Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access® sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.     

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan preschool children: a community-based survey

Background

Zinc protoporphyrin (ZPP) has been used to screen and manage iron deficiency in individual children, but it has also been recommended to assess population iron status. The diagnostic utility of ZPP used in combination with haemoglobin concentration has not been evaluated in pre-school children. We aimed to a) identify factors associated with ZPP in children aged 12–36 months; b) assess the diagnostic performance and utility of ZPP, either alone or in combination with haemoglobin, to detect iron deficiency.

Methods

We used baseline data from 338 Kenyan children enrolled in a community-based randomised trial. To identify factors related to ZZP measured in whole blood or erythrocytes, we used bivariate and multiple linear regression analysis. To assess diagnostic performance, we excluded children with elevated plasma concentrations of C-reactive protein or α ₁-acid glycoprotein, and with Plasmodium infection, and we analysed receiver operating characteristics (ROC) curves, with iron deficiency defined as plasma ferritin concentration < 12 μg/L. We also developed models to assess the diagnostic utility of ZPP and haemoglobin concentration when used to screen for iron deficiency.

Results

Whole blood ZPP and erythrocyte ZPP were independently associated with haemoglobin concentration, Plasmodium infection and plasma concentrations of soluble transferrin receptor, ferritin, and C-reactive protein. In children without inflammation or Plasmodium infection, the prevalence of true iron deficiency was 32.1%, compared to prevalence of 97.5% and 95.1% when assessed by whole blood ZPP and erythrocyte ZPP with conventional cut-off points (70 μmol/mol and 40 μmol/mol haem, respectively). Addition of whole blood ZPP or erythrocyte ZPP to haemoglobin concentration increased the area-under-the-ROC-curve (84.0%, p = 0.003, and 84.2%, p = 0.001, respectively, versus 62.7%). A diagnostic rule (0.038689 [haemoglobin concentration, g/L] + 0.00694 [whole blood ZPP, μmol/mol haem] >5.93120) correctly ruled out iron deficiency in 37.4%–53.7% of children screened, depending on the true prevalence, with both specificity and negative predictive value ≥90%.

Conclusions

In young children, whole blood ZPP and erythrocyte ZPP have added diagnostic value in detecting iron deficiency compared to haemoglobin concentration alone. A single diagnostic score based on haemoglobin concentration and whole blood ZPP can rule out iron deficiency in a substantial proportion of children screened.

Trial registration

ClinicalTrials.gov NCT02073149 (25 February 2014).

     

Effect of malaria on soluble transferrin receptor levels in Tanzanian infants

The diagnosis of iron deficiency anemia in malaria endemic areas is complicated by the influence of the infection on the laboratory tests conventionally used to assess iron status. Determination of soluble transferrin receptor (sTfR) levels has been shown to be a sensitive indicator of iron deficiency in adults and is not affected by a range of infectious and inflammatory conditions. The utility of sTfR levels in the diagnosis of iron deficiency in malaria endemic areas remains unresolved. Three hundred and fourteen infants in a rural area of southern Tanzania living under conditions of intense and perennial malaria transmission were studied to determine the utility of sTfR plasma levels in the assessment of iron deficiency anemia. Independent of the presence of anemia, malaria parasitemia was associated with a significant increase in sTfR plasma levels that were even higher than those found in iron deficiency anemia. We conclude that the measurement of sTfR levels does not have a role in the diagnosis of iron deficiency anemia in young children exposed to malaria infection.     

The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment

Background

In preoperative blood management of colorectal cancer patients, intravenous iron therapy is increasingly used to treat anaemia and prevent red blood cell transfusions. However, while iron deficiency is the most common cause of anaemia, little is known about the prevalence and namely type of iron deficiency in this population, whereas both types of iron deficiency (i.e. absolute and functional iron deficiency) are recommended to be treated differently by international cancer guidelines.

Objective

The aim of present study is to investigate the prevalence and namely type of iron deficiency in colorectal cancer patients, and to assess its clinical relevance.

Methods

Preoperative iron status, clinical parameters (i.e. age, ASA classification, tumour location, tumour stage) and postoperative complications were retrospectively collected for all newly diagnosed colorectal cancer patients in our institution over a 3-year period.

