Utility of plasma transferrin receptor, ferritin and inflammatory markers in children with sickle cell disease

Abstract

Background: Soluble transferrin receptor (sTfR) is generally unaffected by inflammatory status, whereas ferritin increases along with acute-phase proteins. The utility of these iron biomarkers in relation to inflammatory markers in children with sickle cell disease (SCD) with differing grades of severity is unclear.

Objectives: To describe iron biomarker profiles and inflammatory responses in relation to disease severity in children with SCD.

Methods: This cross-sectional study describes plasma levels of sTfR, ferritin, C-reactive protein (CRP) and serum amyloid A (SAA) among 102 Yemeni children with SCD in relation to clinical profiles and disease severity.

Results: Median (IQR) sTfR was 58·5 mg/L (38–81), and concentration was positively correlated with reticulocyte count (r = +0·31, P = 0·002) and splenic enlargement (r = +0·20, P = 0·04), and was negatively correlated with Hb (r = −0·28, P = 0·004). Subcategories of children in a steady state were identified using ferritin and CRP cut-off values to discriminate iron status. In children in a steady state, the prevalence of iron deficiency was 25%, iron repletion 48% and marginal or normal status 27%. Ferritin concentration correlated positively with Hb and 23% of iron-deficient children had severe anaemia. CRP and SAA were increased in the steady state and were higher with acute disease complications (P<0·05 and <0·001, respectively). There was no association between sTfR or sTfR-ferritin index and inflammatory markers or disease severity score.

Conclusion: In SCD, elevated sTfR is related to hypererythropoietic activity and does not correlate with inflammatory status or disease severity. Iron deficiency prevalence was estimated to be 25%. A classification of iron status is proposed.

Keywords:

• Sickle cell
• Soluble transferrin receptor
• Inflammation
• Ferritin
• Iron deficiency

The authors thank Mr Greg Harper, Liverpool School of Tropical Medicine, for technical assistance with the laboratory analyses.