TY - JOUR
T1 - Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded β-thalassemia/HbE patients treated with an oral chelator
AU - Pootrakul, Pensri
AU - Breuer, William
AU - Sametband, Matias
AU - Sirankapracha, Pornpan
AU - Hershko, Chaim
AU - Cabantchik, Z. Ioav
PY - 2004/9/1
Y1 - 2004/9/1
N2 - Persistent levels of plasma nontransferrin bound iron (NTBI) have been associated with tissue iron overload and toxicity. We characterized NTBI's susceptibility to deferoxamine (directly chelatable iron [DCI]) and redox activity (labile plasma iron [LPI]) during the course of long-term, continuous L1 (deferiprone) treatment of patients with hemoglobin E disease and β-thalassemia (n = 17). In 97% of serum samples (n = 267), the LPI levels were more than 0.4 μM (mean ± SEM, 3.1 ± 0.2 μM) and the percent transferrin (Tf) saturation more than 85 (111 ± 6), whereas only in 4% of sera were the LPI levels more than 0.4 μM for Tf saturation less than 85%. Daily administration of L1 (50 mg/kg) for 13 to 17 months caused both LPI and DCI to decrease from respective initial 5.1 ± 0.5 and 5.4 ± 0.6 μM to steady mean levels of 2.18 ± 0.24 and 2.81 ± 0.14 μM. The steady lowest levels of LPI and DCI were attained after 6 to 8 months, with a half time (t1/2) of 2 to 3 months. Serum ferritin and red cell membrane-associated iron followed a similar course but attained steady basal levels only after 10 to 12 months of continuous treatment, with a t 1/2 of 5 to 7 months. These studies indicate that LPI and DCI can serve as early indicators of iron overload and as measures for the effectiveness of iron chelation in reducing potentially toxic iron in the plasma.
AB - Persistent levels of plasma nontransferrin bound iron (NTBI) have been associated with tissue iron overload and toxicity. We characterized NTBI's susceptibility to deferoxamine (directly chelatable iron [DCI]) and redox activity (labile plasma iron [LPI]) during the course of long-term, continuous L1 (deferiprone) treatment of patients with hemoglobin E disease and β-thalassemia (n = 17). In 97% of serum samples (n = 267), the LPI levels were more than 0.4 μM (mean ± SEM, 3.1 ± 0.2 μM) and the percent transferrin (Tf) saturation more than 85 (111 ± 6), whereas only in 4% of sera were the LPI levels more than 0.4 μM for Tf saturation less than 85%. Daily administration of L1 (50 mg/kg) for 13 to 17 months caused both LPI and DCI to decrease from respective initial 5.1 ± 0.5 and 5.4 ± 0.6 μM to steady mean levels of 2.18 ± 0.24 and 2.81 ± 0.14 μM. The steady lowest levels of LPI and DCI were attained after 6 to 8 months, with a half time (t1/2) of 2 to 3 months. Serum ferritin and red cell membrane-associated iron followed a similar course but attained steady basal levels only after 10 to 12 months of continuous treatment, with a t 1/2 of 5 to 7 months. These studies indicate that LPI and DCI can serve as early indicators of iron overload and as measures for the effectiveness of iron chelation in reducing potentially toxic iron in the plasma.
UR - http://www.scopus.com/inward/record.url?scp=4444274916&partnerID=8YFLogxK
U2 - 10.1182/blood-2004-02-0630
DO - 10.1182/blood-2004-02-0630
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C2 - 15155464
AN - SCOPUS:4444274916
SN - 0006-4971
VL - 104
SP - 1504
EP - 1510
JO - Blood
JF - Blood
IS - 5
ER -