Storage lesion: role of red blood cell breakdown

Abstract

As stored blood ages intraerythrocytic energy sources are depleted resulting in reduced structural integrity of the membrane. Thus, stored red blood cells (RBCs) become less deformable and more fragile as they age. This fragility leads to release of cell-free hemoglobin (Hb) and formation of microparticles, submicron Hb-containing vesicles. Upon transfusion, it is likely that additional hemolysis and microparticle formation occurs due to breakdown of fragile RBCs. Release of cell-free Hb and microparticles leads to increased consumption of nitric oxide (NO), an important signaling molecule that modulates blood flow, and may promote inflammation. Stored blood may also be deficient in recently discovered blood NO synthase activity. We hypothesize that these factors play a potential role in the blood storage lesion.

Figure 1

Proposed mechanisms contributing to the storage lesion. Reprinted by permission from Macmillan Publishers Ltd:Nature Medicine (16(4):381-2), copyright (2010). Red cell breakdown leads to release of cell-free hemoglobin and red cell microparticles. These scavenge NO which leads to vasoconstriction, platelet activation and adhesion, and inflammatory pathways.

Figure 2

General hypothesis and approach. Loss of red cell integrity during storage or upon transfusion (to be studied in Aim 1) results in release of free hemoglobin and red cell microparticles which scavenge nitric oxide leading to deleterious effects including susceptibility to platelet activation, inflammation, and poor control of blood flow. This loss of NO bioavailability may also be exacerbated by loss of red cell NOS activity, to be studied as part of Aim 2. In order to counteract these effects, in Aim 3, we will explore ways to reduce red cell breakdown during storage, reduce NO scavenging when there is red cell breakdown, and compensate for loss of NO activity using various donor substances.