Related Experiment Video
Updated: Sep 17, 2025
Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock
Published on: June 6, 2011
The impact of transfusion kinetics on the inflammatory response following major injury
Patrick R Carney1, Ben L Zarzaur, John B Holcomb
1From the Department of Surgery (P.R.C., B.L.Z., S.A.S.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Department of Surgery (E.E.F., C.E.W.), University of Texas Health Science Center at Houston, Houston, Texas; and Department of Surgery (J.B.H.), University of Alabama at Birmingham, Birmingham, Alabama.
Background:
The innate immune response is activated by tissue injury and may quickly become dysregulated in the setting of major trauma. Cytokines are a key component of this response and function to activate and mobilize neutrophils, macrophages, and natural killer cells. The purpose of this study was to understand how the kinetics of blood-based resuscitation may impact the cytokine response. Specifically, we hypothesize that transfusion kinetics make a fundamental contribution to the inflammatory response, beyond the volume of transfusion and injury severity.
Methods:
The Pragmatic, Randomized Optimal Platelet and Plasma Ratio data set was used in this retrospective analysis. Transfusion kinetics were quantified by calculating the total critical administration threshold episodes in three time periods, 1 to 2 hours following injury, 3 to 4 hours, and 5 to 6 hours following injury. The longitudinal response of key cytokines over 72 hours was assessed with a multivariable linear growth model, using critical administration threshold status as a time-varying covariate.
Results:
A total of 522 patients were included in this analysis. Pro-inflammatory cytokines interleukin (IL)-6 (p = 0.0354) and IL-8 (p < 0.0001) were significantly increased. Anti-inflammatory cytokines IL-1ra (p = 0.0001) and IL-10 (p < 0.0001) were significantly increased. Chemokines interferon-γ-inducible protein 10 (p = 0.0433), monocyte chemoattractant protein-1 (p = 0.0064), and macrophage inflammatory protein 1β (p = 0.0003) were significantly increased, while regulated up activation, normal T-cell expressed and secreted chemokine (p = 0.0216) was significantly decreased. Growth factors showed no significant response.
Conclusion:
The kinetics of packed red blood cell transfusion demonstrate a potential association with the expression of cytokines following injury, beyond the total transfusion requirement or the severity of injury. Because cytokines activate and mobilize neutrophils, macrophages, and natural killer cells, these alterations may have a profound effect on degree and coordination of the immune response. As the contribution of various components of major resuscitation to inflammatory activation is clarified, such as types of blood product, tempo of transfusion, and operative care, targets for intervention should become more apparent.
Level Of Evidence:
Therapeutic/Care Management; Level III.
Related Concept Videos
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
01:30Inflammatory Response I: Vascular and Cellular
02:45Blood Transfusion and Agglutination
History
The history of blood transfusion dates back to the 17th century, when early attempts were made in animals. In 1818 James Blundell, a British doctor, performed the first successful human blood transfusion. Later in 1900, Karl...
01:38Inflammation
01:24Inflammatory Response II: Inflammatory Exudate and Tissue Repair
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the...