Low Transferrin Saturation Research Articles

Clinical and biochemical profile of iron deficiency state in preanemic under 5 children in a tertiary care hospital

Background: Anemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. The aim was to identify iron deficiency state early before developing anemia and to analyze the clinical finding with iron deficiency state. Methods: Cross sectional study was done at Vydehi Institute of Medical Sciences and Research Centre, Bangalore, India. 100 children between 6 month to 5 years of age with normal haemoglobin were studied for iron deficiency state. After taking informed consent a detailed history and clinical examination was taken. In those children with normal Hb, investigations like serum ferritin, serum iron and transferrin saturation were done to diagnose the iron deficiency state.Results: Out of 100 children in the study, mean hemoglobin was 11.8 gm/dl, the mean serum ferritin level was 59.1ng/ml and transferrin saturation was 18.77%. The overall prevalence of iron deficiency in this study based on low serum ferritin was 16% and low transferrin saturation was 51%. 7 children has low DQ out of which 3 were ADHD, 2 had hyperactivity and 2 with learning problem. Among them one child has low ferritin and 5 had low transferrin saturation.Conclusions: Iron deficiency is an important public health problem. The findings in this study are consistent compared to other studies. Therefore, prompt screening for iron deficiency, even in non-anemic under five children in developing countries should be encouraged. If evaluation of iron status is done only by Hb early signs of iron depletion can go undetected. By monitoring the status of storage iron(ferritin), we can detect iron deficiency state earlier and initiate appropriate treatment to prevent IDA.

Hemoglobin Kirklareli (α H58L), a New Variant Associated with Iron Deficiency and Increased CO Binding

Mutations in hemoglobin can cause a wide range of phenotypic outcomes, including anemia due to protein instability and red cell lysis. Uncovering the biochemical basis for these phenotypes can provide new insights into hemoglobin structure and function as well as identify new therapeutic opportunities. We report here a new hemoglobin α chain variant in a female patient with mild anemia, whose father also carries the trait and is from the Turkish city of Kirklareli. Both the patient and her father had a His-58(E7) → Leu mutation in α1. Surprisingly, the patient's father is not anemic, but he is a smoker with high levels of HbCO (∼16%). To understand these phenotypes, we examined recombinant human Hb (rHb) Kirklareli containing the α H58L replacement. Mutant α subunits containing Leu-58(E7) autoxidize ∼8 times and lose hemin ∼200 times more rapidly than native α subunits, causing the oxygenated form of rHb Kirklareli to denature very rapidly under physiological conditions. The crystal structure of rHb Kirklareli shows that the α H58L replacement creates a completely apolar active site, which prevents electrostatic stabilization of bound O2, promotes autoxidation, and enhances hemin dissociation by inhibiting water coordination to the Fe(III) atom. At the same time, the mutant α subunit has an ∼80,000-fold higher affinity for CO than O2, causing it to rapidly take up and retain carbon monoxide, which prevents denaturation both in vitro and in vivo and explains the phenotypic differences between the father, who is a smoker, and his daughter.

Childhood Onset Hypoceruloplasminemia Presenting as Early-Onset rebellar Ataxia

The syndrome of hypoceruloplasminemia is a rare autosomal recessive disorder presenting mainly with neurogegeneration, retinal degeneration, and diabetes mellitus. The syndrome, to the best of our knowledge, is not yet recognized in pediatric age group. We screened cases presenting with unexplained cerebellar ataxia and anemia using serum ceruloplasmin, transferrin saturation, and ferritin as biomarkers for hypoceruloplasminemia. An age and sex matched control group was included. Thirty cases (age range 4–17 years) (18 male and 12 female) have been included. The results showed a statistically significant low serum ceruloplasmin and transferrin saturation (18.9±12.1mg/dl and 10.1±5.1%, respectively), and high serum ferritin (124.7±65.7 ng/ml) compared to control group. Four cases have retinal degeneration. The detection of low serum ceruloplasmin concentration and transferrin saturation with high serum ferritin in patients with unexplained cerebellar ataxia is highly suspicious of hypocerluplasminemia which should be subjected for further molecular study.

Anemia and Iron Deficiency in Children With Potential Celiac Disease.

