Impact of cold storage on platelets treated with Intercept pathogen inactivation (original) (raw)
Related papers
Bioactive Compounds in Health and Disease, 2023
Background: Platelet refrigeration could eliminate bacterial contamination and improve the hemostatic function even better than already-used room-temperature storage. This study aimed to assess the effect of cold storage, with and without agitation, on the apheresis platelets' hemostatic, metabolic, and functional activity. Materials and methods: The study included 10 healthy volunteer donors to collect Apheresis PLT. They were submitted to careful clinical examination and standard laboratory workup. Collected samples were processed in accordance with American Association of Blood Banks (AABB) guidelines. Every aliquot collected from each volunteer was stored for up to 5 days at one of the following storage conditions: 1. In an FDA-approved-PLT incubator with agitation at room temperature (RT + AG as a group; GI), 2. In an FDA-approved-refrigerator at 4 oC with agitation (4 oC + AG as a group; GII), 3. In an FDA-approved- refrigerator at 4 oC without agitation (4 oC – AG as a group; GIII). The following PLT workup was done; PLT count and mean platelet volume (MPV), metabolic variables, PLT aggregation studies, PLT receptors expression, and PLT pro-inflammatory mediator’s release. Results:All samples had a significant PLT count decline compared to baseline data. No changes in MPV were observed in all groups on day 3 and day 5, meaning that single PLT size remained unchanged. In addition, GI showed a mark of significant increase in metabolic activity when compared to baseline PLTs in contrast to GII, and GIII, which were more metabolically stable and less active. Comparison between the studied groups regarding PLT aggregation revealed significantly higher PLT aggregation response to ADP and collagen in GII and GIII compared to GI on the 3rd and 5th days. Moreover, it was shown that GII and GIII samples had significantly higher CD62p expression when compared with GI on the 3rd and 5th days despite being less active and more stable. While it was found that TXB2 levels were significantly higher, nearly 3-fold, in GI as compared to GII and GIII. Conclusions: Apheresis platelets (AP) cold storage provides a clear advantage over standard conditions regarding biochemical balance and hemostatic performance, which could markedly improve AP's clinical and economic value in different scenarios. Keywords: Platelet aggregation, P-selectin, Thromboxane B2.
In vitro comparison of cryopreserved and liquid platelets: potential clinical implications
Transfusion, 2014
BACKGROUND: Platelet (PLT) concentrates can be cryopreserved in dimethyl sulfoxide (DMSO) and stored at −80°C for 2 years. These storage conditions improve availability in both rural and military environments. Previous phenotypic and in vitro studies of cryopreserved PLTs are limited by comparison to fresh liquid-stored PLTs, rather than PLTs stored over their clinically relevant shelf life. Further, nothing is known of the effect of reconstituting cryopreserved PLTs in plasma stored at a variety of clinically relevant temperatures. STUDY DESIGN AND METHODS: Apheresis PLTs were either stored at room temperature for 5 days or cryopreserved at −80°C with 5% DMSO. Cryopreserved PLTs were thawed at 37°C and reconstituted in plasma (stored at different temperatures) and compared to fresh and expired liquid-stored PLTs. In vitro assays were performed to assess glycoprotein expression, PLT activity, microparticle content, and function. RESULTS: Compared to liquid PLTs over storage, cryopreserved PLTs had reduced expression of the key glycoprotein receptors GPIbα and GPIIb. However, the proportion of PLTs expressing activation markers CD62P and CD63 was similar between cryopreserved and liquid-stored PLTs at expiry. Cryopreserved PLT components contained significantly higher numbers of phosphatidylserine-and tissue factor-positive microparticles than liquid-stored PLTs, and these microparticles reduced the time to clot formation and increased thrombin generation. CONCLUSION: There are distinct differences between cryopreserved and liquid-stored PLTs. Cryopreserved PLTs also have an enhanced hemostatic activity. Knowledge of these in vitro differences will be essential to understanding the outcomes of a clinical trial comparing cryopreserved PLTs and liquid PLTs stored for various durations. I n Australia, and many other countries including the United States, platelets (PLTs) stored under standard blood banking conditions, 20 to 24°C with constant agitation, currently have a shelf life of 5 days. This short shelf life can result in logistic and supply problems, so alternatives permitting longer storage, such as cryopreservation, are being investigated. Cryopreserved PLTs have been used by the military to treat bleeding since 2001. 1 To date, only a single clinical trial underpins this practice, which demonstrated that cryopreserved PLTs are hemostatically effective when transfused in patients bleeding after cardiopulmonary bypass. 2 Despite this encouraging result, a trial involving 73 patients, only 24 of whom received cryopreserved PLTs, is insufficient to support regulatory approval. In an effort to provide the required clinical evidence to satisfy clinicians and regulatory bodies, a pilot, randomized controlled clinical trial of cryopreserved PLTs, the cryopreserved ABBREVIATIONS: APC = allophycocyanin; DFP = deep-frozen plasma; FFP24 = fresh-frozen plasma stored at 4°C for up to 24 hours; MA = maximum amplitude; R-time = time to clot initiation; TEG = thromboelastogram.
