| Objective: To investigate the impact of splenectomy on iron load and iron metabolism in patients with HbH CS disease.Methods: 1. Iron load in patients with HbH CS diease : 64 patients with HbH CS diease(34 cases splenectomised and 30 cases non-splenectomised)were studied. Medical history, history of blood transfusions and treatment with iron chelator drugs were recorded. Fasting blood was collected from all participants. Red cell parameters including hemoglobin(Hb) concentration,reticulocyte count(Ret) and nucleated red blood cell(NRBC) count were analyzed, Serum concentrations of ferritin and liver function(ALT, AST, total bilirubin and indirect bilirubin) parameters were measured. Hepatic 3.0T Magnetic Resonance Imaging(MRI) T2*was performed in patients(34splenectomised and 30 non-splenectomised) to evaluate the liver iron concentration(LIC).2. Hepcidin in patients with HbH CS diease: Forty patients with HbH CSdiease(20 cases splenectomised and 20 cases non-splenectomised) were studied,along with 22 healthy controls. Serum concentrations of ferritin, soluble transferrin receptors(sTfR), growth differentiation factor 15(GDF15) and hepcidin were measured. Correlations between levels of hepcidin and ferritin as well as hematological parameters were analyzed.Results:1. Iron load in patients with HbH CS diease : There were no significant differences in age, gender composition, age at onset, blood transfusion volume and iron chelator between the two group. The levels of WBC,Hb level and NRBC count were higher while levels of total bilirubin and indirect bilirubin were lower in the splenectomised group than that of non-splenectomised group. There was no significant difference of ALT, AST and Ret levels between the two groups. Napierian Logarithm of serum ferritin(LNSF)levelsand the ratio of iron overload(SF>500ng/ml)patients were significantly elevated in splenectomised group, however, the MRI T2*was also higher. Correlation analyses revealed that MRI T2*levels were negatively correlated with levels of LNSF in both group. The LNSF levels in the splenectomised were negatively correlated with Hb and positively correlated with NRBC and WBC, while no correlations were found between LNSF and Hb,NRBC, WBC levels in non-splenectomised group. Multivariate linear regression analyses revealed that level of T2*, NRBC and WBC were independent risk factors affecting the LNSF level in splenectomised patients while level of T2*was the only independent risk factor affecting the LNSF level in non-splenectomised group.2. Hepcidin in patients with HbH CS diease: Compared with the control group, a higher ferritin level, a lower hepcidin level and lower hepcidin/ferritin ratio were noticed in the non-splenectomised group. In patients who had beensplenectomised, hepcidin/ferritin ratio remained lower, and the ferritin level was even higher than that in the non-splenectomized group. Both in splenectomized and non-splenectomized group, hepcidin/ferritin ratio were significant negatively correlated with the GDF-15 level.Conclusions: 1. Splenectomy reduces liver iron concentration(LIC) measured by 3.0T MRI T2*in patients with HbH CS diease, despite improving serum ferritin levels.2. Serum ferritin can indicate the levels of liver iron concentration in patients whether splenectomised or not. And the same level of serum ferritin may overestimate the LIC in splenectomised patients. The ferritin combined with liver MRI T2*can better indicate the iron load in patients with HbH CS dieases.3. Splenectomy increases the serum ferritin level and upregulates hepcidin level, partly explaining the separation phenomenon of high serum ferritin level and low LIC in splenectomised patients. However, splenectomy does not improve the dysregulation of iron metabolism indicated by inappropriately low hepcidin/ferritin ratios in patients with HbH CS diease.4. GDF15 may contribute most to inhibition of hepcidin levels and play a causal role in the hepcidin-ferritin cascade. |
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