Extended storage and glucose exhaustion are associated with apoptotic changes in platelets stored in additive solution

Johnson, Lacey; Schubert, Peter; Tan, Shereen; Devine, Dana V.; Marks, Denese C.

doi:10.1111/trf.13345

Cited by 28 publications

(22 citation statements)

References 47 publications

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“…As anticipated, cold‐storage was sufficient to prevent the accelerated glycolytic metabolism associated with UVC‐treatment. The availability of an adequate supply of energy during ex vivo storage has a substantial impact on platelets, with depletion of glucose being linked with decreased viability . Thus, the reduction in glycolytic metabolism afforded by cold storage provided UVC‐treated platelets with sufficient glucose for at least an extra two days of storage, compared to RT‐UVC platelets which had exhausted their glucose reserves by day 7.…”

Section: Discussionmentioning

confidence: 99%

The impact of refrigerated storage of UVC pathogen inactivated platelet concentrates on in vitro platelet quality parameters

et al. 2018

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Background and Objectives Refrigeration (cold‐storage) of pathogen inactivated (PI) platelet components may increase the shelf‐life and safety profile of platelet components, compared to conventional room‐temperature (RT) storage. Whilst there is substantial knowledge regarding the impact of these individual treatments on platelets, the combined effect has not been assessed. Materials and methods Using a pool‐and‐split study design, paired buffy‐coat derived platelets in 70% platelet additive solution (SSP+; MacoPharma) were left untreated or PI‐treated using the THERAFLEX UV‐Platelets System (UVC; MacoPharma). Units from each pair were split and stored at room temperature (20–24°C) or cold‐stored (2–6°C) to yield RT, cold, RT‐UVC and cold‐UVC study groups (n = 8 in each group). In vitro quality and function was tested over 9 days. Results Cold‐storage of UVC‐treated platelets reduced glycolytic metabolism (glucose consumption and lactate production) compared to RT‐UVC units. Cold‐UVC platelets demonstrated complete abrogation of HSR by day 5, increased externalisation of phosphatidylserine (annexin‐V binding) and activation of the GPIIb/IIIa receptor (PAC‐1 binding) above the levels observed with the individual treatments. Aggregation responses (ADP and collagen) were enhanced in the cold‐UVC platelets compared to both RT groups, but this was primarily mediated by cold‐storage. Haemostatic function, as measured using TEG, was similar between the groups. Conclusion Cold‐storage of UVC‐treated platelets reduced PI‐induced acceleration of glycolytic metabolism. However, combining cold‐storage and UVC‐treatment resulted in additional phenotypic changes compared to each treatment individually. Further work is required to understand the impact of these changes in clinical efficacy.

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Section: Discussionmentioning

confidence: 99%

The impact of refrigerated storage of UVC pathogen inactivated platelet concentrates on in vitro platelet quality parameters

et al. 2018

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“…Even though the clinical impact is unknown, this automated method did not have an influence on the level of RANTES and sCD40L, and BRS‐A had little or no influence on the accumulation of PDMP, RANTES, and sCD40L in storage media during 3 days of storage. Johnson et al demonstrated that PLT apoptosis (annexin V binding) was initiated for extended storage periods, which was likely linked to exhaustion of glucose in storage media. Like this report, the present study showed that annexin V binding increased largely and aggregation response and HSR deteriorated on Day 7, along with depletion of glucose.…”

Section: Discussionmentioning

confidence: 99%

Impact of the platelet washing process on in vitro platelet properties, and the levels of soluble CD40 ligand and platelet‐derived microparticles in the storage media

