Stem cell treatment for AMI still holds promise. Clinically, these data suggest that improvement over conventional therapy can be achieved. Further, adequately powered trials using optimal dosing, longer term outcome assessments, more reliable, and more patient-centred outcomes are required.

Strategies to modify production, specification, and storage of blood components to help prevent blood shortage Red blood cellsExtend shelf life if validated and within regulations Review manufacturing process. 64,65 Platelets Extend shelf life from 5 days to 7 days with appropriate bacterial testing or pathogen inactivation Recovery and survival of platelets, as well as count increments following transfusion, decline with increasing storage duration. 66,67 Bacterial risk depends on the timing of sampling, sample volume, and the length of culture; delayed culture methods with 7 day storage have been shown to be effective. 68 Depending on screening methodology, a further test at day 4 or at the end of storage might be required.Extend shelf life to 8 days after review of internal laboratory data to guide feasibility Review internal laboratory data to guide feasibility, and review data on bacterial risk. There is scant clinical data beyond day 7. At day 8, the recovery of fresh platelets manufactured from buffy-coats is nearly 70% and platelet survival is 45%. 69,70 Improved recovery and survival of platelets with prolonged storage has been observed with some types of additive solution. 69,70 Reduce dose for prophylactic transfusion (split products) Some countries already issue split products for neonatal transfusion. Consider half doses, or methods to produce two-thirds to three-quarter doses, such as pooling fewer so-called buffy coats or splitting aphaeresis collections into more doses. 71 Consider use of cold-stored platelets with 7-14-day shelf life for patients with bleeding only Studies in healthy volunteers suggest that the survival of platelets from whole blood or platelet concentrates refrigerated for 10-15 days might maintain acceptable viability. Laboratory data suggest that platelets remain functional for 14-21 days without the need for agitation. 72,[73][74][75][76] Consider frozen platelets for bleeding patients only 77,78 Plasma Remove requirements to freeze plasma Consider use of liquid (never frozen) plasma if freezer capacity or staff to freeze plasma are in short supply. 79 Whole BloodUse of whole blood Consider if staff to manufacture components are in short supply or for massive transfusion. [80][81][82][83][84]

Summary Randomized controlled trials of good quality are a recognized means to robustly assess the efficacy of interventions in clinical practice. A systematic identification and appraisal of all randomized trials involving fresh frozen plasma (FFP) has been undertaken in parallel to the drafting of the updated British Committee for Standards in Haematology guidelines on the use of FFP. A total of 57 trials met the criteria for inclusion in the review. Most clinical uses of FFP, currently recommended by practice guidelines, are not supported by evidence from randomized trials. In particular, there is little evidence for the effectiveness of the prophylactic use of FFP. Many published trials on the use of FFP have enrolled small numbers of patients, and provided inadequate information on the ability of the trial to detect meaningful differences in outcomes between the two patient groups. Other concerns about the design of the trials include the dose of FFP used, and the potential for bias. No studies have taken adequate account of the extent to which adverse effects might negate the clinical benefits of treatment with FFP. There is a need to consider how best to develop new trials to determine the efficacy of FFP in different clinical scenarios to provide the evidence base to support national guidelines for transfusion practice. Trials of modified FFP (e.g. pathogen inactivated) are of questionable value when there is little evidence that the standard product is an effective treatment.

Despite the high degree of heterogeneity observed, the results of this systematic review suggest that moderate improvement in global heart function is significant and sustained long-term. However, because mortality rates after successful revascularization of the culprit arteries are very low, larger number of participants would be required to assess the full clinical effect of this treatment. Standardisation of methodology, cell dosing and cell product formulation, timing of cell transplantation and patient selection may also be required in order to reduce the substantial heterogeneity observed among the included studies.

Objective To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery.Design Systematic review and meta-analysis.Data sources Randomised controlled trials involving a threshold for red blood cell transfusion in hospital. We searched (to 2 November 2015) CENTRAL, Medline, Embase, CINAHL, PubMed, LILACS, NHSBT Transfusion Evidence Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical Trials Register. Authors were contacted for data whenever possible.Trial selection Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease.Data extraction and synthesis Data extraction was completed in duplicate. Risk of bias was assessed using Cochrane methods. Relative risk ratios with 95% confidence intervals were presented in all meta-analyses. Mantel-Haenszel random effects models were used to pool risk ratios.Main outcome measures 30 day mortality, and cardiovascular events.Results 41 trials were identified; of these, seven included data on patients with cardiovascular disease. Data from a further four trials enrolling patients with cardiovascular disease were obtained from the authors. In total, 11 trials enrolling patients with cardiovascular disease (n=3033) were included for meta-analysis (restrictive transfusion, n=1514 patients; liberal transfusion, n=1519). The pooled risk ratio for the association between transfusion thresholds and 30 day mortality was 1.15 (95% confidence interval 0.88 to 1.50, P=0.50), with little heterogeneity (I2=14%). The risk of acute coronary syndrome in patients managed with restrictive compared with liberal transfusion was increased (nine trials; risk ratio 1.78, 95% confidence interval 1.18 to 2.70, P=0.01, I2=0%).Conclusions The results show that it may not be safe to use a restrictive transfusion threshold of less than 80 g/L in patients with ongoing acute coronary syndrome or chronic cardiovascular disease. Effects on mortality and other outcomes are uncertain. These data support the use of a more liberal transfusion threshold (>80 g/L) for patients with both acute and chronic cardiovascular disease until adequately powered high quality randomised trials have been undertaken in patients with cardiovascular disease.Registration PROSPERO CRD42014014251.

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