chronic diseases). Although iron restriction is a prominent component of AI, inflammation
also causes decreased erythrocyte survival and a shift of hematopoiesis to leukocyte
production7. These other effects modify the expected iron-restricted phenotype so that the
erythrocytes, although fewer, have a normal size and hemoglobin content. The iron
restriction in AI is mediated by the inflammatory induction of hepcidin, predominantly
through IL-6. In rodent models of AI, ablation of hepcidin significantly but incompletely
ameliorates anemia, consistent with the multiple pathways of AI causation.
Anemia of chronic kidney disease—Anemia is a common consequence of chronic kidney
diseases (CKD), regardless of their specific causation. The development of recombinant Epo
products transformed the treatment of these anemias. More recently, increased awareness
of the side effects of Epo therapy has led to the understanding that anemia of CKD also has
an important component of AI causing iron restriction and shortened erythrocyte lifespan,
manifesting as resistance to Epo. Empiric treatment with IV iron was introduced to
overcome iron restriction and was successful in reducing the requirements for Epo products.
Therapy of iron restrictive anemias—The most efficacious therapy of anemia is to treat the
underlying cause. Atransferrinemia is treated with infusions of human transferrin or blood
plasma, AI will improve when the underlying disease is ameliorated. When fundamental
therapy is not possible, AI and anemia of CKD will improve when treated by a combination of
erythropoietin (or derivatives) with IV iron8. A new treatment modality currently reaching
approval by the regulatory authorities in many countries are prolyl hydroxylase inhibitors
which can be given orally9. Promising antiinflammatory drugs currently undergoing clinical
trials for the treatment of anemia of CKD include anti-IL-6 monoclonal antibodies10. Both
prolyl hydroxylase inhibitors and anti-cytokine therapies work in part by decreasing hepcidin
concentrations and relieving iron restriction.
References
1. Chen C, Wen S, Tan X. Molecular analysis of a novel case of congenital atransferrinemia. Acta
Haematol. 2009;122(1):27-28.
2. Bullock GC, Delehanty LL, Talbot AL, et al. Iron control of erythroid development by a novel
aconitase-associated regulatory pathway. Blood. 2010;116(1):97-108.
3. Heeney MM, Finberg KE. Iron-refractory iron deficiency anemia (IRIDA). Hematol Oncol Clin
North Am. 2014;28(4):637-652, v.
4. Chen JJ, Zhang S. Heme-regulated eIF2alpha kinase in erythropoiesis and
hemoglobinopathies. Blood. 2019;134(20):1697-1707.
5. Talbot AL, Bullock GC, Delehanty LL, Sattler M, Zhao ZJ, Goldfarb AN. Aconitase regulation of
erythropoiesis correlates with a novel licensing function in erythropoietin-induced ERK signaling.
PLoSONE. 2011;6(8):e23850.
6. Khalil S, Delehanty L, Grado S, et al. Iron modulation of erythropoiesis is associated with
Scribble-mediated control of the erythropoietin receptor. J Exp Med. 2018;215(2):661-679.
7. Ganz T. Anemia of Inflammation. N Engl J Med. 2019;381(12):1148-1157.
8. Macdougall IC, White C, Anker SD, et al. Intravenous Iron in Patients Undergoing
Maintenance Hemodialysis. N Engl J Med. 2019;380(5):447-458.
9. Chen N, Hao C, Liu BC, et al. Roxadustat Treatment for Anemia in Patients Undergoing Long-
Term Dialysis. N Engl J Med. 2019;381(11):1011-1022.
10. Pergola PE, Devalaraja M, Fishbane S, et al. Ziltivekimab for Treatment of Anemia of
Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-
Blind, Placebo-Controlled Trial. J Am Soc Nephrol. 2021;32(1):211-222.
SCIENTIFIC PROGRAMME
SESSION I
BONE MARROW
RESPONSE TO VIRAL
INFECTIONS
SESSION II
HAEMATOLOGICAL
RESPONSE TO SARS
COV2 INFECTION
SESSION III
DYSERYTHROPOIESIS IN
CLONAL HAEMOPOIESIS
AND MDS
SESSION IV
ERYTHROPOIESIS
CONTROL
SESSION V
ERYTHROPOIESIS
CONTROL : PHASE 2
SESSION VI
IRON METABOLISM
AND ERYTHROPOIESIS
SESSION VII
INHERITED
DYSERYTHROPOIESIS
SESSION VIII
GENE THERAPY/EDITION
SESSION IX – DRUGS
AND INEFFECTIVE
ERYTHROPOIESIS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
FACULTY DISCLOSURES