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Fulltext Potential Point-of-Care Microfluidic Devices to Diagnose Iron Deficiency Anemia

Yap BK, M Soair SN, Talik NA, Lim WF, Mei I L

Sensors (Basel), 2018 Aug 10;18(8).
PMID: 30103424 DOI: 10.3390/s18082625

Over the past 20 years, rapid technological advancement in the field of microfluidics has produced a wide array of microfluidic point-of-care (POC) diagnostic devices for the healthcare industry. However, potential microfluidic applications in the field of nutrition, specifically to diagnose iron deficiency anemia (IDA) detection, remain scarce. Iron deficiency anemia is the most common form of anemia, which affects billions of people globally, especially the elderly, women, and children. This review comprehensively analyzes the current diagnosis technologies that address anemia-related IDA-POC microfluidic devices in the future. This review briefly highlights various microfluidics devices that have the potential to detect IDA and discusses some commercially available devices for blood plasma separation mechanisms. Reagent deposition and integration into microfluidic devices are also explored. Finally, we discuss the challenges of insights into potential portable microfluidic systems, especially for remote IDA detection.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis*
RBC-Y/MCV as a discriminant function for differentiating carriers of thalassaemia and HbE from iron deficiency

Nadarajan VS, Sthaneshwar P, Jayaranee S

Int J Lab Hematol, 2010 Apr;32(2):215-21.
PMID: 19566741 DOI: 10.1111/j.1751-553X.2009.01174.x

Individuals with alpha-thalassaemia (ATT), beta-thalassaemia (BTT) and HbE trait (HET) are often initially identified based on haematological parameters. However, the values of these parameters usually overlap with iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD). We evaluated the use of RBC-Y in 156 normal individuals and 332 patients; ATT (n = 37), BTT (n = 61), HET (n = 25), HbH disease (n = 5), ACD (n = 67), IDA (n = 83) and ACD with IDA (n = 54). Diagnostic efficiency was analysed by receiver operating characteristics (ROC). MCH was better compared with RBC-Y in discriminating normal from abnormal with sensitivity and specificity of 94% at a cut-off of 26 pg. The Green and King (G&K) index performed the best in discriminating carriers from IDA and ACD with area under the ROC curve (AUC(ROC)) of 0.81. However, if ACD was excluded, RBC-Y/MCV was a good discriminator for carriers from IDA with AUC(ROC) = 0.845. In general screening of populations with ATT, BTT and HET, we propose that hypochromic individuals be first identified by MCH <26 pg and carriers distinguished within these hypochromic individuals from IDA by using RBC-Y/MCV. However, if the prevalence of ACD were high within the screening population, G&K index would be a more suitable discriminator.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis
RET-Y and RBC-Y in the diagnosis of iron deficiency associated with anaemia of inflammation

Jayaranee S, Sthaneshwar P

Int J Lab Hematol, 2010 Oct;32(5):512-8.
PMID: 20109166 DOI: 10.1111/j.1751-553X.2009.01215.x

We evaluated the usefulness of RET-Y and RBC-Y in distinguishing functional iron deficiency from iron-deficiency anaemia (IDA) in patients with anaemia of inflammation (AI). Sixty healthy blood donors constituted the control group. We studied RET-Y and RBC-Y in 115 patients with hypochromic/microcytic anaemia. Of these 42 patients had uncomplicated IDA and 73 had AI. The AI patients were further subdivided into AI with IDA and AI with functional IDA based on soluble transferrin receptor (sTfR) levels. The mean RBC-Y and RET-Y values in iron-deficient patients were 122.4 and 119.8, respectively, which were significantly lower than the control (P < 0.001). The mean level of RET-Y in patients with AI associated with IDA was 149.3 and this level in AI patients with functional iron deficiency was 147.4. RET-Y levels in both subgroups of AI patients were significantly lower than control but no significant difference was observed between the two subgroups. Similar findings were observed for RBC-Y. Receiver operating characteristic analysis also showed lower specificity for RBC-Y and RET-Y compared with that of sTfR and its log ferritin ratio (F-index). RET-Y and RBC-Y are useful in the diagnosis of simple IDA but have limited utility in the diagnosis of IDA with AI.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis*
Use of red blood cell indices for the identification of iron deficiency among blood donors

Nadarajan V, Sthaneshwar P, Eow GI

Transfus Med, 2008 Jun;18(3):184-9.
PMID: 18598281 DOI: 10.1111/j.1365-3148.2008.00862.x

