The effect of iron isomaltoside 1000 on the association between hematopoietic parameters and platelets in subjects with inflammatory bowel disease and iron deficiency anemia

Background: Iron deficiency anemia (IDA) and secondary thrombocytosis, which may lead to increased risk of thromboembolic events, are complications seen with inflammatory bowel diseases (IBD). Intravenous (IV) iron is an established treatment for subjects with IBD and IDA, and iron treatment has also been found to normalize elevated platelets in subjects with IBD-related IDA. Iron isomaltoside 1000 is a new high dose IV iron for fast infusion, which in a recent 8 weeks study in IBD subjects (PROCEED) demonstrated good tolerability and efficacy comparable to other IV iron preparations (Reinisch et al., Am J Gastro, 2013). In this study, we investigated the effect of iron isomaltoside 1000 on the association between hematopoietic parameters, such as hemoglobin (Hb), transferrin saturation (TfS), and sferritin and platelet counts in subjects with IBD-related IDA. Methods: The PROCEED study is a phase III, randomized, comparative, open-label study of 338 IBD subjects with IDA randomized 2:1 to either IV iron isomaltoside 1000 (225 subjects) or oral iron sulphate (113 subjects). This study is a sub-analysis of the subjects treated with iron isomaltoside 1000. The total calculated IV iron requirement was calculated according to an adapted Ganzoni formula, where the target Hb was 13 g/dL. The subjects were randomized to either 2 single once weekly infusion of up to 1000 mg iron over 15 min or to 4 single once weekly 500 mg bolus injections of iron over 2 min. Outcome measures included measures of Hb and iron related biochemistry. Results: 225 subjects were enrolled. Platelet count decreased from a mean of 370 10∧9/L at baseline to 297 10∧9/L at week 8 (p<0.0001), and the decrease was dose-dependent. Thus, subjects treated with >1000 mg iron had a significant higher decrease in platelet count compared to subjects treated with <1000 mg iron (p= 0.001). There was a significant association between the increased levels of Hb and platelets from baseline after 8 weeks (p=0.048). A linear regression showed that at week 8, an increase in Hb of 1 g/dL was associated to a decrease of 10.7 10∧9/L in platelet count. A similar result was observed with TfS. At week 8, an increase in TfS of 1% was associated to a decrease of 2.0 10∧9/L in platelet count (p=0.0025). The same trend was observed for sferritin, but it was non-significant. No major safety issues were reported. Conclusion: There was a dose-dependent decrease in platelet counts from baseline to week 8 in IBD subjects with IDA treated with iron isomaltoside 1000. In addition, there was a statistical significant association between hematopoietic parameters and platelet counts, where increased levels of Hb and TfS was associated with decreased platelet counts. Thus, iron isomaltoside 1000 may have a clinical benefit in reducing secondary thrombocytosis in IBD subjects. No major safety issues were reported.