Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty

Authors

  • N. Islam,

    1. Musculoskeletal Research Unit, 1st Floor Learning & Research Building, Southmead Hospital, University of Bristol, Bristol, United Kingdom
    2. National Centre for Biomedical Engineering Science, National University of Ireland
    3. Shannon Applied Biotechnology Centre, Institute of Technology Tralee, Tralee, County Kerry, Ireland
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  • M. Whitehouse,

    1. Musculoskeletal Research Unit, 1st Floor Learning & Research Building, Southmead Hospital, University of Bristol, Bristol, United Kingdom
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  • S. Mehendale,

    1. Musculoskeletal Research Unit, 1st Floor Learning & Research Building, Southmead Hospital, University of Bristol, Bristol, United Kingdom
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  • M. Hall,

    1. Shannon Applied Biotechnology Centre, Institute of Technology Tralee, Tralee, County Kerry, Ireland
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  • J. Tierney,

    1. Shannon Applied Biotechnology Centre, Institute of Technology Tralee, Tralee, County Kerry, Ireland
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  • E. O'Connell,

    1. National Centre for Biomedical Engineering Science, National University of Ireland
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  • A. Blom,

    1. Musculoskeletal Research Unit, 1st Floor Learning & Research Building, Southmead Hospital, University of Bristol, Bristol, United Kingdom
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  • G. Bannister,,

    1. Musculoskeletal Research Unit, 1st Floor Learning & Research Building, Southmead Hospital, University of Bristol, Bristol, United Kingdom
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  • J. Hinde,

    1. School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, County Kerry, Ireland
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  • R. Ceredig,

    1. National Centre for Biomedical Engineering Science, National University of Ireland
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  • B. A. Bradley

    Corresponding author
    1. Musculoskeletal Research Unit, 1st Floor Learning & Research Building, Southmead Hospital, University of Bristol, Bristol, United Kingdom
    2. National Centre for Biomedical Engineering Science, National University of Ireland
    3. Shannon Applied Biotechnology Centre, Institute of Technology Tralee, Tralee, County Kerry, Ireland
    • Correspondence: B. Bradley, Research Unit, Avon Orthopaedic Centre, Southmead Hospital, University of Bristol, Bristol BS10 5ND, UK.

      E-mail: benjamin.bradley@btinternet.com

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Summary

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.

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