New frontiers in transfusion biology: identification and significance of mediators of morbidity and mortality in stored red blood cells

Abstract

Red cell transfusions are associated with inflammation and thrombosis, both arterial and venous, the mechanisms of which are not understood. Although a necessary life saving procedure in modern medicine, transfusions have rarely been subjected to modern assessments of efficacy and safety, including randomized trials. Storage of red blood cells induces changes, including the release of free hemoglobin and the accumulation of biologically active soluble mediators and microparticles. These mediators likely play a direct role in the inflammatory and pro-thrombotic properties of red cell transfusions. Methods such as leukoreduction, washing of red cells and rejuvenation may improve the quality of red cell transfusions.

Frequency and Specificity of Red Blood Cell Alloimmunization in Chilean Transfused Patients

“…However, despite leukoreduction, alloimmunization continues in RBC transfusion recipients. RBC-free hemoglobin and lipid mediators accumulate in microparticle and supernatant fractions of leukoreduced stored RBCs; moreover, apoptosis and loss of viability of residual white cells in leukodepleted units release immunostimulatory antigens, and mediators can sensitize the recipients [20,21]. In our study, the units transfused are non-leukoreduced, only neonatal and hematooncology patients received some leukoreduced hemocomponents.…”

Storage of Red Blood Cells and Transfusion-Related Acute Lung Injury

“…In a rat model, results showed that perfusion of rat lung with 42-day old purified lysophosphatidlcholine led to significant pulmonary edema and lung injury in LPS-primed rats. The investigators further demonstrated that infusion of a mixture of four non-polar lipids purified from 42-day old leukoreduced RBC from healthy volunteers induced lung injury in LPS-treated rats, but 1-day lipid solution did not [47].…”

“…These RBC membrane-derived MVs have more recently been shown to have physiologic and pathophysiologic significance by playing a role in inflammation and vascular dysfunction [47]. Cardo et al [48] assessed the neutrophilpriming ability of washed and unwashed RBCs stored for different durations and specifically the role of micro vesicles in priming neutrophils in vitro.…”

Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis

“…These changes include changes to the cell shape and membrane, an increase in adhesiveness, a decline in flexibility (rigidity that can hamper blood flow hemodynamics), and reductions in capillary flow. [5][6][7][8][9] Further, older blood is associated with release of free iron that may predispose to vascular dysfunction, thrombosis, and nosocomial infections. [5][6][7][8][9] Finally, the storage medium could be deleterious by generating superoxides and inflammatory mediators that could result in oxidative damage.…”

“…[5][6][7][8][9] Further, older blood is associated with release of free iron that may predispose to vascular dysfunction, thrombosis, and nosocomial infections. [5][6][7][8][9] Finally, the storage medium could be deleterious by generating superoxides and inflammatory mediators that could result in oxidative damage. [10][11][12][13] Observational studies, [14][15][16][17][18][19][20] although potentially confounded, 21,22 have suggested that these complicated mechanisms, often collectively referred to as "storage lesion," may adversely affect patient-important outcomes including infection, organ failure, hospital stay, and death.…”