Transcript Effect of Using Deferazirox on Hemoglobin Levels in

AHMED KADHIM
THALASSEMIA CENTER - DUBAI
Background
 Iron chelating agents (desferroxamine and
deferazirox) are mainly used to prevent the deleterious
effect of iron overload resulted from repeated
transfusions in thalassemia and other type of iron
loading anemias.
Background
 The insight into the mechanism of iron and oxygen
radicals poisoning extended the use of iron chelaters
to conditions in which there is no iron overload, such
as : antioxidant effect - as in rheumatoid arthritis and
favism(2, 9,10),
Background
 antiproliferative effect (some solid tumors) &
antiprotozoal effect (2)
 aluminum intoxication as chelater (as in renal failure)
(3)
Background
 Number of articles report an increase in erythropoiesis
or a reduction in the transfusion requirement during
iron chelation therapy. (1, 4, 6, 7, 9)
 A variety if mechanisms are possible
Background
 Mechanisms
 limited cytoreductive effect (4, 6)
 iron redistribution to the haemopoietic tissue (1, 9)
 ferrokinetic changes (4)
 suppression of increased apoptosis and mitochondrial
damage (4, 8)
Background
 Mechanisms (cont.)
 in patients with renal failure desferroxamine and rHu
Epo may increase transferrine receptors to enhance
cellular uptake of iron. (3, 5)
Aim
 This study is conducted to evaluate the effect of using
the oral iron chelater deferazirox (Exjade) on the
hemoglobin level in thalassemia patients receiving
regular blood transfusion in Dubai thalassemia center
- UAE.
Material and Methods
 A retrospective study.
 135 B thalassemia major patients receiving regular
blood transfusion every 3-4 weeks and taking Exjade as
an iron chelater, started to be given in Sep. 2006.
 63 Desferal taking patients group used for comparison,
during the same period of time.
 Hemoglobin readings were collected from patients
medical records, for the period Mar.-Aug. 2006 ( pre
Exjade era - Pre) and Feb.-Jun. 2008 (post Exjade era –
Post ), for both groups.
Material and Methods
 Mean of 16 hemoglobin readings were calculated using
Microsoft excel software.
 Comparison between the means (pre- and post-) was
done with T-test and p value calculated.
Material and Methods
 As p value results were showing highly significant degrees,

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


for the purpose of comparison these values giving a
significance scale with color coding in order to make
comparison easier, as in below
extremely sig.<=0.0000005,
very high sig.<=0.000005,
high sig.<=0.00005,
very sig.<=0.0005,
sig.<=0.005,
less sig.<=0.05,
non sig.>0.05.
Material and Methods
 Stratification of data had been done according to age
groups, sex, serum Ferritin level, HCV status, and
presence of complications like, hypoparathyroidisim,
hypothyroidism, diabetes, hypogonadisim, cardiac
dysfunction, and size of liver and spleen, and whether
splenectomy done or not. (Maisem et. al. ,
unpublished data)
Results
Study Groups
Exjade
Desferal
No. of pat
135
63
mean age(yrs)
14.55556
17.01587
mode age(yrs)
10
12
Median(yrs)
13
16
Results
Exjade Pat
mean Hb
All PAT
post
pre
11.10343
10.87582
difference
p value
0.227606
1.01E-06
difference
p value
0.264325
1.54E-05
Desferal Pat
mean Hb
All PAT
post
pre
11.09181
10.82748
Exjade Pat
Results
mean Hb
difference
p value
post
pre
age 2-12
11.04022
10.76143
0.278787
2.98E-05
age 13-20
11.25538
10.99464
0.260738
0.001484
age >20
