SQU Med J, December 2010, Vol. 10, Iss. 3, pp. 401-404, Epub. 14th Nov 10 
Submitted 3rd April 10
Revision ReQ. 20th June 10, Revision recd. 6th Aug 10
Accepted 11th Aug

In the past, the impact of cessation or poor compliance with chelation therapy was not easily assessable except by serum ferritin 
levels. These have ultimately been found to be 
relatively unreliable with respect to demonstrating 
the degree of iron load in the heart and liver.1,2  

Liver biopsies, though valuable, were traumatic 
and had low patient acceptance. With the advent 
of magnetic resonance imaging (MRI) techniques 
(T2*), such assessments are more easily accessible 
although expensive.3 The patient described here 
was followed prospectively before and after the 

1Department of Haematology, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman; 2Department of 
Medicine, Sultan Qaboos University Hospital, Muscat, Oman; 3Department of Hematology/Oncology, Children’s Hospital of Los 
Angeles, USA
*Corresponding Author email: shahina@squ.edu.om

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 500
 19.5 48.8

 14.5 12.7 3820
 95 
 28.5 27.5
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




aBstract: Iron loading in patients with transfusion dependent thalassaemia is considered to occur primarily 
in the liver and, once the liver becomes saturated, other organs begin loading.  We report here a splenectomised 
male patient who was treated for hepatitis C virus infection. Prior to starting antiviral therapy, his serum ferritin 
was maintained below 500 ng/ml with deferiprone monotherapy; cardiac T2* by magnetic resonance imaging was 
48.8ms and hepatic T2* was 19.5ms. After twelve months of antiviral treatment during which time he was very 
poorly compliant with his deferoxamine chelation therapy, his ferritin had risen to 3820 ng/ml and cardiac and 
hepatic T2* findings were 12.7 ms and 14.5 ms respectively, indicating increased iron loading in both organs, but 
particularly in the heart. Fifteen months after recommencing combination chelation, his ferritin was 95 ng/ml 
and cardiac and hepatic T2* were 27.5 and 28.4ms respectively, indicating complete clearance of iron load in both 
organs. This case demonstrates that iron overload can develop rapidly and in some cases there is relatively rapid 
iron loading in the heart as compared to the liver. 

Keywords: Thalassaemia Major; Iron overload; Deferiprone; Deferoxamine; Chelation therapy; Magnetic resonance 
imaging; Case report; Oman

Rapid Iron Loading in Heart and Liver in a 
Patient with Transfusion Dependent 

Thalassaemia after Brief Poor Compliance 
with Iron Chelation Therapy

*Shahina Daar,1 Saeed Ahmed,2 Vasili Berdoukas3 

CASE REPORT



Rapid Iron Loading in Heart and Liver in a Patient with Transfusion Dependent Thalassaemia  
after Brief Poor Compliance with Iron Chelation Therapy

402 | SQU Medical Journal, December 2010, Volume 10, Issue 3

period during which he was on interferon therapy 
which precluded the use of deferiprone. This 
demonstrates the impact of poor compliance with 
chelation therapy for a relatively short period of 12 
months.

Case Report
This patient, with transfusion dependent 
thalassaemia, was born in 1974.  He commenced 
regular blood transfusion at 22 months of age  
and regular deferoxamine iron chelation therapy 
at the late age of 19 years, when his ferritin was 
4869 ng/ml. By 2001, aged 27, his ferritin was 3755 
ng/ml. With the availability of the oral chelator 
deferiprone, and information that combination 
therapy with deferiprone and deferoxamine was 
resulting in at least an additive effect with respect 
to iron excretion,4 he commenced combination 
therapy in August 2001. The regime was as follows: 
deferiprone orally at 75 mg/kg/day in three doses 
and deferoxamine at 40 mg/kg infusion for 5 days 
of the week. He was always very compliant with 
his oral chelator and was able to manage 2 days per 
week of Desferoxamine infusions. He did not show 
any cardiac complications and glucose and thyroid 
metabolism were normal. Gonadal function was 
normal until the age of 30, at which time he required 
testosterone replacement. By May 2005, his ferritin 
was 540 ng/ml, the deferoxamine was stopped and 
he continued on deferiprone monotherapy. 

On the basis of being hepatitis C virus (HCV) 
polymerase chain reaction (PCR) positive 
with persistently elevated hepatic enzymes 

(alanine aminotransferase 50-85 IU/l, aspartate 
aminotransferase 80-115 U/l) and his liver biopsy 
showing chronic hepatitis with moderate activity 
and stage 5 fibrosis, he commenced interferon 
and ribavirin treatment in September 2007. He 
had an excellent response with viral load falling 
from >500,000 IU/ml to below detectable limits 
within 9 weeks of commencing treatment. At the 
start of HCV therapy his ferritin level was 335 ng/
ml. As interferon can cause neutropaenia, and as 
deferiprone can also cause both neutropaenia and 
agranulocytosis, the deferiprone was stopped, and 
he continued on deferoxamine treatment alone. 
He was poorly compliant with this treatment and 
his ferritin gradually rose to a peak of 3820 ng/ml 
at the end of his HCV therapy. The effect of his 
poor compliance was compounded by increased 
transfusion requirements over the period of HCV 
therapy (increase of 40 mls/kg/year packed red 
cells). Table 1 shows the liver and cardiac T2* 
before starting interferon, during the treatment, 
soon after ceasing combination therapy and after 
recommencing it, the last reading being 15 months 
after completing HCV therapy. 

