Role of redox iron towards an increase in mortality among patients: a systemic review and meta-analysis

ABSTRACT

An increase in biochemical concentrations of non-transferrin bound iron (NTBI) within the patients with an increase in serum iron concentration was evaluated with the following objectives: (a) Iron overloading diseases/conditions with free radicle form of ‘iron containing’ reactive oxygen species (ROS) and its imbalance mediated mortality, and (b) Intervention with iron containing drugs in context to increased redox iron concentration and treatment induced mortality. Literature search was done within Pubmed and cochrane review articles. The Redox iron levels are increased during dys-erythropoiesis and among transfusion recipient population and are responsive to iron-chelation therapy. Near expiry ‘stored blood units’ show a significant rise in the ROS level. Iron mediated ROS damage may be estimated by the serum antioxidant level, and show reduction in toxicity with high antioxidant, low pro-oxidant levels. Iron drug therapy causes a significant increase in NTBI and labile iron levels. Hospitalized patients on iron therapy however show a lower mortality rate. Serum ferritin is a mortality indicator among the high-dose iron therapy and transfusion dependent population. The cumulative difference of pre-chelation to post chelation ROS iron level was 0.97 (0.62; 1.32; N=261) among the transfusion dependent subjects and 2.89 (1.81–3.98; N=130) in the post iron therapy ‘iron ROS’ group. In conclusion, iron mediated mortality may not be mediated by redox iron among multi-transfused and iron overloaded patients.