[Analysis of the causal relations between serum ferritin elevation and latent pathologic factors by structural...

Serum ferritin increases in various disorders and clinical conditions such as iron overload, tissue disorders, and inflammation. However causal associations between the serum ferritin level and clinical factors that influence serum ferritin level or between these factors are not well characterized. We analyzed the ferritin level and other laboratory data including transferrin saturation (TF%), enzyme activities, and inflammatory protein levels in the sera of 124 patients with hyperferritinemia. We identified latent pathologic factors representing cell damage and inflammatory status and assumed causal relations between serum ferritin elevation and these factors. Structural equation modeling was used to verify causal relations and the adequacy of latent factors. A model that quantitatively explained serum ferritin elevation was identified. The direct effect of the cell damage factor on serum ferritin indicated cell destruction and decreased ferritin clearance. In contrast, the inflammation factor directly increased the ferritin level, but indirectly decreased it via TF%. These causal relations may quantitatively explain the mechanism of serum ferritin levels in patients with hyperferritinemia.