Program: Oral and Poster Abstracts
Session: 102. Regulation of Iron Metabolism: Poster II
Patients and methods. Patients were enrolled if they were regularly followed in a center where the exact number of erythrocyte concentrates (EC) could be obtained, had received in the previous year more than 8 EC, were older than 6 years (limit for MRI without sedation), had no known heart disease related to another pathology, and had given informed consent.
All patients underwent 1.5T myocardial T2*MR imaging after validation of the procedures in the different sites. Assessment of Liver Iron Content (LIC) used two signal intensity ratio of gradient echo imaging (R2*) MRI protocols. Serum Non-Transferrin Bound Iron (NTBI) was measured by the FeROSTM eLPI kit, and serum hepcidin by LC-MSMS.
Results. 20 Thal, 41 SCA and 25 MDS patients were evaluable. We divided SCA in 2 groups, according to the procedure recorded at the time of the study, manual exchange transfusion (G1, N = 30 patients), or erythrocytapheresis (G2, N=11 patients).
We found cardiac overload in 0, 3 (15%), and 4 (16%) of SCA, Thal, and MDS patients respectively. Serum ferritins at beginning of chelation were not statistically different in all categories of patients, as well as Ferritin and LIC at the time of the study. Increased LIC and abnormal T2* were associated in Thal and MDS patients (p=0.04), with no correlation between abnormal T2* and parameters of transfusion and chelation.
Plasmatic iron level was increased in Thal and MDS patients but remained at normal range in SCA patients. NTBI level was high in Thal and MDS but completely absent in SCA groups.
The major discrepancy was in the values of hepcidin, which were collapsed in Thal, at normal range in SCA, and highly elevated in MDS patients.
Discussion and conclusion.
We confirm that SCA patients are relatively protected from cardiac iron overload. This results probably from massive consummation of iron through effective erythropoiesis, making toxic free iron (NTBI) less available in the circulation. In addition, since iron overload in SCA results from a massive outflow of hemoglobin (Hb) due to intravascular hemolysis and transfusion, the heme/Hb-bound iron must be efficiently handled in liver macrophages, limiting its release in the bloodstream.
In Thal patients, underlying defects in erythropoietic processes, together with low hepcidin that stimulates intestinal iron absorption and increases NTBI, must provoke more organ damages. Hepcidin levels were high in MDS patients, suggesting that transfusion-dependent iron overload was a more effective regulator of hepcidin production than dyserythropoiesis. The % of T2*<20 ms we observed in MDS patients (16%) was quite comparable with previous publications.
Finally, we observe that, in opposition with previous reports, SCA patients undergoing eythrocytapheresis may experience severe iron overload and need iron chelation.
|
Thal |
SCA G1 |
SCA G2 |
MDS |
p |
Age at beginning of transfusion (yrs) |
8.5[0-45] |
7[0-45] |
16.5[1-55] |
66[38-83] |
<0.001 |
Duration of transfusion (yrs) |
10[1-39] |
7[1-22] |
10.5[0-25] |
3[1-10] |
<0.001 |
N EC since diagnosis |
359[21-1360] |
139[24-791] |
201[14-888] |
77[16-544] |
0.0005 |
N CE/yr |
24[8-67] |
21[4-62] |
35[17-58] |
27[7-65] |
0.09 G1vsG2=0.03 |
% patients chelated |
95 |
90 |
72.7 |
72 |
0.12 |
Age at beginning of chelation (yrs) |
11[1-48] |
9[2-47] |
18[6-31] |
68[38-84] |
<0.0005 |
Ferritin at beginning of chelation (ng/ml) |
1148[713-2400] |
2075[448-3670] |
1500[905-2804] |
2398[482-5140] |
0.22 |
N T2*<20 ms |
3(15%) |
0 |
0 |
4(16%) |
0.01 |
LIC (mg/g d.w.) |
10.4[0.8-20.2] |
10.7[0.8-37.1] |
14[0.8-19.7] |
15.2[3.0-45.3] |
0.29 |
Plasmatic iron(μmol/l) |
36.9[31-57] |
22.5[6-42.2] |
21[13-46] |
38.2[11.9-72] |
<0.001 |
NTBI (mg/ml) |
7.1[0-31.1] |
0[0-18.3] |
0[0-12.4] |
4.45[0-25.5] |
0.0005 |
Ferritin (ng/ml) |
870[169-4339] |
2739[393-5596] |
2404[33-20030] |
1611[223-6813] |
0.08 |
Hepcidin (ng/ml) |
1.35[0-12.3] |
9.95[0-67.9] |
2.10[0-52.4] |
36.35[3-143.2] |
<0.001 |
Deferasirox dosage<0.5 μg/ml |
3/8(38%) |
3/10(29%) |
3/5(60%) |
0/11(0%) |
0.03 |
Disclosures: De Montalembert: Addmedica: Membership on an entity’s Board of Directors or advisory committees ; Novartis: Speakers Bureau . Guerci-Bresler: ARIAD: Speakers Bureau ; BMS: Speakers Bureau ; Novartis: Speakers Bureau ; PFIZER: Speakers Bureau .
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