The Effect of Cold on Platelets. II. Platelet Function After Short-term Storage at Cold Temperatures
Blood, 1972
Citrated platelet-rich plasma (PRP) was kept at cold temperatures or room temperature. After 4 hr or more at these temperatures, the PRPs were warmed 1 hr at 37°C. This prevents the spontaneous aggregation seen in chilled PRP that is stirred immediately after warming. Platelet aggregation in response to connective tissue (CT), epinephrine, and adenosine diphosphate (ADP) was considerably greater in the PRPs originally kept at cold temperatures. In addition, chilling would restore the aggregation of platelets whose function had deteriorated due to prolonged storage at warm temperatures. Neither ADP-induced refractoriness, serotonin uptake, or CT-induced serotonin release was affected by cold. Retention in glass bead columns was greater in platelets that had been chilled than in platelets kept at room temperature or 37°C. Thus, the storage of platelets at cold temperatures leads to changes that improve platelet aggregation but may also increase platelet adhesion, which would account f...
Cold stored platelets in treatment of bleeding
ISBT Science Series, 2017
The success of whole blood transfusion in military operational settings has engaged a debate on reintroduction of cold-stored whole blood in treatment of critical bleeding in civilian health care. The haemostatic function of platelets stored cold at 4°C has however been questioned. In this review, we discuss the effects of cold storage on platelets, whether stored in whole blood or as platelet concentrates. Cold storage of platelets was abandoned during the 1970s due to reduced circulation time. Haemostatic superiority of cold-stored platelets was however suggested. In vitro studies show reduced risk of bacterial contamination and equal or superior haemostatic qualities in cold-stored platelet concentrates when evaluated by metabolic measures and aggregation response. Data on cold-stored platelet concentrates from thrombocytopenic patients and healthy volunteers indicate improved platelet aggregation and reduced bleeding. A randomized controlled trial in paediatric patients undergoing cardiac surgery, showed reduced blood loss and improved platelet aggregation responses after transfusion with whole blood stored cold for up to 48 h, and platelets stored cold within whole blood for up to 15 days provide similar post-storage platelet viability as platelet concentrates or apheresis platelets stored for less than 3 days. Animal studies also suggest efficacy of cold-stored platelets. A study investigating the effects of cold-stored apheresis platelets in patients undergoing cardiothoracic is currently being performed in Bergen, Norway showing promising results. We conclude that in vitro and clinical studies indicate that cold-stored platelets may be beneficial in treatment of critical bleeding.
Transfusion, 2019
BACKGROUND: Cold storage of platelets may extend shelf life compared to room temperature storage. This study aimed to investigate in vitro platelet quality and function in cold-stored and delayed-cold-stored nonagitated apheresis platelets in platelet additive solution during storage for 21 days. STUDY DESIGN AND METHODS: Ten double apheresis platelet concentrates in 37% plasma/63% PAS-IIIM were split into two groups; nonagitated 2 to 6 C storage (CSPs) and delayed cold storage (DCSPs) with 7 days agitated storage at 20-24 C followed by nonagitated cold storage for 14 additional days. Platelet count, metabolism, viscoelastic properties, and aggregation ability were measured on Days 1, 7, 14, and 21. RESULTS: All platelet units, both CSPs and DCSPs, complied with the EU guidelines throughout storage for 21 days. Swirling was not detectable after cold storage. Cold storage improved platelet function; however, DCSP on Day 7 showed poorer results compared to CSP. Cold storage slowed down metabolism, with lower lactate and higher glucose concentrations in the CSP compared to the DCSP throughout storage for 21 days. CONCLUSION: Cold storage of platelets improved platelet function in in vitro assays, even though delayed cold storage on Day 7 showed poorer results compared to continuous cold storage. This difference could be explained by accelerated metabolism and higher glucose consumption during the period of room temperature storage. Cold storage and delayed cold storage could ease inventory management. Further studies investigating the in vitro and clinical effects of cold-stored and delayed-cold-stored platelets are encouraged. T he introduction of a balanced transfusion approach in treatment of hemorrhagic shock using RBC concentrates, plasma, and platelet concentrates (PCs) has been associated with improved outcomes. 1-3 The platelet storage lesion and risk of bacterial growth limit the shelf life of room temperature-stored PCs. 4-7 Short shelf life leads to wastage and creates logistical challenges. It also increases pressure to recruit donors, which is a growing problem for blood centers. 8 Studies have shown that cold storage of platelets reduces bacterial growth and preserves mitochondrial function, in vitro aggregation response, and clot formation longer. 9-14 Thus, the shelf life of apheresis PCs could be extended through cold storage. In the past, platelets were routinely stored cold at 4 C. However, this practice was abandoned when studies showed that cold storage led to a reduction in circulation time. 15-17 Slichter et al. 15 reported a reduction of in vivo viability from
