Plasma sphingomyelin levels were negatively correlated with ferritin levels in splenectomized thalassemia patients

Abstract Beta thalassemia results from decreased production of beta chains due to either mutations or deletions in the beta-globin gene, leading to impaired production of hemoglobin A. Thalassemia patients take frequent blood transfusions to compensate for hemolytic anemia and iron overload. Iron overload is monitored by serum ferritin levels in these patients. Extra-medullary hematopoiesis in beta thalassemia major leads to hypersplenism which often necessitates splenectomy to increase red cell life span and decrease transfusion need. Sphingomyelin is the second most abundant phospholipid in human plasma after phosphatidylcholine. In contrast to the well-defined roles of sphingolipids in cell membranes, their possible physiological role in lipoprotein metabolism has recently gained attention. Increased circulating levels of sphingomyelins and ceramides were observed in obesity, diabetes, and cardiovascular diseases. Although lipid abnormalities such as hypocholesterolemia and relatively increased triglycerides were reported in beta-thalassemia patients, there is no study investigating sphingolipid levels in thalassemia. Therefore, we investigate certain long chain and very long chain sphingomyelins and ceramides in beta-thalassemia patients who are under routine follow-up in our hospital. Thalassemia major patients who applied to the hospital for regular blood transfusion and gave consent were included in the study. Blood samples were obtained before transfusion. Plasma sphingomyelin (C16, C18 and C24) and ceramide (C16, C18, C20, C22, C24) species were measured by triple quadruple LC-ESI-MS/MS (Shimadzu, Japan). D-erythrosphingosine-D9 (Matreya) was used as an internal standard, all other lipid standards were from Avanti. Body iron stores of the patients were monitored by serum ferritin levels. A total of thirty patients were included in the study. All patients typically received regular erythrocyte suspension transfusions every three weeks and continuous oral iron chelation therapy. Twenty of the patients had a previous splenectomy. The mean age was 34.5 ±8.1 years in the splenectomy group and 32.8 ±8 years in the group without splenectomy. Mean ferritin levels were not different between the groups, being 1073.2±563.5 µg/L in splenectomy and 1709 ±1660.4 µg/L in non-splenectomy groups. All measured sphingolipid levels were similar between splenectomy and non-splenectomy groups. When correlation analysis was performed between measured sphingolipid and ferritin levels, significant negative correlations were found between sphingomyelin C16 (r= -0.591 p<0.006) and C18 (r= -0.594 p<0.006) with ferritin levels in the splenectomy group. However, this negative correlation was absent in the non-splenectomy group. In conclusion, we found that iron overload is associated with lower plasma sphingomyelin levels in splenectomized thalassemia patients. We have been working on the lipidomic analysis of the plasma and erythrocytes of thalassemia patients and other hemolytic anemias. The results may further help to get a better picture of lipid metabolism in thalassemia.