Active screening for celiac disease frequently detects seropositive children with normal villous morphology (potential celiac disease). It remains unclear whether these subjects should be treated. We here investigated the prevalence of anemia and iron deficiency in children with potential and mucosal atrophy celiac disease. The prospective study involved 19 children with potential disease, 67 with partial or subtotal villous atrophy (P/SVA), and 16 with total villous atrophy (TVA). Twenty-three healthy children comprised the control group. The groups were compared for various clinical, histological, and laboratory parameters and hepcidin. The prevalence of abnormal parameters was as follows (controls, potential celiac disease, P/SVA, and TVA, respectively): anemia 0%, 15%, 22%, and 63%; low iron 5%, 0%, 14%, and 50%; increased transferrin receptor 1 5%, 16%, 20%, and 47%; low ferritin 0%, 21%, 35%, and 87%; and low transferrin saturation 10%, 11%, 41%, and 71%. One subject had low folate and none had low vitamin B12. The median values for hemoglobin, total iron, ferritin, and transferrin saturation were significantly lower and transferrin receptor 1 values higher in TVA group compared with other groups. After a median of 7 months on a gluten-free diet hemoglobin, total iron, ferritin, and albumin in children with P/SVA exceeded the baseline values in the potential celiac disease group. The development of anemia and iron deficiency in celiac disease is a continuum and may already be present in children with normal villous morphology, advocating an early diagnosis and possible dietary treatment of these patients.

Association of Erythropoietin Resistance with Fatigue in Hemodialysis Patients: A Cross-Sectional Study

Background/Aims: Fatigue is a common symptom in patients receiving hemodialysis (HD) and is generally associated with anemia. However, it can be difficult to resolve, even when anemia has been treated using erythropoiesis-stimulating agents and iron replacement therapy. In the present study, we examined the associations of anemia, the erythropoietin resistance index (ERI) and iron deficiency with fatigue during HD. Methods: In this cross-sectional study, fatigue score was calculated on the basis of questionnaire responses in HD patients. Participants were divided into 3 groups according to their hemoglobin (Hb) levels (low, normal and high). Iron deficiency was assessed as a transferrin saturation (TSAT) of <20%. Results: We included 571 HD patients (men/women 368/203; mean age 62.2 ± 10.8 years). Among the 3 groups, fatigue scores increased significantly with decreasing Hb levels. HD patients with low Hb levels (<90 g/l) had significantly higher fatigue scores than those with higher Hb levels (≥120 g/l). In the multiple regression analysis, we showed that a high ERI (β = 0.208) and a low TSAT (β = -0.155), but not the Hb level, were significantly associated with increased fatigue score. Moreover, this was independent of age, gender and modifiable confounders linked to anemia. Even after restricting patients to those without iron deficiency (TSAT ≥20%), the ERI (β = 0.258) retained a significant and independent association with the fatigue score. Conclusion: Iron deficiency and a high ERI despite iron sufficiency may cause fatigue in HD patients.

Iron Parameters Determine the Prognosis of Critically Ill Patients.

Because iron is both an essential and toxic micronutrient influencing the development of microbial infections, we evaluated the usefulness of iron parameters as outcome predictors in ICU patients. Prospective clinical single-center non-interventional study. General internal medicine ICU; German University hospital. One hundred and twelve septic and 43 nonseptic ICU patients, 156 healthy blood donors. Serum iron parameters at admission were correlated with short and long term mortality in ICU subjects. Both hepcidin and ferritin concentrations were significantly elevated in ICU patients compared with blood donors and were the highest in septic patients. On the contrary, serum iron and transferrin levels were decreased in ICU subjects with lowest values among septic patients. Hepcidin values correlated with ferritin levels, and serum iron correlated strongly with transferrin saturation. A moderate correlation of hepcidin, ferritin, and transferrin with inflammatory parameters was noted. Both short- and long-term survivors displayed higher ferritin/transferrin levels and lower transferrin saturation. In Kaplan-Meier analyses, low iron levels (cutoff 10.5 μmol/mL), low transferrin saturation (cutoff 55%), and high serum transferrin concentrations (cutoff 1.6 g/L) were associated with short- and long-term survival. In the subgroup of septic ICU subjects, low iron levels and transferrin saturation went along with a nonlethal outcome. Our findings demonstrate that parameters of iron metabolism, particularly transferrin saturation, that reflect serum iron availability, are strong outcome predictors in ICU patients. These data suggest that a failure of iron homeostasis with increased iron availability in serum occurs in lethally ill ICU patients and should trigger prospective clinical trials evaluating the usefulness of iron-chelating therapy in critical illness and sepsis.

