Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

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]

Analysis 5.1. Comparison 5: Subgroup analysis: antibodies in recipients detected at baseline for the comparison of convalescent plasma versus placebo or standard care alone for individuals with moderate to severe disease, Outcome 1: All-cause mortality at up to day 28..

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.

Combined with the 2004 review, 80 RCTs have investigated FP with no consistent evidence of significant benefit for prophylactic and therapeutic use across a range of indications evaluated. There has been little improvement in the overall methodologic quality of RCTs conducted in the past few years.

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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.

Rationale: Cell-based therapies are a promising intervention for the treatment of heart failure (HF) secondary to ischemic and nonischemic cardiomyopathy. However, the clinical efficacy of such new treatment requires further evaluation. Objective: To assess available clinical evidence on the safety and efficacy of cell-based therapies for HF. Methods and Results: Electronic databases (CENTRAL, DARE, NHSEED & HTA, PubMed, MEDLINE, EMBASE, CINAHL, LILACS, KoreaMed, PakMediNet, IndMed, and the Transfusion Evidence Library) were searched for relevant randomized controlled trials to June 2014. Trials of participants with HF and where the administration of any dose of autologous cells by any delivery route was compared with no intervention or placebo were eligible for inclusion. Primary outcomes were defined as mortality and rehospitalization as a result of HF. Secondary outcomes included performance status, quality of life, incidence of arrhythmias, brain natriuretic peptide levels, left ventricular ejection fraction, myocardial perfusion, and adverse events. Thirty-one independent trials (1521 participants) were included. The treatment significantly reduced the risk of mortality and rehospitalization caused by HF. There was a significant improvement in favor of stem cell treatment in performance status and exercise capacity, left ventricular ejection fraction, and quality of life. The treatment was also associated with a reduction of brain natriuretic peptide levels and no increase in the incidence of arrhythmias. However, there was considerable risk of performance, selection, and reporting bias among the included trials. Conclusions: This study shows evidence that autologous cell therapy may be beneficial for patients having HF, but further evidence is required.