Iron restriction is an important treatment of hemoglobin SC disease
Authors: François Lionnet, Nadjib Hammoudi, Katia Stankovic Stojanovic, Virginie Avellino, Gilles Grateau, Robert Girot, Jean‐Philippe Haymann
Journal: American Journal of Hematology (2016)

To the Editor: We read with interest the article by Luchtman-Jones et al. about hydroxyurea in the treatment of hemoglobin SC (HbSC) disease 1, and were surprised that phlebotomy was not considered as a key treatment as it is the case in HbSC adults. As mentioned in the article, hyperviscosity is the key point in HbSC disease. HbC induces intracellular dehydration, increases mean corpuscular hemoglobin concentration (MCHC) 2 and HbS concentration, leading to falciformation 2. Fabry et al. noted in 1982 that the change in MCHC needed to correct the abnormalities and to decrease HbS polymerization is small (only 37–33 g/dL) 2, and this change is easily achieved with iron restriction induced by phlebotomies. Iron restriction has the other interest to decrease hemoglobin level, since 90% of HbSC patients have hemoglobin levels above 10 g/dL with a general agreement that 10–11g/dL would represent a threshold for vaso-occlusive outcomes 3. In a series of 64 patients with HbSC disease having vaso-occlusive painful crisis, acute chest syndrome, priapism, or thrombotic events, we found that phlebotomies induced a good clinical response in 71% of cases 3. It was only a retrospective study, just as the study reported here with hydroxyurea. If hydroxyurea is safe and inexpensive, so are phlebotomies, which have moreover no deleterious effect on male fertility and are feasible without requiring sophisticated infrastructures. Furthermore, hydroxyurea may induce cytopenia and may aggravate thrombopenia due to hypersplenism which is encountered in 30% of HbSC patients 3. The beneficial effect of phlebotomies on hyperviscosity is indeed obvious in clinical practice, whereas the first sessions are technically difficult with frequent clotting of the line, the following next sessions being progressively much easier and performed in a short time frame, as viscosity decreases. Moreover, phlebotomy may decrease the blood viscosity-related life-threatening complications, as pulmonary embolism, extensive medullary necrosis with acute multiorgan failure syndrome, and myocardial or cerebral infarction 3. Prospective studies are however warranted because it is not known whether iron restriction is safe in younger patients and whether it could prevent the main chronic complications of HbSC disease, proliferative retinopathy, and otological disorders. Finally, we strongly believe that practitioners and patients, especially HbSC females, should be sensitized not to correct a spontaneous iron defect, as it provides a natural and strong protection against hyperviscosity. François Lionnet,1* Nadjib Hammoudi,2,3,4,5 Katia Stankovic Stojanovic,1 Virginie Avellino,1 Gilles Grateau,3,6,7 Robert Girot,3,7,8 and Jean-philippe Haymann3,9,10 1Service de Médecine Interne, Centre de Référence de la Drépanocytose, Paris, France; 2Service de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France; 3Faculté de Médecine, Université Pierre et Marie Curie, Paris 6, France; 4Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; 5UMR S Inserm-UPMC 1166 & ICAN, Paris, France; 6Service de Médecine Interne, Hôpital Tenon, AP-HP, Paris, France; 7Centre de Référence de la Drépanocytose, Paris 6, France; 8Service d'Hématologie Biologique, Hôpital Tenon, AP-HP, Paris, France; 9Service des Explorations Fonctionnelles, Hôpital Tenon, AP-HP, Paris, France; 10INSERM, UMRS-702, Paris, France