Prevalence and spectrum of iron deficiency in heart failure patients in south Rajasthan

ObjectiveTo estimate the prevalence and pattern of iron deficiency (ID) in heart failure (HF) patients with or without anemia. MethodsThis is a single-center observational study, conducted at a tertiary care hospital of south Rajasthan. Patients admitted to hospital with clinical diagnosis of HF based on validated clinical criteria were included in the study. ID was diagnosed based on complete Iron profile, including serum iron, serum ferritin, total iron binding capacity, and transferrin saturation (TSAT). Anemia was defined as hemoglobin (Hb) <13g/dl for males and <12g/dl for females, based on World Health Organization definition. Absolute ID was taken as serum ferritin<100μg/L and functional ID was defined as normal serum ferritin (100–300μg/L) with low TSAT (<20%). ResultsA total of 150 patients of HF (68% males and 32% females) were studied. Most of the patients were of high-functional NYHA class (mean NYHA 2.89±0.95). ID was present in 76% patients with 48.7% patients having absolute and 27.3% patients having functional ID. Females were having significantly higher prevalence of ID than males (91.6% vs 68.6%; p=0.002). Nearly one-fourth of the patients were having ID but without anemia, signifying importance of workup of ID other than Hb. ConclusionOur study highlights the yet underestimated and neglected burden of ID in HF patients in India. This study suggests further large-scale studies to better characterize this easily treatable condition and considering routine testing in future Indian guidelines.

Comparative Effectiveness of Iron and Erythropoiesis-Stimulating Agent Dosing on Health-Related Quality of Life in Patients Receiving Hemodialysis

The potential effects of iron-dosing strategies and erythropoiesis-stimulating agents (ESAs) on health-related quality of life (HRQoL) in the dialysis population are unclear. We examined the independent associations of bolus versus maintenance iron dosing and high versus low ESA dosing on HRQoL. Retrospective cohort design. Clinical data (2008-2010) from a large dialysis organization merged with data from the US Renal Data System. 13,039 patients receiving center-based hemodialysis were included. Iron and ESA dosing were assessed during 1-month (n=14,901) and 2-week (n=15,296) exposure periods. HRQoL was measured by the Kidney Disease Quality of Life (KDQOL) instrument (0-100 scale) during a 3-month follow-up period. Generalized linear mixed models, adjusting for several covariates, were used to estimate associations between iron and ESA dosing and HRQoL overall and for clinically relevant subgroups. For the 1-month exposure period, patients with lower baseline hemoglobin levels who received higher ESA dosing had higher physical health and kidney disease symptom scores (by 2.4 [95% CI, 0.6-4.2] and 5.6 [95% CI, 2.8-8.4] points, respectively) in follow-up than patients who received lower ESA dosing. For the 2-week exposure period, patients with low baseline hemoglobin levels who received bolus dosing had higher mental health scores (by 1.9 [95% CI, 0.0-3.8] points) in follow-up. Within the low-baseline-hemoglobin subgroup, individuals with a catheter or dialysis vintage less than 1 year who received higher ESA dosing had higher HRQoL scores in follow-up (by 5.0-9.9 points) and individuals with low baseline transferrin saturations who received bolus dosing had higher HRQoL scores in follow-up (by 2.6-5.8 points). Observational design; short duration of observation. For individuals with low baseline hemoglobin levels, higher ESA dosing and bolus iron dosing were associated with slightly higher HRQoL scores in follow-up. These differences became more pronounced and clinically relevant for specific subgroups.