11.03704
10.94521
0.091832
0.388641
Age2-20 Exjade
1.28E-07
Desferal Pat
mean Hb
difference
p value
post
pre
11.09485
10.7859
0.308942
2.23E-06
11.17183
10.97524
0.19659
0.174942
age 2-12
age 13-20
age >20
Exjade Pat
Results
mean Hb
difference
p value
post
pre
female
11.24339
10.97114
0.272257
3.86E-05
male
10.93363
10.76019
0.173439
0.007705
Desferal Pat
mean Hb
difference
p value
11.13483
0.261351
0.002435
10.72281
0.287451
0.000189
post
pre
female
11.39618
male
11.01026
Exjade Pat
Results
mean Hb
hcv
difference
p value
post
pre
no
11.14925
10.9251
0.22415
1.98E-05
yes
11.13354
10.90947
0.224065
0.063829
Desferal Pat
mean Hb
hcv
difference
p value
10.78794
0.252137
0.000542
10.93814
0.379334
0.003752
post
pre
no
11.04008
yes
11.31747
Exjade Pat
Results
mean Hb
S Ferritin
difference
p value
post
pre
<2000
11.20192
10.93624
0.265676
1.49E-05
=>2000
11.06804
10.90319
0.16485
0.04037
Desferal Pat
mean Hb
S Ferritin
difference
p value
10.714
0.29792
0.011908
10.87749
0.273764
0.000295
post
pre
<2000
11.01192
=>2000
11.15125
Exjade Pat
Results
Diabetes
mean Hb
difference
p value
10.92234
0.253472
1.27E-06
10.89824
0.21834
0.877005
post
pre
no
11.17582
yes
11.11658
Desferal Pat
Diabetes
mean Hb
difference
p value
10.79611
0.307178
4.37E-06
11.06492
0.053556
0.792094
post
pre
no
11.10329
yes
11.11847
Exjade Pat
Results
Hypothyroidism
mean Hb
difference
p value
post
pre
no
11.12937
10.90366
0.225714
6.28E-06
yes
11.12014
10.90792
0.212221
0.275271
Desferal Pat
Hypothyroidism
mean Hb
difference
p value
10.80169
0.289802
9.41E-06
11.22426
0.04518
0.905152
post
pre
no
11.09149
yes
11.26944
Results
Exjade Pat
Hypoparathyroidisim
mean Hb
difference
p value
10.91948
0.22292
1.06E-05
10.95076
0.23521
0.205683
post
pre
no
11.1424
yes
11.18597
Desferal Pat
Hypoparathyroidisim
mean Hb
difference
p value
10.82866
0.27549
1.3E-05
10.76059
0.351405
0.323714
post
pre
no
11.10415
yes
11.112
Exjade Pat
Results
Hypogonadisim
mean Hb
difference
p value
10.89602
0.264869
5.05E-06
11.01332
0.085446
0.308713
post
pre
no
11.16089
yes
11.09876
Desferal Pat
Hypogonadisim
mean Hb
difference
p value
10.77701
0.266015
0.000187
10.90241
0.309108
0.012811
post
pre
no
11.04303
yes
11.21152
Exjade Pat
Results
Liver Size(cm)
mean Hb
difference
p value
post
pre
<3
11.17167
10.9111
0.260572
1.24E-06
>=3
11.07777
10.94971
0.128063
0.224906
Desferal Pat
Liver Size(cm)
mean Hb
difference
p value
10.8402
0.2962
0.000204
10.77565
0.242259
0.01067
post
pre
<3
11.13641
>=3
11.0179
Exjade Pat
Results
Spleen Size (cm)
mean Hb
difference
p value
post
pre
<3
11.15398
10.8903
0.263674
2.54E-06
>=3
10.95084
10.87917
0.071671
0.53241
Desferal Pat
Spleen Size (cm)
mean Hb
difference
p value
10.80418
0.318601
2.88E-05
10.73617
0.285958
0.029966
post
pre
<3
11.12278
>=3
11.02213
Exjade Pat
Results
Splenectomy
mean Hb
difference
p value
post
pre
No
11.07125
10.83904
0.232211
3.12E-06
yes
11.50563
11.33559
0.170037
0.06638
Desferal Pat
Splenectomy
mean Hb
difference
p value
post
pre
no
11.02013
10.74587
0.274259
4.32E-07
yes
11.08583
11.13047
-0.04464
0.846177
11.6
Exjade using patients - Mean Hemoglobin
11.4
Mean hemoglobin g/dl
11.2
11
pre
10.8
10.6
10.4
10.2
post
11.4
Desferal using patients - Mean Hemoglobin
11.2
Mean hemoglobin g/dl
11
10.8
pre
post
10.6
10.4
10.2
0.4
Changes in hemoglobin level
0.35
0.3
Hemoglobin changes g/dl
0.25
0.2
difference exjade
difference desferal
0.15
0.1
0.05
0
-0.05
p values
Sig.
