title: Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial.
abstract: BACKGROUND
  Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis.
  
  
  METHODS
  We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6.
  
  
  RESULTS
  A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression.
  
  
  CONCLUSIONS
  FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.
authors: Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Stefanie
authors: S
authors: Kulnigg-Dabsch
authors: Werner
authors: W
authors: Schmid
authors: Stefanie
authors: S
authors: Howaldt
authors: Jürgen
authors: J
authors: Stein
authors: Oliver
authors: O
authors: Mickisch
authors: Thomas
authors: T
authors: Waldhör
authors: Rayko
authors: R
authors: Evstatiev
authors: Houman
authors: H
authors: Kamali
authors: Ivo
authors: I
authors: Volf
authors: Christoph
authors: C
authors: Gasche
mesh_terms: D000293:Adolescent; D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000503:physiopathology*; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use*; D064451:Hepcidins / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008320:Maltose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D010976:Platelet Count; D011379:Prognosis; D011446:Prospective Studies; D013922:Thrombocytosis / Q000188:drug therapy / Q000209:etiology*; D055815:Young Adult
chemical_list: D005290:Ferric Compounds; D064451:Hepcidins; D036341:Intercellular Signaling Peptides and Proteins; D019007:P-Selectin; D004921:Erythropoietin; C522335:ferric carboxymaltose; D008320:Maltose