Fibroblast growth factor is associated to left ventricular mass index, anemia and low values of transferrin saturation

BackgroundFibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy (LVH) is a potent risk factor for mortality in CKD, and FGFs have been implicated in the pathogenesis of myocardial hypertrophy. In addition, the effect of anemia on CV disease and LVH is well known in CKD. A relation between iron and FGF-23 metabolism is mentioned in a few studies. The aim of this study was to test the association of FGF-23 levels with echocardiographic (ECHO) and iron parameters in peritoneal dialysis patients (PD). MethodsIn this cross-sectional study, 61 subjects with PD (29 women and 32 men, mean age: 46.9±13.3 years, mean PD vintage: 69.5±39 months) underwent echocardiograms to assess left ventricular mass index (LVMI). Medical treatments and average values of the basic laboratory results of the last 6 months for all patients were recorded. Serum FGF-23 concentrations were measured using intact FGF-23 (iFGF-23) human enzyme-linked immunosorbent assay (ELİSA) kit. According to the median levels of serum FGF-23 the patients were grouped into two (FGF-23 high and low groups). ResultsSignificant positive correlation was recorded between serum FGF-23 levels and LVMI (P=0.023). There was also significant difference in terms of hemoglobin (12.1±2 versus 11.0±2, P=0.017), transferrin saturation (TSAT) (24.9±16.8 versus 19.5±10.8, P=0.042) between low and high FGF-23 group. Also in linear regression analysis the negative relation between FGF-23 and hemoglobin is persisted (r=0.199, P=0.045). ConclusionsFGF-23 is associated with LVMI, anemia and low TSAT in patients with PD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy and anemia in patients with end-stage renal disease (ESRD) requires further study.

Fibroblast growth factor is associated to left ventricular mass index, anemia and low values of transferrin saturation

BackgroundFibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy (LVH) is a potent risk factor for mortality in CKD, and FGFs have been implicated in the pathogenesis of myocardial hypertrophy. In addition, the effect of anemia on CV disease and LVH is well known in CKD. A relation between iron and FGF-23 metabolism is mentioned in a few studies. The aim of this study was to test the association of FGF-23 levels with echocardiographic (ECHO) and iron parameters in peritoneal dialysis patients (PD). MethodsIn this cross-sectional study, 61 subjects with PD (29 women and 32 men, mean age: 46.9±13.3 years, mean PD vintage: 69.5±39 months) underwent echocardiograms to assess left ventricular mass index (LVMI). Medical treatments and average values of the basic laboratory results of the last 6 months for all patients were recorded. Serum FGF-23 concentrations were measured using intact FGF-23 (iFGF-23) human enzyme-linked immunosorbent assay (ELİSA) kit. According to the median levels of serum FGF-23 the patients were grouped into two (FGF-23 high and low groups). ResultsSignificant positive correlation was recorded between serum FGF-23 levels and LVMI (P=0.023). There was also significant difference in terms of hemoglobin (12.1±2 versus 11.0±2, P=0.017), transferrin saturation (TSAT) (24.9±16.8 versus 19.5±10.8, P=0.042) between low and high FGF-23 group. Also in linear regression analysis the negative relation between FGF-23 and hemoglobin is persisted (r=0.199, P=0.045). ConclusionsFGF-23 is associated with LVMI, anemia and low TSAT in patients with PD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy and anemia in patients with end-stage renal disease (ESRD) requires further study.

Conflicting effects of BMI and waist circumference on iron status

The association between obesity and iron status has a long history and is still receiving attention. However comparative analysis of the association between general obesity (BMI) and visceral obesity (waist circumference) with iron status has not been extensively researched. The aim of the present study is thus to determine if body mass index and waist circumference have the same correlation with iron status. One thousand one hundred and thirty people (225 men and 905 women) aged 30 years and above participated in this study. Anthropometric parameters, haemoglobin, iron and total iron binding capacity concentrations were measured using standard methods. Percentage transferrin saturation was calculated and ferritin concentrations were measured using an enzyme linked immunosorbent assay. Obese or overweight women had significantly lower iron and transferrin saturation concentration when compared to non-obese women. In contrast, women with high waist circumference had comparable plasma iron and transferrin saturation to women with normal waist circumference. Partial correlation analysis and linear regression analysis showed that BMI is negatively and significantly associated with plasma iron, transferrin saturation, Hb and ferritin concentration, whilst waist circumference is positively but insignificantly associated with plasma iron, transferrin saturation, Hb and ferritin concentration. Binary regression analysis showed that obese or overweight people are more likely to have iron deficiency, whilst those with raised waist circumference are more likely to have iron overload. Multivariate analysis showed that body mass index is negatively and significantly associated with low iron status, while waist circumference is positively and insignificantly associated with iron status. This is supported by a comparison of plasma iron, transferrin saturation and ferritin concentrations in participants with high body mass index and normal waist circumference and participants with normal body mass index and high waist circumference to those participants having normal body mass index and normal waist circumference. The present study suggests that in women body mass index is associated with low plasma iron, transferrin saturation and ferritin concentrations, while waist circumference is associated with high plasma iron, transferrin saturation and ferritin concentrations.

