Limited evidence suggests that older donors, gender matched donors (male-to-male) and donors who have been tested for infections may improve survival in blood transfusion recipients. The review had no significant methodological weaknesses beyond the lack of exploration of sources of heterogeneity; however, the authors acknowledged that the evidence is insufficient to draw definitive conclusions about any donor characteristics. Further well-designed, adequately powered, high-quality studies that place more emphasis on age, gender and other donor characteristics are needed to more fully address the present review question.
Overall summary Low risk of bias in the review
The authors acknowledged that the small number of eligible studies for each donor characteristic and outcome made it impossible to perform meaningful prespecified subgroup or sensitivity analysis. Statistical heterogeneity was reported to be high for some outcomes; no attempts were made to explore the source of this heterogeneity.
|A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4?||Probably yes|
|B. Was the relevance of identified studies to the review's research question appropriately considered?||Probably yes|
|C. Did the reviewers avoid emphasizing results on the basis of their statistical significance?||Probably yes|
|Risk of bias in the review||Low|
|Number of studies||59|
|Number of participants||More than 422,421|
|Last search date||January 2015|
|Objective||To evaluate the association of blood donor characteristics with the risk of short-term and long-term clinical outcomes of red blood cell transfusion recipients.|
|Population||In-hospital or outpatient patients of any age with any medical condition requiring at least 1 red blood cell (RBC) unit.
Patients receiving "whole blood transfusions" or "blood products" were excluded.
|Outcome||Primary outcome: mortality.
Secondary outcomes: any clinical or surrogate outcomes related to donor characteristics.
Studies reporting expected (rather than actual) associations between donor and recipients were excluded.
|Study design||Observational and interventional studies.
Case series were excluded unless an interrupted time-series design was used; case reports (≤2 cases), duplicates or subcohorts of already published studies were also excluded.
|Exposure||Whole blood transfusion.
At least one whole blood donor characteristic had to be reported (for example, age, gender).
Studies in which intervention labelled as whole blood transfusion specifically and studies reporting blood products without any further description regarding the type of blood products transfused were excluded.
In terms of donor age, one study reported a reduction in hospital mortality for patients receiving red blood cells [RBS] or other blood products from older donors compared to younger donors (mean difference [MD] -6.24, 95% confidence interval [CI] -12.43 to -0.05; 1 study, n=60 participants).
In terms of donor gender, one study reported an improvement in survival in male recipients who received RBCs from male donors at both 90 days (hazard ratio [HR] 2.60, 95% CI 1.09 to 6.20, 1 study) and 6 months (HR 2.40, 95% CI 1.10 to 5.24; 1 study); no such association was reported for female recipients.
In terms of white blood cell [WBC] antibodies, one study reported no association between donor WBC antibodies and receipient mortality (odds ratio [OR] 0.45, 95% CI 0.14 to 1.48; 1 study)
In terms of RBC antigen selection, one study reported no association between donor-recipient cross-match and the risk of clinical haemolysis (compared to no crossmatch) (OR 0.74, 95% CI 0.03 to 15.83; 1 study).
In terms of HLA-DR selection, one study reported no association between HLA-DR selection and mortality (OR 0.45, 95% CI 0.16 to 1.29; 1 study, n=100 participants).
In terms of previous alloexposure, one study reported no association between previous alloexposure and mortality (OR 1.48, 95% CI 0.48 to 4.51; 1 study).
In terms of donor infectious testing, pooled analysis reported a reduction in HCV infection (OR 0.12, 95% CI 0.02 to 0.84; 3 studies, n=5757 participants) and HTLV infection (OR 0.02, 95% CI 0.00 to 0.09; 4 studies) following infectious testing compared to no testing; a single study reported a reduction in HHV8 infection (OR 0.52, 95% CI 0.27 to 0.98; 1 study) and parvovirus B19 (OR 0.03, 95% CI 0.00 to 0.58; 1 study) following infectious testing compared to no testing. Pooled analysis reported no difference in babesiosis infection (rate ratio [RR] 0.16, 95% CI 0.02 to 1.31; 2 studies) or CMV infection (OR 1.13, 95% CI 0.86 to 1.48; 2 studies); and a single study reported no difference in HBV infection (OR 0.61, 95% CI 0.32 to 1.17; 1 study) following infectious testing compared to no testing.