Results

Iron deficiency was observed in 163 (48.1%) of 339 patients. Of these iron-deficient patients, 3.7% had an isolated absolute iron deficiency (AID) and 15.3% a functional iron deficiency (FID), while the rest had a combination of AID and FID. Anaemia was present in 66.1% of iron-deficient patients. Iron deficiency was significantly associated with an increased postoperative complication rate (univariable OR 1.94, p = 0.03, multivariable OR 1.84, p = 0.07), with right-sided tumours (p < 0.001), high ASA classification (p = 0.002), advanced tumour stage (p = 0.01) and advanced age (p = 0.04). In comparing clinical parameters between patients with AID and FID, advanced age was significantly associated with FID (p = 0.03), and the presence of anaemia with AID (p = 0.02).

Conclusion

In preoperative colorectal cancer patients, there is a high prevalence of iron deficiency, including a high percentage of patients with—a component of—functional iron deficiency, associated with the increased postoperative complication rate. As both types of iron deficiency require a different treatment strategy, our results illustrate the therapeutic potential of especially intravenous iron supplementation in patients with severe iron deficiency and stress the urgency of routinely monitoring preoperative iron status and differentiation between types of iron deficiency. As iron therapy may also be potentially harmful in respect to stimulation of tumour growth, future clinical trials assessing the long-term effect of iron therapy are necessary.

     

Comorbidities,repeated hospitalizations,and age ≥ 80 years as indicators of anemia development in the older population

Anemia represents a common condition among the elderly; however, its prevalence and causes are not well known. This retrospective analysis was performed on 981 patients aged ≥?60 in Poland over 2013–2014. The prevalence of anemia was 17.2% and increased with age. The predominant causes of anemia were the following: anemia of chronic disease (33.1%), unexplained anemia (28.4%), deficiency anemia (22.5%, including iron deficiency 13%), and chemo-/radiotherapy-induced anemia (8.9%). In the multivariate logistic regression model, factors increasing the risk of anemia were the following: age?≥?80 years (OR 2.29; 95%CI 1.19–4.42; P?=?0.013), the number of comorbidities (two diseases OR 2.85; 95%CI 1.12–7.30; P?=?0.029, three diseases OR 6.28; 95%CI 2.22–17.76; P?=?0.001, four diseases OR 4.64; 95%CI 1.27–17.01; P?=?0.021), and hospitalizations (OR 1.34; 95%CI 1.13–1.58; P?=?0.001). After a 2-year follow-up, the cumulative survival among patients without anemia in relation to the group with anemia was 90.76 vs. 78.08% (P?<?0.001). In the multivariate model, anemia (HR 3.33, 95%CI 1.43–7.74, P?=?0.005), heart failure (HR 2.94, 95%CI 1.33–6.50, P?=?0.008), and cancer (HR 3.31, 95%CI 1.47–7.49, P?<?0.004) were all significantly correlated with mortality. In patients ≥?60 years, the incidence of anemia increases with age, number of comorbidities, and frequency of hospitalizations and has an adverse impact on survival.     

Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia

The aim of the present study is to evaluate in an elderly hospitalized population the diagnostic value of the serum transferrin receptor (sTfR) in distinguishing IDA (iron deficiency anemia) from ACD (anemia of chronic disease) as compared to conventional laboratory tests of iron metabolism, especially serum ferritin. In a prospective study, 34 patients with IDA and 38 patients with ACD (a chronic disorder in 23 and an acute infection in 15) were evaluated using iron status tests including serum transferrin receptor assay. The iron stores were assessed by bone marrow examination. sTfR levels were elevated (>28.1 nmol/L) in 68% of the IDA patients but also in 43% of the patients with ACD-chronic inflammation and 33% with ACD-acute infection. Serum ferritin was the best test to differentiate IDA from ACD patients. We conclude that serum ferritin is a more sensitive and specific parameter than the sTfR assay to predict the bone marrow iron status in an elderly anemic population.     

Long-Term Outcomes and Prognostic Factors for Patients with Endoscopy-Negative Iron Deficiency

Background and Aim

Iron deficiency anemia (IDA) is a common problem among the elderly, and often no cause is identified after routine upper endoscopy and colonoscopy exams. The purpose of this study was to determine the long-term outcomes and predictors of gastrointestinal pathology and death in patients with endoscopy-negative IDA.

Methods

This was a retrospective review of consecutive endoscopy negative-IDA patients during 2002–2004 at the VA San Diego Healthcare System.