Functional and clinical implications of ferroportin mutation p.Arg178Gln

Ferroportin disease is an autosomal dominant iron storage condition with different phenotypic expression, where a clear genotype to phenotype correlation has been reported for selected mutations. Ferroportin disease is primarily caused by private mutations in the gene SLC40A1, which encodes an iron export protein. Genetic defects can cause a loss of iron export function which is typically associated with low transferrin saturation and hepatolienal siderosis. In contrast a gain of function is usually associated with high transferrin saturation and hepatic siderosis, where the spleen is unaffected. Liver disease has been described primarily in the latter group of patients. The toxic effect of stored iron in patients with loss of function mutations is apparently mild.

Iron deficiency anemia in women: a practical guide to detection, diagnosis, and treatment.

Iron deficiency anemia (IDA) remains a widely underdiagnosed and unappreciated women's health issue, affecting women of all ages. Despite the fact that IDA is easily diagnosed and treated, it continues to be a major public health issue. The World Health Organization estimates that 30% of nonpregnant and more than 42% of pregnant women have anemia. A multidisciplinary Group for the Research and Education on Anemia Therapy in Women (GREAT Women II) was formed, sponsored by the Society for the Advancement of Blood Management. The goal was to focus attention on the impact of IDA on women at various stages of life and evaluate and use published literature to provide a simple, evidence-based approach to diagnose and treat IDA. The group developed specific recommendations for evaluating and treating IDA in women. Initial diagnosis is defined as hemoglobin less than 12 g/dL in nonpregnant women. A trial of iron therapy (4 weeks) can be considered a first-line diagnostic tool. Alternatively, a low or normal mean corpuscular volume (<100 fL), low serum ferritin (<30 μg/L), and/or low transferrin saturation (transferrin saturation <20%) is sufficient to confirm IDA. If the patient does not fit the diagnosis of IDA or fails to respond to a trial of oral iron, or mean corpuscular volume is elevated, further diagnostic evaluation is needed, including iron studies, B12, folate levels, and renal function tests. If results are not definitive, and IDA persists, a hematology referral is recommended. Clinicians should routinely identify and treat IDA, thereby decreasing its negative impact on health and quality of life of women.

Iron-refractory iron deficiency anemia.

Iron is essential for life because it is indispensable for several biological reactions, such as oxygen transport, DNA synthesis, and cell proliferation. Over the past few years, our understanding of iron metabolism and its regulation has changed dramatically. New disorders of iron metabolism have emerged, and the role of iron as a cofactor in other disorders has begun to be recognized. The study of genetic conditions such as hemochromatosis and iron-refractory iron deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis. In the future, these advances may be exploited to improve treatment of both genetic and acquired iron disorders. IRIDA is caused by mutations in TMPRSS6, the gene encoding matriptase-2, which downregulates hepcidin expression under conditions of iron deficiency. The typical features of this disorder are hypochromic, microcytic anemia with a very low mean corpuscular volume of erythrocytes, low transferrin saturation, no (or inadequate) response to oral iron, and only a partial response to parenteral iron. In contrast to classic iron deficiency anemia, serum ferritin levels are usually low-normal, and serum or urinary hepcidin levels are inappropriately high for the degree of anemia. Although the number of cases reported thus far in the literature does not exceed 100, this disorder is considered the most common of the “atypical” microcytic anemias. The aim of this review is to share the current knowledge on IRIDA and increase awareness in this field.

Low transferrin saturation is associated with impaired fasting glucose and insulin resistance in the South Korean adults: the 2010 Korean National Health and Nutrition Examination Survey.

