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.
CONCLUSION: FCM lowers platelet counts and platelet activation in patients with 
IBD-associated secondary thrombocytosis.