Effect of iron therapy on platelet counts in patients with inflammatory bowel disease-associated anemia

Abstract

Background and aims: Secondary thrombocytosis is a clinical feature of unknown significance. In inflammatory bowel disease (IBD), thrombocytosis is considered a marker of active disease; however, iron deficiency itself may trigger platelet generation. In this study we tested the effect of iron therapy on platelet counts in patients with IBD-associated anemia.

Methods: Platelet counts were analyzed before and after iron therapy from four prospective clinical trials. Further, changes in hemoglobin, transferrin saturation, ferritin, C-reactive protein, and leukocyte counts, before and after iron therapy were compared. In a subgroup the effect of erythropoietin treatment was tested. The results were confirmed in a large independent cohort (FERGIcor).

Results: A total of 308 patient records were available for the initial analysis. A dose-depended drop in platelet counts (mean 425 G/L to 320 G/L; p<0.001) was found regardless of the type of iron preparation (iron sulphate, iron sucrose, or ferric carboxymaltose). Concomitant erythropoietin therapy as well as parameters of inflammation (leukocyte counts, C-reactive protein) had no effect on the change in platelet counts. This effect of iron therapy on platelets was confirmed in the FERGIcor study cohort (n=448, mean platelet counts before iron therapy: 383 G/L, after: 310 G/L, p<0.001).

Conclusion: Iron therapy normalizes elevated platelet counts in patients with IBD-associated anemia. Thus, iron deficiency is an important pathogenetic mechanism of secondary thrombocytosis in IBD.

Figure 1. Primary dataset analysis.

* FCM=ferric carboxymaltose. ** cumulative iron dose. Plt=platelets.

Figure 2. The changes in platelet counts upon iron therapy.

(A) Platelet counts pre and post iron replacement therapy according to iron preparation (black column – iron sucrose n=122, grey column – ferric carboxymaltose n=130, white column – iron sulphate n=56), p<0.001 pre vs. post for all iron preparations. (B) Mean drop in platelet counts upon intravenous iron replacement therapy according to the cumulative iron dose (p=0.002). Group 0–1200 mg n=97, group 1201–2000 mg n=103, group 2001–3600 mg n=52. Error bars represent standard deviation.

Figure 3. The changes of platelet counts and erythropoietin levels.

Continuous drop in platelet counts (A, p=0.703) and serum erythropoietin levels (B, p=0.021) in Crohn's patients receiving iron sucrose (200–400 mg/week) and erythropoietin (150 mg/KG 3 times per week; light column/line) or iron sucrose (200–400 mg/week) and placebo (dark column/line). N=20 for each group. Error bars represent standard deviation.

Figure 4. The changes in platelet counts in the FERGIcor trial.

(A) Platelet counts pre and post iron therapy according to the iron preparation (black column – ferric carboxymaltose n=228, grey column – iron sucrose n=220), p<0.001 pre vs. post for both iron preparations. (B) Mean drop in platelets upon iron therapy according to the cumulative iron dose (p<0.001). Group 800–1200 mg n=228, group 1201–2000 mg n=220. Error bars represent standard deviation.