Oikawa

Minegishi²,

Endo

et al. 2018

Transfusion

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BACKGROUND A new platelet (PLT) additive solution, bicarbonated Ringer's solution supplemented with acid‐citrate‐dextrose Formula A, termed BRS‐A, as well as a new automated closed system cell processor for washing PLTs have recently been developed. This study evaluated the in vitro properties of PLTs with the automated system versus the manual method, using the BRS‐A additive solution for washing and storage. METHODS ABO‐identical apheresis PLTs in 100% plasma were pooled and split equally for control (in 100% plasma or a manual method) and test (ACP215 automated system) units. In vitro characteristics of PLTs washed with the automated system were compared to those of PLTs in 100% plasma (Study 1) or washed with a manual method (Study 2) during the 7‐day storage. RESULTS In Study 1, hypotonic shock response, aggregation response, mitochondrial membrane potential, adenosine triphosphate, and CD42b mean fluorescence intensity were comparable in the control and test groups during the 7‐day storage. CD62P expression was lower in the test group than controls on Days 3 and 7. The level of platelet‐derived microparticles (PDMPs) in the test group on Days 1 and 2 were higher than those in controls. In contrast, the levels of soluble CD40 ligand (sCD40L) and regulated upon activation of normal T‐cell expressed and secreted (RANTES) in the test units were lower than controls. In Study 2, no significant differences were found in all in vitro properties except for PLT count and the levels of PDMPs in the test units were higher than controls during storage. CONCLUSION Apheresis PLTs washed with the automated system using BRS‐A additive solution maintained in vitro properties during storage. Washing methods influenced PDMP levels but not sCD40L and RANTES.

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“…The heterogeneity of platelet concentrates increases with storage [10, 13, 32, 33] and with pathogen-reduction processing [5, 13] and varies greatly between normal donors [13, 34–36]. The largest contributor to platelet heterogeneity is the microparticle content (Figure 1(b)).…”

Section: Platelet Quality From the Perspective Of Productionmentioning

confidence: 99%

“…Because the emphasis is to detect degradation from the beginning to the end of the current 5-day shelf life [5, 6], the resolution of current quality measures has been tuned to be high for small changes on the “resting/viable” end of the quality spectrum but becomes low on the “activated/functional” end of the quality spectrum. Additional changes are seen upon extended shelf life which become more important as bacterially tested or pathogen inactivated platelets may be stored for 7 days.…”

Section: Introductionmentioning

confidence: 99%

Could Microparticles Be the Universal Quality Indicator for Platelet Viability and Function?

Maurer‐Spurej

Chipperfield

2016

Journal of Blood Transfusion

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High quality means good fitness for the intended use. Research activity regarding quality measures for platelet transfusions has focused on platelet storage and platelet storage lesion. Thus, platelet quality is judged from the manufacturer's point of view and regulated to ensure consistency and stability of the manufacturing process. Assuming that fresh product is always superior to aged product, maintaining in vitro characteristics should preserve high quality. However, despite the highest in vitro quality standards, platelets often fail in vivo. This suggests we may need different quality measures to predict platelet performance after transfusion. Adding to this complexity, platelets are used clinically for very different purposes: platelets need to circulate when given as prophylaxis to cancer patients and to stop bleeding when given to surgery or trauma patients. In addition, the emerging application of platelet-rich plasma injections exploits the immunological functions of platelets. Requirements for quality of platelets intended to prevent bleeding, stop bleeding, or promote wound healing are potentially very different. Can a single measurable characteristic describe platelet quality for all uses? Here we present microparticle measurement in platelet samples, and its potential to become the universal quality characteristic for platelet production, storage, viability, function, and compatibility.

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Extended storage and glucose exhaustion are associated with apoptotic changes in platelets stored in additive solution

Abstract: Exhaustion of glucose was associated with a proapoptotic phenotype. Results such as these should be considered before extending the PLT shelf life beyond 7 days, particularly when stored in ASs lacking glucose with low plasma carryover.

Cited by 28 publications

References 47 publications

The impact of refrigerated storage of UVC pathogen inactivated platelet concentrates on in vitro platelet quality parameters

The impact of refrigerated storage of UVC pathogen inactivated platelet concentrates on in vitro platelet quality parameters

Impact of the platelet washing process on in vitro platelet properties, and the levels of soluble CD40 ligand and platelet‐derived microparticles in the storage media

Could Microparticles Be the Universal Quality Indicator for Platelet Viability and Function?

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