Erythropoiesis and Iron Homeostasis in Non-Transfusion-Dependent Thalassemia Patients with Extramedullary Hematopoiesis.

Yumei Huang,Rongrong Liu,Yongrong Lai,Gaohui Yang,Xiaoyun Wei,Lingyuan Pan,Jiaodi Liu

doi:10.1155/2019/4504302

Abstract

Background Extramedullary hematopoiesis (EMH) is common in non-transfusion-dependent thalassemia (NTDT) patients. Clinical presentations of EMH vary as MRI screening is not feasible. Hence, serum biomarkers are used to predict the risk of EMH. Materials and Methods 52 NTDT patients, including 26 EMH (+) and 26 EMH (-), together with 26 healthy controls, were enrolled in this case-control study from 2013 to 2016. EMH was confirmed by computed tomography or MRI. Demographic, transfusion, genetic, laboratory, and liver iron concentration (LIC) data, as well as clinical complications, were analyzed. Results EMH (+) patients had significantly higher serum ferritin (SF), growth differentiation factor 15 (GDF15), and erythropoietin (EPO) levels compared with EMH (-) patients and controls. The levels of erythroferrone (ERFE), hepcidin, and sTfR did not differ significantly between EMH (+) and EMH (-) patients (p>0.05). In NTDT patients, serum ERFE was not related to SF, LIC, hepcidin, sTfR, EPO, GDF15, and Hb levels. GDF15, EPO concentrations, and GDF15 to sTfR and GDF15 to EPO ratios are able to determine the presence of EMH with considerable sensitivity and specificity. Conclusions GDF15, EPO, and GDF15 to EPO and GDF15 to sTfR ratios are potential biomarkers for the early prediction of NTDT in patients who are at risk for EMH.

Highlights

In contrast to transfusion-dependent thalassemia (TDT) which requires regular and ongoing lifelong transfusions for survival, non-transfusion-dependent thalassemia (NTDT) is defined as a disease state not requiring regular transfusion, occasional or even frequent transfusions under certain clinical situations may be accepted for a restricted period of time
Extramedullary hematopoiesis (EMH) (+) patients had a higher incidence of cholelithiasis compared to EMH (–) patients (53.8% vs 15.4%, p=0.028)
We believe the differences seen in our study may be due to EMH being related to chronic anemia and ineffective erythropoiesis, while in TDT patients optimal transfusion therapy reduces erythroid marrow stimulation and expansion [14]

Summary

Introduction

In contrast to transfusion-dependent thalassemia (TDT) which requires regular and ongoing lifelong transfusions for survival, non-transfusion-dependent thalassemia (NTDT) is defined as a disease state not requiring regular transfusion, occasional or even frequent transfusions under certain clinical situations may be accepted for a restricted period of time. Extra-medullary hematopoiesis (EMH) is the proliferation and expansion of blood forming tissues outside the typical anatomic locations, in order to compensate for physiologically defunct erythrocytes insufficient which cannot meet the demands of a normal circulatory system This uncontrolled expansion of early erythroid progenitors can lead to reduced bone marrow function and increased erythropoiesis as well as erythrocytes which have impaired oxygen exchange capacity [2]. The levels of erythroferrone (ERFE), hepcidin, and sTfR did not differ significantly between EMH (+) and EMH (-) patients (p>0.05). In NTDT patients, serum ERFE was not related to SF, LIC, hepcidin, sTfR, EPO, GDF15, and Hb levels. GDF15, EPO, and GDF15 to EPO and GDF15 to sTfR ratios are potential biomarkers for the early prediction of NTDT in patients who are at risk for EMH

Methods

Results

Conclusion