Almost Normal Transferrin Saturation in Thalassemic Patients on Deferasirox May Predict Better Outcome

Iron overload is a serious consequence of the repeated blood transfusions required in the treatment of Thalassaemia major patients. Transferrin saturation (TfS) above 75% is a marker of iron overload of any cause. In thalassemia TfS levels can reach 80% to 100% and even higher. Most of the Non Transferrin Bound Iron (NTBI) is chelated by iron chelators. The fraction of NTBI, which in thalassemia is referred to as ‘’directly chelatable iron”, has also recently been termed labile plasma iron (LPI). Labile iron appears in plasma and interstitial fluids when the transferrin binding capacity is surpassed. Iron chelators are agents designed to remove LPI and iron from the cells. There are now 3 different classes of iron chelators used mainly as monotherapy and one combination regimen with Desferrioxamine (DFO) and Deferiprone (DFP). Deferasirox (DFS) is a new active oral chelator. The mode of action of each chelator is different and the choice is individualized.

Aim: To evaluate the effect of 4 different types of chelation therapy on TfS.

Methods: Serum iron (Fe, normal range 60–180μg/dl), Total Iron Binding Capacity (TIBC, normal range 155–300μg/dl), TfS (which was calculated by the formula (serum Fex100/TIBC) and serum Ferritin were measured in 100 thalassaemia patients (46M/54F, median age 30,4 ± 8,4 years (range 18–54 years). All patients were regularly transfused (pre-transfusion hemoglobin: 9,7g/dl) and well chelated. Twenty-nine of the above-mentioned 100 patients were on DFS (Group A), 32 on DFP (Group B), 25 on combination therapy (Group C) and 14 on DFO (Group D). Median duration of therapy was 16±7 months for group A and 5,2±2,8, 3,4±2,1 and 29,8±4,3 years for groups B, C and D respectively. T-test was used in statistical analysis to compare means.

Results: All patients of groups B, C and D had low levels of TIBC below normal values (40±26, 67±35 and 104±39μg/dl respectively) but patients on DFS (A) had values in the normal range (292±114μg/dl). Patients on DFS had the lowest TfS (103±46%), followed by patients on DFO (251±132%). The DFP group had the highest TfS value 1245±1510%, while the combined therapy group’s value was 531±545%. Group’s A ferritin was 1617±1363 ng/ml while ferritin of groups B, C and D were 1210±799, 1683±1950 and 1058±514 ng/ml respectively. Although TfS differed significantly between groups (T-test: A vs B, A vs C and A vs D: p=0,0001, p=0,0006 and p= 0,001 respectively) differences in ferritin were not statistically significant.

Conclusions: TfS can theoretically be used to predict with whatever type of treatment applied, the NTBI and consequently the LPI. Very high TfS values may mean a great amount of circulating toxic NTBI which is not successfully chelated. In our patients TfS was found lowest in those on DFS. Differences in TIBC and TfS can be explained by the different mode of action of the three chelators used. Further comparative studies are needed to conclude whether DFS therapy, leads to not only the lowest TfS levels but also to the lowest LPI values. In that case it could be considered a more “reasonable” therapy than other chelators