Some patients without clear-cut iron-deficiency anemia seem to benefit from iron-replacement therapy, although this may partially represent a degree of undiagnosed iron deficiency. However, caution should be used in giving extended iron treatments in patients who do not have an underlying iron deficiency, because this may actually aggravate underlying rheumatic disease. Iron overload is also a risk for patients receiving repeated iron therapy.8
Erythropoietin-Stimulating Agents, Blood Transfusions & Target Hemoglobin
Erythropoietin-stimulating agents may be helpful in some patients with anemia of inflammation. Patients may also benefit if they have both anemia of inflammation and true iron deficiency but fail to respond to iron therapy. Erythropoietin-stimulating agents have been shown to improve anemia in patients with systemic inflammatory diseases, but response rates vary based on disease type, activity, iron availability and other factors. Use of erythropoietin-stimulating agents has been associated with gains in quality of life and reduced blood transfusions. However, treatment can result in iron deficiency due to increasing demands of iron for red blood cell production.1
Dr. Koury explains some other concerns with the use of these agents. “The degree of anemia with chronic disease is not usually that severe, and whenever you give [erythropoietin] to patients, you should be aware of the possibility of thromboses. When a patient is receiving EPO and producing red cells at an increased level, the retic[ulocyte] count can become high relative to the degree of anemia. There may be occasions for EPO administration, but it should be specific to the individual patient.”
Blood transfusions can be used to rapidly treat patients with life-threatening anemia. However, concerns about long-term safety of blood transfusions make this an option that should be used only when necessary. Dr. Koury notes, “I think it’s pretty clear if you are having angina or TIAs and your hematocrit and hemoglobin are low, you have to treat, but you have to be careful. You don’t want to overshoot those situations, because you could actually precipitate a stroke or a heart attack.”
There are no randomized controlled trials on target hemoglobin levels in patients with rheumatic disease. Dr. Weiss notes, “In patients with persistent inflammation, it appears that a hemoglobin of 11–12 is better than a normalization based on data obtained with patients on hemodialysis who also suffer from a chronic inflammatory state.”
New Treatment Options on the Horizon
“New therapeutic strategies are emerging based on our expanding knowledge of the pathophysiology of inflammatory anemia,” notes Dr. Weiss. “Anti-hepcidin strategies, which either block hepcidin formation or neutralize this peptide, have been developed and are currently in phase I–III trials for the treatment of inflammatory anemia in different diseases.” The hope is that compounds targeting hepcidin may provide safer and more effective ways of addressing anemia of inflammation.