The research objective was clearly stated and appropriate eligibility criteria were defined. No restrictions were imposed based on the study characteristics or sources of information.
|1.1 Did the review adhere to pre-defined objectives and eligibility criteria?||Probably yes|
|1.2 Were the eligibility criteria appropriate for the review question?||Probably yes|
|1.3 Were eligibility criteria unambiguous?||Probably yes|
|1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)?||Probably yes|
|1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)?||Probably yes|
|Concerns regarding specification of study eligibility criteria||Low|
MEDLINE, EMBASE and the Cochrane Central databases were searched for relevant studies. Reference lists of published narrative reviews, systematic reviews and eligible studies were searched for additional references. A manual search of journals such as Blood, Transfusion Medicine Reviews, British Journal of Haematology, Vox Sanguinis, and Transfusion was also performed to find additional studies. The search strategy was reported in full and appeared adequate. Searches were not restricted to the date, publication format or language. Two review authors were independently involved in the study selection and disagreements were resolved by consensus or by consulting with a third review author.
|2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports?||Yes|
|2.2 Were methods additional to database searching used to identify relevant reports?||Yes|
|2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible?||Probably yes|
|2.4 Were restrictions based on date, publication format, or language appropriate?||Probably yes|
|2.5 Were efforts made to minimise error in selection of studies?||Yes|
|Concerns regarding methods used to identify and/or select studies||Low|
There was no information provided on the number of reviewers involved in data extraction. Sufficient study characteristics appear to have been extracted to allow interpretation of the results. Study results were appropriately collected for the synthesis. Methodological quality of the included studies in this systematic review was evaluated using the Downs and Black tool. Two independent reviewers were involved in the risk of bias assessment.
|3.1 Were efforts made to minimise error in data collection?||Probably yes|
|3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results?||Probably yes|
|3.3 Were all relevant study results collected for use in the synthesis?||Probably yes|
|3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria?||Probably yes|
|3.5 Were efforts made to minimise error in risk of bias assessment?||Probably yes|
|Concerns regarding methods used to collect data and appraise studies||Low|
The synthesis appeared to include all eligible studies. The method of analysis was explained and appeared appropriate. Statistical heterogeneity was reported to be high for some outcomes; no attempts were made to explore the source of this heterogeneity. The small number of included studies prevented the authors performing subgroup analysis or assessing publication bias. The quality of individual studies was considered in the synthesis.
|4.1 Did the synthesis include all studies that it should?||Probably yes|
|4.2 Were all pre-defined analyses reported or departures explained?||Probably yes|
|4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies?||Probably yes|
|4.4 Was between-study variation minimal or addressed in the synthesis?||Probably no|
|4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses?||Probably yes|
|4.6 Were biases in primary studies minimal or addressed in the synthesis?||Probably yes|
|Concerns regarding synthesis and findings||High|
Optimal selection of blood donors is critical for ensuring the safety of blood products. The current selection process is concerned principally with the safety of the blood donor at the time of donation and of the recipient at the time of transfusion. Recent evidence suggests that the characteristics of the donor may affect short- and long-term transfusion outcomes for the transfused recipient. We conducted a systematic review with the primary objective of assessing the association between blood donor characteristics and red blood cell (RBC) transfusion outcomes. We searched MEDLINE, EMBASE, and Cochrane Central databases and performed manual searches of top transfusion journals for all available prospective and retrospective studies. We described study characteristics, methodological quality, and risk of bias and provided study-level effect estimates and, when appropriate, pooled estimates with 95% confidence intervals using the Mantel-Haenszel or inverse variance approach. The overall quality of the evidence was graded using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. From 6121 citations identified by our literature search, 59 studies met our eligibility criteria (50 observational, 9 interventional). We identified the evaluation of association of 17 donor characteristics on RBC transfusion outcome. The risk of bias and confounding of the included studies was high. The quality of evidence was graded as very low to low for all 17 donor characteristics. Potential associations were observed for donor sex with reduced survival at 90 days and 6 months in male recipients that receive donated blood from females (hazard ratio 2.60 [1.09, 6.20] and hazard ratio 2.40 [1.10, 5.24], respectively; n = 1), Human Leukocyte Antigen - antigen D Related (HLA-DR) selected transfusions (odds ratio [OR] 0.39 [0.15, 0.99] for the risk of transplant alloimmunization, n = 9), presence of antileukocyte antibodies (OR 5.84 [1.66, 20.59] for risk of transfusion-related acute lung injury, n = 4), and donor RBC antigens selection (OR 0.20 [0.08, 0.52] for risk of alloimmunization, n = 4). Based on poor quality evidence, positive antileukocyte antibodies, female donor to male recipients, HLA-DR selected RBC transfusion, or donor RBC antigen selection may affect RBC transfusion outcome. Our findings that donor characteristics may be associated with transfusion outcomes warrant establishing vein-to-vein data infrastructure to allow for large robust evaluations. PROSPERO registration number: CRD42013006726. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.