Results

Mean age was 69.3 years (range 42–93), and included 105 men and nine women. Mean length of follow-up was 65.1 months. IDA resolved in 56 patients. None of these patients developed evidence of any clinically significant gastrointestinal pathology. The remaining 58 patients had persistent anemia (n = 47) or recurrent anemia (n = 11). Only 2/47 patients with persistent anemia were found to have clinically significant but benign gastrointestinal pathology during follow-up. In contrast, 6/11 patients with recurrent anemia were subsequently found to have gastrointestinal pathology. Deaths during follow-up occurred in 7 (12.5 %) patients with resolved anemia, compared with 20 (34.5 %) patients with recurrent or persistent anemia (p = 0.006). Significant independent predictors of death included persistent or recurrent anemia, anti-platelet or anticoagulant use, and congestive heart failure.

Conclusions

Patients with iron deficiency anemia and negative upper endoscopy and colonoscopy often have a favorable outcome, especially if the anemia resolves with treatment. In patients with recurrent anemia a malignancy within reach of standard endoscopy and colonoscopy are possible, and repeating these procedures is warranted before consideration of further investigations.     

Anemia among Children Exposed to Polyparasitism in Coastal Kenya

Anemia represents a substantial problem for children living in areas with limited resources and significant parasite burden. We performed a cross-sectional study of 254 Kenyan preschool- and early school-age children in a setting endemic for multiple chronic parasitic infections to explore mechanisms of their anemia. Complete venous blood cell counts revealed a high prevalence of local childhood anemia (79%). Evaluating the potential links between low hemoglobin and socioeconomic factors, nutritional status, hemoglobinopathy, and/or parasite infection, we identified age < 9 years (odds ratio [OR]: 12.0, 95% confidence interval [CI]: 4.4, 33) and the presence of asymptomatic malaria infection (OR: 6.8, 95% CI: 2.1, 22) as the strongest independent correlates of having anemia. A total of 130/155 (84%) of anemic children with iron studies had evidence of iron-deficiency anemia (IDA), 16% had non-IDA; 50/52 of additionally tested anemic children met soluble transferrin-receptor (sTfR) criteria for combined anemia of inflammation (AI) with IDA. Children in the youngest age group had the greatest odds of iron deficiency (OR: 10.0, 95% CI: 3.9, 26). Although older children aged 9–11 years had less anemia, they had more detectable malaria, Schistosoma infection, hookworm, and proportionately more non-IDA. Anemia in this setting appears multifactorial such that chronic inflammation and iron deficiency need to be addressed together as part of integrated management of childhood anemia.     

Anemia in patients with ulcerative colitis in remission: A study from western India

Background

Anemia is common in patients with active ulcerative colitis. We aimed to study the anemia profile in patients with ulcerative colitis in clinical remission.

Methods

Sixty-four patients with ulcerative colitis and with a clinical Mayo score less than 3 for at least 3 months were evaluated for anemia. Initial screening was done by hemogram and only patients with anemia were evaluated further for the cause of anemia. We also screened a control population for anemia. Patients with mild anemia were given oral iron, moderate anemia were given intravenous iron and severe anemia were given blood transfusion.

Results

The mean hemoglobin in ulcerative colitis patients was 11.75 g/dL and in controls was 13.1 g/dL (p=0.011). The prevalence of anemia was 53.1% in the ulcerative colitis patients and 13.3% in the controls (p=<0.001). 58.8% had mild anemia, 29.4% had moderate anemia and 8.8% had severe anemia. Iron deficiency was the most common cause of anemia (70.5%) followed by anemia of chronic disease combined with iron deficiency in 23.5%. Ferritin levels did not correlate with hemoglobin levels. Oral iron increased the hemoglobin by 1.4 g/dL and intravenous iron by 2.2 g/dL at 1 month.

Conclusion

Anemia was seen in more than half of patients with ulcerative colitis in clinical remission, iron deficiency being the most common cause.

     

The clinical value of magnetic resonance defecography in males with obstructed defecation syndrome

Background

The aim of the present study was to assess the relationship between symptoms of obstructed defecation and findings on magnetic resonance (MR) defecography in males with obstructed defecation syndrome (ODS).

Methods

Thirty-six males with ODS who underwent MR defecography at our institution between March 2013 and February 2016 were asked in a telephone interview about their symptoms and subsequent treatment, either medical or surgical. Patients were divided into 2 groups, one with anismus (Group 1) and one with prolapse without anismus (Group 2). The interaction between ODS type and symptoms with MR findings was assessed by multivariate analysis for categorical data using a hierarchical log-linear model. MR imaging findings included lateral and/or posterior rectocele, rectal prolapse, intussusception, ballooning of levator hiatus with impingement of pelvic organs and dyskinetic puborectalis muscle.

