Iron Metabolism, Iron Deficiency, Thrombocytosis, and the Cardiorenal Anemia Syndrome

Abstract

In treating moderate to severe anemia of chronic kidney disease (CKD), oral iron is effective only in a minority of nondialysis patients. Intravenous iron is more effective and can raise levels of hemoglobin even without the use of erythropoiesis-stimulating agents (ESAs). Unfortunately, the current assays of iron status that are presently widely available are not especially helpful in predicting response. In patients on dialysis, i.v. iron is effective over a wide range of serum ferritin from <100 ng/ml to 800 ng/ml. None of the three available randomized controlled trials comparing oral with i.v. iron showed evidence of nephrotoxicity caused by i.v. iron.Iron deficiency is a risk factor for thrombocytosis and should, wherever possible, be avoided. Optimal coadministration of iron may reduce the risk for ESA-driven cardiovascular events. Increased total body iron stores (imperfectly reflected by serum ferritin levels in CKD) do not appear to be related to such events or hospitalization in CKD; it is unclear what other risk factors and mechanisms need to be considered.In the appreciable proportion of patients with both renal and cardiac dysfunction, management is further complicated by a vicious circle (which can be characterized as cardiorenal anemia syndrome) in which CKD, heart failure, and anemia exacerbate each other. In such patients, correction of anemia appears to improve cardiac function and quality of life without a greater risk for adverse events. The Oncologist 2009;14(suppl 1):22-33

Anemia Management in Oncology and Hematology

“…It is likely that decreased EPO production and inhibition of its activity by inflammatory cytokines are responsible for abnormalities such as reduced iron absorption and decreased erythroblast transferrin-receptor expression [16]. The role of iron metabolism in anemia is discussed in further detail in this supplement in the article by Anatole Besarab, Walter Hörl, and Donald Silverberg [17].…”

Eisenmangel, Thrombozytose und Thromboembolie

“…Ein unbehandelter Eisenmangel erhöht die Mortalität bei Patienten mit chronischer Niereninsuffizienz [82,83]. Es wird vermutet, dass die durch den funktionellen Eisenmangel hervorgerufene sekundäre Thrombozytose wesentlich zu der Erythropoetin-assoziierten Steigerung der Häufigkeit von kardiovaskulären Ereignissen beiträgt [41,84] [49,50]. In der großen prospektiven CATS Studie war die Thrombozytose mit einem HR für venöse Thromboembolien von 3,50 assoziiert [51].…”

Iron Deficiency Anemia in Cancer Patients

“…5 This results in impaired iron transport, both from the GI tract and from reticuloendothelial cells (which acquire iron stores during the phagocytosis and breakdown of red blood cells phagocytosis, resulting in a return to the macrophage iron stores of ~20-25 mg daily. 11 Ferroportin is a key player in iron recycling and is responsible for exporting intracellular iron stores from macrophages and enterocytes (see Figure 1A). In the absence of ferroportin, iron recycling is severely affected.…”