Transfusion science最新文献

The concept of non-transferrin bound iron (NTBI) was introduced 22 years ago by Hershko et al. (Brit. J. Haematol. 40 (1978) 255). It stemmed from a suspicion that, in iron overloaded patients, the large amounts of excess iron released into the circulation are likely to exceed the serum transferrin (Tf) iron-binding capacity (TIBC), leading to the appearance of various forms of iron not bound to Tf. In accordance with this assumption, NTBI was initially looked for and detected in patients with ⩾100% Tf-saturation. As techniques for its detection became more sophisticated and sensitive, NTBI was also found in conditions where Tf was not fully saturated, leading to a revision of the original view of NTBI as a simple spillover phenomenon. In this review, we will discuss some of the properties of NTBI, methods for its detection, its significance and potential value as an indicator for therapeutic regimens of iron chelation and supplementation.

Iron is essential for all living organisms. Under normal conditions there is no regulatory and rapid iron excretion in humans and body iron levels are mainly regulated from the absorption of iron from the gut. Regular blood transfusions in thalassaemia and other chronic refractory anaemias can result in excessive iron deposition in tissues and organs. This excess iron is toxic, resulting in tissue and organ damage and unless it is removed it can be fatal to those chronically transfused. Iron removal in transfusional iron overload is achieved using chelation therapy with the chelating drugs deferoxamine (DF) and deferiprone (L1). Effective chelation therapy in chronically transfused patients can only be achieved if iron chelators can remove sufficient amounts of iron, equivalent to those accumulated in the body from transfusions, maintaining body iron load at a non-toxic level. In order to maintain a negative iron balance, both chelating drugs have to be administered almost daily and at high doses. This form of administration also requires that a chelator has low toxicity, good compliance and low cost. DF has been a life-saving drug for thousands of patients in the last 40 years. It is mostly administered by subcutaneous infusion (40–60 mg/kg, 8–12 h, 5 days per week), is effective in iron removal and has low toxicity. However, less than 10% of the patients requiring iron chelation therapy worldwide are able to receive DF because of its high cost, low compliance and in some cases toxicity. In the last 10 years we have witnessed the emergence of oral chelation therapy, which could potentially change the prognosis of all transfusional iron-loaded patients. The only clinically available oral iron chelator is L1, which has so far been taken by over 6000 patients worldwide, in some cases daily for over 10 years, with very promising results. L1 was able to bring patients to a negative iron balance at doses of 50–120 mg/kg/day. It increases urinary iron excretion, decreases serum ferritin levels and reduces liver iron in the majority of chronically transfused iron-loaded patients. Despite earlier concerns of possible increased risk of toxicity, all the toxic side effects of L1 are currently considered reversible, controllable and manageable. These include agranulocytosis (0.6%), musculoskeletal and joint pains (15%), gastrointestinal complaints (6%) and zinc deficiency (1%). The incidence of these toxic side effects could in general be reduced by using lower doses of L1 or combination therapy with DF. Combination therapy could also benefit patients experiencing toxicity with DF and those not responding to either chelator alone. The overall efficacy and toxicity of L1 is comparable to that of DF in both animals and humans. Despite the steady progress in iron chelation therapy with DF and L1, further investigations are required for optimising their use in patients by selecting improved dose protocols, by minimising their toxicity and by identifying