of platelet concentrates (PCs) during storage results from the appearance of storage lesions affecting the hemostatic functions and posttransfusion survival of platelets. These lesions depend on the preparation and pathogen inactivation methods used, duration of storage, and platelet additive solutions (PASs) present in storage bags. Methods: We investigated the effects of citrate contained in third-generation PAS (PAS-III) on storage lesions in buffy-coat PCs with or without photochemical (amotosalen-ultraviolet A) treatment over 7 days. Results: Platelet counts were conserved in all groups during storage, as was platelet swirling without appearance of macroscopic aggregates. Glycoprotein (GP) IIbIIIa and GPVI expression remained stable, whereas GPIbα declined similarly in all groups during storage. Removal of citrate from PAS-III, resulting in global reduction of citrate from 11 to 5 mM, led to a significant decrease in glucose consumption, which largely countered a modest deleterious effect of photochemical treatment. Citrate reduction also resulted in decreased lactate generation and better maintenance of pH during storage, while photochemical treatment had no impact on these parameters. Moreover, citrate-free storage significantly reduced exposure of P-selectin and the apoptosis signal phosphatidylserine, thereby abolishing the activating effect of photochemical treatment on both parameters. Citrate reduction benefited platelet aggregation to various agonists up to Day 7, whereas PCT had no impact on these responses. Conclusion: Removal of citrate from PAS-III has a beneficial impact on platelet metabolism, spontaneous activation, and apoptosis, and improves platelet Abbreviations: ADP, adenosine 5 0 diphosphate; BC-PCs, buffy-coat platelet concentrates; GP, glycoprotein; MPV, mean platelet volume; PAS, platelet additive solution; PAS-III, third-generation platelet additive solution; PC, platelet concentrate; pCO 2 , partial pressure of carbon dioxide; PCT, photochemically treated; pO 2 , partial pressure of oxygen; PS, phosphatidylserine; TRAP-6, thrombin receptor activator peptide 6; UVA, ultraviolet A.

show abstract

Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Removal of citrate from PAS‐III additive solution improves functional and biochemical characteristics of buffy‐coat platelet concentrates stored for 7 days, with or without INTERCEPT pathogen reduction

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Finally, PC transfusion carries a greater risk of bacterial contamination, which can be life threatening especially in severely immuno-compromised patients ( 51 ). The introduction of Pathogen Reduction Technologies has abrogated much of the adverse effects associated with pathogen contamination of platelet products ( 52 , 53 ). Pre-storage leukoreduction proved to significantly reduce inflammatory reactions as well as viral infections ( 54 ).…”

Section: A Brief Overview Of Pc Transfusion Benefits and Complicationmentioning

confidence: 99%

The Non-Hemostatic Aspects of Transfused Platelets

et al. 2018

View full text Add to dashboard Cite

Platelets transfusion is a safe process, but during or after the process, the recipient may experience an adverse reaction and occasionally a serious adverse reaction (SAR). In this review, we focus on the inflammatory potential of platelet components (PCs) and their involvement in SARs. Recent evidence has highlighted a central role for platelets in the host inflammatory and immune responses. Blood platelets are involved in inflammation and various other aspects of innate immunity through the release of a plethora of immunomodulatory cytokines, chemokines, and associated molecules, collectively termed biological response modifiers that behave like ligands for endothelial and leukocyte receptors and for platelets themselves. The involvement of PCs in SARs—particularly on a critically ill patient’s context—could be related, at least in part, to the inflammatory functions of platelets, acquired during storage lesions. Moreover, we focus on causal link between platelet activation and immune-mediated disorders (transfusion-associated immunomodulation, platelets, polyanions, and bacterial defense and alloimmunization). This is linked to the platelets’ propensity to be activated even in the absence of deliberate stimuli and to the occurrence of time-dependent storage lesions.

show abstract

“…Several studies have reported reduced platelet function upon Intercept treatment (19,21,(32)(33)(34). Intercept has been shown to induce activation of p38, diminish the level of CD42 (also known as GpIb, which, in its complex, allows platelet adhesion and platelet clogging) (35), and deregulate expression of the pro-survival gene Bcl-xl and anti-apoptotic genes (21). In addition, to modulate the platelet mRNA transcriptome (19), Intercept was reported to alter platelet characteristics (mean volume), activation level, and aggregation response to physiological agonists (21).…”

Section: Discussionmentioning

confidence: 99%

Platelet Pathogen Reduction Technologies Alter the MicroRNA Profile of Platelet-Derived Microparticles

Diallo

Benmoussa

Laugier

et al. 2020

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Despite improvements in donor screening and increasing efforts to avoid contamination and the spread of pathogens in clinical platelet concentrates (PCs), the risks of transfusion-transmitted infections remain important. Relying on an ultraviolet photo activation system, pathogen reduction technologies (PRTs), such as Intercept and Mirasol, utilize amotosalen, and riboflavin (vitamin B2), respectively, to mediate inactivation of pathogen nucleic acids. Although they are expected to increase the safety and prolong the shelf life of clinical PCs, these PRTs might affect the quality and function of platelets, as recently reported. Upon activation, platelets release microparticles (MPs), which are involved in intercellular communications and regulation of gene expression, thereby mediating critical cellular functions. Here, we have used small RNA sequencing (RNA-Seq) to document the effect of PRT treatment on the microRNA profiles of platelets and derived MPs. PRT treatment did not affect the microRNA profile of platelets. However, we observed a specific loading of certain microRNAs into platelet MPs, which was impaired by treatment with Intercept or its Additive solution (SSP+). Whereas, Intercept had an impact on the microRNA profile of platelet-derived MPs, Mirasol did not impact the microRNA profile of platelets and derived MPs, compared to non-treated control. Considering that platelet MPs are able to transfer their microRNA content to recipient cells, and that this content may exert biological activities, those findings suggest that PRT treatment of clinical PCs may modify the bioactivity of the platelets and MPs to be transfused and argue for further investigations into PRT-induced changes in clinical PC content and function.

show abstract

Amotosalen/UVA pathogen inactivation technology reduces platelet activability, induces apoptosis and accelerates clearance

Cited by 7 publications

References 11 publications

Removal of citrate from PAS‐III additive solution improves functional and biochemical characteristics of buffy‐coat platelet concentrates stored for 7 days, with or without INTERCEPT pathogen reduction

Removal of citrate from PAS‐III additive solution improves functional and biochemical characteristics of buffy‐coat platelet concentrates stored for 7 days, with or without INTERCEPT pathogen reduction

The Non-Hemostatic Aspects of Transfused Platelets

Platelet Pathogen Reduction Technologies Alter the MicroRNA Profile of Platelet-Derived Microparticles

Contact Info

Product

Resources

About