The objective of this study was to identify haematological parameters useful in screening for iron deficiency among blood donors. Iron deficiency is a common complication of blood donation and often goes unrecognized until anaemia develops. Biochemical markers such as soluble transferrin receptor (TfR), ferritin and log(TfR/F) have been proposed as more valid indicators of body iron status. Red blood cell (RBC) parameters are, however, more easily measured and have also been proposed as indicators of iron depletion. We measured ferritin and TfR in 192 blood donors together with RBC analysis, performed on two haematology analysers. Thirteen donors had parameters suggestive of haemoglobinopathy and were excluded from further analysis. Overall, 10% (18/179) of the remaining donors had iron deficiency, as defined by log(TfR/F) exceeding the 95th percentile of the value in the population of first-time donors. Using receiver operating characteristic analysis, the sensitivity of ferritin was 100%, with a specificity of 90% at a cut-off of 15 mug L(-1). The sensitivity and specificity of RBC-Y at a cut-off of 152 for detecting iron deficiency were 81 and 89%, respectively. Haemoglobin content of reticulocytes, meanwhile, showed sensitivity of 69% and specificity of 93% when a cut-off of 28 pg was used. Both measures compare favourably with haemoglobin which only showed a sensitivity of 50%, although specificity was 91% at a cut-off value of 125 g L(-1). The parameter RBC-Y can be useful as a screening measure for iron deficiency in blood donors.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis*
Microcytic to hypochromic ratio as a discriminant index of thalassaemia trait in subjects with hypochromic anaemia

Wee SY, Muhamed Said SS, Raja Sabudin RZA, Alauddin H, Ithnin A

Malays J Pathol, 2020 Aug;42(2):195-201.
PMID: 32860371

INTRODUCTION: Differentiating between thalassaemia and iron deficiency anaemia (IDA) in hypochromic anaemia is a challenge to pathologists as it influences the choice of subsequent specialized confirmatory tests. In this study, we aimed to evaluate the performance of microcytic to hypochromic ratio (MicroR/ Hypo-He, M/H ratio) as a discriminant index in hypochromic anaemia.
MATERIALS AND METHODS: A retrospective study was carried out on 318 subjects with hypochromic anaemia, which comprised 162 IDA and 156 thalassaemia trait subjects with α-thalassemia, β-thalassemia and HbE trait. Optimal cut-off value, sensitivity and specificity of M/H ratio for thalassaemia trait discrimination was determined using Receiver Operating Characteristic (ROC) analysis.
RESULTS: Subjects with thalassaemia trait showed higher MicroR compared to IDA ( p< 0.001) while subjects with IDA demonstrated higher Hypo-He than thalassaemia trait (p < 0.001). M/H ratio was significantly higher in thalassaemia trait compared to IDA, with medians of 3.77 (interquartile range: 2.57 - 6.52) and 1.73 (interquartile range: 1.27 - 2.38), respectively (p < 0.001). M/H ratio ≥ 2.25 was the optimal cut-off value for discriminating thalassaemia trait from IDA in hypochromic anaemia, with the area under ROC curve (AUC) of 0.83, sensitivity of 80.8% and specificity of 71.6%.
CONCLUSIONS: M/H ratio is a useful discriminant index to distinguish thalassaemia trait from IDA in hypochromic anaemia prior to diagnostic analysis for thalassaemia confirmation. High M/H ratio is suggestive of thalassaemia trait than of IDA. However, more studies are required to establish the role of M/H ratio as a screening tool for thalassaemia discrimination in hypochromic anaemia.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis
Fulltext Serum soluble transferrin receptor in hypochromic microcytic anaemia

Jayaranee S, Sthaneshwar P

Singapore Med J, 2006 Feb;47(2):138-42.
PMID: 16435056

The objective of this study was to assess the clinical significance of soluble transferrin receptor (sTfR) in hypochromic microcytic anaemia.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis*
A study of serum ferritin levels among male blood donors in Hospital Universiti sains Malaysia

Norashikin J, Roshan TM, Rosline H, Zaidah AW, Suhair AA, Rapiaah M

Southeast Asian J. Trop. Med. Public Health, 2006 Mar;37(2):370-3.
PMID: 17125001

Iron deficiency is the commonest cause of anemia worldwide and healthy blood donors are estimated to lose about 236 mg of iron with each donation. The objective of this study was to determine the serum ferritin levels among first time and regular male blood donors, and also to correlate the serum ferritin levels with the number of donations and hemoglobin levels. Hemoglobin levels and serum ferritin were measured in three groups of donors divided into first time donors; (n = 92), donors with 2-4 donations (n = 41), and regular donors (n = 78). The mean hemoglobins in the first time donors, second group and regular blood donor group were 14.95 +/- 1.08, 15.12 +/- 1.44 and 15.56 +/- 1.48, respectively. The serum ferritin level were found to be significantly lower among the regular donors (62.0 +/- 39.78 ng/ml) compared to first time donors (90.7 +/- 66.63) and second group donors (114.12 +/- 66.97). The serum ferritin levels gradually decrease according to the number of donations and there was a significant correlation between frequency of donations and the serum ferritin level (r2 = 0.082). Significant correlation between the number of donations and hemoglobin level r2 = 0.061) was noted. However, there was no significant correlation between hemoglobin and serum ferritin levels (r2 = 0.015). Eleven percent of regular donors had depleted iron stores. This was not noted in donors who donated less than 5 times within 2 years.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis
Fulltext Anemia and iron status of Malay women attending an antenatal clinic in Kubang Kerian, Kelantan, Malaysia

