Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.
Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding.
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory on Molecular Cancer Chemoprevention, Medical University of Vienna, Vienna, Austria.
Rayko
R
Evstatiev
Adam
A
Bukaty
Kristine
K
Jimenez
Stefanie
S
Kulnigg-Dabsch
Lidia
L
Surman
Werner
W
Schmid
Robert
R
Eferl
Kathrin
K
Lippert
Barbara
B
Scheiber-Mojdehkar
Hans Michael
HM
Kvasnicka
Vineeta
V
Khare
Christoph
C
Gasche
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D007501:Iron / Q000097:blood* / Q000378:metabolism; D000090463:Iron Deficiencies; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D038042:Myelopoiesis / Q000502:physiology*; D010641:Phenotype; D010974:Platelet Aggregation / Q000502:physiology; D010976:Platelet Count / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013926:Thrombopoietin / Q000378:metabolism*
D013926:Thrombopoietin; D007501:Iron