Concepts and goals in the management of transfusional iron overload

Abstract

In this review, current concepts and goals of iron chelation therapy for thalassemias, sickle cell disease, and myelodysplastic syndromes are discussed. The primary goal of iron chelation therapy is to prevent the accumulation of iron reaching harmful levels by matching iron intake from blood transfusion, with iron excreted by iron chelation. Over 30 years of experience with deferoxamine has shown iron chelation to be an effective therapeutic modality. However, chelation efficiency is limited because most of the body's iron stores are not directly chelatable, and only a small fraction of body iron is chelatable at any moment. Once iron has been deposited in organs other than the liver, for example the heart, removal by chelation is slow and inefficient. Chelation efficiency can be improved by designing regimes where chelators are available 24 hr a day to bind labile iron pools in cells and plasma. Deferoxamine has a short plasma half-life and the parenteral infusions required to achieve steady plasma levels are demanding, with consequent variable adherence to therapy. Once-daily oral administration of deferasirox achieves continuous chelation with trough concentrations sufficient to decrease plasma labile iron species progressively, and achieves an efficiency of chelation not obtainable with deferiprone or deferoxamine monotherapy. Am. J. Hematol. 82:1136Hematol. 82: -1139Hematol. 82: , 2007

Management of the Thalassemias

“…A follow-up report identified one death from cardiac disease in the 1980 -1984 birth cohort and no such deaths in subsequent birth cohorts (Borgna-Pignatti et al 2004a). These findings show that accumulation of iron in heart is not inevitable, provided that body storage iron is controlled (Porter 2007). These North American and Italian data are paralleled in expert programs in the United Kingdom (Porter and Davis 2002), although poorer results are reported in centers in that country where erratic compliance and other impediments to effective treatment are likely less well managed (Modell et al 2000).…”

Iron poisoning in lethal dose: Case report

“…Bu kompleks hidrofilik ve büyük ağırlıklı bir molekül olduğundan emilimi yoktur. [10] Bu kompleks idrarla atılır ve idrara gülkurusu rengini verir. Bizde olgumuzda şelasyon tedavisi endikasyonu olduğundan dolayı desferoksmin uyguladık.…”

“…Ancak demir düzeyinin <350 µgr/dl olması ciddi zehirlenme olmadığı anlamında değerlendiril-memelidir. [10] Chyka ve ark.nın [8] yaptığı bir çalışmada hastanın kliniği ve semptomlarının serum demir miktarı ile ilişkili olmadığı bildirilmiştir. Bu nedenle kan demir düze-yinin her zaman akut toksisiteyi göstermeyebileceği bildirilmiştir.…”

Cardiovascular evaluation and management of iron overload cardiomyopathy in sickle cell disease

“…This is similar to the findings by Odour et al 4 The absence of complete reversal of LV dysfunction may be attributed to established myocardial injury, persistent iron overload, or limited efficacy of iron chelators as only a portion of total body iron content is directly chelatable, with hemosiderin being the least accessible form of the three forms of stored iron. 5 Thus it may be postulated that in lieu of initiating iron chelation therapy when T2* values are <20 milliseconds on MRI, it may be beneficial to initiate therapy earlier when T2* values are 20-30…”

“…1 However, while splenectomy can relieve abdominal pain, it may be of no benefit for correcting anemia and carries an exceptionally high risk of thromboembolic complications (at least in the context of PIEZO1 mutations). 5 The central role of KCNN4 in the red blood cell dehydration of HX has led to the proposed use of the KCNN4 (Gardos channel) blocker, senicapoc, to prevent dehydration and subsequent hemolysis of red blood cells. …”