Transfusion-related immunomodulation: review of the literature and implications for pediatric critical illness

Abstract

Transfusion-related immunomodulation (TRIM) in the intensive care unit (ICU) is difficult to define and likely represents a complicated set of physiologic responses to transfusion, including both proinflammatory and immunosuppressive effects. Similarly, the immunologic response to critical illness in both adults and children is highly complex and is characterized by both acute inflammation and acquired immune suppression. How transfusion may contribute to or perpetuate these phenotypes in the ICU is poorly understood, despite the fact that transfusion is common in critically ill patients. Both hyperinflammation and severe immune suppression are associated with poor outcomes from critical illness, underscoring the need to understand potential immunologic consequences of blood product transfusion. In this review we outline the dynamic immunologic response to critical illness, provide clinical evidence in support of immunomodulatory effects of blood product transfusion, review preclinical and translational studies to date of TRIM, and provide insight into future research directions.

Fig. 1.

The dynamic immune response to critical illness. Some patients experience severe hyperacute inflammation that results in early death before the immunosuppressive effects of the compensatory anti-inflammatory response can become clinically evident (A). Those who survive the initial proinflammatory insult can develop severe persistent immune suppression that is associated with increased risks for nosocomial infection and late death (B). An important goal of critical care management is to promote prompt restoration of immunologic homeostasis through resolution of systemic inflammation and normalization of immune function (C). The immunologic effects of a transfusion at a given point in time (white star) have the potential to be quite variable depending on the context, with some subjects being too ill to detect an effect (A), others being too well to have a clinical impact (C), and others in a highly dynamic state where pro- or anti-inflammatory effects of transfusion could greatly influence overall immune function. SIRS = systemic inflammatory response syndrome.