Profile of Iron Overload in Nontransfusion Dependent Hb E Beta Thalassaemia Patients- Is It Different?

Introduction

Iron (Fe) overload is directly related to the morbidity & ultimate survival. NTDT is different. Overloading occurs from ineffective erythropoiesis, dietary absorption & rescue transfusions (Taher-Cappellini, 2009, p 634-40), the result - organ dysfunction related morbidity and mortality. Other than Serum ferritin (SFr) (Origa-Galanello, 2007, p583-8) MRI has been used for organ specific Fe content estimation (Taher-Musallam, 2010, p 288-90). We will try to establish Fe overload exists in subjects of HbE β NTDT & assess the best method for Fe overload in patients & it's relation to increasing age. This is the 1st attempt to study Fe overload in HbE β NTDT patients of India.

Study proper

Diagnosed by HPLC and confirmed by Sanger sequencing, 105 NTDT HbE β thalassaemia patients of either sex, -ve for hepatitis B, C & HIV, with age ranging of 4 - 55 years, receiving <1 unit to a maximum of 15 transfusions till date, were included. SFr was tested by CLIA and LIC by MRI from Resonance Health, Ferriscan (St Pierre-Clark, 2005, p 855-61). Age, SFr, LIC and complications were collected & their interrelationship analyzed statistically.

Results & Discussion

Out of the 105 subjects, 51(48.5%) were males, mean age ± SD was 19±9.5 yrs. (range 4 - 54); 41.8% were splenectomized; 31% were transfusion naive & none had received prior chelation. Mean SFr was 1211.9 ± 2048 ng/ml, mean LIC was 11.76 ± 12.41 mg / g DLT. The correlation between age & LIC - 0.159; age & SFr - 0.173 and LIC & SFr - 0.62.

Study shows despite the NTDT status, HbE β thalassaemia patients develop Fe overload as evidenced by SFr level > 200-450 ng/ml & LIC by MRI s >3 mg/g of DLT in 63.8%.

In this study, mean LIC was 11.76 ±12.41 mg/g DLT, significantly lower than base line of 13.8± 7.6 mg/g DLT, in THALSA (Taher-Porter, 2014, p 521-26) and 14.5±8.8 mg/g DLT (Taher-Porter, 2012, p 970-7).

In 61% LIC was >5 mg/g DLT, but SFr <800 ng/ml in 44.6%; in 7.5% LIC <5 mg/g DLT, but SFr level was > 800 ng/ml. So SFr, may lie on both sides of LIC, and is not to be interpreted in isolation. SFr levels may underestimate Fe load in NTDT (Taher-Hershko, 2009, p 634-40), this study shows that it may be higher.

In thalassaemia intermedia (TI) patients, advancing age is associated with > SFr and serious morbidities (Taher-Musallam, 2010, p 486-9), but not universally, this study showed that, 83% recorded increased LIC with increaseing age in subjects >15 yrs., 79% age >10 yrs. yearly increase in LIC, & total body Fe was 0.144 mg/g DLT/yr. or 0.57 - 2.49 mg/kg/yr. lower than 1.0 - 3.5 g/yr. by other authors (Taher-Vipraksit, 2013, p 409-15),could be due to Fe deficient diet & black tea consumption.

As reported others, +ve correlation between SFr & LIC was observed in NTDT (Taher-Porter, 2012 p 970-77; Taher-Rassi, 2008, p 1584 - 86), high +ve correlation between SFr & LIC (0.81), when SFr level was < 300 ng/ml & LIC of <3 mg/g DLT, in age group ≤10 years in both sexes, also true in >30 yrs. group, +ve correlation of 0.849, but no linear correlation was obtained. In 8 diabetic patients , all had LIC > 6 mg/g DLT but 37.5% had SFr >2500 ng/ml, value of SFr above which complication occurs, so LIC is better predictor of complications. This was comparable to the study among 168 patients of β TI, LIC was ≥ 6mg/g DLT, suffered from endocrine/bone disease & 1mg increase in LIC was independently associated with significantly increased risk of vascular, endocrine & osteogenic morbidities (Musallam-Cappellini, 2011, p 1605-12), this is true for patients with LIC > 6mg/g DLT, as in our study.

Conclusion

This study concludes that even in the absence of transfusion, Fe overload occurs in NTDT. SFr, an invasive procedure, is a bad predictor of Fe overload, especially in NTDT, it may under / over estimate Fe overload. LIC estimation by MRI is a better predictor of total body Fe than SFr. It bears correlation if SFr is below 300 ng/ml & that of liver Fe is <3mg/g DLT. Iron overload increases with age but the rate can be controlled with Fe deficient diet & regular tea intake. Complications also occur in NTDT from Fe overload & is better predictable by LIC estimation than by SFr levels.