Results

There were 21 males with ODS due to anismus (Group 1) and 15 with ODS due to rectal prolapse/intussusception (Group 2). Mean age of the entire group was 53.6 ± 4.1 years (range 18–77 years). Patients in Group 1 were slightly older than those in Group 2 (age peak, sixth decade in 47.6 vs 20.0%, p < 0.05). Symptoms most frequently associated with Group 1 patients included small volume and hard feces (85.0%, p < 0.01), excessive strain at stool (81.0%, p < 0.05), tenesmus and fecaloma formation (57.1 and 42.9%, p < 0.05); symptoms most frequently associated with Group 2 patients included mucous discharge, rectal bleeding and pain (86.7%, p < 0.05), prolonged toilet time (73.3%, p < 0.05), fragmented evacuation with or without digitation (66.7%, p < 0.005). Voiding outflow obstruction was more frequent in Group 1 (19.0 vs 13.3%; p < 0.05), while non-bacterial prostatitis and sexual dysfunction prevailed in Group 2 (26.7 and 46.7%, p < 0.05). At MR defecography, two major categories of findings were detected: a dyskinetic pattern (Type 1), seen in all Group 1 patients, which was characterized by non-relaxing puborectalis muscle, sand-glass configuration of the anorectum, poor emptying rate, limited pelvic floor descent and final residue ≥ 2/3; and a prolapsing pattern (Type 2), seen in all Group 2 patients, which was characterized by rectal prolapse/intussusception, ballooning of the levator hiatus with impingement of the rectal floor and prostatic base, excessive pelvic floor descent and residue ≤ 1/2. Posterolateral outpouching defined as perineal hernia was present in 28.6% of patients in Group 1 and were absent in Group 2. The average levator plate angle on straining differed significantly in the two patterns (21.3° ± 4.1 in Group 1 vs 65.6° ± 8.1 in Group 2; p < 0.05). Responses to the phone interview were obtained from 31 patients (18 of Group 1 and 13 of Group 2, response rate, 86.1%). Patients of Group 1 were always treated without surgery (i.e., biofeedback, dietary regimen, laxatives and/or enemas) which resulted in symptomatic improvement in 12/18 cases (66.6%). Of the patients in Group 2, 2/13 (15.3) underwent surgical repair, consisting of stapled transanal rectal resection (STARR) which resulted in symptom recurrence after 6 months and laparoscopic ventral rectopexy which resulted in symptom improvement. The other 11 patients of Group 2 were treated without surgery with symptoms improvement in 3 (27.3%).

Conclusions

The appearance of various abnormalities at MR defecography in men with ODS shows 2 distinct patterns which may have potential relevance for treatment planning, whether conservative or surgical.

     

贫血患者血清转铁蛋白受体测定的临床意义

采用Ｄｏｔ－ＥＬＩＳＡ法定量测定了６８例不同贫血患者的血清转铁蛋白受体（ｓＴＩＲ）水平,发现缺铁性贫血,溶血性贫血和急性失血性贫血患者ｓＴＩＲ均显高于正常人（Ｐ〈０．００１）,而慢性再生障碍性贫血患者ｓＴｆＲ显著低于正常人（Ｐ〈０．００１）,缺铁性贫血ｓＴｆＲ水平与血清铁蛋白水平呈负相关（Ｐ〈０．００５）,溶血性贫血ｓＴｆＲ与网织红细胞计数呈正相关（Ｐ〈０．００５）,ｓＴｆＲ可以反映机体贮存铁和骨     

Ferric carboxymaltose reduces transfusions and hospital stay in patients with colon cancer and anemia

Purpose

The purpose of the study was to evaluate the efficacy of preoperative intravenous (IV) ferric carboxymaltose (FCM) administration vs. no-IV iron in colon cancer (CC) anemic patients undergoing elective surgery with curative intention.

Methods

This was a multicenter, observational study including two cohorts of consecutive CC anemic patients: the no-IV iron treatment group was obtained retrospectively while FCM-treated patients were recorded prospectively.

