Recent studies have underscored questions about the balance of risk and benefit of RBC transfusion. A better understanding of the nature and timing of molecular and functional changes in stored RBCs may provide strategies to improve the balance of benefit and risk of RBC transfusion. We analyzed changes occurring during RBC storage focusing on RBC deformability, RBC-dependent vasoregulatory function, and S-nitrosohemoglobin (SNO-Hb), through which hemoglobin (Hb) O(2) desaturation is coupled to regional increases in blood flow in vivo (hypoxic vasodilation). Five hundred ml of blood from each of 15 healthy volunteers was processed into leukofiltered, additive solution 3-exposed RBCs and stored at 1-6 degrees C according to AABB standards. Blood was subjected to 26 assays at 0, 3, 8, 24 and 96 h, and at 1, 2, 3, 4, and 6 weeks. RBC SNO-Hb decreased rapidly (1.2 x 10(-4) at 3 h vs. 6.5 x 10(-4) (fresh) mol S-nitrosothiol (SNO)/mol Hb tetramer (P = 0.032, mercuric-displaced photolysis-chemiluminescence assay), and remained low over the 42-day period. The decline was corroborated by using the carbon monoxide-saturated copper-cysteine assay [3.0 x 10(-5) at 3 h vs. 9.0 x 10(-5) (fresh) mol SNO/mol Hb]. In parallel, vasodilation by stored RBCs was significantly depressed. RBC deformability assayed at a physiological shear stress decreased gradually over the 42-day period (P < 0.001). Time courses vary for several storage-induced defects that might account for recent observations linking blood transfusion with adverse outcomes. Of clinical concern is that SNO levels, and their physiological correlate, RBC-dependent vasodilation, become depressed soon after collection, suggesting that even "fresh" blood may have developed adverse biological characteristics.

https://www.pnas.org/content/pnas/104/43/17063.full.pdf

Evolution of adverse changes in stored RBCs.

Context Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit. Objective To assess the safety of HBBSs in surgical, stroke, and trauma patients. Data Sources PubMed, EMBASE, and Cochrane Library searches for articles using hemoglobin and blood substitutes from 1980 through March 25, 2008; reviews of Food and Drug Administration (FDA) advisory committee meeting materials; and Internet searches for company press releases. Study Selection Randomized controlled trials including patients aged 19 years and older receiving HBBSs therapeutically. The database searches yielded 70 trials of which 13 met these criteria; in addition, data from 2 other trials were reported in 2 press releases, and additional data were included in 1 relevant FDA review. Data Extraction Data on death and myocardial infarction (MI) as outcome variables. Results Sixteen trials involving 5 different products and 3711 patients in varied patient populations were identified. A test for heterogeneity of the results of these trials was not significant for either mortality or MI (for both, I2 = 0%, P ≥ .60), and data were combined using a fixed-effects model. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30; 95% confidence interval [CI], 1.05-1.61) and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71; 95% CI, 1.67-4.40) with these HBBSs. Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication. Conclusion Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.Published online April 28, 2008 (doi:10.1001/jama.299.19.jrv80007).

Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death: A Meta-analysis

Chemically modified or genetically engineered haemoglobins (Hbs) developed as oxygen therapeutics (often termed 'blood substitutes') are designed to correct oxygen deficit due to ischaemia in a variety of clinical settings. These modifications are intended to stabilize Hb outside its natural environment--red blood cells--in a functional tetrameric and/or polymeric form. Uncontrolled haem-mediated oxidative reactions of cell-free Hb and its reactions with various oxidant/antioxidant and cell signalling systems have emerged as an important pathway of toxicity. Current protective strategies designed to produce safe Hb-based products are focused on controlling or suppressing the 'radical' nature of Hb while retaining its oxygen-carrying function.

Oxygen therapeutics: can we tame haemoglobin?

https://www.scielo.br/pdf/clin/v64n8/a16v64n8.pdf

A review of blood substitutes: examining the history, clinical trial results, and ethics of hemoglobin-based oxygen carriers

Worldwide, trauma is a leading cause of death and disability. Haemorrhage is responsible for up to 40% of trauma deaths. Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy. We undertook a systematic review of randomized controlled trials (RCT) which evaluated trauma patients with hemorrhagic shock within the first 24 hours of injury and appraised how the interventions affected three outcomes: bleeding and/or transfusion requirements; correction of trauma induced coagulopathy and mortality. Comprehensive searches were performed of MEDLINE, EMBASE, CENTRAL (The Cochrane Library Issue 7, 2010), Current Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) and the National Health Service Blood and Transplant Systematic Review Initiative (NHSBT SRI) RCT Handsearch Database. A total of 35 RCTs were identified which evaluated a wide range of clinical interventions in trauma hemorrhage. Many of the included studies were of low methodological quality and participant numbers were small. Bleeding outcomes were reported in 32 studies; 7 reported significantly reduced transfusion use following a variety of clinical interventions, but this was not accompanied by improved survival. Minimal information was found on traumatic coagulopathy across the identified RCTs. Overall survival was improved in only three RCTs: two small studies and a large study evaluating the use of tranexamic acid. Despite 35 RCTs there has been little improvement in outcomes over the last few decades. No clear correlation has been demonstrated between transfusion requirements and mortality. The global trauma community should consider a coordinated and strategic approach to conduct well designed studies with pragmatic endpoints.

