Possibility of enhanced risk of retinal neovascularization in repeated blood donors: blood donation and retinal alteration

Abstract

Repeated blood donors manifest clinical, subclinical, and biochemical signs of iron deficiency anemia, have significantly higher erythropoietin and vascular endothelial growth factor (VEGF) concentrations, and decreased tissue oxygen saturation, oxygenated tissue hemoglobin, and regional cerebral oxygen saturation. Erythropoietin and VEGF are potent retinal angiogenic factors which may initiate and promote the retinal angiogenesis process independently or simultaneously. Increases in circulating levels of erythropoietin and VEGF are proportionate to the levels of hematocrit, hypoxemia, and tissue hypoxia. It is suggested that higher erythropoietin production following iron deficiency anemia-induced chronic hypoxemia/ hypoxia may, hypothetically, enhance the risk of retinal angiogenesis and/or neovascularization, possibly by inducing hypoxia inducible factor-1 alpha, which consequently upregulates genes stimulating angiogenesis, resulting in formation of a new vasculature, possibly by modulation of signal transducer and activator of transcription 3 signaling in the retina. Implications of this hypothesis cover erythropoietin doping, chronic hypoxia, and hypoxemic situations, such as angiogenesis-related cardiac and pulmonary diseases.

Anemia: A Potential Source of Bias in Clinical Trials of Angiogenesis Inhibitors: A Hypothesis

“…Most of the recently published articles benefit from elegant and sophisticated methodology. 4 However, although anemia is causally related to angiogenesis and neovas-cularization, 5 especially in ocular situations, 6 neither the published nonrandomized clinical trials nor the registered nonrandomized clinical trials have reported the anemia status as inclusion or exclusion criteria in their design. The main methodological issue here is that whether the iron-deficiency status in enrolled patients confound the efficacy of angiogenesis inhibitors, since a low hemoglobin level is associated with increased serum levels of vascular endothelial growth factor (VEGF) and it has been suggested that anemia might increase the progression of angiogenesis.…”

Safety of Cabergoline in the Management of Pituitary Prolactin-Induced Symptoms with Patients Treated with Atypical Neuroleptics

“…But hyperprolactinemia, particularly in women and also in men, has been associated to treatment with both typical and atypical antipsychotics such as risperidone and probably to others [1][2][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”