Cold stored platelets in the management of bleeding: is it about bioenergetics?

When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more important for the treatment of chemotherapy-induced thrombocytopenia, research into ways to increase supply intensified. During the late 1960s/early 1970s, it was demonstrated through radioactive labeling of platelets that room temperature platelets (RTP) had superior post-transfusion recovery and survival compared with cold-stored platelets (CSP). This led to a universal switch to room temperature storage, despite CSP demonstrating superior hemostatic effectiveness upon being transfused. There has been a global resurgence in studies into CSP over the last two decades, with an increase in the use of PC to treat acute bleeding within hospital and pre-hospital care. CSP demonstrate many benefits over RTP, including longer shelf life, decreased bacterial risk and easier logistics for transport, making PC accessible in areas where they have not previously been, such as the battlefield. In addition, CSP are reported to have greater hemostatic function than RTP and are thus potentially better for the treatment of bleeding. This review describes the history of CSP, the functional and metabolic assays used to assess the platelet storage lesion in PC and the current research, benefits and limitations of CSP. We also discuss whether the application of new technology for studying mitochondrial and glycolytic function in PC could provide enhanced understanding of platelet metabolism during storage and thus contribute to the continued improvements in the manufacturing and storage of PC.

What is the context? To transition into an activated state, platelets require a highly efficient source of energy that is met through the production of ATP ­ this is referred to as "platelet bioenergetics"Platelets can be removed from healthy donors and used to make platelet concentrates for clinical usePlatelet concentrates are used clinically either therapeutically (to halt bleeding) or prophylactically (to prevent bleeding in patients with low platelet counts)They are stored at room temperature (20­24^oC) with constant gentle agitation, in packs that allow gas exchange and have a 7-day shelf life in some jurisdictionsStoring platelets in the cold (2­6^oC) has historically been shown to improve their ability to halt bleedingWhat is new? There is a renewed interest in cold stored platelets for use in actively bleeding patientsThere are benefits to cold-storing platelets over room temperature storageCold stored platelets are licensed in the US and Norway for certain indications for 14 daysWhat is next? Cold stored platelets have the potential to improve logistics of clinical supply of platelets, enable supply of platelet concentrates where access is currently limited, such as pre-hospital care and on the battlefield and provide improved hemostatic effects for bleeding patients.New research measuring the bioenergetic profiles of cold stored platelets could advance understanding of metabolism in cold stored platelets and support decisions on their re-introduction on a wider scale.

Fresh whole blood from walking blood banks for patients with traumatic hemorrhagic shock: A systematic review and meta-analysis.

BACKGROUND: Whole blood is optimal for resuscitation of traumatic hemorrhage. Walking Blood Banks provide fresh whole blood (FWB) where conventional blood components or stored, tested whole blood are not readily available. There is an increasing interest in this as an emergency resilience measure for isolated communities and during crises including the coronavirus disease 2019 pandemic. We conducted a systematic review and meta-analysis of the available evidence to inform practice. METHODS: Standard systematic review methodology was used to obtain studies that reported the delivery of FWB (PROSPERO registry CRD42019153849). Studies that only reported whole blood from conventional blood banking were excluded. For outcomes, odds ratios (ORs) and 95% confidence interval (CI) were calculated using random-effects modeling because of high risk of heterogeneity. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. RESULTS: Twenty-seven studies published from 2006 to 2020 reported >10,000 U of FWB for >3,000 patients (precise values not available for all studies). Evidence for studies was "low" or "very low" except for one study, which was "moderate" in quality. Fresh whole blood patients were more severely injured than non-FWB patients. Overall, survival was equivalent between FWB and non-FWB groups for eight studies that compared these (OR, 1.00 [95% CI, 0.65-1.55]; p = 0.61). However, the highest quality study (matched groups for physiological and injury characteristics) reported an adjusted OR of 0.27 (95% CI, 0.13-0.58) for mortality for the FWB group (p < 0.01). CONCLUSION: Thousands of units of FWB from Walking Blood Banks have been transfused in patients following life-threatening hemorrhage. Survival is equivalent for FWB resuscitation when compared with non-FWB, even when patients were more severely injured. Evidence is scarce and of relative low quality and may underestimate potential adverse events. Whereas Walking Blood Banks may be an attractive resilience measure, caution is still advised. Walking Blood Banks should be subject to prospective evaluation to optimize care and inform policy. LEVEL OF EVIDENCE: Systematic/therapeutic, level 3.