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

Abstract

SummaryMajor 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.

Platelet Toll-like Receptor 4–Related Innate Immunity Potentially Participates in Transfusion Reactions Independent of ABO Compatibility: An Ex Vivo Study

“…TLR4 recognizes DAMPs [ 13 ], which are associated with host cell components released after cell damage [ 5 , 14 , 15 ]. We revealed that levels of certain DAMPs, including HMGB1, S100A8, and S100A9, were elevated after blood mixing, and this finding was corroborated by other reports [ 16 , 17 , 18 , 19 , 20 ] on blood transfusions ( Figure 3 ). For example, first, a transfusion of red blood cells increases vulnerability to lung inflammation through HMGB1 release and induces lung endothelial cell necroptosis [ 19 ].…”

Effects of Parecoxib Sodium Application Combined with Enhanced Recovery After Surgery Nursing on Inflammatory Factors and Knee Joint Function in Elderly Patients After Total Knee Arthroplasty

“…We found that the levels of Hb in the patients of the combine group were significantly higher than those of the control group, while the levels of WBC, ESR, serum IL-1β, TNF-α, and IL-6 in the patients of the combine group were all significantly lower than those of the control group on the third and seventh postoperative days, which suggested that patients in the combine group had lower postoperative inflammation in peripheral blood. Tissue damage caused by TKA can activate the complement system and immune cells, causing the body to release a variety of inflammatory factors such as IL-1β, IL-6, and TNF-α (23)(24)(25)(26). IL-1β and IL-6 are the main proinflammatory factors of acute inflammatory response and play an important role in regulating body damage, infection, etc.…”

Current Status of the Use of Salvaged Blood in Metastatic Spine Tumour Surgery

“…Autologous transfusion decreases the risk of postoperative infections and tumour recurrence as a result of transfusion-related immunomodulation [ 74 ]. In fact, SBT even reverses ‘the immunosuppression associated with surgical trauma and blood loss.’ [ 75 , 76 ] Furthermore, SBT reduces the amount of allogeneic blood required [ 19 , 21 ], thereby diminishing or possibly avoiding the risks associated with ABT [ 23 , 28 ]. Studies have also shown that RBCs in salvaged blood exhibit a higher mean viability [ 77 ] & deformability [ 78 ] than those in allogeneic blood, which translates to a longer survival of the transfused RBCs [ 77 , 79 , 80 ].…”