Although blood suppliers are seeing short-term reductions in blood demand as a result of initiatives in patient blood management, modelling suggests that during the next 5–10 years, blood ...availability in developed countries will need to increase again to meet the demands of ageing populations. Increasing of the blood supply raises many challenges; new approaches to recruitment and retainment of future generations of blood donors will be needed, and care will be necessary to avoid taking too much blood from these donors. Integrated approaches in blood stock management between transfusion services and hospitals will be important to minimise wastage—eg, by use of supply chain solutions from industry. Cross-disciplinary systems for patient blood management need to be developed to lessen the need for transfusion—eg, by early identification and reversal of anaemia with haematinics or by reversal of the underlying cause. Personalised medicine could be applied to match donors to patients, not only with extended blood typing, but also by using genetically determined storage characteristics of blood components. Growing of red cells or platelets in large quantities from stem cells is a possibility in the future, but challenges of cost, scaling up, and reproducibility remain to be solved.
This article reviews 3 products: pathogen-inactivated platelets, cold-stored platelets, and cryoplatelets. These are all coming to a transfusion service near you in the next few years. The article ...reviews the limitations of these new products and highlights the gaps in our understanding of their place in patient treatment.
Platelet concentrates are currently stored at room temperature (RP) under constant agitation for up to 5–7 days depending on national regulations. However, platelet quality deteriorates during ...storage and room-temperature storage also increases the risk of bacterial growth. Previous studies have shown that cold-stored platelets (CPs) have higher hemostatic functions and can be stored for up to 3 weeks. While these studies have compared the metabolic phenotypes of CPs and RPs, they have neither compared the impact of storage temperature and cold agitation (CPAs) on platelet function nor identified metabolic correlates to such parameters. In vitro analysis showed that CPAs and CPs had reduced count, faster CD62P expression, and increased lactadherin binding. Furthermore, CPAs and CPs had higher maximal aggregation and a reduced aggregation lag phase compared to RPs. Metabolomic analysis revealed that CPAs and CPs exhibited lower oxidative stress shown by preserved glutathione and pentose phosphate pools. CPAs and CPs also had reduced markers of beta-oxidation and amino acid catabolism, demonstrating reduced needs for energy. Agitation did not significantly impact in vitro function or metabolomic parameters of cold-stored platelets. Correlation of in vitro and metabolomic results highlighted important metabolites that may contribute to stored platelet functions. Raw data are publicly available through Metabolomics Workbench with the study identifier ST001644.
Cold-stored platelets are making a comeback. They were abandoned in the late 1960s in favor of room-temperature stored platelets due to the need for longer post-transfusion platelet recoverability ...and survivability in patients with chronic thrombocytopenia. However, the current needs for platelet transfusions are rapidly changing. Today, more platelets are given to patients who are actively bleeding, such as ones receiving cardiac surgeries. It has been established that cold-stored platelets are more hemostatically effective, have reduced bacterial growth, and have longer potential shelf lives. These compelling characteristics led to the recent interest in bringing back cold-stored platelets to the blood systems. However, before reinstating cold-stored platelets in the clinics again, a thorough investigation of in vitro storage characteristics and in vivo transfusion effects is required. This review aims to provide an update on the recent research efforts into the storage characteristics and functions of cold-stored platelets using modern investigative tools. We will also discuss efforts made to improve cold-stored platelets to be a better and safer product. Finally, we will finish off with discussing the relevance of in vitro data to in vivo transfusion results and provide insights and directions for future investigations of cold-stored platelets.
The current implementation of Pathogen Reduction Technologies (PRTs) offers advantages and disadvantages to transfusion medicine. PRT rollout may significantly reduce the incidence of ...transfusion-transmitted infections and immune reactions, while offering a ‘one-size-fits-all’ solution to future pathogens in blood products. However, the decrease in transfusion efficacy of PRT-treated blood products suggests that the demand for blood products may increase, further straining the already limited supply of these cells. Conversely, cold-stored platelets and whole-blood transfusions have re-emerged, potentially granting more effective transfusion options to bleeding patients. The renewed focus on donor variability, storage quality, and transfusion outcome presents another avenue through which transfusion quality and supply may be improved.
Apoptosis is a critical process for the maintenance of cell populations, and involves mitochondrial depolarization, the sequential cleavage of caspase-9 and -3, followed by the externalization of ...phosphatidylserine (PS) on the plasma membrane. The actin cytoskeleton and its accessory proteins are known regulators of apoptotic signaling in nucleated cells but their roles in platelet apoptosis are undefined. Filamin A (FLNA) is a ubiquitously expressed actin-crosslinking protein that also serves as an intracellular signaling scaffold. Here we used platelets from mice with a platelet-specific FLNA deficiency (Flnafl/Y, Pf4-cre/+, termed platelet-specific knockout) to test the role of FLNA in platelet apoptosis. Treatment with the BH3-mimetic drug ABT-737 induced caspase-3 cleavage and PS exposure in platelets from floxed mice (Flnafl/Y, termed control) but these effects were essentially abrogated in FLNA-null platelets (platelet-specific knockout). Protein kinase C (PKC), a known FLNA ligand, was also activated by ABT-737, and PKC's phosphorylation of its downstream substrates was attenuated in FLNA-null platelets. The PKC inhibitor bisindolylmaleimide (BIM) also reduced caspase-3 cleavage, thus essentially phenocopying the FLNA-null platelets. Notably, the caspase-3 cleavage defect in FLNA-null platelets was rescued by the PKC-activating phorbol ester PMA, suggesting that FLNA and PKC share a common pathway in regulating platelet apoptosis. Mitochondrial depolarization and caspase-9 cleavage were unaffected by BIM treatment, suggesting that PKC specifically controls the downstream caspase-3 point of the pro-apoptotic signaling pathway. These data point to a novel role for FLNA in the regulation of platelet apoptosis, thus providing an improved understanding of how circulating platelet counts are maintained.
Background
There is increasing interest in leukoreduced whole blood (WB) as a transfusion product for trauma patients. In some jurisdictions, few leukoreduced filters are approved or appropriate for ...WB leukoreduction and quality information is therefore limited. This study assessed the impact of filtration timing of WB collected in CPDA‐1 versus CPD on in vitro quality.
Study Design and methods
WB was collected in CPDA‐1 or CPD and leukoreduction filtered either after 3–8 h (early) or 18–24 h (late) from stop bleed time. In vitro quality was assessed after filtration and throughout 5 weeks of storage at 4°C. Cell count and hemoglobin levels were determined by hematology analyzer, platelet activation and responsiveness to ADP by surface expression of P‐selectin by flow cytometry, hemolysis by HemoCue, and metabolic parameters by blood gas analyzer. Hemostatic properties were assessed by rotational thromboelastometry. Plasma protein activities and clotting times were determined by automated coagulation.
Results
Although there were some data points which showed statistically significant differences associated with anticoagulant choices or the filtration timing, no general trend in inferiority/performance could be discerned. After 35 days' storage, only clotting time, alpha angle and factor II in the early filtration arm comparing anticoagulants and prothrombin time and factor II in the CPDA‐1 study arm comparing filtration timing showed a significant difference.
Conclusion
In vitro WB quality seems to be independent on the choice of anticoagulant and filtration timing supporting WB hold‐times to up to 24 h, increasing operational flexibility for transfusion services.
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