Improved Diagnosis of Iron Deficiency Anemia in the Critically Ill via Fluorescence Flowcytometric Hemoglobin Biomarkers

Abstract

Background: Iron deficiency anemia (IDA) is common in critically ill patients treated in the intensive care unit (ICU), and it can lead to severe consequences. Precise and immediate diagnostics are not available, but they are inevitably needed to administer adequate therapy. Serological parameters such as serum ferritin and transferrin saturation (TSAT) are heavily influenced by simultaneous inflammation reactions, resulting in the need for more suitable parameters. Reticulocyte biomarkers such as reticulocyte hemoglobin content (RET-He) and Delta-hemoglobin equivalent (Delta-He) determined by fluorescence flowcytometry are more specific for the diagnosis of IDA-based anemia and should be investigated for this purpose.

Methods: In a prospective cohort single-center study, serum ferritin and transferrin saturation (TSAT) were collected and compared to RET-He and Delta-He by performing a receiver operating curve (ROC) analysis. The sensitivity and specificity of a single variable or the combination of two variables, as well as cutoff values, for the diagnosis of IDA were calculated. A group comparison for IDA patients without IDA was performed for a control group.

Results: A total of 314 patients were enrolled from an interdisciplinary ICU. RET-He (area under the curve (AUC) 0.847) and Delta-He (AUC 0.807) did indicate iron-deficient anemia that was more specific and sensitive in comparison to serum ferritin (AUC 0.678) and TSAT (AUC 0.754). The detection of functional iron deficiency (FID) occurred in 28.3% of cases with anemia.

Conclusions: Determination of RET-He and Delta-He allows for the increased precision and sensitivity of iron-deficient anemia in the ICU.

Keywords: anemia; functional iron deficiency; intensive care; iron deficiency; reticulocyte hemoglobin content (RET-He); reticulocyte parameters.

Figure 1

Illustrated are the receiver operating characteristics (ROCs) of RET-He and Delta-He for the group of patients with IDA and FID. The calculated optimal cutoff points (criterion) with their sensitivity and specificity, the area under the curve (AUC), and the level of significance (P) are also included.

Figure 2

Comparison of the AUC in the IDA group and FID group.

Figure 3

Ability of RET-He, Delta-He serum ferritin, and CRP to discriminate between anemic, iron-deficient, and inflammatory states. Group comparison by Kruskal–Wallis. The colored band marks the reference range; ○, mild outliers (value between 1.5 to 3 IQR from the box); ∗, extreme outliers (value more than 3 IQR from the box); p, p-value.