The associations of transferrin saturation with diabetes have not been well evaluated and conflicting results have been reported. The purpose of this study is to examine the association of iron indices (serum ferritin and transferrin saturation) with risk of impaired fasting glucose and insulin resistance. We conducted a cross-sectional study in 2413 individuals (1150 men and 1263 women) aged 20-50years who participated in the 2010 Korean National Health and Nutrition Examination Survey. Participants were free of diabetes, malignancy, liver cirrhosis, chronic renal failure, anaemia, pregnancy and menopause. Fasting plasma glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as the outcomes. Impaired fasting glucose was more prevalent in the highest compared with the lowest serum ferritin quartile among men (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.20-3.24) after adjustment for multiple covariates. Following the same adjustment, impaired fasting glucose was less prevalent in the highest compared with the lowest transferrin saturation quartile among men (OR, 0.45; 95% CI, 0.25-0.80) and women (OR, 0.33; 95% CI, 0.14-0.77). Moreover, a higher ferritin level was significantly associated with higher HOMA-IR after adjusting for confounders in men. Lower transferrin saturation was also significantly associated with higher insulin levels and HOMA-IR in both sexes. Lower transferrin saturations were associated with an increased risk of impaired fasting glucose and insulin resistance among general South Korean population.

Anemia ferropénica en la enfermedad inflamatoria intestinal

Anemia is the most common extraintestinal complication in patients with inflammatory bowel disease. It is so frequent that it is indispensable to perform periodic analytical controls for early detection and treatment. The mechanisms that generate it could be diverse, being iron deficiency (genuine or functional) the most common, followed by and usually associated with chronic inflammation. We evaluated these mechanisms, esentially with ferritin, transferrin saturation and inflammatory markers. A low transferrin saturation indicated iron deficiency, “genuine” if ferric deposits are also low, or “functional” if they are normal or even high. Iron deposits are not easily assessed because their usual marker, ferritin, is substantially influenced by the existence of an inflammation. This is not always easy to estimate either, usually it is evaluated with the CRP. We consider iron deposits are diminished if ferritin is <30μg/l without inflammation, and <100μg/l when inflammation is present. Other parameters less influenced by inflammation could be useful to discriminate between both types of anemia. Endovenous iron, essential in some situations, is increasingly recommended versus the oral treatment because it avoids the adverse gastrointestinal effects, it is safe, efficient and faster. It is also very convenient for the patient if new formulas are being used, since they can administer all necessary iron in only 1 or 2 doses. The goal of this treatment is to bring hemoglobin back to normal levels, and ideally reach a ferritin of >400μg/l, thus reducing the elevated risk of recurrence of anemia. Once corrected, periodic controls must be conducted, at least quarterly during the first year.

PREVALENCE OF ALPHA THALASSEMIA IN MICROCYTIC ANEMIA: A TERTIARY CARE EXPERIENCE FROM NORTH INDIA

IntroductionCases with microcytosis not responding adequately to iron supplementation are diagnostic dilemma and have been reported to harbor alpha (α) thalassemia mutations. The aim of this study was to determine the common α globin gene deletions in cases with microcytic anemia.MethodsFifty four patients selected (22 females and 32 males) had microcytic anemia (MCV < 80 fl, Hb <12gm/dl) with raised TRBC (> 5M/mm3) but normal Hb HPLC. They had either low or normal Transferrin Saturation (TS). Gap-PCR for four common α-gene deletions (-α3.7, -α4.2, - -αSA and --αSEA) was done.ResultsOut of the total fifty-four cases nineteen (35.2%) cases were found to have α gene mutations; Three homozygous and sixteen heterozygous cases including -α3.7 deletions and a single case of -- α SA ; but no -α4.2 and –SEA mutations were found.Conclusionα gene mutations can confound iron deficiency anemia, but no RBC indices, or a discriminant function can identify it is presence Molecular studies have to be resorted to. Gap PCR for common α thalassemia mutation including –α SA should be done even in the face of low iron stores in subjects who respond incompletely to iron supplementation.

Functional and clinical impact of novel TMPRSS6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies.

