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P168 Adjusting serum ferritin concentrations to remove the effects of acute-phase response in patients with IBD and iron deficiency: is using C-reactive protein sufficient?

K. Farrag*1,2, V. Ademaj-Kospiri1,2, I. Mavrommataki1,2, A. Aksan1,3, E. Leventi1,2, F-P. Armbruster4, A. Dignass5, J. Stein1,2

1Interdisciplinary Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Germany, 2DGD Clinics Sachsenhausen, Frankfurt/Main, Germany, 3Hacettepe University, Ankara, Turkey, 4Immundiagnostik AG, Bensheim, Germany, 5Agaplesion Markuskrankenhaus, Frankfurt/Main, Germany

Background

Patients with IBD have high rates of iron deficiency (ID) with adverse clinical consequences. Serum ferritin is normally a sensitive marker for iron status, but as an acute-phase reactant, ferritin becomes elevated in response to inflammation, complicating the diagnosis.1 ECCO guidelines recommend adjusting serum ferritin concentrations by concurrently measuring C-reactive protein (CRP) to remove effects of subclinical inflammation.2 The WHO suggests measuring α1-acid glycoprotein (AGP) as a second biomarker, since CRP and AGP reflect different—acute and chronic—stages of the acute-phase reaction.3 We aimed to estimate inflammation-related increase in ferritin in IBD patients using two acute-phase proteins (APPs), CRP and AGP, individually and in combination, and to calculate factors to remove the influence of inflammation from ferritin levels.

Methods

Up to October 2018, 118 patients (38 with Crohn’s disease [CD], 47 with ulcerative colitis [UC], 33 controls) with a mean age of 45.48 ± 15.25 years, 47.46% female, who consecutively attended the ICCC Rhein-Main, Frankfurt, Germany for routine evaluation, were included. Elevated concentrations of CRP (>5 mg/l) and/or AGP (>0.65 g/l) were used to define inflammation status to correct ferritin levels (cut-off 30 µg/ml) for inflammation.

Results

In this interim analysis of IBD patients, inflammation caused ferritin to increase by 28.78% (19/66) using CRP or 53.03% (35/66) using AGP or both (p < 0.05). Elevated AGP levels were relatively more common than raised CRP in UC (36.17% vs. 14.89%) than in CD (63.16 vs. 47.37%). Using CRP,4 8 patients were classified with ID, 18 functional ID, 1 anaemia of chronic disease (ACD), and 1 mixed anaemia (ACD/IDA). By using CRP and AGP, 25 patients were classified with functional ID and 4 with ACD. Overall, inflammation increased ferritin in 77.65% of IBD patients and was associated with a 31.04% underestimation of ID (defined according to Weiss and Goodnough4) using CRP as single marker.

Conclusion

Our data highlight the challenge of assessing ID and IDA using only serum ferritin as marker of iron status for patients with IBD and active inflammation. We demonstrate that correction of serum ferritin levels for inflammation using CRP alone would underestimate ID in IBD patients by ∼50%, indicating the need to utilise both APPs.

References

1. Dignass A et al. Int J Chronic Dis 2018.

2. Dignass A et al. J Crohns Colitis 2015.

3. Thurnham D et al. Am J Clin Nutr 2010.

4. Weiss G, Goodnough L. New Engl J Med 2005.