Download Document

Iron Overload in
Chronic Anaemias
Thalassemia Center
1
We cope well with iron
shortage…
Thalassemia Center
2
…but poorly with iron excess.
There is no physiologic mechanism
to excrete excessive iron
Thalassemia Center
3
Blood transfusion overwhelms
the iron balance
• Normal daily iron
flux:
1-2 mg
• Each unit of PRBC:
200-250 mg
Thalassemia Center
4
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.
Thalassemia Center
5
Why too much iron is a bad thing
Thalassemia Center
6
Free
Iron
Dying
RBC
Liver
CIRRHOSIS
Endocrine
organs
DIABETES
Heart
ARRHYTHMIA
Thalassemia Center
HEART FAILURE
7
Lessons from thalassaemia
Thalassemia Center
8
When does iron become a
problem?
• Tissue damage when total body iron is
7 – 15 grams
– After 30-50 units of red blood cells
Thalassemia Center
9
How do we know if there’s too
much iron?
• Serum ferritin concentration
• Liver biopsy
• Magnetic resonance imaging (MRI)
Thalassemia Center
10
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
Thalassemia Center
11
Iron chelation
Thalassemia Center
12
What is Chelation Therapy?
Toxic
Chelator
+
Metal
Non-Toxic
Chelator Metal
Outside
the
Body
“Chelate”
Thalassemia Center
13
How to chelate?
– Deferoxamine
– Deferiprone (L1)
– Deferasirox (ICL670, Exjade)
Thalassemia Center
14
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
15
• Zinc deficiency
Thalassemia Center
Are we certain it helps?
Survival of patients with thalassaemia
Thalassemia Center
16
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.
Thalassemia Center
17
ICL670: Deferasirox, Exjade
 Oral, dispersible
tablet
 Taken once daily
 Highly specific for
iron
Thalassemia Center
18
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
Thalassemia Center
19
What do the experts say?
Thalassemia Center
20
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
Thalassemia Center
21
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.
Thalassemia Center
22
Thank you!
Thalassemia Center
23