Transfusion | 2019
Iron deficiency–related symptoms in whole blood donors: a systematic review
Abstract
W hole blood donation has frequently been related to iron deficiency. A blood donor loses about 250 mg of iron with each whole blood donation of 500 mL, which is 8% to 13% of the iron stores in men and nonmenstruating women and as much as 81% in menstruating women. To replenish the iron lost by blood donation in the minimum donation interval of 56 days, a donor needs to absorb 4.5 mg of iron per day. This amount exceeds the reported maximal amount of absorbed iron of 3 to 4 mg/day; consequently, iron stored in the parenchymal tissues (liver) and the reticuloendothelial macrophages will be released for erythropoiesis, eventually leading to iron deficiency. Importantly, iron deficiency in non–blood donors with and without anemia has been associated with decreased physical endurance and work capacity; fatigue; pica; restless legs syndrome (RLS); and impaired attention, concentration, and other cognitive functions. Therefore, it can be presumed that serial blood donation may lead to depletion of iron stores and ultimately lowering of hemoglobin (Hb) levels, eventually leading to discomfort and iron deficiency–related symptoms. The main function of Hb is oxygen transport from the lungs to all body tissues and carbon dioxide back to the lungs. As a consequence of low Hb levels, fatigue may occur (Web reference: Schrier SLApproach to the adult with anemia. Uptodate, February 15, 2018). Importantly, even nonanemic people with low ferritin levels may suffer from fatigue. Other symptoms that may occur due to decreased oxygen transport are dyspnea and signs and symptoms of the hyperdynamic state in which the cardiac output is increased at rest. In addition, pica, which is the craving for eating nonnutritive substances, has been described as a symptom of iron deficiency anemia. All forms of pica are associated with iron deficiency, but the strongest association is with pagophagia, the ingestion of ice. Although the etiology of pica is unknown, it was suggested that addiction centers in the brain may be selectively affected by cerebral iron deficiency. Moreover, RLS has been associated with iron deficiency. Patients with RLS showed decreased iron stores, especially in the substantia nigra, shown by magnetic resonance imaging. Although not all patients with RLS have systemic iron deficiency, defined as low iron levels in the serum, they may have low iron levels in the brain. Animal models and studies in patients suggest that iron deficiency in the brain may have an effect on the dopaminergic systems resulting in RLS. Iron deficiency may also lead to cognitive changes. Alterations or abnormalities in brain energy or neurotransmitter metabolism and decreased myelin formation have been described as possible drivers of these cognitive changes, although the exact mechanism is still unclear. Overall, most of the symptoms of iron deficiency seem to be associated with lower iron levels in the brain. Iron supplementation trials have found that symptoms decreased or disappeared after restoring serum iron levels, which indicates that serum iron levels are associated with iron status in the brain. Currently, there is considerable interest in iron deficiency in blood donors. A number of studies investigated advantages of iron deficiency after blood donation, such as decreased risk of cardiovascular diseases and cancer. A recent review discussed management of iron deficiency after blood donations and possible negative consequences of iron deficiency in blood donors, with inconclusive