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.
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.
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.
FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.
Article first published online 2 May 2013
*Division of Gastroenterology and Hepatology, Department of Medicine III and
†Institute of Physiology, Centre for Physiology & Pharmacology, Medical University of Vienna, Vienna, Austria;
‡IBD Centre North, Hamburg, Germany;
§Gastroenterology and Clinical Nutrition, Katharina Kasper-Clinics, Frankfurt, Germany;
‖Gastroenterologische Schwerpunktpraxis, Mannheim, Germany;
¶Department of Epidemiology, and
**Christian Doppler Laboratory on Molecular Cancer Chemoprevention, Medical University of Vienna, Vienna, Austria;
††Vifor Pharma, Austria; and
‡‡Loha for Life, Medizinisches Kompetenzzentrum Eisenmangel, Vienna, Austria.
Reprints: Christoph Gasche, AKH Wien, Abteilung für Gastroenterologie und Hepatologie, Währinger Gürtel 18-20, Vienna A-1090, Austria (e-mail: email@example.com).
S. Kulnigg-Dabsch received speaker honoraria from Vifor International and Pharmacosmos A/S; W. Schmid, S Howaldt: no conflicts; J. Stein received honoraria from Vifor International; J. Kuhn, R. Evstatiev, T. Waldhör, and I. Volf: no conflicts; H. Kamali is employee of Vifor International; C. Gasche received honoraria from Vifor International, Pharmacosmos A/S, Fresenius Medical Care, Renapharma Sweden; grant and consultancy honoraria from Vifor International; Advisory board: Vifor International, Pharmacosmos A/S.
Supported by Austrian Science Fund (FWF P21200) and Vifor Pharma, Glattbrugg, Switzerland. The authors have no other conflicts of interest to disclose.
Received October 23, 2012
Accepted November 1, 2012