{"doi":"10.1111/trf.17912","title":"Heavy metals in red blood cells: From “Iron Maiden” to “Lead” Zeppelin","abstract":"Blood transfusion is a life-saving medical intervention, which makes packed red blood cells (RBCs) a life-saving drug. Unlike other drugs, whose chemical synthesis ensures standardization of the production process, RBCs are biological products that result from the essential, altruistic gift of tens of millions of donors around the world every year. As blood is stored under blood bank conditions, a series of biochemical and morphological changes occur – the so-called storage lesion(s)1—that have been posited to negatively impact the safety and efficacy of transfusion therapies,2-4 such as the capacity of stored RBCs to circulate5 or deliver oxygen6 after transfusion. As prospective randomized clinical trials have provided reassuring evidence about the non-inferiority of standard of practice versus the selective transfusion of the freshest available products,7 the focus of the transfusion research community has gradually shifted toward the appreciation of the impact of donor biology and genetic factors on the onset, progression, and, ultimately, severity of the so-called storage lesion.8, 9 Informed by the convergent interpretation of population studies on ex vivo and in vivo hemolysis both in humans10, 11 and rodent models of storage and transfusion,12 a new paradigm has evolved to reevaluate the storage lesion in light of the role of factors such as processing (additive solutions, plasticizers, irradiation, and pathogen reduction) and donor biology (age, sex, ethnicity, and body mass index)—as well as donor diet or other exposures (e.g., smoking, alcohol consumption, and drugs that are not grounds for blood donor deferral).13-19 Since what is in a blood unit ends up in the circulatory system of a recipient, certain donor exposures are of special relevance to certain categories of vulnerable recipients, especially pediatric recipients who rely on massive transfusion as part of invasive surgical procedures (e.g., cardiopulmonary bypass) or life-long transfusions secondary to hematological disorders (e.g., sickle cell disease). Such exposures include factors such as plasticizers that leach from the blood bag,20 all the way to “forever chemicals” such as perfluoroalkyl and polyfluoroalkyl substances (PFAS), whose accumulation in the bloodstream is exacerbated in some volunteer donors owing to professional exposures (e.g., firemen).21 Historically, heavy metal metabolism in RBCs has almost exclusively focused on iron, owing to the essential role of this element in hemoglobin synthesis and oxygen transport (2.6 g, 66% of bodily iron is in RBCs22). However, other heavy metals warrant further investigation in RBCs, not just from a basic science standpoint, but also from a translational, transfusion medicine-centered perspective. Indeed, in this issue of TRANSFUSION, Hadjesfandiari et al. from the Devine lab report the results from an impressive study entitled, “Measurement of Lead, Mercury, and Cadmium in Blood Donors in Canada”. The investigators conducted an impressive and comprehensive analysis of these heavy metals across 2529 Canadian blood donors to assess potential risk associated with transfusions, particularly in neonates. Utilizing inductively coupled plasma mass spectrometry, the team aimed to identify the prevalence of these metals above the recommended safety thresholds for neonatal transfusion, with reportedly 2.2% and 0.4% of donations testing above such thresholds for lead or mercury, respectively. Cadmium was present at generally lower levels, though was still of concern. The study revealed significant correlations between higher metal levels and older donor age, emphasizing the need for targeted blood selection in transfusions, especially for vulnerable groups. Sex dimorphism was also observed, with higher levels of lead in male donors and cadmium in females. Geographical variations were also notable; clinics near industrial sites or mines showed elevated metal concentrations, suggesting local environmental factors a","journal":"Transfusion","year":2024,"id":491117,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9615,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28360,"name":"Angelo D’Alessandro","orcid":"0000-0002-2258-6490","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:41.211111Z","pmid":"38847096","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}