Hassan R, Abdullah WZ, Nik Hussain NH

Southeast Asian J. Trop. Med. Public Health, 2005 Sep;36(5):1304-7.
PMID: 16438162

The purpose of this study was to detect the frequency of iron deficiency anemia in women attending their first antenatal clinic at a Maternal and Child Health Clinic in Kubang Kerian, a district of Kelantan that is located on the East coast of Malaysia. A cross-sectional study was done over a two-month period and fifty-two Malay women were enrolled in this study. Red blood cell indices and serum ferritin were used as a screening tool for anemia and iron status. Eighteen patients (34.6%) were anemic. The majority were classified as having mild anemia (90%). Four of them had hypochromic microcytic anemia. Of 52 women, 7 had iron deficient erythropoiesis and 11 (61.1%) had iron deficient anemia. The prevalence of iron deficiency anemia in pregnant women was 21.2%, which is similar to other developing countries. The serum ferritin level was significantly associated with the hemoglobin level (p=0.003). Other red blood cell indices were not useful in predicting iron deficient erythropoiesis. It is important to detect iron deficient erythropoiesis during the first antenatal check-up, as it is an early manifestation of iron deficiency anemia. In conclusion, screening for iron deficient is recommended during first antenatal visit because iron deficiency anemia is still the leading cause of nutritional deficiency in pregnant women. This will initiate an early therapeutic intervention so as to reduce public health problem.
Study site: Hopital Universiti Sains Malaysia (HUSM) and the Maternal and Child Health Clinic, Kubang Kerian, Kelantan, Malaysia

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis
Fulltext Severe chronic iron deficiency anaemia secondary to Trichuris dysentery syndrome - a case report

Azira N MS, Zeehaida M

Trop Biomed, 2012 Dec;29(4):626-31.
PMID: 23202608

Trichuris dysentery syndrome is caused by Trichuris trichiura which contributes to one of the most common helminthic infections in the world. It is associated with heavy colonic infection that manifests as mucoid diarrhoea, rectal bleeding, rectal prolapse, iron deficiency anaemia, and finger clubbing. Here, we report a case of trichuris dysentery syndrome complicated with severe chronic iron deficiency anaemia in a 4-year-old girl who required blood transfusion. The nematode was visualized on stool microscopic and colonoscopic examination. A longer duration of anti-helminthic treatment is required to achieve effective and better outcome.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis*
Serum prohepcidin concentrations in rheumatoid arthritis

Jayaranee S, Sthaneshwar P, Sokkalingam S

Pathology, 2009 Feb;41(2):178-82.
PMID: 18972320 DOI: 10.1080/00313020802436840

AIM: Hepcidin, a recently identified peptide, acts as a central regulator of iron metabolism. It is regarded as a factor regulating the uptake of dietary iron and its mobilisation from macrophages and hepatic stores. It is considered as a mediator of anaemia of inflammation. The aim of this study was to assess whether serum prohepcidin concentration is able to distinguish iron deficiency from anaemia of inflammation in patients with rheumatoid arthritis (RA).
METHOD: Blood samples were obtained from 20 healthy blood donors, 30 RA patients who presented with anaemia and 30 patients who had pure iron deficiency anaemia (IDA). The samples were analysed for full blood count, iron, ferritin, transferrin, soluble transferrin receptor and prohepcidin.
RESULTS: The mean prohepcidin level in the control subjects was 256 microg/L. The prohepcidin level was significantly lower in IDA patients (100 microg/L; p < 0.0001) but not significantly different from that of control in RA patients (250 microg/L; p > 0.05). Higher serum soluble transferrin receptor (sTfR) levels were observed in IDA (p < 0.0001) but not in RA compared with that of control (p > 0.05). RA patients were divided into iron depleted and iron repleted subgroups based on the ferritin level. Prohepcidin in the iron depleted group was significantly lower than the iron repleted group and the control (p < 0.0001) and higher levels were observed in the iron repleted group (p < 0.01). sTfR levels in the iron depleted group were significantly higher than the control and the iron repleted patients (p < 0.001). In the iron repleted group, sTfR level was not statistically different from that of control (p > 0.05).
CONCLUSION: Serum prohepcidin is clearly reduced in uncomplicated iron deficiency anaemia. The reduced prohepcidin levels in the iron depleted RA patients suggests that there may be conflicting signals regulating hepcidin production in RA patients. In RA patients who have reduced hepcidin in the iron depleted group (ferritin <60 microg/L) where sTfR levels are increased suggests that these patients are iron deficient. Further studies with a larger cohort of patients are required to substantiate this point.

Matched MeSH terms: Anemia, Iron-Deficiency/diagnosis