Storage lesion in banked blood due to hemolysis-dependent disruption of nitric oxide homeostasis

Whereas blood storage is associated with an increased risk of cardiovascular events and multiorgan failure, the fundamental mechanisms underlying the 'storage lesion' in blood remain uncertain. A major abnormality in aged blood is the reduced red cell life-span after infusion, which is associated with microparticle and free hemoglobin release, and age-related loss of enzymatic functionality. However, the degree of intravascular hemolysis and microparticle formation in humans post-transfusion due to both storage and physiological shear has not been well studied.

Our laboratories have discovered that even low levels of intravascular hemolysis severely disrupt nitric oxide bioavailability at the endothelium, via accelerated nitric oxide dioxygenation reactions with free plasma hemoglobin. This process contributes to endothelial dysfunction, adhesion molecule expression, platelet and hemostatic activation, and reactive oxygen species generation. Recent studies also suggest that red cells possess nitric oxide-generating functionality via nitrite reduction and red cell endothelial nitric oxide synthase activity, potentially providing novel pathways to therapeutically alleviate the 'storage lesion'.

The understanding of the pathological effects of red cell hemolysis on endothelial function suggests that nitric oxide dysregulation may underlie the red cell storage lesion, driven by increased nitric oxide catabolism and loss of nitric oxide-generating functionality.