Blood Journal
Leading the way in experimental and clinical research in hematology

Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo

  1. Maura Poli1,
  2. Domenico Girelli2,
  3. Natascia Campostrini2,
  4. Federica Maccarinelli1,
  5. Dario Finazzi1,
  6. Sara Luscieti1,
  7. Antonella Nai3, and
  8. Paolo Arosio1,*
  1. 1 Dipartimento Materno Infantile e Tecnologie Biomediche, Universita di Brescia, Brescia, Italy;
  2. 2 Department of Medicine, University of Verona, Verona, Italy;
  3. 3 Vita-Salute San Raffaele University, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele, Milan, Italy
  1. * Corresponding author; email: arosio{at}


Hepcidin is a major regulator of iron homeostasis, and its expression in liver is regulated by iron, inflammation and erythropoietic activity with mechanisms that involve bone morphogenetic proteins (BMPs) binding their receptors and co-receptors. Here we show that exogenous heparin strongly inhibited hepcidin expression in hepatic HepG2 cells at pharmacological concentrations, with a mechanism that probably involves BMP6 sequestering and the blocking of SMAD signaling. Treatment of mice with pharmacological doses of heparin inhibited liver hepcidin mRNA expression and SMAD phosphorylation, reduced spleen iron concentration while increasing serum iron. Moreover, we observed a strong reduction of serum hepcidin in five patients treated with heparin to prevent deep vein thrombosis and this was accompanied by an increase of serum iron and a reduction of C-reactive protein levels. The data show an unrecognised role of heparin in regulating iron homeostasis and indicate novel approaches to the treatment of of iron restricted iron deficiency anemia.

  • Submitted June 8, 2010.
  • Accepted October 15, 2010.