ironjustice

Effect of Iron Chelators on Labile Iron and Oxidative
Status of Thalassaemic Erythroid Cells.
Prus E, Fibach E.
Acta Haematol. 2009 Nov 18;123(1):14-20.
Department of Haematology,
Hadassah Hebrew University Medical Centre,
Jerusalem, Israel.

Background/Aims:
Iron ac***ulation in vital organs such as heart and liver
is a major pathology in beta-thalassaemia.
It may also affect mature RBCs and developing erythroid
precursors.
The cellular damage is mainly caused by the labile iron
pool (LIP) and is mediated by reactive oxygen species
(ROS).
We have previously shown that thalassaemic RBCs and
their precursors have more LIP and ROS than their normal
counterparts.
We now report the effect of clinically relevant iron
chelators on these parameters.
Methods:
RBCs, reticulocytes and cultured erythroid precursors
derived from patients with beta-thalassaemia were studied
for LIP and oxidative stress parameters by flow-cytometry.
Results:
In vitro treatment with deferiprone, deferasirox and
deferoxamine reduced the cytosolic LIP in RBCs and
reticulocytes, and both the cytosolic and mitochondrial
LIP in cultured erythroid precursors.
This was associated with reduced oxidative stress (ROS
and external phosphatidylserine).
While the effect of deferiprone and deferasirox was fast
(within 10 min), deferoxamine affected these parameters
after 24 h, suggesting a slower rate of entry.
Conclusion:
The chelators studied reduce the LIP and the oxidative
status of thalassaemic RBC and their precursors.
Whether these effects directly improve ineffective
erythropoiesis and RBC survival remains to be shown.
Copyright © 2009 S. Karger AG, Basel.

PMID: 19923794


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Published at http://www.nejm.org November 17, 2009 (10.1056/NEJMoa0908355)


Ferric Carboxymaltose in Patients with Heart Failure and Iron
Deficiency
Stefan D. Anker, M.D., Ph.D., Josep Comin Colet, M.D., Gerasimos
Filippatos, M.D., Ronnie Willenheimer, M.D., Kenneth ****stein, M.D.,
Ph.D., Helmut Drexler, M.D., Thomas F. Lüscher, M.D., Boris Bart,
M.D., Waldemar Banasiak, M.D., Ph.D., Joanna Niegowska, M.D.,
Bridget-
Anne Kirwan, Ph.D., Claudio Mori, M.D., Barbara von Eisenhart Rothe,
M.D., Stuart J. Po****, Ph.D., Philip A. Poole-Wilson, M.D., Piotr
Ponikowski, M.D., Ph.D., for the FAIR-HF Trial


Investigators
ABSTRACT
Background Iron deficiency may impair aerobic performance. This study
aimed to determine whether treatment with intravenous iron (ferric
carboxymaltose) would improve symptoms in patients who had heart
failure, reduced left ventricular ejection fraction, and iron
deficiency, either with or without anemia.
Methods We enrolled 459 patients with chronic heart failure of New
York Heart Association (NYHA) functional class II or III, a left
ventricular ejection fraction of 40% or less (for patients with NYHA
class II) or 45% or less (for NYHA class III), iron deficiency
(ferritin level <100 µg per liter or between 100 and 299 µg per
liter,
if the transferrin saturation was <20%), and a hemoglobin level of 95
to 135 g per liter. Patients were randomly assigned, in a 2:1 ratio,
to receive 200 mg of intravenous iron (ferric carboxymaltose) or
saline (placebo). The primary end points were the self-reported
Patient Global Assessment and NYHA functional class, both at week 24.
Secondary end points included the distance walked in 6 minutes and
the
health-related quality of life.
Results Among the patients receiving ferric carboxymaltose, 50%
reported being much or moderately improved, as compared with 28% of
patients receiving placebo, according to the Patient Global
Assessment
(odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75
to 3.61). Among the patients assigned to ferric carboxymaltose, 47%
had an NYHA functional class I or II at week 24, as compared with 30%
of patients assigned to placebo (odds ratio for improvement by one
class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients
with anemia and those without anemia. Significant improvements were
seen with ferric carboxymaltose in the distance on the 6-minute walk
test and quality-of-life assessments. The rates of death, adverse
events, and serious adverse events were similar in the two study
groups.
Conclusions Treatment with intravenous ferric carboxymaltose in
patients with chronic heart failure and iron deficiency, with or
without anemia, improves symptoms, functional capacity, and quality
of
life; the side-effect profile is acceptable.


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