Year: 2015
Type: article
Abstract: In 1973, Lincoln et al. 1 hypothesized that induction of iron deficiency, by lowering erythrocyte mean corpuscular hemoglobin concentration (MCHC), should also decrease Hb S polymerization and thereby improve the clinical course of sickle cell anemia. They wrote: “The net effect would be to replace an anaemia characterised by excessive red-cell destruction by a less detrimental microcytic hypochromic anaemia.” The polymerization of HbS is very sensitive to its concentration in erythrocytes. Even small decrements in MCHC have a marked inhibitory effect on HbS polymerization, which is dependent on the 30th power of the deoxy-Hb S concentration 2. This principle is supported also by the natural occurrence of α-thalassemia in some patients with sickle cell anemia, which results in lower MCHC, less hemolysis, and less severe anemia 3. A paper just published by Das et al. now shows that in a sickle mouse model, iron restriction not only lowers hemolysis but also improves the anemia 4. During the four decades elapsed since the Lincoln et al. paper, a few case reports and case series suggested that naturally occurring or experimental iron restriction decreases pain events and/or lowers hemolysis in sickle cell disease patients 5-10. These observations, while interesting, were uncontrolled and did not lead to the implementation of clinical studies. It is probable that the theoretical benefit of iron restriction was insufficient to overcome a reluctance to add iron deficiency to the anemia of sickle cell patients. Furthermore, phlebotomies were used to induce iron restriction in these clinical reports, and phlebotomies seem counterintuitive in anemic patients. We believe, however, that the recently demonstrated reduction of hemolysis and improvement of anemia in iron-restricted sickle mice not only represent “proof of principle” for iron restriction as sickle cell disease therapy, but have also lowered the risk/benefit ratio of this intervention as experimental treatment. Hence we also believe it is time for carefully controlled clinical studies to determine whether iron restriction can become a new therapeutic option for sickle cell patients. Questions that could be initially addressed include: (a) the safety of regular phlebotomies in sickle patients, (b) whether hepcidin administration or iron chelation could eliminate or decrease the need for phlebotomies to lower MCHC and hemolytic rate, (c) whether iron restriction effects are additive in sickle patients also being treated with hydroxyurea, and (d) whether iron restriction is beneficial in leg ulcers and SC retinopathy, complications not typically treated with hydroxyurea. Oswaldo Castro1* Gregory J. Kato2 1Department of Medicine, Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, 2Division of Hematology-Oncology, Department of Medicine, Heart, Lung, and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
Source: American Journal of Hematology
DOI: 10.1002/ajh.24193
Authors: Oswaldo Castro, Gregory J. Kato
Institutions: Howard University, University of Pittsburgh
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1833227179