Regulation of platelet count by erythropoiesis-stimulating agents – iron axis in hemodialysis patients

Abstract

Higher doses of erythropoiesis-stimulating agents (ESAs) contribute to atherothrombotic cardiovascular disease in hemodialysis (HD) patients. Thrombocytosis is associated with increased mortality in ESA-treated HD patients. We investigated variables affecting platelet count and its variability (platelet count increment [∆platelet count]) in HD patients. This retrospective longitudinal and observational study of HD outpatients was carried out over 3 years. The outcome was independent determinants of platelet count and ∆platelet count, which were associated with iron indices, ESA dose, and C-reactive protein. In univariate regression analysis, V-shaped relationship was observed between platelet count and transferrin saturation (TSAT), ferritin, serum iron, and hemoglobin (Hb) with the bottom of 0.21, 330 ng/mL, 49 µg/ dL, and 10.3 g/dL, respectively. Mixed-effect multivariate regression analysis revealed that TSAT (inversely), Hb #10.3 g/dL (inversely), C-reactive protein, and ESA dose were independently associated with platelet count. ∆platelet count was independently and inversely correlated with ∆TSAT and directly correlated with ∆ferritin. TSAT was independently and inversely associated with ESA dose. ESA dose was directly correlated with iron dose and inversely correlated with TSAT, ferritin #330 ng/mL, and Hb #10.3 g/dL. ESA dose and TSAT were correlated in determining platelet count and ∆platelet count. Targets of iron indices that reflect iron supply sufficient to avoid platelet count increment and variability may be .21% of TSAT and 300 ng/mL of serum ferritin for appropriate ESA therapy in HD patients.