Code
all pat
Age
Extr. sig.
<=12
Exj
Desf
1.01E-06
1.54E-05
2.98E-05
2.23E-06
Very H.sig
13-20
0.001484
High sig.
>20
0.388641
0.174942
F
3.86E-05
0.002435
M
0.007705
0.000189
Neg
1.98E-05
0.000542
Pos
0.063829
0.003752
<2000
1.49E-05
0.011908
>=2000
0.04037
0.000295
Neg
1.27E-06
4.37E-06
Pos
0.877005
0.792094
Sex
Very sig.
Signif.
Hcv
Less sig.
Non sig.
s ferrit
Inverse
Diab
age2-20 Exjade
1.28E-07
Hypothy
Sig.
Extr. sig.
Code
Hypoparat
Very H.sig
High sig.
Hypogona
Very sig.
Signif.
Liver
Less sig.
Non sig.
Spleen
Inverse
Splenectomy
Exj
Desf
Neg
6.28E-06
9.41E-06
Pos
0.275271
0.905152
Neg
1.06E-05
1.3E-05
Pos
0.205683
0.323714
Neg
5.05E-06
0.000187
Pos
0.308713
0.012811
<3
1.24E-06
0.000204
>=3
0.224906
0.01067
<3
2.54E-06
2.88E-05
>=3
0.53241
0.029966
No
3.12E-06
4.32E-07
Yes
0.06638
0.846177
Comparison between the
Mean Hb Difference of
Both groups
Mean Hb of All
Exjade Patients
Mean Hb of All
Desferal
Patients
P value
0.227606
0.264325
0.609803
Discussion
 Despite absolute raise in Hb levels was more
prominent in Desferal group (not sig.), it was the
Exjade group that had the more significant P value
between the pre- and post- means.
 Sample size could explained this difference.
 However knowing that subjects in both groups
exposed to a similar conditions, an Exjade effect
cannot be neglected.
Discussion
 All of the highly significant P values seen where
complications are not present, an exception is found in
HCV +ve and s. Ferritin >2000 patients in the Desferal
group.
 All the post Hb levels are higher than the pre Hb levels
in both groups except Desferal taking splenectomized
patients who are older in age and remnant splenic
tissue may be responsible.
Discussion
 Younger patients had the best P values in both groups,
those also had more reduction in their s.ferritin
(Khawla et. al., unpublished data) when using Exjade,
better compliance is a possible explanation.
 Gender was not conclusive.
 Smaller liver and spleen size was associated with a
valuable P.
Discussion
 The mean, median and mode age for Desferal group
were 2-3 yrs higher than that of Exjade group, this
could be a partial contributor to the difference in P
values.
 The absolute raise in Hb level is clinically not
significant (0.2-0.4 g/dl), however in a center serving
more than 400 patients such raise may have an
economic impact on blood supply to the center.
Conclusion
 Both groups had raise in their Hb levels.
 Desferal raise was bigger, but not significant.
 Exjade raise was more significant.
 The raises are minute but may have effect on making
better blood economy.
 More studies are needed to prove or disprove effect of
Exjade on Hb levels in transfusion dependent
thalassemia patients.
THANK YOU
Thanks To
 Dr. Khawla Belhoul
 Dr. Maisem Baker
 Dr. Hamid Al Qaissy
 Miss Maitha Mohamed Hassan
 Rashid Medical library staff.
References
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