title: Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty.
abstract: Major trauma increases vulnerability to systemic infections due to poorly defined immunosuppressive mechanisms. It confers no evolutionary advantage. Our objective was to develop better biomarkers of post-traumatic immunosuppression (PTI) and to extend our observation that PTI was reversed by anti-coagulated salvaged blood transfusion, in the knowledge that others have shown that non-anti-coagulated (fibrinolysed) salvaged blood was immunosuppressive. A prospective non-randomized cohort study of patients undergoing primary total knee arthroplasty included 25 who received salvaged blood transfusions collected post-operatively into acid-citrate-dextrose anti-coagulant (ASBT cohort), and 18 non-transfused patients (NSBT cohort). Biomarkers of sterile trauma included haematological values, damage-associated molecular patterns (DAMPs), cytokines and chemokines. Salvaged blood was analysed within 1 and 6 h after commencing collection. Biomarkers were expressed as fold-changes over preoperative values. Certain biomarkers of sterile trauma were common to all 43 patients, including supranormal levels of: interleukin (IL)-6, IL-1-receptor-antagonist, IL-8, heat shock protein-70 and calgranulin-S100-A8/9. Other proinflammatory biomarkers which were subnormal in NSBT became supranormal in ASBT patients, including IL-1β, IL-2, IL-17A, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and annexin-A2. Furthermore, ASBT exhibited subnormal levels of anti-inflammatory biomarkers: IL-4, IL-5, IL-10 and IL-13. Salvaged blood analyses revealed sustained high levels of IL-9, IL-10 and certain DAMPs, including calgranulin-S100-A8/9, alpha-defensin and heat shock proteins 27, 60 and 70. Active synthesis during salvaged blood collection yielded increasingly elevated levels of annexin-A2, IL-1β, Il-1-receptor-antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, transforming growth factor (TGF)-β1, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. Elevated levels of high-mobility group-box protein-1 decreased. In conclusion, we demonstrated that anti-coagulated salvaged blood reversed PTI, and was attributed to immune stimulants generated during salvaged blood collection.
authors.affiliation: Musculoskeletal Research Unit, 1st Floor Learning & Research Building, Southmead Hospital, University of Bristol, Bristol, United Kingdom; National Centre for Biomedical Engineering Science, National University of Ireland, Galway; Shannon Applied Biotechnology Centre, Institute of Technology Tralee, Tralee, County Kerry, Ireland.
authors.forename: N
authors.initials: N
authors.lastname: Islam
authors.forename: M
authors.initials: M
authors.lastname: Whitehouse
authors.forename: S
authors.initials: S
authors.lastname: Mehendale
authors.forename: M
authors.initials: M
authors.lastname: Hall
authors.forename: J
authors.initials: J
authors.lastname: Tierney
authors.forename: E
authors.initials: E
authors.lastname: O'Connell
authors.forename: A
authors.initials: A
authors.lastname: Blom
authors.forename: G
authors.initials: G
authors.lastname: Bannister
authors.forename: J
authors.initials: J
authors.lastname: Hinde
authors.forename: R
authors.initials: R
authors.lastname: Ceredig
authors.forename: B A
authors.initials: BA
authors.lastname: Bradley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D016913:Blood Component Transfusion; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000097:blood / Q000276:immunology* / Q000628:therapy*
chemical_list: D015415:Biomarkers
keywords: DAMPs; arthroplasty; cytokines; post-traumatic immunosuppression; sterile trauma
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