Results

A total of 266 patients were included: 111 received FCM (median dose 1000 mg) and 155 were no-IV iron subjects. Both groups were similar in terms of demographic characteristics, tumor location, surgical approach, and intra-operative bleeding severity. The FCM group showed a significant lower need for red blood cell (RBC) transfusion during the study (9.9 vs. 38.7 %; OR: 5.9, p?<?0.001). In spite of lower hemoglobin levels at baseline diagnosis and lower transfusion rates in the FCM group, the proportion of responders was significantly higher with respect to the no-IV group both at hospital admission (48.1 vs. 20.0 %, p?<?0.0001) and at 30 days post-surgery (80.0 vs. 48.9 %, p?<?0.0001). The percentage of patients with normalized hemoglobin levels was also higher in the FCM group (40.0 vs. 26.7 % at 30 days, p?<?0.05). A lower number of reinterventions and post-surgery complications were seen in the FCM group (20.7 vs. 26.5 %; p?=?0.311). The FCM group presented a significant shorter hospital stay (8.4?±?6.8 vs. 10.9?±?12.4 days to discharge; p?<?0.001).

Conclusions

Preoperative ferric carboxymaltose treatment in patients with CC and iron deficiency anemia significantly reduced RBC transfusion requirements and hospital length of stay, reaching higher response rates and percentages of normalized hemoglobin levels both at hospital admission and 30 days post-surgery.

     

Combined cobalamin and iron deficiency anemia: a diagnostic approach using a model based on age and homocysteine assessment

Macrocytosis, the hallmark of cobalamin/folate deficiency anemia, is frequently absent. Clinicians have to be aware of coexisting conditions that can mask the macrocytosis expression of megaloblastic anemia, especially iron deficiency. The objective of this work was to investigate the degree of overlap between iron deficiency anemia (IDA) and cobalamin deficiency and to develop a predictive model for differentiating IDA from combined deficiency. A prospective case and control study was carried out to investigate vitamin B₁₂ and folate status in iron deficiency anemia. A total of 658 patients were recruited, 41 of whom (6.2 %) were excluded. The remaining 617 subjects consisted of 130 controls and 487 with IDA. Low vitamin B₁₂ (LB12) was considered when serum vitamin B₁₂ was ≤200 pmol/L. High serum homocysteine (Hcy) was defined by Hcy >17 μM/L. A multivariate analysis (including a logistic regression) was performed to develop a diagnostic model. Low vitamin B₁₂ levels were found in 17.8 % of IDA subjects. Ten out of 11 subjects (91 %) with IDA and serum vitamin B₁₂ (B12) ≤100 pmol/L showed vitamin B₁₂ deficiency. Moreover, vitamin B₁₂ deficiency was demonstrated in 48 % of cases with IDA and B12 between 101 and 150 pmol/L and in 40 % with IDA and B12 between 151 and 200 pmol/, respectively. As a result of multivariate logistic analysis, neutrophil counts and age predicted subjects with vitamin B₁₂ ≤200 and Hcy >17 μmol/L, $ y=1/1+{e^{{-\left( {-5.45 + 0.057\,\mathrm{age} - 0.187\ \mathrm{neutrophils}} \right)}}} $ . Using the age of 60 as a cutoff, sensitivity was 91 % (39 out of the 43 patients with vitamin B₁₂ deficiency and IDA were identified). In summary, low vitamin B₁₂ was found in 18 % of patients with IDA. Vitamin B₁₂ deficiency was demonstrated in many patients with LB12 and IDA. Age over 60 years was used to separate patients with combined deficiency (sensitivity 91 %). Therefore, for a diagnostic purpose, serum vitamin B₁₂ should be evaluated in IDA patients over 60 years. This diagnostic model needs to be validated in a different population.     

Serum hepcidin levels,iron status,and HFE gene alterations during the first year of life in healthy Spanish infants

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7?±?1.5 to 52.0?±?1.5 ng/mL; p?<?0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8?±?1.5 vs 37.9?±?1.3 ng/mL, p?<?0.018, and 54.3?±?1.5 vs 44.0?±?1.4 ng/mL, p?<?0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p?=?0.046 and p?=?0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.     

Prevalence and Predictive Factors for Gastrointestinal Pathology in Young Men Evaluated for Iron Deficiency Anemia

Background

The prevalence of gastrointestinal lesions in young men with iron deficiency anemia (IDA) is unknown, and there are no evidence-based recommendations for the evaluation of the gastrointestinal tract in this population.

