An in vitro pilot study of apheresis platelets collected on Trima Accel system and stored in T‐PAS+ solution at refrigeration temperature (1‐6°C)

Reddoch-Cardenas, Kristin M; Sharma, Umang; Salgado, Christi; Montgomery, Robbie K.; Cantu, Carolina; Cingoz, Neslihan; Bryant, Ron; Darlington, Daniel N.; Pidcoke, Heather F.; Kamucheka, Robin M; Andrew, P.

doi:10.1111/trf.15150

Cited by 21 publications

(29 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our experiments, addition of VX-702 resulted in increased HSR levels of cold-stored and thermocycled-stored platelets. After one week of storage, room-stored platelets maintained HSR levels better than any cold conditions, as has been described in the literature [14,17,29,30,40]. However, after two weeks of storage, HSR levels were better preserved during storage at cold and thermocycled temperatures than at room temperature and this was further improved in presence of VX-702.…”

Section: Discussionsupporting

confidence: 73%

“…Cold temperature storage also generates changes in cell surface glycoprotein glycosylation, GPIbα clustering [ 11 , 12 ] and transforms integrin αIIbβ3 conformation to an activated state [ 13 ]. Similarly, cold storage manifests in platelet activation which results in lysosomal and granule release [ 13 ] as well as increased microparticle formation [ 14 ]. Overall, the cold storage lesion appears to make platelets more procoagulant [ 15 ] and likely to be effective when transfused into actively bleeding patients [ 16 ] even though their circulation time is reduced [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

P38 mitogen activated protein kinase inhibitor improves platelet in vitro parameters and in vivo survival in a SCID mouse model of transfusion for platelets stored at cold or temperature cycled conditions for 14 days

2021

View full text Add to dashboard Cite

Platelets for transfusion are stored at room temperature (20–24°C) up to 7 days but decline in biochemical and morphological parameters during storage and can support bacterial proliferation. This decline is reduced with p38MAPK inhibitor, VX-702. Storage of platelets in the cold (4–6°C) can reduce bacterial proliferation but platelets get activated and have reduced circulation when transfused. Thermocycling (cold storage with brief periodic warm ups) reduces some of the effects of cold storage. We evaluated in vitro properties and in vivo circulation in SCID mouse model of human platelet transfusion of platelets stored in cold or thermocycled for 14 days with and without VX-702. Apheresis platelet units (N = 15) were each aliquoted into five storage bags and stored under different conditions: room temperature; cold temperature; thermocycled temperature; cold temperature with VX-702; thermocycled temperature with VX-702. Platelet in vitro parameters were evaluated at 1, 7 and 14 days. On day 14, platelets were infused into SCID mice to assess their retention in circulation by flow cytometry. VX-702 reduced negative platelet parameters associated with cold and thermocycled storage such as an increase in expression of activation markers CD62, CD63 and of phosphatidylserine (marker of apoptosis measured by Annexin binding) and lowered the rise in lactate (marker of increase in anaerobic metabolism). However, VX-702 did not inhibit agonist-induced platelet aggregation indicating that it does not interfere with platelet hemostatic function. In vivo, VX-702 improved initial recovery and area under the curve in circulation of human platelets infused into a mouse model that has been previously validated against a human platelet infusion clinical trial. In conclusion, inhibition of p38MAPK during 14-days platelet storage in cold or thermocycling conditions improved in vitro platelet parameters and platelet circulation in the mouse model indicating that VX-702 may improve cell physiology and clinical performance of human platelets stored in cold conditions.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

P38 mitogen activated protein kinase inhibitor improves platelet in vitro parameters and in vivo survival in a SCID mouse model of transfusion for platelets stored at cold or temperature cycled conditions for 14 days

2021

View full text Add to dashboard Cite

show abstract

“…12 RTP in PAS retracted for up to 21 days while those stored in AP failed to retract past 10 days, likely due to the better buffering capability and metabolic support provided by PAS over plasma. [30][31][32][33] Interestingly, we observed an increase in retraction in 5-day RTP in AP and PAS independent of platelet or fibrin incorporation, while these platelets generated 50% less contractile stress than fresh platelets indicating semifunctional contractile machinery at 5 days of storage. This suggested that the seemingly increased retraction is not a function of platelet contractility, prompting a deeper investigation of clot microstructure and serum composition.…”

Section: Discussionmentioning

confidence: 77%

Cold‐stored platelets have better preserved contractile function in comparison with room temperature‐stored platelets over 21 days

et al. 2021

Self Cite

View full text Add to dashboard Cite

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature‐stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold‐stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14‐day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet‐mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS‐stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP.

show abstract

“…In addition, Filip and Aster 15 found that cold‐stored PLTs were less effective after 72 hours of storage when compared to RT‐stored PLTs in vivo. Multiple in vitro studies have shown that PLTs maintain good hemostatic properties when stored for periods of up to 21 days in cold conditions, 16–19 but these studies have not yet identified the root cause of why long‐term (>5 days) cold‐stored PLTs do not function as well as those stored short term (<3 days).…”

Section: Introductionmentioning

confidence: 99%

Antioxidant prevents clearance of hemostatically competent platelets after long‐term cold storage

et al. 2020

View full text Add to dashboard Cite

Background Cold storage of platelets (PLTs) has the potential advantage of prolonging storage time while reducing posttransfusion infection given the decreased likelihood of bacterial outgrowth during storage and possibly beneficial effects in treating bleeding patients. However, cold storage reduces PLT survival through the induction of complex storage lesions, which are more accentuated when storage is prolonged. Study Design and Methods Whole blood–derived PLT‐rich plasma concentrates from seven PLT pools (n = 5 donors per pool). PLT additive solution was added (67%/33% plasma) and the product was split into 50‐mL bags. Split units were stored in the presence or absence of 1 mM of N‐acetylcysteine (NAC) under agitation for up to 14 days at room temperature or in the cold and were analyzed for PLT activation, fibrinogen‐dependent spreading, microparticle formation, mitochondrial respiratory activity, reactive oxygen species (ROS) generation, as well as in vivo survival and bleeding time correction in immunodeficient mice. Results Cold storage of PLTs for 7 days or longer induces significant PLT activation, cytoskeletal damage, impaired fibrinogen spreading, enhances mitochondrial metabolic decoupling and ROS generation, and increases macrophage‐dependent phagocytosis and macrophage‐independent clearance. Addition of NAC prevents PLT clearance and allows a correction of the prolonged bleeding time in thrombocytopenic, aspirin‐treated, immunodeficient mice. Conclusions Long‐term cold storage induces mitochondrial uncoupling and increased proton leak and ROS generation. The resulting ROS is a crucial contributor to the increased macrophage‐dependent and ‐independent clearance of functional PLTs and can be prevented by the antioxidant NAC in a magnesium‐containing additive solution.

show abstract

An in vitro pilot study of apheresis platelets collected on Trima Accel system and stored in T‐PAS+ solution at refrigeration temperature (1‐6°C)

Cited by 21 publications

References 21 publications

P38 mitogen activated protein kinase inhibitor improves platelet in vitro parameters and in vivo survival in a SCID mouse model of transfusion for platelets stored at cold or temperature cycled conditions for 14 days

P38 mitogen activated protein kinase inhibitor improves platelet in vitro parameters and in vivo survival in a SCID mouse model of transfusion for platelets stored at cold or temperature cycled conditions for 14 days

Cold‐stored platelets have better preserved contractile function in comparison with room temperature‐stored platelets over 21 days

Antioxidant prevents clearance of hemostatically competent platelets after long‐term cold storage

Contact Info

Product

Resources

About