Use of haematological iron parameters alone or in combination to detect iron deficiency in inflammatory bowel disease

Introduction Iron deficiency (ID) is a common extraintestinal manifestation of inflammatory bowel disease (IBD). The European Crohn’s and Colitis Organization (ECCO) 2015 anaemia guidelines recommend basing diagnosis of ID in IBD patients on serum ferritin alone. ID is underdetected in IBD patients due to unawareness of subtle clinical symptoms, imprecisions of lab tests and interpretative difficulties.

Aims We investigated which sole parameter or combination of parameters can best predict ID in IBD patients.

Methods In a retrospective cross-sectional study, we analysed routine blood samples from patients with IBD for CBC, iron status (serum ferritin, SF; transferrin saturation, TSAT; mean corpuscular volume, MCV), the inflammation marker high sensitivity CRP (hsCRP) and soluble transferrin receptor (sTfR) by standard methods. A multiparameter index test (MCV, TSAT, SF) was performed to detect ID when at least 2 of the 3 markers indicated ID. sTfR ferritin index (sTfR-F) was calculated (sTfR (mg/L)/log¹⁰ SF (μg/L)). Cut-off values for TSAT (<20%) and SF (<30μg/L or<100μg/L) were defined per ECCO guidelines and for MCV (80fL) per the literature. Absolute ID (AID) was defined as hsCRP<5mg/L, SF 30μg/L and TSAT<20%; functional ID (FID) as hsCRP≥5mg/L, SF<100 μg/L and TSAT<20%.

Results 240 IBD patients (120f/120m;120CD/120UC;42.9±14.6y) were enrolled. 71 (29.6%) had inflammation. 47 patients had ID (25 FID, 22 AID). ROC analysis was done to compare markers as detectors of ID (Tab. 1). In the absence of inflammation, TSAT and SF<30μg/L in combination detected a large majority of cases of ID. In patients with inflammation, a combination of TSAT and SF<100μg/L detected most ID cases. Addition of MCV, which was highly specific regardless of inflammation, added additional value to the diagnosis, especially in the context of inflammation (p<0.001).

Conclusion No single parameter was suitable to diagnose ID in IBD as sole marker. Independent of inflammation, TSAT and SF seemed to adequately define ID; however, in both cases the addition of MCV had additional value, particularly when inflammation was present. Addition of sTfR (or sTfR-F) is questionable due its high cost and limited availability: Prospective large-scale studies are needed to evaluate whether determination of sTfR and sTfR-F could be worthwhile.

Table 1. Analytical performance of iron status parameters to detect ID in patients with IBD with/without co-presence of inflammation.

Patient group	Outcome	MCV	TSAT	SF	sTfR	sTfR-F
All patients	AUCROC	0.810	0.985	0.850	0.820	0.878
	Sens./Spe.%	25.0/98.7	100.0/89.2	53.3/94.3	47.5/94.7	65.0/88.8
Patients with inflammation	AUCROC	0.729	1.000	0.806	0.755	0.866
	Sens./Spe.%	20.0/96.3	100.0/86.3	96.0/55.6	34.8/96.2	43.5/96.2
Patients without inflammation	AUCROC	0.843	0.991	0.970	0.948	0.987
	Sens./Spe.%	31.6/99.0	100.0/95.6	89.5/96.2	76.5/92.9	100.0/88.9