Aims

The purpose of this study was to assess the prevalence of significant GI lesions among young males with IDA, and to shed light on potential predictors of their presence.

Methods

Clinical, endoscopic, and histological data was retrospectively collected from medical records of 347 young males with IDA.

Results

Clinically significant GI lesions were diagnosed in 62 %. Upper GI lesions were found in 35 %. Peptic disease was the most common finding, diagnosed in 30 %. Celiac disease was diagnosed in 4 %. Lower GI tract lesions were diagnosed in 34 %. The most common findings were hemorrhoids (17 %) and inflammatory bowel disease (16 %). Malignant lesions were not detected. GI lesions were encountered more frequently when respective symptoms were obtained. Multivariate analysis showed that the presence of GI symptoms and the use of proton pump inhibitors were associated with an increased likelihood of significant GI lesions.

Conclusions

GI lesions are common among young men with IDA. GI evaluation is mandatory in symptomatic men and in asymptomatic men when the anemia is resistant to iron therapy. Symptoms may dictate the order of evaluation.     

Usefulness of Reticulocyte Parameters for Diagnosis of Hereditary Spherocytosis in Children

Innovations in laboratory equipment have enabled a widening of the spectrum of hematological parameters obtained from single measurements of peripheral blood samples, including reticulocyte parameters. The usefulness of reticulocytes indices to confirm the diagnosis of pediatric anemia was analyzed in this study. The study group consisted of 163 children, aged 1 month–17 years, with anemia. Complete blood count extended with an analysis of reticulocyte parameters were measured using a Beckman Coulter LH 750. The mean sphered corpuscular volume (MSCV) in the group of children with hereditary spherocytosis (HS) was 66.71 ± 8.45 fL, whereas in other anemic patients MSCV was 87.76 ± 11.22 fL, p < 0.0001. In HS children the average mean corpuscular volume of red blood cells was higher than the MSCV value, while an inverse correlation was observed in the group of children with other anemias, p < 0.0001. A significant difference was found between the ratio of absolute reticulocyte count and IRF fraction (Ret#/IRF)—0.6 ± 0.28 in the HS group and 0.23 ± 0.16 in the non-HS group, respectively. Our results suggest that analysis of reticulocyte parameters is useful in the diagnosis of anemia and should be included in the routine CBC analysis in anemic children.     

Prevalence of celiac disease in nutritional anemia at a tertiary care center

Background

While anemia occurs in 80 % to 90 % of patients with celiac disease (CD), it may be the sole manifestation of CD. The prevalence of CD in Indian patients with nutritional anemia is not known.

Patients and Methods

Adolescent and adult patients presenting with nutritional anemia were prospectively screened for CD using IgA anti-tissue transglutaminase antibody (anti-tTG Ab) followed, if positive, by upper gastrointestinal endoscopy and duodenal biopsy.

Results

Ninety-six patients [mean?±?SD age 32.1?±?13.1 years and median duration of anemia 11 months (range 1 to 144 months)] were screened. Of these patients, 80 had iron deficiency anemia, 11 had megaloblastic anemia, and 5 had dimorphic anemia. Seventy-three patients were on hematinics and 36.4 % had received blood transfusions. Nineteen had a history of chronic diarrhea and the mean?±?SD duration of diarrhea in them was 9.7?±?35.8 months. IgA anti-tTG Ab was positive in 13 patients, of whom 12 agreed to undergo duodenal biopsy. Ten patients had villous atrophy (Marsh grade 3a in three, 3b in one, and 3c in six) and two did not. Thus, 10 patients with nutritional anemia (iron deficiency 9, vitamin B₁₂ deficiency 1) were diagnosed to have CD. On multivariate logistic regression, age, duration of symptoms, and presence of diarrhea were found to be the predictors of CD. All the patients with CD were put on gluten-free diet and with iron and vitamin supplementations and showed a significant improvement in hemoglobin concentration.

Conclusions

CD screening should be included in the work up of otherwise unexplained nutritional anemia.     

Serumhepcidin bei Eisenmangelanämie und Anämie chronischer Erkrankungen im geriatrischen Kollektiv

Background

Iron deficiency anemia (IDA) and anemia of chronic diseases (ACD) are common in the geriatric population. However, differentiation between IDA and ACD is still problematic. Hepcidin is a key regulator of iron homeostasis: downregulation in the presence of iron deficiency allows enteral iron resorption, while upregulation in case of chronic inflammation blocks it. We aimed at studying whether serum hepcidin levels might serve as diagnostic parameter to differentiate between IDA and ACD among elderly.