/pdf/the-acute-management-of-trauma-hemorrhage-a-systematic-4j6dgalqmc.pdf

The acute management of trauma hemorrhage: a systematic review of randomized controlled trials

A major cause of death in patients with severe hemorrhagic shock following trauma is the subsequent occurrence of multiple organ failure due to tissue hypoxia. Early administration of an oxygen carrier may reduce the occurrence of organ failures and improve survival. It may also reduce the need of blood products. Prospective multicenter study in a university clinic. 121 patients with severe hemorrhagic shock. Patients were randomly assigned "on-scene" to receive either up to 1000 ml of a 10% diaspirin cross-linked hemoglobin (DCLHb) solution or the study center's standard therapy. Demographic and physiological characteristics of the two treatment groups at baseline were comparable. Organ failures and survival rates until day 5 and day 28 showed no significant differences. The sponsor therefore terminated this trial prematurely after an interim evaluation of the data indicated no evidence of efficacy to offset concerns raised about the safety of DCLHb. Median volumes of cumulative blood products administered on 1 (1595 vs. 3716 ml) and 7 days (3139 vs. 4746 ml) after admission were lower in the DCLHb group. The early application of an oxygen carrier (DCLHb) to patients with severe hemorrhagic shock following trauma had no significant effect on the occurrence of organ failure or on 5- and 28-day survival in this abbreviated trial. However, early infusion of up to 1000 ml DCLHb reduces the need for blood products without changing morbidity or survival.

DCL-Hb for trauma patients with severe hemorrhagic shock: the European "On-Scene" multicenter study.

§§Departments of *General Anesthesiology, †Department of Orthopedic Surgery, ‡Department of Urology, §Department ofBiostatistics & Epidemiology, The Cleveland Clinic Foundation; Cleveland Clinic Foundation Health Science Center of theOhio State University; ¶Department of Pathology, Ohio State University, Cleveland; #Department of Medicine, University ofWisconsin, Madison; **Division of Vascular Surgery, University of Arkansas for Medical Sciences, Little Rock; ††BaxterHemoglobin Therapeutics, Boulder, Colorado; ‡‡Pfizer Global Research and Development, New York City; and §§RichardPrielipp, MD, Bowman Gray School of Medicine; Gerald Fulda, MD, Christiana Health Care Services; Irwin Gratz, DO, CooperHospital/UMC; Michael Salem, MD, George Washington University Medical Center; Ronald Kline, MD, Harper Hospital;Benjamin Guslits, MD, Henry Ford Hospital; Michael Pasquale, MD, Lehigh Valley Hospital; Lauraine Stewart, MD, McGuireVA Medical Center; Larry Hollier, MD, Mt. Sinai Medical Center; Bhatar Desai, MD, St. Anthony Hospital; Marc J. Shapiro,MD, St. Louis University Hospital; Ronald Pearl, MD, Stanford University Medical Center; Michael J. Williams, MD, ThomasJefferson University; Dennis Doblar, PhD, MD, University of Alabama-Birmingham; Marc Hudson, MD, University of PittsburghMedical Center; Michael P. Eaton, MD, University of Rochester Medical Center; Lewis Gottschalk, MB, University of Texas-HoustonHealth Sciences Center; Mali Mathru, MD, University of Texas Medical Branch; Daniel Herr, MD, Washington Hospital CenterIn this randomized, prospective, double-blinded clinicaltrial, we sought to investigate whether diaspirin-crosslinked hemoglobin (DCLHb) can reduce the periop-erativeuseofallogeneicbloodtransfusion.One-hundred-eighty-one elective surgical patients were enrolled at 19clinical sites from 1996 to 1998. Selection criteria includedanticipated transfusion of 2–4 blood units, aortic repair,and major joint or abdomino-pelvic surgery. Once a deci-sion to transfuse had been made, patients received ini-tially up to 3 250-mL infusions of 10% DCLHb (

Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery: a multicenter, randomized, controlled, double-blinded trial.

Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Michael E. Saunders

Author Tools

Chat about Author

Papers

DCL-Hb for trauma patients with severe hemorrhagic shock: the European "On-Scene" multicenter study.

Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery: a multicenter, randomized, controlled, double-blinded trial.

Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery