The Cost-effective Usefulness of Oral Iron Absorption Test- Prospective Evaluation in Premenopausal Women with Newly Diagnosed Iron Deficiency Anemia

Research Article

Ann Hematol Oncol. 2018; 5(4): 1201.

The Cost-effective Usefulness of Oral Iron Absorption Test- Prospective Evaluation in Premenopausal Women with Newly Diagnosed Iron Deficiency Anemia

Islam MS1,2*, Dayley D1 and Thanigaikumar M2

1Department of Haematology, Broomfield Hospital, UK

2Department of Haematology, Lewisham Hospital, UK

*Corresponding author: Islam MS, Department of Haematology, Broomfield Hospital, CM1 7ET, Chelmsford, UK

Received: April 02, 2018; Accepted: May 07, 2018; Published: May 21, 2018


Background: We explored the cost-effective usefulness of oral iron absorption test (OIAT) to predict gastrointestinal lesions associated with iron malabsorption in premenopausal iron deficient women.

Materials and Methods: 238 premenopausal women referred to the haematology for evaluation of Iron deficiency anemia (IDA) were prospectively recruited by consecutive sampling. Patients with an identifiable cause of iron deficiency were not enrolled in the study. If any patient with abnormal OIAT was further investigated with IgA anti-TTG, IgG H pylori and IgG anti G-PCA antibody levels and 36 of those patients with abnormal OIAT also had gastrointestinal endoscopy and biopsy.

Results: Among the 238 study population 85 patients had an abnormal test. A high prevalence of celiac disease (7.5%), H pylori positivity (62%) and autoimmune gastritis (9.4%) was found among iron deficient women who had an abnormal OIAT. No significant difference was found in the occurrence of these gastrointestinal conditions with respect to menstrual flow. All patients who had a normal OIAT had a successful response to therapeutic iron supplementation. The OIAT based approach is 17-fold more economical compared to blanket approach which include serological tests and endoscopy and biopsy in all patients.

Conclusion: OIAT is a useful simple inexpensive test which helps to target the appropriate patients for invasive and expensive tests for the evaluation of unexplained iron deficiency anemia.

Keywords: Iron deficiency anemia; Oral iron absorption test; Premenopausal; Celiac disease; H pylori


OIAT: Oral Iron Absorption Test; IDA: Iron Deficiency Anemia; G-PCA: Tissue Transglutaminase, Gastric Parietal Cell Antibody; DALYs: Disability-Adjusted Life-Years; GI: Gastrointestinal; H pylori: Helicobacter Pylori; CRP: C-Reactive Protein; ESR: Erythrocyte Sedimentation Rate; MVC: Mean Corpuscular Volume; Hb: Hemoglobin; FBC: Full Blood Counts; EDTA: Ethylene Di-amine Tetra-acetic Acid; ELISA: Enzyme-Linked Immunosorbent Assay


The prevalence of Iron deficiency anemia is very common as 30%- 50% of anemia is caused by iron deficiency [1]. Though the full global extent of iron deficiency is unknown, nearly two billion people suffer from anemia [2] roughly half of which is assumed to be attributable to a lack of adequate iron [3] the most common cause globally [4]. Iron deficiency is also implicated in nearly 200,000 deaths and 45 million disability-adjusted life-years (DALYs) lost annually (4.5% of all risk-attributable DALYs) in the most recent 2013 Global Burden of Disease Study, predominantly due to iron deficiency anemia [5]. Furthermore, iron deficiency in the absence of anemia has been linked to many detrimental outcomes: lowered cognitive ability, reduced work capability, and greater rate of maternal and child mortality [6].

In the western world, IDA is prevalent in 5% of women aged ‹50 years [7]. Premenopausal women constitute a significant proportion of patients with unexplained IDA referred to hematologists. The evaluation of iron deficiency in the absence of evidence of excessive blood loss is often difficult. A popular clinical approach in such patients is to perform gastrointestinal (GI) endoscopy and at times more sophisticated tests like video capsule endoscopy, mesenteric angiography or isotope red cell scan, to identify occult GI hemorrhage.

The diagnostic pathway for young women affected by IDA is not clearly established. The British Society for Gastroenterology recommends gastroscopy for iron deficient women younger than 45 years only in the presence of GI symptoms [8]. However, symptoms are often mild and patients often refuse to undergo the invasive procedure. A large study which evaluated gastroscopy in patients with IDA concluded that it was unnecessary in about a third of premenopausal women [9].

Previous studies have shown that regardless of the menstrual flow, non-bleeding silent alimentary conditions which impair iron absorption may be the cause for IDA among premenopausal women [10]. The above conditions include subclinical forms of celiac disease [11-13], Helicobacter pylori (H pylori) infection [14,15] and autoimmune (atrophic) gastritis [16]. Oral iron absorption test (OIAT) may help to identify iron malabsorption in these patients and could potentially reduce the number of invasive investigations and unsuccessful trials of oral iron therapy. However, the utility of this investigation has not been verified in large prospective trials among this group of patients.

We prospectively assessed iron absorption among premenopausal women with newly diagnosed IDA referred to the hematology clinic. The primary objective of this study was to ascertain the usefulness of OIAT in predicting upper GI tract conditions associated with impaired iron absorption. The secondary objective was to compare the costs of an OIAT based approach with that of standard endoscopic evaluation.


Study design and patients

The study was conducted in two hospitals in UK between June 2013 and December 2017. Women aged 18-50 years referred to the haematology department for evaluation of IDA were prospectively recruited to the study by consecutive sampling. Patients with an identifiable cause of iron deficiency including manifest blood loss, acute GI hemorrhage and epistaxis were not enrolled in the study. Relevant data was collected from clinical notes and electronic patient database. Details on hematological, biochemical, serological and histopathological parameters were merged with the clinical data for each patient. Ethical approval for this study was obtained from the respective institutional review boards.

Exclusion criteria

Patients with one or more of the following criteria were excluded from the study: pregnancy; raised inflammatory markers (CRP >1 mg/l or ESR >20 mm/1st hour); specific symptoms attributable to upper GI tract disease including dysphagia, odynophagia, heartburn, dyspepsia, nausea, vomiting, anorexia and upper abdominal pain related to meals or relieved by antacids; specific symptoms of lower GI tract pathology including hematochezia, recent change in bowel habits, diarrhea, constipation and lower abdominal pain that was colicky or relieved by defaecation; positive faecal occult blood test; known coeliac disease; severe nutritional problems including anorexia nervosa; inflammatory bowel disease; parasitic infestation;known bleeding diatheses.

Study definitions

Iron deficiency anaemia was defined by the combination of Hb ‹12 g/dl, mean corpuscular volume (MCV) ‹80 fL, transferrin saturation ‹16% and a serum ferritin level ‹15 ug/l [16].

Premenopausal status was ascertained by clinical history and was defined as ongoing menstruation. The menstrual cycle was considered as normal if the duration of each cycle was between 3 and 5 days, with an interval of 25-32 days between successive cycles. Menstrual flow was expressed as days per year, according to the formula: 365 days x days of menses/days of menstrual intervals + days of menses = days of menses/year [17]. Accordingly, 31-61 days of menses/year represented the normal range. Heavy menstrual flow was defined as >62 days of menses/year.

Oral iron absorption test

OIAT was performed in the outpatient setting, as outlined in previous studies [18,19]. After an overnight fast, venous sample for baseline (T0) serum iron was drawn and a single ferrous sulphate tablet 200 mg equivalent to 65 mg elemental iron was administered orally. Serum iron levels were rechecked at 1 hour (T1h) and 2 hours (T2h) following ingestion of the tablet. Patients had no food or drink except still water between T0 and T2h. The difference between T2h and T0 was taken as the estimate of iron absorption [20].

Measurement of aematological parameters

Full blood counts (FBC) were performed on EDTA anticoagulated blood using an automated COULTER ®LH 750 Hematology analyser calibrated daily with standards provided by the manufacturer. Serum iron and ferritin levels were measured by Latex agglutination method on venous blood collected in lithium heparin, using AU2700/5400/ AU5800 Beckman Coulter Chemistry analyser. The normal premenopausal female reference ranges were 59-158 ug/dl for serum iron and 15-200 ug/l for serum ferritin. The analyser units were subjected to external quality control at regular monthly intervals.

Subsequent investigations

An increase in serum iron level by at least 100 ug/dl from baseline at either T1h or T2h was regarded as evidence of adequate absorption of iron from the gut [19]. In all other patients, the OIAT was considered abnormal.

If the OIAT was normal, no further tests were performed and the patient proceeded with oral iron supplementation. Patients with abnormal OIAT had subsequent investigations which included anti- TTG, serological tests to detect H pylori infection and anti G-PCA levels for all those patient and an upper GI endoscopy with biopsy on patients who agreed to have this invasive investigation. These patients were treated with intravenous iron.

All endoscopic procedures were performed by gastroenterologist after obtaining informed consent. Antral, gastric body and duodenal biopsies were collected, which were evaluated by conventional histology. IgA anti-TTG levels were assessed by ELISA (Bio-Rad Laboratories, Milan, Italy), with titres >15 IU/ml considered as positive. IgG H pylori antibodies were tested by ELISA (Biohit, Helsinki, Finland), with titres >1.1 IU/ml considered as positive. IgG anti-PCA levels were estimated using an indirect immunofluorescence semi-quantitative antibody test (IMMCO diagnostics, Buffalo, NY, USA).


Prevalence of subclinical disease among patients with impaired OIAT

Of the 85 patients with impaired OIAT, 66 had at least one abnormal test, indicative of the presence of celiac disease, H pylori infection/chronic gastritis, or autoimmune gastritis. The combined prevalence of ‘disease’ in this subgroup of patients was 77.6%. The individual prevalence for each of these GI pathologies was as follows:

Celiac disease

6 of 85 patients had tested positive for anti-TTG, of whom 4 also had histopathological features of coeliac disease (Fig 1). Among these 6 women, 2 had coexisting IgG H pylori antibody and 1 had concurrent anti-PCA. The prevalence of celiac disease was 7% in the patient with abnormal OIAT.

H pylori infection and chronic gastritis

IgG H pylori antibodies were detected in the sera of 53 patients (Figure 1). As many as 19 of 36 patients who underwent endoscopy and biopsy had histological evidence of H pylori related chronic gastritis. Those patients who had histological evidence of chronic gastritis, 13 of them also had IgG H. Pylori antibody. Hence the prevalence of H pylori infection among the women with abnormal OIAT was 62.3%.