Patients and methods

A total of 37 patients (age 69–97 years) were divided into 4 groups: group I (IDA), group II (ACD), group III (controls), and group IV (IDA/ACD). Serum hepcidin levels were analyzed using a commercially available ELISA kit (DRG Instruments, Marburg, Germany). Differences in hepcidin levels were tested with nonparametric methods.

Results

We could show a strong positive correlation between serum hepcidin and ferritin (Spearman rho 0.747) and a statistic significant difference of hepcidin levels among all groups (p?=?0.034). Hepcidin levels between ACD and controls differed significantly (p?=?0.003).

Conclusion

Despite the small number of patients included in this study, which reduces the strength of the study’s evidence, results conform with the current literature: it can be assumed that hepcidin will be used as a diagnostic parameter to differentiate between IDA and ACD in the future. However, more studies with larger patient groups are urgently needed to answer this question.     

Serum transferrin receptors: Distribution and diagnostic performance in pre-school children

Soluble transferrin receptors have gained interest in the field of diagnosing anemias. Reference ranges differ according to the method used for the quantification of sTfR. We aim to explore the distributional properties and diagnostic performance of sTfR in pre-school healthy children as well as in children with β-thalassemia carriers, iron deficiency with normal hematological phenotype (ID) and iron deficiency anemia (IDA). Circulating sTfR as well as biochemical and hematological indices were determined in 521 pre-school children and four groups (normal children, β-thalassemia traits, ID and IDA) were formed. Diagnostic performance and distribution of sTfR according to age and in relation to several parameters were evaluated in every group. Three hundred eighty one children (261 normal, 60 β-thalassemia traits, 44 ID and 16 IDA) aged 1–6 years were included. We found that distribution of sTfR differed significantly among the four groups (Kruskal Wallis p < 0.001) with children in the normal group exhibiting lower concentrations compared to all other. A negative correlation between sTfR and age occurred in the normal (β = − 0.12, p < 0.001) and the ID groups (β = − 0.13, p = 0.035). In the β-thal and IDA groups sTfR is correlated to HbA₂ (β = 0.34, p = 0.001) and ferritin (Spearman's rho = − 0.6, p = 0.014) respectively. An area under the curve equal to 0.63 was achieved by sTfR in distinguishing between normal and ID children. Sensitivity and specificity were 70.5% and 50% respectively at a cut-off of 2.5 mg/l. Levels of sTfR are negatively correlated to age in pre-school children while dyserythropoietic procedures like β-thal, ID, and IDA significantly affect them. These findings indicated that the accuracy of sTfR in diagnosing ID from normal children is limited. Standardization will allow the use of formulas that combine sTfR and ferritin which are of greater diagnostic value than sTfR alone.     

Progression of liver fibrosis can be controlled by adequate chelation in transfusion-dependent thalassemia (TDT)

A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection has been implicated in the development of liver fibrosis. Hepatic siderosis and fibrosis were assessed in 99 transfusion-dependent thalassemia (TDT) patients using transient elastography (TE) and liver iron concentration (LIC) assessed by T2*MRI at baseline and after 4 years. Data were analyzed retrospectively. At baseline, the overall mean liver stiffness measurement (LSM) was 7.4 ± 3.2 kPa and the mean LIC was 4.81 ± 3.82 mg/g dw (n = 99). Data available at 4 ± 1.5 years showed a significant reduction in LSM (6.6 ± 3.2 kPa, p 0.017) and hepatic siderosis measured by LIC (3.65 ± 3.45 mg/g dw, p 0.001). This result was confirmed when considering patients with iron overload at the time of the first measurement (n = 41) and subjects treated with a stable dose of deferasirox over the entire period of observation (n = 39). A reduction of LSM, yet not statistically significant, was achieved in patients on combined deferoxamine + deferiprone, while the group on deferoxamine (n = 11) remained stable over time. HCV-RNA positivity was found in 33 patients at T0, 20 of which were treated during the observation period. Patients who underwent anti-HCV therapy showed a more evident reduction in LSM (9 ± 3 vs 7 ± 3.1 kPa, p 0.016). Adequate chelation therapy is mandatory in order to prevent liver disease progression in TDT. Patients could benefit from regular non-invasive assessment of liver fibrosis by TE to indirectly monitor treatment adequacy and therapeutic compliance.