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Effect of Using Deferazirox on Hemoglobin Levels in Transfusion Dependent β -Thalassemia Major Patients. AHMED KADHIM THALASSEMIA CENTER - DUBAI. Background. - PowerPoint PPT Presentation
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AHMED KADHIMTHALASSEMIA CENTER - DUBAI
BackgroundIron 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.
BackgroundThe 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),
Backgroundantiproliferative effect (some solid tumors) &
antiprotozoal effect (2)
aluminum intoxication as chelater (as in renal failure) (3)
BackgroundNumber 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
BackgroundMechanismslimited cytoreductive effect (4, 6)iron redistribution to the haemopoietic tissue
(1, 9)ferrokinetic changes (4)suppression of increased apoptosis and
mitochondrial damage (4, 8)
BackgroundMechanisms (cont.)in patients with renal failure desferroxamine
and rHu Epo may increase transferrine receptors to enhance cellular uptake of iron. (3, 5)
AimThis 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 MethodsA 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 MethodsMean 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 MethodsAs p value results were showing highly significant
degrees, 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 MethodsStratification 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
Exjade Desferal
No. of pat 135 63
mean age(yrs) 14.55556 17.01587
mode age(yrs) 10 12
Median(yrs) 13 16
Study Groups
Results mean Hb
difference p value post pre
All PAT 11.10343 10.87582 0.227606 1.01E-06
Exjade Pat
Desferal Pat
mean Hbdifference p value
post pre
All PAT 11.09181 10.82748 0.264325 1.54E-05
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
Exjade Pat
Desferal Pat mean Hb
difference p value post pre
age 2-1211.09485 10.7859 0.308942 2.23E-06
age 13-20
age >20 11.17183 10.97524 0.19659 0.174942
Age2-20 Exjade 1.28E-07
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
Exjade Pat
Desferal Pat mean Hb
difference p value post pre
female 11.39618 11.13483 0.261351 0.002435
male 11.01026 10.72281 0.287451 0.000189
Resultshcv mean Hb
difference p value post pre
no 11.14925 10.9251 0.22415 1.98E-05
yes 11.13354 10.90947 0.224065 0.063829
Exjade Pat
Desferal Pat hcv mean Hb
difference p value post pre
no 11.04008 10.78794 0.252137 0.000542
yes 11.31747 10.93814 0.379334 0.003752
ResultsS Ferritin mean Hb
difference p value post pre
<2000 11.20192 10.93624 0.265676 1.49E-05
=>2000 11.06804 10.90319 0.16485 0.04037
Exjade Pat
Desferal Pat S Ferritin mean Hb
difference p value post pre
<2000 11.01192 10.714 0.29792 0.011908
=>2000 11.15125 10.87749 0.273764 0.000295
ResultsDiabetes mean Hb
difference p value post pre
no 11.17582 10.92234 0.253472 1.27E-06
yes 11.11658 10.89824 0.21834 0.877005
Exjade Pat
Desferal PatDiabetes mean Hb
difference p value post pre
no 11.10329 10.79611 0.307178 4.37E-06
yes 11.11847 11.06492 0.053556 0.792094
ResultsHypothyroidism 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
Exjade Pat
Desferal PatHypothyroidism mean Hb
difference p value post pre
no 11.09149 10.80169 0.289802 9.41E-06
yes 11.26944 11.22426 0.04518 0.905152
ResultsHypoparathyroidisim mean Hb
difference p value post pre
no 11.1424 10.91948 0.22292 1.06E-05
yes 11.18597 10.95076 0.23521 0.205683
Exjade Pat
Desferal PatHypoparathyroidisim mean Hb
difference p value post pre
no 11.10415 10.82866 0.27549 1.3E-05
yes 11.112 10.76059 0.351405 0.323714
Results Hypogonadisim mean Hb
difference p value post pre
no 11.16089 10.89602 0.264869 5.05E-06
yes 11.09876 11.01332 0.085446 0.308713
Exjade Pat
Desferal Pat Hypogonadisim mean Hb
difference p value post pre
no 11.04303 10.77701 0.266015 0.000187
yes 11.21152 10.90241 0.309108 0.012811
ResultsLiver 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
Exjade Pat
Desferal Pat Liver Size(cm) mean Hb
difference p value post pre
<3 11.13641 10.8402 0.2962 0.000204
>=3 11.0179 10.77565 0.242259 0.01067
ResultsSpleen 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
Exjade Pat
Desferal PatSpleen Size (cm) mean Hb
difference p value post pre
<3 11.12278 10.80418 0.318601 2.88E-05
>=3 11.02213 10.73617 0.285958 0.029966
ResultsSplenectomy
mean Hbdifference p value
post pre
No 11.07125 10.83904 0.232211 3.12E-06
yes 11.50563 11.33559 0.170037 0.06638
Exjade Pat
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
p values
Exj Desf
all pat 1.01E-06 1.54E-05
Age <=12 2.98E-052.23E-06
13-20 0.001484
>20 0.388641 0.174942
Sex F 3.86E-05 0.002435
M 0.007705 0.000189
Hcv Neg 1.98E-05 0.000542
Pos 0.063829 0.003752
s ferrit <2000 1.49E-05 0.011908
>=2000 0.04037 0.000295
Diab Neg 1.27E-06 4.37E-06
Pos 0.877005 0.792094
Sig. Code
Extr. sig.Very H.sigHigh sig.
Very sig.Signif.
Less sig.Non sig.Inverse
age2-20 Exjade 1.28E-07
Exj Desf
Hypothy Neg 6.28E-06 9.41E-06
Pos 0.275271 0.905152
Hypoparat Neg 1.06E-05 1.3E-05
Pos 0.205683 0.323714
Hypogona Neg 5.05E-06 0.000187
Pos 0.308713 0.012811
Liver <3 1.24E-06 0.000204
>=3 0.224906 0.01067
Spleen <3 2.54E-06 2.88E-05
>=3 0.53241 0.029966
Splenectomy No 3.12E-06 4.32E-07
Yes 0.06638 0.846177
Sig. Code
Extr. sig.Very H.sigHigh sig.
Very sig.Signif.
Less sig.Non sig.Inverse
Mean Hb of All Exjade Patients
Mean Hb of All Desferal
Patients
P value
0.227606 0.264325 0.609803
Comparison between the Mean Hb Difference of
Both groups
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.
DiscussionAll 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.
DiscussionYounger 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.
DiscussionThe 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.
ConclusionBoth 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 ToDr. Khawla BelhoulDr. Maisem BakerDr. Hamid Al QaissyMiss Maitha Mohamed HassanRashid Medical library staff.
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