Anemia of Chronic Disease: Key Mechanisms of Pathogenesis in Patients with Malignancies and Feasible Classification Approaches

Abstract

Aim. To study the effect of hepcidin, soluble transferrin receptor (sTfR), and cytokines on iron metabolism and occurrence of anemia in patients with malignancies and to propose, on this basis, a draft classification of anemia of chronic disease (ACD) based on the major pathogenic factor. Materials & Methods. The trial included 63 patients with malignancies of stage II/IV: 41 patients with anemia (34 men, 7 women, mean age 67.1 ± 9.9 years), 22 patients without anemia (17 men, 5 women, mean age 60.2 ± 14.9 years). Comparative analysis was based on the values of iron metabolism, C-reactive protein (CRP), hepcidin, sTfR, as well as pro-inflammatory (interleukin-6 [IL-6], tumour necrosis factor α [TNF-α]) and anti-inflammatory (IL-10) cytokines in solid malignancy patients with and without anemia. The correlation analysis between IL-6, IL-10, TNF-α, hepcidin, sTfR, and blood count was performed. Results. Compared with the control group patients with anemia show lower levels of iron concentration, total iron-binding capacity (TIBC), and percent transferrin saturation (TSAT), as well as higher level of CRP, hepcidin, sTfR, IL-6, IL-10, and TNF-α (p < 0.05). IL-6 (r = -0.58), TNF-α (r = -0.32), and hepcidin (r = -0.57) proved to negatively affect erythrocyte level. A negative correlation was established between hemoglobin concentration and IL-6 (r = -0.57), IL-10 (r = -0.64), TNF-α (r = -0.65), hepcidin (r = -0.3), and sTfR (r = -0.57). A correlation was identified between concentrations of hepcidin and IL-6 (r = 0.58), IL-10 (r = 0.33), TNF-α (r = -0.4), as well as between concentrations of sTfR and IL-10 (r = 0.58), TNF-α (r = -0.53). A relationship was identified between IL-6 concentration and iron status (r = -0.38), TIBC (r = -0.56), TSAT (r = -0.31), ferritin (г = 0.56), transferrin (r = -0.72), CRP (r = 0.86) as well as between concentrations of IL-10 and iron (r = -0.63), TSAT (r = -0.67), transferrin (r = -0.7), ferritin (r = 0.55), CRP (r = 0.65), TIBC (r = -0.71). A correlation between the levels of TNF-α and TIBC (r = -0.36), transferrin (r = -0.5) was confirmed. Conclusion. The paper deals with multi-factorial pathogenesis of anemia in patients with malignancies. Most important factors are iron deficiency and erythropoietic disorder. A draft ACD classification based on the major pathogenic factor of anemia (ACD with dominating iron deficiency, ACD with impaired regulatory mechanism of erythropoiesis, and ACD with insufficient erythropoietin production) is proposed.