Iron-refractory iron-deficiency anemia (IRIDA) is a rare autosomal-recessive disorder characterized by hypochromic microcytic anemia, low transferrin saturation, and inappropriate high levels of the iron hormone hepcidin. The disease is caused by variants in the transmembrane protease serine 6 (TMPRSS6) gene that encodes the type II serine protease matriptase-2, a negative regulator of hepcidin transcription. Sequencing analysis of the TMPRSS6 gene in 21 new IRIDA patients from 16 families with different ethnic origin reveal 17 novel mutations, including the most frequent mutation in Southern Italy (p.W590R). Eight missense mutations were analyzed in vitro. All but the p.T287N variant impair matriptase-2 autoproteotylic activation, decrease the ability to cleave membrane HJV and inhibit the HJV-dependent hepcidin activation. Genotype-phenotype studies in IRIDA patients have been so far limited due to the relatively low number of described patients. Our genotype-phenotype correlation analysis demonstrates that patients carrying two nonsense mutations present a more severe anemia and microcytosis and higher hepcidin levels than the other patients. We confirm that TMPRSS6 mutations are spread along the gene and that mechanistically they fully or partially abrogate hepcidin inhibition. Genotyping IRIDA patients help in predicting IRIDA severity and may be useful for predicting response to iron treatment.

Clinical significance of microcytosis in patients with primary myelofibrosis

Microcytosis is a relatively frequent finding in primary myelofibrosis (PMF); however its prognostic significance is unknown. We identified factors associated with microcytosis in PMF and measured its impact on outcomes. Among 725 patients with PMF, 140 (19%) showed microcytosis. In multivariate analysis, factors associated with microcytosis were absence of prior therapy, low iron, low transferrin saturation (satTF), and splenomegaly. Among 375 untreated patients, low satTF and splenomegaly were associated with microcytosis. Overall, microcytosis was associated with a higher risk of transformation to leukemia (p=0.03), but not shorter leukemia-free survival. Microcytosis in PMF may be related to dysregulation of iron homeostasis.

Prevalence and possible causes of anemia in the elderly: a cross-sectional analysis of a large European university hospital cohort.

BackgroundAnemia in later life is associated with increased morbidity and mortality. The purpose of this study was to evaluate the prevalence and possible causes of anemia in the elderly in a well defined hospital cohort.MethodsParticipants in this cross-sectional, retrospective analysis included all inpatients and outpatients aged ≥64 years with complete blood counts treated at Innsbruck Medical University Hospital between October 1, 2004 and September 29, 2005 (n=19,758, median age 73 years).ResultsAccording to World Health Organization criteria, 21.1% of these patients were anemic, ie, 30.7% and 37.0% at 80+ years and 90+ years, respectively. The prevalence of anemia was significantly correlated with advanced age (r=0.21; P<0.001) and male sex (P<0.001). In anemic patients, renal insufficiency with a glomerular filtration rate <30 mL/min/1.73 m2 (11.3% versus 2.1%), hyperinflammation (62.1% versus 31.4%), absolute (14.4% versus 6.9%) or functional (28.2% versus 11.8%) iron deficiency, and folate deficiency (6.7% versus 3.0%) were observed significantly more often than in nonanemic subjects (P<0.001). The pathogenesis of anemia was multifactorial, with decreased renal function (glomerular filtration rate <60 mL/min/1.73 m2), signs of inflammation, and functional iron deficiency detected in 11.4% of anemic patients. Hemoglobin was significantly correlated with elevated C-reactive protein (r= −0.296; P<0.001) and low transferrin saturation (r=0.313; P<0.001). Mean corpuscular volume correlated only weakly with the various anemia subtypes. Cytopenias and morphologic alterations suggestive of underlying myelodysplastic syndromes were found in a substantial proportion of anemic patients, including thrombocytopenia (5.4%), leukopenia (8.26%), and macrocytic alterations (18.4%).ConclusionAnemia was frequently diagnosed in this series of elderly patients. Partly treatable nutritional deficiencies, such as iron or folate deficiency, were identified as possible causes. A complex and heterogeneous interplay of chronic inflammation, functional iron deficiency, and renal impairment was identified in a large proportion of patients. A hitherto undiagnosed myelodysplastic syndrome can be assumed in a relevant proportion of patients. Morphologic classification based on mean corpuscular volume is inadequate from the standpoint of pathogenesis. New parameters are needed to differentiate the multifactorial pathogenesis of anemia in the elderly.