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

VT Sakhin1, ER Madzhanova1, EV Kryukov3, AV Sotnikov2, AV Gordienko2, OA Rukavitsyn3

1 1586 Military Clinical Hospital, 4 Mashtakova str., Moscow Region, Podolsk, Russian Federation, 142110

2 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

3 NN Burdenko Central Military Clinical Hospital, 3 Gospital’naya sq., Moscow, Russian Federation, 105229

For correspondence: Valerii Timofeevich Sakhin, MD, PhD, 4 Mashtakova str., Moscow Region, Podolsk, Russian Federation, 142110; Tel.: +7(916)314-31-11; e-mail: SahinVT@yandex.ru

For citation: Sakhin VT, Madzhanova ER, Kryukov EV, et al. Anemia of Chronic Disease: Key Mechanisms of Pathogenesis in Patients with Malignancies and Feasible Classification Approaches. Clinical oncohematology. 2019;12(3):344–9 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-344-349


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 (< 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 (r = 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.

Keywords: cancer, anemia, iron metabolism, interleukin-6, interleukin-10, tumor necrosis factor alpha, hepcidin, soluble transferrin receptor.

Received: January 21, 2019

Accepted: June 18, 2019

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Erythroferron: Modern Concepts of Its Role in Iron Metabolism Regulation

VT Sakhin1, NV Kremneva1, AV Gordienko2, OA Rukavitsyn3

1 Military Clinical Hospital No. 1586 under the Ministry of Defense of Russia, 4 Mashtakova str., Podol’sk, Moscow Oblast, Russian Federation, 142110

2 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

3 NN Burdenko Principal Military Clinical Hospital under the Ministry of Defense of Russia, 3 Gospital’naya pl., Moscow, Russian Federation, 105229

For correspondence: Valerii Timofeevich Sakhin, PhD, 4 Mashtakova str., Podol’sk, Moscow Oblast, Russian Federation, 142110; Tel: +7(916)314-31-11; e-mail: SahinVT@yandex.ru

For citation: Sakhin VT, Kremneva NV, Gordienko AV, Rukavitsyn OA. Erythroferron: Modern Concepts of Its Role in Iron Metabolism Regulation. Clinical oncohematology. 2017;10(1):25–8 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-25-28


ABSTRACT

The article presents the results of experimental and clinical studies evaluating the importance of supposed erythroid regulators of hepcidin levels and mechanism of their action. It demonstrates that the role of growth differentiation factor 15 and twisted gastrulation protein homolog 1 in regulation of hepcidin levels in humans has not been confirmed yet. The data confirming the importance of erythroferron in the pathogenesis of anemia related to blood loss, hemolysis, and hereditary anemias with ineffective erythropoiesis are presented. The studies demonstrated that erythroferron plays the greatest role in the regulation of hepcidin levels in pathological conditions and at stress and does not play a leading role in erythropoiesis under normal conditions. Erythroferron suppresses the hepcidin synthesis by affecting the liver cells directly through an unknown receptor cellular pathway.

Keywords: anemia of chronic disease, hepcidin, erythroferron.

Received: September 14, 2016

Accepted: November 13, 2016

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Iron Metabolism in Normal and Pathological Conditions

E.A. Lukina, A.V. Dezhenkova

Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Elena Alekseevna Lukina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-09-23; e-mail: elenalukina02@gmail.com

For citation: Lukina EA, Dezhenkova AV. Iron Metabolism in Normal and Pathological Conditions. Clinical oncohematology. 2015;8(4):355–361 (In Russ).

DOI: 10.21320/2500-2139-2015-8-4-362-367


ABSTRACT

This review describes modern conceptions of the physiological and pathological roles of iron, as well as the main mechanisms of iron metabolism regulation. In recent years, it has been shown that both deficiency and excess of iron can have damaging effects on the body, and the existence of homeostatic mechanisms controlling the total iron content of the body has been proved. The body of an average healthy adult human contains 3 to 5 g iron, most of which is contained in blood cells, bone marrow and liver; it is bound to proteins and this is important for prevention of cytotoxic effects of free iron ions. This review summarizes data on the main proteins involved in iron metabolism and their role in iron homeostasis. The processes of iron recirculation and the functional role of hepcidin, the key protein regulating extracellular iron concentration, are emphasized. The review provides brief data on pathogenic mechanisms of functional iron deficiency development and its role in anemia of chronic disease, as well as the pathogenesis, diagnostics and management of secondary iron overload.


Keywords: iron metabolism, ferritin, hepcidin, iron recirculation, anemia of chronic disease, iron overload.

Received: July 1, 2015

Accepted: November 9, 2015

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