Studies have shown that patients who have 
a cardiac T2* result of <10 ms are at high risk 
for cardiac disease due to iron overload, and that 
those whose T2* is above 20 ms are in the ‘normal’ 
range.3,5 Our patient’s cardiac T2* fell from well 
within the normal range to just above the high risk 
cut-off in a relatively short period of time [Table 1 
and Figure 1]. He had no cardiac symptoms and his 
echocardiogram was normal.  His liver iron load, as 
assessed by MRI, also increased during this period 

 

0

500

1000

1500

2000

2500

3000

3500

4000

4500

S 
Fe

rr
iti

n 
(n

g/
m

l)

0

5

10

15

20

25

30

35

40

45

50

Ca
rd

ia
c 

T2
* 

(m
s)

S ferritin Cardiac T2*
20 

Start of  
HCV  
 treatment  

 

Cardiac T2*  
 Sep 2006 
48.8ms  

Completion of 
HCV  treatment. 
Restart combined 
chelation  

 

Months

32.5ms  

12.7ms  

0 40 

Figure 1: Changes in serum ferritin and cardiac T2* before starting interferon therapy and the subsequent course



Shahina Daar, Saeed Ahmed and Vasili Berdoukas

Case Report | 403

from completely normal to the upper limit of mild 
iron loading after 12 months. His most recent study 
2 years after recommencing combination therapy 
shows complete removal of iron in the liver and 
normalisation of cardiac T2* at 27.5ms. Figure 1 
shows serial values of cardiac T2* and ferritin levels 
over the period before, during, and after HCV 
therapy,

It is important to note that the T2* of both the 
liver and heart started reducing within two months 
of ceasing chelation therapy. The most striking 
feature of his results was that the cardiac T2* fell 
from absolutely normal to a level that was a cause 
for concern. This was associated with his hepatic 
iron load reaching the upper limit of mild iron 
loading. In the past, such levels of iron loading in 
the liver were considered safe, but it has now been 
shown that in many patients liver iron does not 
correlate to cardiac iron.3,6  

Discussion
This case report demonstrates the rapid iron 
loading that occurred in one patient after the 
cessation of effective iron chelation therapy and 
failure to comply with deferoxamine infusion. A 
case of a pregnant woman showing increased rapid 
loading after completely ceased chelation therapy 
for 12 months has been reported.7 However, unlike 
that patient, whose cardiac iron status remained the 
same, our patient had a greater rate of iron loading 
in his heart than in his liver. Noetzli et al. have 
shown that in many patients cardiac iron loading 
and unloading lags behind liver iron. 8 Our patient, 
however, is similar to the small number of patients 
in that study who loaded more rapidly in their 

hearts than in their livers. He also demonstrated a 
rapid reversal of cardiac iron which is also different 
to the results of the above study. It would seem 
that differential iron loading may be very different 
from one patient to another, hence the need for 
MRI monitoring, particularly during phases of 
inadequate iron chelation. The differences in relative 
rate of uptake of iron in various organs in different 
patients have not yet been adequately explained. It 
may be that viral infections such as hepatitis play a 
role, but larger studies are needed to evaluate this. 
Patients should be properly counselled prior to 
any therapy that may compromise their chelation 
even though this may be short term. The use of 
deferoxamine is standard therapy, but compliance 
is a problem. As the oral chelator deferasirox 
rarely causes neutropaenia, it may be the chelator 
of choice in these patients, provided there is no 
contraindication to its use. As in the case with rapid 
loading during pregnancy,7 it is also likely that the 
free iron that results from the iron overload may be 
very avidly taken up in the liver and may be taken 
up even more quickly in the heart. 

Another interesting point in this patient is that 
he has recently reversed his hypogonadism. In April 
2009, eight months after restarting combination 
chelation, he was azoospermic. However, he was 
able to cease hormone replacement therapy in June 
2009, and in October 2009 his sperm count was 
76 million/ml, with 10% abnormal forms and 90% 
motility. These encouraging outcomes are similar 
to those recently published in which a reversal of 
hypogonadism was associated with very low ferritin 
levels. 9 Our patient had very low ferritin levels from 
July 2009 to March 2010 and this was associated 
with the marked improvement in the sperm count. 

Table 1:  Serum ferritin and T2* readings before, during, and after interferon therapy

Date  Serum Ferritin
ng/ml

T2* Heart
(ms)

T2* Liver
(ms)

LIC mg/gdw

Sept 2006 309 48.8 19.5 1.5

Aug 2007 335

Nov 2007 2,366 32.5 8.6 3.2

Jul 2008 3,820

Nov 2008 1,792 12.7 4.5 6.8

Jul 2009 162 18.8 16.5 1.4

Oct 2009 95 27.5 28.4 0.4

Legend: LIC = Liver iron concentration



Rapid Iron Loading in Heart and Liver in a Patient with Transfusion Dependent Thalassaemia  
after Brief Poor Compliance with Iron Chelation Therapy

404 | SQU Medical Journal, December 2010, Volume 10, Issue 3

It is very likely that such low ferritin levels are 
essential to achieve such improvements. 

Conclusion
In all transfusion dependent patients, cessation or 
change to possibly less acceptable chelation therapy 
may result in rapid iron overload of the heart 
over a relatively short period of time. Patients and 
physicians should be aware of this risk in order to 
encourage patients to maintain consistent chelation 
therapy.

c o n f l i c t o f i n t e r e s t 
Shahina Daar has received funding for clinical 
studies from Novartis Inc. and been a speaker for 
ApoPharma Inc. as well as attending key opinion 
leader meetings sponsored by ApoPharma Inc. 
Vasili Berdoukas is a consultant for ApoPharma Inc. 
and has a confidentiality agreement with Novartis 
Inc. with respect to the development of deferasirox. 
Saaed Ahmed has no conflicts of interest to declare. 

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