Future of platelet formulations with improved clotting profile: a short review on human safety and efficacy data

Cancelas, José A.

doi:10.1111/trf.15163

Cited by 8 publications

(6 citation statements)

References 67 publications

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“…Because cryopreserved platelets are procoagulant, they seem ideally suited to treat actively bleeding patients like in (acute) trauma [33,[50][51][52]. Clinical trials in acute trauma are a practical challenge and most published studies are observational [53,54].…”

Section: Efficacymentioning

confidence: 99%

Platelet Biochemistry and Morphology after Cryopreservation

Six

Compernolle

Feys

2020

IJMS

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Platelet cryopreservation has been investigated for several decades as an alternative to room temperature storage of platelet concentrates. The use of dimethylsulfoxide as a cryoprotectant has improved platelet storage and cryopreserved concentrates can be kept at −80 °C for two years. Cryopreserved platelets can serve as emergency backup to support stock crises or to disburden difficult logistic areas like rural or military regions. Cryopreservation significantly influences platelet morphology, decreases platelet activation and severely abrogates platelet aggregation. Recent data indicate that cryopreserved platelets have a procoagulant phenotype because thrombin and fibrin formation kicks in earlier compared to room temperature stored platelets. This happens both in static and hydrodynamic conditions. In a clinical setting, low 1-h post transfusion recoveries of cryopreserved platelets represent fast clearance from circulation which may be explained by changes to the platelet GPIbα receptor. Cryopreservation splits the concentrate in two platelet subpopulations depending on GPIbα expression levels. Further research is needed to unravel its physiological importance. Proving clinical efficacy of cryopreserved platelets is difficult because of the heterogeneity of indications and the ambiguity of outcome measures. The procoagulant character of cryopreserved platelets has increased interest for use in trauma stressing the need for double-blinded randomized clinical trials in actively bleeding patients.

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Section: Efficacymentioning

confidence: 99%

Platelet Biochemistry and Morphology after Cryopreservation

Six

Compernolle

Feys

2020

IJMS

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“…The procedures for the production and storage of platelet concentrates (PCs) intended for transfusion are continually evolving with the use of novel pathogen-reduction technologies, new platelet (PLT) additive solutions, extended conditions of storage, and improved preparation methods and devices. [1][2][3][4][5][6][7][8][9] These new strategies enhance the safety of the recipients and help to optimize utilization of blood reserves, human and technical resources, and management of the PLT supply.…”

Section: Introductionmentioning

confidence: 99%

Human platelets labeled at two discrete biotin densities are functional in vitro and are detected in vivo in the murine circulation: A promising approach to monitor platelet survival in vivo in clinical research

et al. 2021

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Background The production of platelet concentrates (PCs) is evolving, and their survival capacity needs in vivo evaluation. This requires that the transfused platelets (PLTs) be distinguished from those of the recipient. Labeling at various biotin (Bio) densities allows one to concurrently trace multiple PLT populations, as reported for red blood cells. Study Design and Methods A method is described to label human PLTs at two densities of Bio for future clinical trials. Injectable‐grade PLTs were prepared in a sterile environment, using injectable‐grade buffers and good manufacturing practices (GMP)‐grade Sulfo‐NHS‐Biotin. Sulfo‐NHS‐Biotin concentrations were chosen to maintain PLT integrity and avoid potential alloimmunization while enabling the detection of circulating BioPLTs. The impact of biotinylation on human PLT recirculation was evaluated in vivo in a severe immunodeficient mouse model using ex vivo flow cytometry. Results BioPLTs labeled with 1.2 or 10 μg/ml Sulfo‐NHS‐Biotin displayed normal ultrastructure and retained aggregation and secretion capacity and normal expression of the main surface glycoproteins. The procedure avoided detrimental PLT activation or apoptosis signals. Transfused human BioPLT populations could be distinguished from one another and from unlabeled circulating mouse PLTs, and their survival was comparable to that of unlabeled human PLTs in the mouse model. Conclusions Provided low Sulfo‐NHS‐Biotin concentrations (<10 μg/ml) are used, injectable‐grade BioPLTs comply with safety regulations, conserve PLT integrity, and permit accurate in vivo detection. This alternative to radioisotopes, which allows one to follow different PLT populations in the same recipient, should be valuable when assessing new PC preparations and monitoring PLT survival in clinical research.

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“…7,32,33 In our study, CSP are significantly more pro-coagulant in transfusion recipients suggesting that the hemostatic effect of extended-stored CSP may be more akin to cryopreserved (i.e., frozen) or lyophilized platelets, albeit with a shorter circulation time. 34,35 Surprisingly, a recent trial with lyophilized platelets did not show increased thrombin generation in transfusion recipients. 36 This may have been due to the low dose tested in the trial.…”

Section: Discussionmentioning

confidence: 99%

Platelet dysfunction reversal with cold-stored vs. room temperature-stored platelet transfusions

Kogler,

Miles,

Özpolat

et al. 2023

Preprint

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Background: Platelets are stored at room temperature for 5-7 days (RSP). Due to frequent and severe shortages, the FDA recently approved up to 14-day cold-stored platelets in plasma (CSP). However, the post-transfusion function of CSP is unknown and it is unclear which donors are best suited to provide either RSP and/or CSP. Objective: To evaluate the post-transfusion function and predictors of post-transfusion function for platelets stored for the maximum approved storage times (7-day RSP, 14-day CSP) in healthy volunteers on acetylsalicylic acid (ASA). Methods: We conducted a randomized cross-over study in ten healthy humans. Subjects donated one platelet unit stored at either RT (RSP) or 4C (CSP) based on randomization. Before transfusion, subjects ingested ASA to inhibit endogenous platelets. Transfusion recipients were tested for platelet function and lipid mediators. Platelet units were tested for lipid mediators only. A second round with transfusion of the alternative product and an identical testing sequence followed. Results: RSP reversed platelet inhibition significantly better in aIIbbeta3 integrin activation-dependent assays. In contrast, CSP led to significantly more thrombin generation in recipients, which was not dependent on platelet microparticles, but CSP themselves. Lysophosphatidylcholine-O (Lyso-Platelet Activating Factor) species levels predicted the procoagulant capacity of CSP. In contrast, polyunsaturated fatty acid concentration predicted the aggregation response of RSP. Conclusion: We provide the first efficacy data of extended-stored CSP in plasma. Our results suggest that identifying ideal RSP and CSP donors is possible and pave the way for larger studies in the future.

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Future of platelet formulations with improved clotting profile: a short review on human safety and efficacy data

Cited by 8 publications

References 67 publications

Platelet Biochemistry and Morphology after Cryopreservation

Platelet Biochemistry and Morphology after Cryopreservation

Human platelets labeled at two discrete biotin densities are functional in vitro and are detected in vivo in the murine circulation: A promising approach to monitor platelet survival in vivo in clinical research

Platelet dysfunction reversal with cold-stored vs. room temperature-stored platelet transfusions

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