When platelets are left in the cold
Annals of Blood, 2020
Storage of platelets typically is at room temperature (RT) in large, gas permeable bags that allow some CO 2 and O 2 exchange. The bags are kept on an orbital shaker in a thermostable cabinet (22±2 ℃). These physical storage conditions were rationally selected following scientific breakthroughs in the previous century (1,2). RT storage was selected over storage at 4 ℃ based on the observation that cold-stored platelets are cleared significantly faster from circulation compared to RT (3). Although gold standard for decades now, RT storage is suboptimal because of the higher risk for bacterial bloom compared to 4 ℃ storage (4). Recent estimates suggest that still between 1:1,000 to 1:2,500 platelet concentrates (PC) are contaminated with bacteria (5). Transfusion of a contaminated concentrate can cause sepsis and because patients often receive multiple units, their individual clinical risk for transfusion transmitted infection is a multiplicate of the mathematical risk for contamination of a single PC (6). It should be noted however that bacterial infection caused by platelet transfusion, and resulting in a serious adverse event is very rare in the EU with only 16 cases on 2.3 million platelet transfusions and one death in 2017 (EU DG Health and Food Safety 147152-10/01/2020). Nonetheless, to limit bacterial contamination PC shelf lives are mandatorily short and typically range from 4 to 7 days. This limitation continuously strains the inventory management of blood banks worldwide. Novel ways to extend platelet shelf life without risking sterility or quality, represent a major goal in transfusion medicine.
Transfusion, 2007
BACKGROUND: The increasing demand for platelet (PLT) transfusions has focused attention on appropriate use. Coated PLTs are a subpopulation of highly procoagulant PLTs formed by simultaneous stimulation by the agonist's collagen and thrombin hypothesized to drive clot formation at the site of vascular injury. Prolonged storage of PLTs may reduce their ability to support optimal hemostasis upon transfusion. STUDY DESIGN AND METHODS: PLT concentrates (PCs) stored for 1, 4, 6, and 8 days were costimulated with thrombin and the collagen glycoprotein VI (GPVI) receptor agonist convulxin, and their ability to form coated PLTs was determined by flow cytometry. Further, a plasma-based thrombin generation assay and thrombelastography were used to evaluate the aged PCs' capacity to support thrombin generation and clot formation, respectively. The stored PCs were additionally tested by standard quality control methods. RESULTS: PLT quality as measured by standard analyses was acceptable according to current practice. The hemostatic potential, however, was impaired with increasing storage time. The formation of coated PLTs decreased significantly from approximately 85 to 55 percent with increasing storage time (p < 0.05). The velocity of clot formation was significantly increased from Day 4 (p < 0.05). The velocity of thrombin generation and resistance against fibrinolysis were significantly reduced on Day 8 compared to Day 1 of storage (p < 0.05). CONCLUSION: Data in the present study suggest that storage significantly reduced the stored PLTs' ability to respond to conditions expected to exist at the site of vascular injury and that storage-induced reduction in PLT activation sensitivity correlated with a loss of hemostatic potential.
Vox Sanguinis, 2018
Conventional storage of platelet concentrates limits their shelf life to between 5 and 7 days due to the risk of bacterial proliferation and the development of the platelet storage lesion. Cold storage and cryopreservation of platelets may facilitate extension of the shelf life to weeks and years, and may also provide the benefit of being more haemostatically effective than conventionally stored platelets. Further, treatment of platelet concentrates with pathogen inactivation systems reduces bacterial contamination and provides a safeguard against the risk of emerging and re‐emerging pathogens. While each of these alternative storage techniques is gaining traction individually, little work has been done to examine the effect of combining treatments in an effort to further improve product safety and minimize wastage. This review aims to discuss the benefits of alternative storage techniques and how they may be combined to alleviate the problems associated with conventional platelet s...