Transcript Document

Iron Overload in
Chronic Anaemias
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We cope well with iron
shortage…
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…but poorly with iron excess.
There is no physiologic mechanism
to excrete excessive iron
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Blood transfusion overwhelms
the iron balance
• Normal daily iron
flux:
1-2 mg
• Each unit of PRBC:
200-250 mg
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Summary: Iron is in a fine balance
• In normal circumstances, not much iron
enters or leaves the body
• The body cannot increase its excretion
of iron.
• Blood transfusions contain much iron,
so patients who need frequent
transfusions will build up excess iron.
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Why too much iron is a bad thing
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Free
Iron
Dying
RBC
Liver
CIRRHOSIS
Endocrine
organs
DIABETES
Heart
ARRHYTHMIA
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HEART FAILURE
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Lessons from thalassaemia
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When does iron become a
problem?
• Tissue damage when total body iron is
7 – 15 grams
– After 30-50 units of red blood cells
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How do we know if there’s too
much iron?
• Serum ferritin concentration
• Liver biopsy
• Magnetic resonance imaging (MRI)
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Summary: Too much iron is bad
• Iron overload caused by transfusions
causes malfunction of the liver, heart,
and endocrine organs.
• Problems may begin after 30 units of
RBC (or even earlier)
• We use serum ferritin level to estimate
iron levels
– MRI might be better
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Iron chelation
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What is Chelation Therapy?
Toxic
Chelator
+
Metal
Non-Toxic
Chelator Metal
Outside
the
Body
“Chelate”
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How to chelate?
– Deferoxamine
– Deferiprone (L1)
– Deferasirox (ICL670, Exjade)
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Common Side Effects of
Deferoxamine
• Local reactions
– Erythema (localized redness)
– Induration (localized swelling)
– Pruritus (itchiness)
• Ophthalmologic
–
–
–
–
Reduced visual acuity
Impaired color vision
Night blindness
Increased by presence of diabetes
• Hearing loss
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• Zinc deficiency
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Are we certain it helps?
Survival of patients with thalassaemia
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Summary: Iron chelation and
deferoxamine
• Chelation works by attaching a drug to
iron, which allows the body to excrete it.
• Deferoxamine is awful stuff…
– Inconvenient and uncomfortable to take
– Many nasty side effects
• …but it works
– Enormous extension of lifespan in
thalassaemia.
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ICL670: Deferasirox, Exjade
 Oral, dispersible
tablet
 Taken once daily
 Highly specific for
iron
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ICL670 is Generally Tolerable
 The most common adverse events were mild
and transient:
–
–
–
–
–
Nausea (10%)
Vomiting (9%)
Abdominal pain (14%)
Diarrhea (12%)
Skin rash (8%)
 Rarely required discontinuation of study drug
 Mild increases in serum creatinine
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What do the experts say?
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Recommended Treatment for
Iron Overload
• Why: to prevent end-organ complications of
iron overload and extend lifespan
• Whom: transfusion-dependent patients with
expected survival > 1 year
• When: after 25 units RBC transfused, ferritin
>1000.
• How: Desferal by subcutaneous infusion (for
now); keep ferritin<1000
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Summary
• Iron overload is an inevitable consequence of
chronic RBC transfusion
• Iron toxicity affects the function of the liver,
heart, and endocrine organs
• Chelation therapy should be offered to iron
overloaded patients
• Desferal is the drug currently STOOD TEST
OF TIME ; Exjade is available too.
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Thank you!
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